Blueprints Neurology Notes.docx

Ch. 2 Neurologic Investigations CSF Analysis Getting a Lumbar Puncture (LP)  Patent should be lying in a fetal position on their side (legs and arms flexed) with their back straight and parallel with the edge of the bed. Apparently this helps with getting accurate opening pressures.  Needle should be inserted bevel up (decrease chance for transverse shearing of ligaments) at the level of: o Adults: L3-L4 interspace (level of the Anterior Superior Iliac Spine ASIS) o Older children: L2-L3, L3-L4, or L5-S1 interspace (spinal column grows more quickly the the spinal cord in childhood) o Infants <12 months: L2-L3 interspace (tip of spinal cord sits at L3 vertebrae) LP Results  Normal: clear fluid; glucose is 2/3 of blood glucose; 40-50mg/dL of protein; <5 WBCs per mm3 with lymphocyte predominance; Opening pressure 60-150 mm H2O in fetal position  RBC presence: o No xanthochromia: traumatic tap (may be some in first few samples of CSF) o Xanthochromia: yellowish discoloration of spun CSF supernatant due to lysed RBCs in the sample from in vivo bleeding into the CSF  Positive EBV on PCR: strongly suggests CNS lymphoma in immunosuppressed/AIDS patients  14-3-3 protein: specific for Creutzfeldt-Jakob disease Disease Bacterial Meningitis

Cell PMNs (neutrophils)

Protein High

Viral meningitis /Encephalitis TB meningitis

Lymphocytes

High

Lymphocytes

High

Guillain-Barre syndrome

Normal

Multiple Sclerosis (MS)

Lymphocytes

Acute Disseminated Encephalomyelitis Subarachnoid Hemorrhage

PMNs (neutrophils) or lymphocytes Lymphocytes or many RBCs

Normal - High Slight Normal increase High Normal Normal - High

Glucose Other Findings Low Culture/Gram stain may be positive Normal Viral PCR may be positive Very low Normal

Normal

Acid-fast bacilli positive

Oligoclonal Bands may be present Ologoclonal Bands often absent (differentiates from MS) Xanthochromia

Safety/complications  Contraindications to LP o Mass lesion in the brain: increase intracranial pressure and the LP will decrease pressure in the spinal cord; the difference in pressure could cause cerebral/cerebellar herniation o Fourth ventricle/quadrigeminal cistern: similar to mass lesion o Always do a CT before an LP to check for mass lesions; if they’re present you cannot do the LP o Only special situation is suspected bacterial meningitis where disease process is so urgent that LP needs to be performed emergently for treatment purposes  Post-LP low-pressure headache: common complication; have patient lie flat and increase fluid/caffeine intake. Epidural Blood Patch may be needed in severe situations

Computed Tomography (CT) Basics  CT measures degree of X-ray attenuation by the tissue; if the tissue/substance the X-ray is trying to pass through blocks/scatters it, then the image will be brighter where the X-rays couldn’t hit  Remember that X-ray film (and CTs by convention) are white at the beginning and darken to black with more exposure to X-rays; described as “hypodense” to “hyperdense”.  Houndsfield Units are the measuring system for density on a CT scan: o Air: -1000 (darkest) o Fat: -100 to -50 o Water: 0 (often the CT is normalized to water) o CSF: 15 o Muscle: 10-40 o White matter: 20-30 o Grey matter: 35-45 o Bone: +1000 o Metal: +3000 (brightest)  Often seen as 2-D images but can be 3-D with spiral CT construction Use  Head CT (called ‘head’ because it poorly shows soft tissue) is very quick and best utilized for quick evaluation of patients in acute situation  CT with contrast is a very useful tool in evaluating acute bleeding o Iodinated contrast can get into the brain tissue because of bleed disrupting the BBB o Often this is the first step in evaluating a stroke patient to rule-out hemorrhagic stroke o Fresh blood = bright; old blood = dark  Assessing presence of metal fragments in the body; these are very dense thus will show up nicely and MRI may shift metal objects thus hurting the patient Safety/Other  Be wary in using this on pregnant women as the X-rays can hurt the fetus  Iodinated contrast used in CT can cause nephrotoxicity/allergic reaction in some patients  Claustrophobic patients may prefer CT as it is much quicker to perform than MRI Magnetic Resonance Imaging (MRI) Basics  Uses radiofrequency (RF) pulses to excite hydrogen atoms (“protons”). After excitation these protons will release some energy (“echo”) which is detected by the MRI machine, generating the image. o Time to Echo (TE): a time interval after an RF pulse. At the end of this time interval, the machine measures the intensity of the echo released from the protons of the tissue o Time to Repetition (TR): the time between the release of RF pulses  T1 weighted imaging – uses a short TE and TR causing fat to be brighter on imaging o White matter tracts will be brighter here due to myelin o Water/CSF will be dark on these o Often uses Gadolinium contrast for detecting tumors, abscesses, inflammation, and MS lesions  T2 weighted imaging – uses a long TE and TR causing water/CSF to be bright o Very useful in evaluating the spinal cord  FLAIR imaging – a strong T2 weighted image where CSF/water signals have been inverted (darkened) o “FLuid-Attenuated Inversion Recovery”

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o Gives an extremely high resolution image; best for imaging most CNS pathologies o Very useful in detecting total lesion burden in MS Susceptibility Weighted imaging (SWI) - special sequence sensitive to disruptive effects of substances on the magnetic field (calcium, bone, blood breakdown products o Increased susceptibility areas are black on imaging Diffusion Weighted imaging (DWI) – measures random Brownian motion of water molecules in the tissue, detecting acute changes that are often not seen in other modalities o Best shows cellular toxicity in acute ischemic stroke; it can be positive within 1 hour of onset o Restricted diffusion due to ischemia appear bright

Use  High definition anatomic imaging and the specific uses listed above  Imaging of the posterior fossa and craniocervical junction (bone artifact makes CT useless in these) Safety/Other  MRI can only be used in absence of metal objects (because it’s a giant magnet) thus be wary of metal present in the patient which can shift/injure the patient during procedure  Pacemakers/defibrillators can be disrupted by the MRI magnetic field  Because the machine is a tighter fit, claustrophobic patients/children may be scared by it Vascular Imaging Conventional Angiography: the gold standard and most sensitive test for detecting changes to the vasculature of the head/neck/brain  Injects contras dye into the blood vessels using imaging to bring out the vasculature for examination  Invasive: contrast dye reaction, plaque dislodgement from catheter, and bleeding are all risk factors Magnetic Resonance Angiography (MRA): uses MRI techniques and blood flow as contrast for imaging  Less invasive, faster, less expensive but may not pick up subtle changes to vasculature  “Fat suppressed” MRA of the neck is used to detect vertebral/carotid dissections Magnetic Resonance Venography (MRV): same as MRA but for the veins  Used often in detecting venous sinus thrombosis Extracranial Doppler sonography: uses ultrasound to visualize vasculature  Totally non-invasive but less accurate way to image head vasculature  Used to detect stenosis/occlusion of extracranial cartoid branches or planning for carotid endarterectomy Transcranial Doppler (TCD): same as extracranial but for deeper vessels. Many intracranial vessels are not accessible via this method Other Imaging 18-fluorodeoxyglucose-PET scan: uses radioactive glucose to measure regional brain metabolism  Areas of heightened brain activity use more glucose giving a proxy for brain activity; hypermetabolic areas will show up brighter on scans  Use: o Planning epilepsy surgery to find areas of epileptic activity via hypermetabolism o Alzheimer’s Disease: hypometabolism in the temporal/parietal lobes o Frontotemporal dementia: hypometabolism in temporal/frontal lobes o Lewy Body dementia: hypometabolism in occipital lobe Single-photon emission computed tomography (SPECT): uses radioactive isotopes to detect increased bloodflow in the brain (increased brain activity means more blood flow to that area)  Lower resolution PET scan with similar correlates for seizure/dementias

Magnetic Resonance spectroscopy: can help show areas of neuronal damage/dysfunction  Doesn’t seem to be a huge part of clinical practice; more of a reasearcher thing CNS electrical Studies Electroencephalography (EEG): measures the electrical activity of the cortex via electrodes on the scalp.  Activity is demonstrated in different waves-forms correlating with brain activity o Beta (14-30Hz) – eyes open or REM sleep activity o Alpha (8-13Hz) – relaxed state with eyes closed o Theta (4-7Hz) – drowsiness/early sleep o Delta (0.5-3 Hz) – drowsiness/early sleep  Electrodes are placed in an array on the scale and connected in specific ways called the “montage” o Bipolar montage: all electrodes are active; recordings are made based off the differences in detected activity between adjacent electrodes o Referential montage: activity is recorded in an electrode relative to a distant electrode or is a common average signal  Wave forms are made by the sum of the post-synaptic potentials in the cortical neurons o Excitatory is positive; inhibitory is negative  Can be used for helping diagnose CNS disorders, especially epilepsy, and detecting seizure/sleep activity but is NOT particularly specific to any given disease process Evoked Potentials: these are measurements of brain activity in response to a stimulus  Often the goal is to detect the latency of response by the brain to the stimulus with delay in response indicating dysfunction at some point  Visual Evoked Potentials: visual stimulus is presented to patient and latency of P100 waves are detected; delay indicates dysfunction of the optic nerve  Somatosensory Evoked Potentials: sensory stimulus presented and latency of N20 potentials are detected; delay indicates problem with peripheral nerves/spinal cord or anoxic brain damage; also used to monitor neurologic function during spinal surgery  Brainstem Auditory Evoked Potentials: abnormality in brainstem dysfunction/vestibular Schwannoma PNS electrical studies Nerve Conduction Studies (NCS)/Electromyography (EMG)  honestly the way this is written in the book is really confusing to me. You may want to just come back at a later time to try and figure this out [p.14-15]

Ch.3 Coma and Altered Consciousness Approaches Definitions Coma is a state of unarousable unresponsiveness with eyes closed without response to stimuli  Verbal stimuli, sternal rub, nasal tickle, and nailbed pressure are all classic ways to illicit a response from a patient with altered consciousness  Drowsiness, lethargy, obtundation, and stupor all are ways to describe altered consciousness but are often used imprecisely. It may be better simply to describe what the patient responds to Glasgow Coma Scale (GCS) – a widely used way of determining/describing the severity of a coma. It gives no information about the cause, but extremely useful for quick evaluation of head trauma Clinical Approach The following algorithm is used to assess coma/altered consciousness. Know it and use it! 1. Remember your ABCs: airway, breathing, and circulation are critical for life and must be checked/maintained first to ensure the patient will not die 2. Look for obvious clues to etiology: brief history/physical exam should be done promptly. This may be elicited from the family, signs on the patient (wrist band, breath, wounds, etc), or the situation they are found in. Meningeal signs are important to check as meningitis/subarachnoid hemorrhage may depress consciousness 3. Try reversing common reversible etiologies: Nalxone (opioid overdose), Thiamine (Wernicke-Korsakoff syndrome), and Dextrose (hypoglycemia) should always be given in that order. Remember that Dextrose before Thiamine may precipitate worsening Wernicke’s encephalopathy! 4. Check brainstem reflexes and look for focal signs: via the neurologic exam you need to check for these two things to assess possible causes/clinical intervention for the patient a. Assess level of consciousness with different stimuli b. Assess Cranial Nerve reflexes i. Pupillary (CN II | III) – shine light into eye and look for direct/consensual constriction ii. Oculocephalic (CN VIII | CN III, IV, VI) – forcibly turn head horizontal/vertical to assess for present conjugate eye movements. Don’t do this in a neck injury patient. iii. Caloric testing (CN VIII | CN III, IV, VI) – inject 50mL ice water into each ear and observe for conjugate eye deviation toward the ear injected. OK in neck injury pts. iv. Corneal (CN V1 | VII) – touch lateral cornea with cotton swab and observe for direct/consensual blink reflex v. Gag (IX | X, XI) – touch posterior pharynx with cotton swab and observe for gag c. Do any other parts of the neurologic exam you can do try and final focal signs i. Hemiparesis, aphasia, reflex asymmetry, facial droop, unilateral Babinski (+), etc. 5a. Focal signs present -> suspect structural cause -> Urgent neuroimaging 5b. Focal signs absent -> suspect diffuse cause -> metabolic, toxic, or infectious workup/neuroimaging This algorithm can help up in determining what is damaged in the brain in a quick/imprecise manner:  Brainstem damage – lack of Cranial Nerve reflexes  Unilateral Cortical damage (stroke, abcess, tumor, hemorrhage) – Focal signs present on exam  Diffuse Cortical Damage (toxic, metabolic, infectious, ischemic) – no focal signs present

Labs and Imaging Studies If structural cause is suspected CT should be done immediately to rule out acute hemorrhage or rapidly enlarging mass lesion from bleeding into the lesion If diffuse cause if suspected:  Blood testing: CBC, glucose level, LFTs, toxicology screen  Infection testing: CXR, urinanalysis, blood/urine cultures  CT with lumbar puncture/empiric antibiotics if meningitis is suspected  MRI may be used for imaging purposes  EEG may be useful for assessment of coma/altered consciousness or can reveal specific findings like non-convulsive status epilepticus Treatment and Prognosis Basically treat the underlying cause; no surprises here.  Raised intracranial pressure can be an emergency and should be treated with prompt interventions like hyperventilation, raising head of the bed, osmotic diuretics (mannitol)  Prognosis rests on the etiology; some may recover while some may lose significant function/die Specific Cases Persistent Vegetative State: loss of all awareness and cognitive function but remain with eyes open, exhibit sleep-wake cycles, and maintain respiration/other autonomic functions. May progress to coma. Locked-in Syndrome: inability to move extremities and most of face; often limiting patients to only blinking/vertical eye movements  Consciousness is NOT altered, although they may appear vegetative  Typically, due to large lesions at the base of the pons Brain Death: declaration of death based on irreversible cessation of all brain/brainstem functions  Patient is comatose, lacks brainstem reflexes, and does not spontaneously breath with increased PCO 2  Hyperthermia or drug overdose must not be present  EEG electrocerebral silence (‘flat lilne’) or cerebral bloodflow absence on angiography are confirmatory Acute Confusional State: essentially a fancy term these folks are using in place of ‘confusion’, ‘encephalopathy’, or ‘delerium’ to describe a disturbance in mental status where a patient cannot logically follow a plan or respond to questioning due to lack of attention  This is often the result of some underlying etiology. Work the patient up to search for it and then treat it as best possible to resolve the delirium

Ch.4 Neuro-Ophthalmology Anatomy and Function The visual pathway:  Light enters through the retina, stimulates rods/cones  Optic nerve senses this, sending neural signals into the visual pathway  Some axons cross over while some stay on the same side, with 90% of both pathways terminating in the Lateral Geniculate Nucleus (subcortical nucleus of visual pathway)  LGN sends signals through the optic radiations to the primary visual cortex (Occipital lobe, Brodmann 17) or the striate cortex from the contralateral visual hemifield  Info then goes to associative visual cortex (Brodmann 18/19) and relayed to the posterior parietal/inferior temporal cortices to make up what we see. Neuro-ophthalmologic Lesions Visual Field Defects: specific changes to the visual field can accompany certain lesions, letting us localize the lesion better for further workup/treatment. These are listen in the image below.  Temporal lobe lesions -> superior contralateral quadrantoanopia  Parietal lobe lesions -> inferior contralateral quadrantanopia  Occipital lobe lesions -> congruous hemianopia with macular sparing (often PCA infarct) o Macular sparing from dual blood supply from MCA [insert eye image]

Visual Field Testing: Certain tests can help you parse out what deficits a person is having.  Monocular/Binocular: if the problem is in one eye, it suggests a problem in the eye/optic nerve/optic chiasm. If binocular it suggests a problem in the optic chiasm or after the chiasm.  Visual Acuity: use your visual acuity card to assess the ability of the person to see o If looking through a 2mm pinhole improves vision, the eye is fine, it’s a problem with the lens and the person likely needs glasses o Counting fingers, perception of movement, and perception of bright light can all be used if the person has failing vision and cannot read the letter.  Color: Ishihara plates are used to test this o May reveal color blindness o Red desaturation can be an early sign of optic nerve damage  Pupillary testing: test for direct/consensual pupillary reflex and note the size of the pupils o Relative Afferent Pupillary Defect (RAPD): aka the Marcus Gunn pupil, this pupil will constrict consensually to light but not directly. A “swinging light test” will show the pupil constricting consensually but dilating when the light is shown on it.  Visual Field: fingers in the visual field to test the width/presence of their field  Opthalmoscopic Exam: break it out and have a look! You might get something interesting!

Pupillary Disorders Pupil constriction/dilation is controlled by the following pathway:  Afferent signal comes from normal visual pathway (retina -> optic nerve -> chiasm -> optic tract ->)  Sympathetic (mydriasis; pupillary dilation): controlled by cervical sympathetic neurons o 1st order: Ipsilateral posteriolateral hypothalamus receives afferent visual signaling o 2nd order: Intermediolateral cell column at C8-T1 in the brainstem receives IPH signaling o 3rd order: Superior cervical ganglion receives ICC signaling, travels along the internal carotid, enters the cavernous sinus and innervates the pupillodilator muscle  Parasympathetic (miosis; pupillary constriction): controlled by the Edinger-Westphal Nucleus (EWN) o 1st order: EWN receives input from the afferent visual signaling and parasympthetic fibers from EWN travel with CNIII, following the inferior division of CNIII o 2nd order: Synapse with the ciliary ganglion in the posterior orbit to Innervate the pupilloconstrictor muscle Evaluating Pupillary Defects  Anisocoria (uneven pupils) may be normal. You can tell this if the pupils react normally to light  If they’re not reacting properly to light, consider the following steps to find which is the abnormal one: o If the small pupil is abnormal: lesion is likely in the sympathetic innervation  Dim the lights and see how the small pupil reacts: delayed/no dilation of the small pupil suggests sympathetic dysfunction  Because the ‘large’ pupil will dilate normally, the anisocoria will be exacerbated o If the large pupil the abnormal: lesion is likely in the parasympathetic system  Midbrain damage: CNIII originates in the midbrain, thus damage here can also damage parasympathetic fibers running with it. Presents with focal signs.  CNIII palsy: parasympathetic fibers run along the outside of CNIII, making 3 scenarios:  Compression: pupil is dilated but eye function spared (only parasymp. affected)  CN III Ischemia: pupil is normal but ptosis/eye muscle weakness present  Severe damage: ptosis, dilated pupil, and opthalmoplegia of eye muscles present  Ciliary ganglion damage: anisocoria, photophobia, and blurred near vision with poor reaction to light but normal accomadation (Adie’s pupil). 0.1% pilocarpine produces enhanced constriction in affected eye.  Syphilis: both pupils small/irregular showing poor reaction to light, but normal accomidation; will not react to mydriatic agents  Light-near dissociation: typically, pupillary constriction to light is more intense than to a object getting near to the eye. In this situation, it’s reversed and the pupil will not react to light as well, but near objects illicit a normal response. Feature of Adie’s pupil and Argyl-Robinson pupil

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Horner’s Syndrome is a classic syndrome of myosis, ptosis, and anhydrosis on one side of the face due to damage to one of the neurons in the sympathetic system of the pupil (outlined above). o 1st order (central) damage: hypothalamus infarcts, mesencephalic stroke, brainstem damage/compression, Wallenberg syndrome, Spinal cord damage/compression o 2nd order (preganglionic) damage: cervicothoracic cord/root trauma, cervical spondylosis, Pancoast Tumor o 3rd order (postganglionic) damage: superior cervical ganglion damage, internal carotid artery trauma/dissection/tumor/etc., tumor/trauma at the base of the skull, cavernous sinus tumor/ inflammation/aneurysm/etc o Evaluating Horner’s can be done with several tests:  Cocaine eyedrops fail to dilate the pupil  Apraclonidine (a1/a2 agonist) dilates the pupil  Hydroxyamphetamine will dilate pre-ganglionic Horner’s but fail in postganglionic

Optic Disc Disorders Papilledema: optic disc swelling specifically caused by increased intracranial pressure (ICP) resulting in impaired in blocked axoplasmic transport in the optic nerve  Any other form of optic disc swelling should simply be called optic disc swelling Drusen: calcified hyaline bodies resulting from slowed normal resorption of rods/cones Uhthoff’s phenomenon: worsening visual function during exercise/hot baths/etc; classic sign of MS Foster Kennedy syndrome: ipsilateral optic disc atrophy with contralateral papilledema; results from compression of optic disc by mass (compression = atrophy on that side and overall increased ICP) Abnormality Symptoms/Fundoscopy Diagnosis/Therapy Increased ICP - Morning headache, ataxia, MRI/CT showing some lesion or LP transient visual obstruction. with increased opening pressure - No RAPD, color loss, or loss of visual acuity

Drusen or pseudopapilledema

- Fundi: bilateral disc hyperemia - Enlarged blind spot with normal visual acuity

Optic neuritis

- Fundi: hyaline bodies without disc changes - Painful visual loss, Uhthoff’s Phenomenon, RAPD, loss of color discrimination, central scotoma

Ischemia

- Fundi: variable - Sudden painless visual loss (pt >50yrs w/ cardiac problems) - Fundi: usually unilateral segmental disc edema

Treat the underlying cause

Diagnose with funduscopic exam/clinical exam. No real treatment MRI for demyelination, visual evoked potential slowing IV methylprednisolone; likely from Multiple sclerosis TIA, diabetes, HTN, vasculitis workup. MRA/ultrasound of carotid arteries Treat underlying cause

Eye movement and Misalignment Motor innervation of the eye  CNIII (oculomotor): innervates superior/medial/inferior recti, inferior oblique muscles, levator palpebrae superioris, and pupillary constrictor (parasympathetic). Lesion produces ptosis, mydriasis, and down/out gaze  CNIV (trochlear): innervates superior oblique muscle. Lesion produces oblique diplopia that’s worse on downgaze. Pt often has diplopia when reading or going down stairs. Improves with head-tilt away from the site of the lsion  CN VI (abducens): innervates lateral rectus muscle. Produces esotropia where one eye will simply not look toward the ear while the other is full range of motion. May be a sign of increased ICP. Medial Longitudinal Fasiculus (MLF) lesion  The MLF connects CNIII to the contralateral abduces (CNVI) nucleus. This allows for both eyes to look in the same direction laterally  Internuclear opthalmoplegia (INO): lesion of the MLF where conjugate gaze is disrupted. The ipsilateral eye will fail to adduct and the contralateral eye will move/demonstrate nystagmus o Left INO = left eye fails to abduct, right eye moves with nystagmus o Bilateral INO is possible in some situations  One-and-a-half syndrome: syndrome where one eye cannot move laterally at all, and other other can move laterally in only one direction (1.5/2 lateral eye movements are impaired. o Lesion of PPRF or CN VI and the MLF on the same side o Abduction of the contralateral eye is intact o Figure on right shows a lesion on the left-side (shown as if you were looking at a patient’s eyes)  Parinaud’s syndrome: pineal gland tumor compression of the rostral interstitial nucleus of the MLF (riMLF; responsible for upgaze). Causes upgaze disturbance, light-near dissociation, and nystagmus upon upgaze (eyes pull apart and retract when looking up) Note that the “doll eye’s maneuver” or ice water calorics will produce intact eye saccades if the nuclei of eye cranial nerves are intact. Thus, if these tests are normal, the lesion causing the neurologic problem must be ‘supranuclear’ [Note different types of nystagmus p.35 Table 4-4]  Nystagmus is named based on it’s fast component

Ch.5 The Approach to Weakness 1. Make sure true weakness is the complaint  Sometimes “weakness” really means clumsiness, numbness, or pain with movement. You must be careful to test the muscles for strength objectively when considering weakness. 2. Identify which muscles are weak  You MUST be specific muscles in order to properly use weakness to search for the source 3. Determine the pattern of weakness is ascending order of motor innervation  Muscle – typically causes proximal, symmetric muscular weakness earlier with distal muscles later o Associated symp: lack of sensory signs and normal reflexes are often a feature. Limbs may appear to lack reflex if they’re near paralyzed. May be painful if inflammatory o Labs: elevated serum creatinine kinase (CK) and myopathic changes on muscle biopsy o Differential: myopathies or muscular dystrophies 

NMJ – typically proximal muscle weakness, ptosis, and extraocular/neck muscle weakness are prominent signs. They key is the pattern of weakness should change with muscle use; either getting weaker with use (myasthenia gravis) or stronger with use (Lambert-Eaton syndrome) o Associated symp: no sensory deficits; may have autonomic features o Labs: EMG/NCS can show changes in muscle fatigability and are often pathognomonic. Serum markers like anti-acetylcholine recpetor antibodies (myasthenia gravis) o Differential: NMJ disorders (mentioned above)

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Nerve (neuropathy) – specific muscles are weak corresponding directly to nerve pathology. o Mononeuropathies: single nerve injured. Numbness/tingling are common. Usually due to entrapment of the nerve by muscle/bone o Mononeuropathy multiplex: succession of nerves damaged. Associated with pain. Usually due to vasculitis or other rheumatologic diseases. o Polyneuropathies: diffuse nerve distribution. Often affect long nerves first, causing distal muscle weakness, sensory loss, and depressed reflexes. Can be demyelinating or acquired and often have some underlying etiology. o Labs: EMG/NCS can test nerves to determine the exact damage caused to the nerve o [p.40 table 5-1 has a listing of muscles and their nerve innervation]

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Root (radiculopathy) – similar to a neuropathy but the pattern of muscle weakness can be traced back to the nerve root, causing a more diffuse syndrome of muscle weakness. Reflex Root o Associated symp: tingling and pain in the root distribution are Biceps C5 common. Muscle stretch reflexes may be depressed if the Brachioradialis C6 particular root is disrupted (shown on the right) Triceps C7 o Labs: EMG/NCS can help parse out whether it’s a root or peripheral Finger Flexor C8/T1 nerve problem. MRI of the spine to check for compression of the Patellar (knee jerk) L4 spinal cord as the source (monoradiculopathies) or LP to rule out Hip adductor L3 infection/inflammation (polyradiculopathies) Ankle Jerk S1 o Differential: disc herniation, shingles, inflammatory/infectious conditions of the CNS/PNS

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Plexus (plexopathy) – similar to radiculopathy, but multiple muscles that do not conform to a specific root/nerve will be weak. Often you’ll get some muscles from a root & not others, across multiple roots. o Associated symp: sensory loss and multiple weak muscle stretch reflexes o Labs: EMG/NCS for determining what area is affected in the plexus. MRI of brachial plexus/pelvis to rule out mass lesions o Differential: fairly diffuse, look for other predisposing signs of disease. Diabetic amyotrophy is a classic lumbrosacral plexopathy to be on the lookout for

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Spinal Cord – two major results happen when you damage the cord. First, you get lower motor symptoms at the level of the lesion from anterior horn cell destruction. Upper motor symptoms will occur below the level of the lesion due to corticospinal tract disruption. o Associated symp: May be sensory loss of spinothalamic or dorsal columnar tracts. Bladder/bowel dysfunction may be present.  UMN signs: weakness, spasticity, hyperactive reflexes, Babinski/Hoffmann reflexes  LMN signs: weakness, muscle wasting, fasciculations o Labs: MRI (structural assessment) and LP (inflammation/infection) o Differential: wide-spread, look for the signs of lesion then search for disease process

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Brain/Brainstem – lesions will cause widespread weakness, often with lateralization depending on the site of the lesions o Hemisphere – will cause weakness/UMN signs on opposite side of body to lesion  Lower extremities affected more when the parasagittal portion of the motor strip (think homunculus) are affected -> ACA infarcts tend to do this  Upper extremities affected more when the parasagittal portion of the motor strip (think homunculus) are affected -> MCA infarcts tend to do this  Dominant side lesions may cause aphasias  Non-dominant side lesions may cause neglect o Internal Capsule – will cause weakness/UMN signs on the entire body (face/upper/lower extremities) contralateral to the lesion  All of the homunculus is bundled at that level, so it’s all knocked out o Base of the pons – will cause weakness/UMN signs on the ipsilateral face but contralateral arm/leg in relation to the lesion  This is below the point where the corticospinal tract crosses over in the brainstem for the face but not quite for the body  May cause cranial nerve problems depending on site of the lesion o Labs: Brain/brainstem CT/MRI is paramount for localizing/finding etiology of the lesion o Differential: stroke, demyelinating disease, tumor, infection, trauma, possible others

Ch.6 The Sensory System Sensory Neural Pathways Two major spinal sensory tracts are present, which utilize specific neurons/distributions to carry out their function:  Spinothalamic Tract – carries pain/temperature sensation from extremities to brain o 1st order: A-delta (fast) and C (slow) fibers for different sensory modalities which synapse at the dorsal horn of the spinal cord o 2nd order: cross over at the level of the spinal cord they entered in and ascend contralaterally to synapse at the VPL nucleus of the thalamus o 3rd order: thalamus projects to the post-central gyrus (primary somatosensory cortex) o Note: this tract is somatotopically arranged so that they ascending fibers entering at the level of the sacrum are lateral and cervical spine are medial  Dorsal Columns – carries light touch, proprioception, and vibratory sense from extremities to brain o 1st order: A-alpha and A-beta neurons run from the periphery ipsilaterally up to the medulla where they’ll synapse with the nucleus gracillis (lower extremity) or nucleus cuneatus (upper) o 2nd order: cross over in the medulla and ascend to synapse at the VPL nucleus of the thalamus o 3rd order: project from thalamus to the post-central gyrus (primary somatosensory cortex) o Note: somatoatopic arrangement is sacral medial/cervical lateral  Trigeminal nerve – carries facial sensation to the brainstem terminating in the VPM nucleus of the thalamus, which subsequently projects to the post-central gyrus (primary somatosensory cortex) Testing for Sensory Deficits Testing for light touch, pain, heat/cold sensation, proprioception/joint position sense, and vibratory sense are the extent of the sensory exam. Some deficits are defined below:  Paresthesia – abnormal sensation of tingling/prickling/pins and needles  Dysesthesia – unpleasant sensation triggered by normally non-painful stimuli  Hyperesthesia – increased sensitivity to sensory stimuli  Allodynia – pain provoked by normally non-painful stimuli  Dissociated sensory loss – loss specifically of either the posterior columns or spinothalamic tract When sensory loss is observed, it’s distribution can be used to determine the site of the lesion  Peripheral nerve – loss of sensory modalities in distribution of the nerve; associated with motor loss  Root – dermatomal distribution of sensory loss  Plexus – sensory loss of two or more peripheral nerve sensory distributions  Spinal cord – variable loss of sensation at and below the level of the lesion in the spine  Brainstem – sensory loss in the ipsilateral face and contralateral arm/leg  Thalamus – contralateral hemisensory loss  Posterior limb of internal capsule – contralateral hemisensory loss  Cortex - contralateral hemisensory loss  Psychogenic – variable and changing sensory loss possibly with confusing associated signs/symptoms. A good history/physical will help elucidate these losses

Ch.7 Dizziness, Vertigo, and Syncope Vertigo Vertigo is a sensation that the “room is spinning” due to acute asymmetric/unbalanced activity in the vestibular systems of the ear; slow changes often are compensated for by the brain!  Central Vertigo: result of some central process of the brain often featuring diplopia, dysarthria, dysphagia, difficulty with walking/posture, vertical nystagmus (brainstem dysfunction)  Peripheral vertigo: result of some peripheral process often featuring tinnitus, nausea, vomiting  Unidirectional nystagmus can occur in vertigo from central or peripheral causes Vestibular neuronitis: sudden, spontaneous vertigo/nausea/vomiting (minutes to hours) typically improving over days to weeks.  Due to peripheral dysfunction of the ear’s vestibular system  Unilateral nystagmus that is suppressed by visual fixation may be present  Recovery is spontaneous; occurs when CNS compensates for the vestibular dysfunction Labyrinthine concussion: head injury causing ear labyrinth damage, thus spontaneous vertigo, hearing loss, and tinnitus; may or may not feature a skull fracture Infarction  Labyrinth: lack of bloodflow to the internal auditory artery (branch of AICA); results in sudden onset deafness/vertigo  Brainstem/cerebellum: lack of bloodflow to these structures causing a sudden central vertigo with deficits in cranial nerves, weakness, ataxia, and sensory changes. The lack of isolated vertigo is the hallmark of brainstem/cerebellar damage here. Meniere Disease: episodic vertigo, progressive hearing loss, tinnitus, pressure sensation in the ear, and nausea/vomiting. Caused by increased endolymphatic volume in the ear Perilymph fistula: abrupt onset of vertigo preceded by hearing a “pop” (disruption of endolymphatic system), sudden middle ear pressure, sneezing/nose blowing/coughing/straining Benign Positional Paroxysmal Vertigo (BPPV): brief attacked of vertigo triggered by positional changes lasting only a brief period of time. Classically symptoms occur when patient lays down for bed or awakens in the morning. Attacks can occur with asymptomatic periods for months at a time!  Pathophys: free moving calcium carbonate crystals precipitate in the semi-circular canals of the vestibule. When the head moves, these crystals move differently than the normal fluid in the canals resulting in improper stimulation of hair cells. The brain attempts to compensate for the movement causing nystagmus and vertigo.  Dix-Hallpike Maneuver: diagnostic maneuver for BPPV o Offending ear is tilted toward the ground with 30o neck extension. The patient is quickly layed back into a laying position so the offending ear is on the table. If vertical/horizontal nystagmus results, it’s BPPV.  Epley Maneuver: therapeutic maneuver for BPPV o Starts as a Dix-Hallpike but the head is then rotated 90o, the patient turns onto their side, then sits up allowing re-positioning of the crystals to alleviate the nystagmus.

Syncope Syncope is a transient loss of consciousness/postural tone due to brain hypoperfusion  Often before passing out patients experience presyncope (light headedness, blurry/darkened visual fields). If the patient doesn’t pass out, it’s simply called presyncope.  Many causes; most are cardiovascular; some are neurologic/drug related Neurogenic Syncope: syncope produced by sudden changes in autonomic function. Sudden afferent impulses triggered by things listed below stimulate the vagus nerve (CN X), resulting in hypotension/bradycardia severe enough to cause brain hypoperfusion  Micturition syncope: rapid empty of a distended bladder  Carotid sinus hypersensitivity: compression of the carotid sinus  Neurocardogenic syncope: vigorous contraction of an underfilled ventricle  Vasovagal syncope: strong emotions (often fear) or acute pain Autonomic Failure: failure of sympathetic activation (no NE release) to compensate for orthostatic hypotension produced by abrupt positional changes (standing up too fast).  When evaluating syncope, be sure to get a thorough history/physical as this has man central/peripheral causes that are both neural AND non-neural. Autonomic failure should not be the first thing to jump at when you hear syncope!  If other causes (cardiovascular, hematologic, etc.) have been ruled out and neurologic cause is suspected, a tilt-table test can consistently produce syncope/presyncope in patients with autonomic failure, aiding in diagnosis. Drug causes: diuretics, anti-hypertensives, vasodilators, and antidepressants can all affect blood pressure/volume, allowing for syncope. Consider medication review whenever syncope is the problem

Ch.8 Ataxia and Gait Disorders Ataxia Cerebellar Ataxia results directly from cerebellar damage. The cerebellum refines movements and maintains rhythm (like in walking properly!), thus damage here makes smooth/purposeful movement difficult  Vermal: damage to the central vermis causes truncal/gait ataxia (central movements)  Hemispheric: damage to a hemisphere causes ipsilateral limb ataxia (lateral movements) Sensory Ataxia results from some sensory deficit that makes it difficult to sense limb movements (like position sense), thus making walking more difficult/clumsy. Specific Causes of Ataxia Cerebellar Stroke (Hemorrhage/Infarction): abrupt onset of vertigo, vomiting, and ataxia.  Depressed consciousness may be a feature as bleeding/swelling can press against the brainstem resulting in altered consciousness, respiratory depression, and death!  Tx: immediate diagnosis/treatment for stroke with physical therapy gives best chance for recover Alcoholic Cerebellar Degeneration: the most common acquired cerebellar ataxia result of long-standing alcohol abuse resulting in progressive, worsening ataxia over weeks-months  Often vermis is primarily damaged (truncal/gait ataxia)  Tx: stop drinking and vitamin supplementation to halt progression/regain some function Post-infectious Cerebellitis: acute limb/gait ataxia with dysarthria ranging from mild to severe  Occurs in children age 2-7 following varicella or other viral infection (virus regressing into neurons may be the source for the nerve dysfunction)  A diagnosis of exclusion after ruling out more common causes (brain tumor, etc.)  Tx: supportive therapy; disease lasts for a few weeks before complete resolution Paraneoplastic Cerebellar Degeneration: acute/subacute pan-cerebellar dysfunction causing truncal/gait/limb ataxia, dysarthria, and oculomotor disturbance (dysmetria, nystagmus, etc.)  Often progressive until a plateau, then stays at this severity causing disability  Gynecologic or small cell lung cancer are classic causes of this  Neural MRI is often normal and CSF is often normal or may have some elevated protein/WBCs  May be caused by autoantibodies Friedreich Ataxia: autosomal recessive disorder with onset in childhood  Always causes progressive ataxia (arms > legs) and dysarthria  Associated symptoms: loss of normal reflexes, spasticity, (+)Babinski, and impaired vibratory/position sense Inherited Episodic Ataxia (EA): brief episodes of ataxia, vertigo, nausea/vomiting with two distinct subtypes  EA-1: caused by voltage-gated K+ mutations featuring brief episodes and inter-attack skeletal muscle myokymia (localized muscle quivering)  EA-2: caused by mutations in the a1-subunit of the P/Q-type voltage-gated Ca2+ channel featuring longer attacks and inter-attack nystagmus. May become progressive/irreversible. Associated with the SCA6 allele

Autosomal Dominant Spinocerebellar Degeneration: cerebellar ataxia, with/without additional neurologic signs that shows a familial autosomal dominant inheritance Hx. Often caused by CAG trinucleotide repeats Miller-Fisher Syndrome: triad of sensory ataxia (proprioceptive loss), areflexia, and ophthalmoplegia  Understood as a “Guillain-Barre syndrome subtype” where anti-GQb1 IgG antibodies are generated by patients after an infection (90% of patients)  Tx: Supportive care. Typically self-limited with good prognosis Other Gait Disorders Hemiparetic Gait: one stiff leg that does not flex at the hip/knee/ankle where the toes often scrape the floor with walking with ipsilateral arm flexed/adducted without free swinging  Result of unilateral brainstem/cerebral hemisphere damage (often stroke) Paraparetic Gait: essentially a hemiparetic gait on both sides  Result of bilateral cerebral hemisphere or spinal cord damage Akinetic-Rigid Gait: stooped posture (flexion of shoulders, neck, trunk) with narrow-based, slow, shuffling steps and reduced arm-swing.  Initiation of gait is difficult and postural reflexes are often impaired  Patient may take tiny steps (festination) forward or backward to preserve balance  Classic gait for Parkinson’s Disease, but may appear in other disorders Frontal Gait: flexed posture with “magnetic” steps (pt struggles to lift feet of the ground taking small, hesitant steps). The most severe forms do not allow the patient to advance himself with steps  Result of damage to the frontal lobe (classically normal pressure hydrocephalus) Waddling Gait: hip abductor weakness fails to stabilize the weight-bearing hip during walking causing the trunk to tilt toward the opposite side to offset the “dip in the hips”  Result of muscular/neural damage affecting the hip-girdle Slapping Gait: loss of proprioception drives patient to “slap” the foot against the ground to sense where it is to manage the legs position in space. Often wide-based and slow.  Often uneven surfaces or walking in darkness results in inability to walk  Classically a result of B12 deficiency or Tabes Dorsalis (dorsal column damage) Psychogenic Gait: a wide-ranging designation that catches any abnormal gait that can result from psychogenic disease processes. Astasia-abasia is a classic description of a more interesting “acrobatic” swinging of the body to maintain gait. Pt will NOT fall over, although may look quite uncoordinated while walking.

Ch.9 Urinary and Sexual Dysfunction Bladder Incontinence Bladder control is coordinated through both skeletal and smooth muscles:  Smooth muscle (involuntary) – bladder and urethra  Skeletal muscle (voluntary) – external urethral sphincter Three major circuits control reflexes to coordinate emptying/storage in the bladder  First Circuit: connects dorsomedial frontal lobe to the medial (M) part of the pontine micturition center (PMC). Allows for urination through detrusor contraction/sphincter relaxation. o Note the lateral PMC does the opposite of medial PMC to stop urination o Damage to PMC will cause failure of both these processes and result in involuntary voiding (incontinence) and detrusor hyperreflexia  Second Circuit (spinobulbarspinal): afferent from the bladder to the PMC. Efferent from PMC to the parasympathetic sacral spinal motor nucleus (involuntary micturition)  Third Circuit (spinal segmental): afferent from detrusor to Onuf’s nucleus (S2-S4). Efferent to striated muscles of the bladder via pudendal nerve (voluntary micturition) Workup  Thorough history of incontinence, initiation, and voiding  Urinanalysis (rule out infection)  Post-voidal Residual (PVR) volume by bladder ultrasound (normal <50 mL) Classification Urge incontinence: huge urge to pee and you cannot hold it (“spastic bladder”) resulting in decreased urinary capacity, reduced compliance of bladder wall, increased urinary frequency  Detrusor hyperreflexia: neurologic hyper-stimulation of the detrusor causing urge incontinence with frontal lobe/pons/suprasacral spinal cord problem  Typically a supraspinal (brain/UMN) cause (cerebrovascular disease, Parkinson’s, etc.)  Tx: o Anticholinergics (Tolerodine, Oxybutinin, Trospium, Solifenacin/darifenacin) – decrease sympathetic outflow to decrease spastic contractions. Concern of anti-cholinergic overdose o TCAs (Imipramine/Amiytiptyline) – concern of side effects (cardiotoxicity, coma, convulsions) and anti-cholinergic effects o Desmopressin (DDAVP) – best used in nocturia, but will decrease voiding frequency o Intravesical capsaicin – for intractable detrusor hyperreflexia; kills afferent C fibers to decrease strength of signaling for contraction o Other: Acetanilide (B3 receptor antagonist) / Sildenafil (PDE inhibitor) / Botulinum toxin / Nerve stimulation (sacral, tibial, pudendal) Detrusor-sphincter Dyssyndergia: uncoordinated contraction of both the detrusor and urethral sphincter so that you’re trying to pee out a closed sphincter  Concerns of increased back-pressure causing kidney damage are huge here  Often caused by spinal cord disease (injury, MS) causing UMN damage  Tx: Cathaterization, sacral nerve stimulation, or doxazocin (a1-adrenergic blocker; decrease urethral tone)

Stress incontinence: peeing inappropriately with some increase in abdominal pressure (laughing, sneezing, etc.); no detrusor muscle contraction or bladder overdistention in this one  Classic in women with weakened pelvic muscle floors (multiparous) / cystoceles  Tx: Pseudoephedrine / Midodrine (alpha agonists) – increase urethral tone to hold back urine Mixed incontinence: mix of urge/stress Overflow incontinence: involuntary urination with bladder over-distention  Due to lower motor neuron damage resulting in an atonic bladder (the bladder doesn’t contract well and the urine builds up to overwhelming levels)  Increase capacity/compliance. Low voiding pressure and flow rate  Tx: o Crede’s or Valsalva maneuver to fully empty bladder when urinating o Self-cathaterization o Bethanechol (25-100 mg qid) may be used to increase muscle tone but is rarely effective Erectile Dysfunction Physiology of a Boner  Point (erection) - Parasympathetic nerve in S2-S4 send impulses via the pudendal nerve to release cGMP and nitric oxide to allow for filling of the penis  Shoot (ejaculation) - Sympathetic nerves in T11-T12 go through the hypogastric plexus and ultimately through the pudendal nerve to make a mess on the floor Etiology  Organic: neuropathy, myopathy, vascular disease, trauma, hypothyroidism, anti-depressants, alcohol, hyperprolactinemia, etc., etc.  Psychogenic: if you’re nervous in bed or having recent trouble with your partner you may have trouble having sex with them resulting in physical manifestations Diagnosis  Hx and physical, neurologic exam, endocrine panel, sleep studies (to see if pt gets nightly erections), and vascular studies are all important  If the patient is getting erections spontaneously, but not in sexual situations consider neurogenic! Tx  cGMP-PDE inhibitors (sildenafil, cardenafil) are the mainstays of treatment, although the underlying etiology must be found for proper treatment.

Ch.10 Headache and Facial Pain Primary Headache Disorders Migraine Headache: unilateral; throbbing/pulsating; associated with nausea/vomiting; exacerbated by movement, light, or sound; last from several-72hr  Migraine with aura – headache preceded/followed/accompanied visual zig-zags/flashing or scintillating scotoma for around 15-20 minutes  Migraine without aura – aura phenomenon does not occur  Cortical spreading depression – a wave of hyperpolarization that spreads among the cortex at about 23mm/minute releasing neuronal substances and stimulating the trigeminal neve afferents o Auras are thought to be due to this spreading across the visual corticies o Pain is thought to be from trigeminal nucleus caudalis stimulation  Diagnosis: clinical signs/symptoms allow for diagnosis without investigation  Tx: o Stop the Migraine: Triptans (5-hydroxytryptamine 1B, 1D, 1F receptor agonists) are the best and often a mainstay of treatment PRN; move into a quiet dark place and rest it off. o Prevent Further Migraines: several drugs exist for this purpose and the book doesn’t really care to delve into them! Tension Headache: recurrent; bilateral/holocranial; tension sensation “like a vice”; ranges from 30 min – several days; lack of nausea/exacerbation by physical activity.  Dx: clinical, although must be careful not to just lump any headache into this  Tx: NSAIDs/relaxation techniques; withdrawal from caffeine, barbiturates, and NSAIDs may cause tension headaches so watch out for that! Cluster Headache: episodic/clustered; strictly unilateral; searing, intense pain over the eye orbital or temporal region; accompanied by autonomic symptoms (lacrimation, conjunctival injection, swelling, edema, rhinorrhea, transient Horner’s Syndrome)  Pts are often quite restless and feel they need to be moving around  Dx: clinical from description  Tx: o Stop the Headache: Triptans are best; Steroids may help shorten the duration of clusters o Prevent Further Headaches: Verapamil/lithium have been used; avoidance of alcohol has been shown to help prevent Paroxysmal Hemicrania: strictly unilateral headache with autonomic symptoms similar to cluster headache with two major distinctions:  Headaches only last 10-30 minutes  Headaches occur CRAZY frequently (>40 attacks in a single day)  Tx: indomethacin apparently works like a charm for these folks Secondary Headache Disorders Subarachnoid Hemorrhage: “the worst headache of my life”; headache starts suddenly a peaks within seconds (“thunderclap headache”)  Dx: Head CT (shows acute bleed) and LP (shows blood or xanthochromia of CSF)  We’ll talk more about this in another chapter!

Low-Pressure Headache: acute headache resulting from low CSF pressure  Classically due to post-LP leakage of CSF but can be spontaneous; production of CSF fails to keep pace with the leak, resulting in the headache  Headache worse in the upright position  Tx: recumbency (laying back), aggressive fluid replacement, and caffeine; epidural blood patch may be used in severe cases (injecting patient’s blood into CSF so it can clot the leak) Idiopathic Intracranial Hypertension (Pseudotumor Cerebri): headache associated with increased severeity when recumbent/alleviation in upright position; worse in the morning  Associated symptoms: pulsatile tinnitus, brief blurring/vision loss, papilledema, CN VI nerve palsies  Classically in overweight young women with menstrual irregularities  Etiology: elevated CSF/intracranial pressure caused by a debated mechanism  Dx: elevated CSF pressure without intracranial mass; exclusion of venous sinus thrombosis (mimic)  Tx: Drain CSF and relieve pressure (repeated lumbar puncture, diuretics, optic nerve sheath fenestration, lumboperitoneal shunt)  Compression/damage of the optic nerve can occur and treatment seeks to avoid this complication! Giant-cell Temporal Arteritis: granulomatous arteritis affecting medium-large arteries classically in people >age 50 in the extracranial carotid branches (ophthalmic, temporal, etc.)  Symptoms: jaw claudation with chewing, amaurosis fugax, fever, weight loss, fatigue, “hard” prominent temporal artery  Feared complication is anterior ischemic optic neuropathy causing irreversible blindness  Dx: elevated ESR, elevated C-Reactive Protein, segmental biopsy of temporal artery showing granulomatous vasculitis (normal biopsy does NOT exclude this disease)  Tx: immediate high dose prednisone (corticosteroid) to preserve vision Chronic Daily Headache Headache of any etiology that is present for >15 days each month. It sucks so try and help these people Facial Pain Trigeminal Neuralgia: hypersensitivity of the trigeminal nerve causing extreme “electric” pain to stimuli of the face in the trigeminal region. Often due to CN V compression.  MRI is prudent to rule out other causes of this pain  Tx: Carbamazepine or other anti-convulsant medication are first-line in symptom relief. Persistent symptoms may be treated with surgical ablation of the nerve. Post-herpetic Neuralgia: neuropathic pain resulting AFTER shingles (acute varicella zoster reactivation) described as burning, itching, and hypersensitivity to light touch.  Tx: early acyclovir (anti-viral) treatment of shingles decreases chance for PHN. Symptomatic treatment with TCAs or Gabapentin can be used in severe situations when pharmacotherapy is warranted.

Ch.11 Aphasia and Friends Aphasia Acquired abnormality of language, often from a focal brain lesion  Affects fluency, comprehension, or repetition (or a combination of the three  Articulation is NOT affected (this is more likely dysarthria)  Anomnia is impaired naming; often a feature of aphasia o High frequency objects: pen/shirt/tie are things some patients may recognize and name but cannot do with a more severe aphasia o Low frequency objects: pen tip/lapel/tie knot are specific parts of objects and inability to name these may reveal a more subtle aphasia Broca’s Aphasia – Fluency/Repetition/Comprehension  Speech features “tip-of-the-tongue” phenomenon, telegraphic speech, and phonemic word substitutions  Due to damage of Broca’s Area (dominant side, posterior part of inferior frontal gyrus) typically by a left MCA stroke (left side because most people are left-dominant)  Patients often know they have the deficit and are quite frustrated by it  Common phrases, song lyrics, and expletives are often preserved  May be accompanied by contralateral hemiparesis Transcortical Motor Aphasia – Fluency/Repetition/Comprehension  May be accompanied by contralateral hemiparesis Wernicke’s Aphasia – Fluency/Repetition/Comprehension  Comprehension difficulty; but also cannot comprehend the words they say resulting in unintelligible speech termed “word salad” and may feature substitutions or neologisms  Often are unaware of deficit, but become frustrated when others cannot understand  Due to damage of Wernicke’s Area (dominant side, posterior part of superior temporal gyrus) typically a left, inferior MCA stroke (left is often dominant)  May be accompanied by a contralateral homonymous superior quadrantanopia Transcortical Sensory Aphasia – Fluency/Repetition/Comprehension  Due to inferior portion of dominant temporal lobe damage, typically from PCA infarct  Due to damage to supplementary motor are in the anterior basal ganglia Conduction Aphasia – Fluency/Repetition/Comprehension  A subtle aphasia due to damage to the arcuate fasciculus (tissue around Broca’s and Wernicke’s areas)  May make paraphasic errors (unintended syllables, words, phrases) Global Aphasia – Fluency/Repetition/Comprehension  Large dominant side lesions affecting Broca’s/Wernicke’s areas  May be accompanied by severe contralateral hemiparesis Subcortical Aphasias  Can mimic Broca’s or Wernicke’s but set off by lesion presence in the deeper brain (basal ganglia/thalamus) and hypophonia of voice (quietness)

Alexia without Agraphia  Inability to read with retain ability to write (pt can write a spontaneous sentence but cannot read it back to you)  Caused by damage to the splenium of corpus callosum  May be accompanied by a contralateral homonymous hemianopia Apraxia Inability to carry out a learned motor task despite having the primary abilities to do the task (hammer a nail)  May know how to hammer a nail and can do it with real objects, but cannot mime it out  May know what to do but cannot do it regardless  May only recognize when someone else is doing it right/wrong  May be unable to do anything with the task, but still SHOULD technically be able to do it Diagnosis  Ask pt to do a task and see if they screw it up o Ask them to pretend to perform a simple task and see what they do o Mimic an examiner o Actually do the action with real objects Etiology  Frontal lobe dominant side lesion – can recognize proper execution of the task but not perform it  Parietal lobe dominant side lesions – cannot recognize or do the task Agnosia Inability to recognize objects through the senses, although the senses are intact  Visual agnosia (cannot recognize things through vision, despite proper visual testing) is a common modality. Pt may recognize an object if allowed to touch it  Caused by damage to the sensory association areas around sensory areas that integrate sensory information into more complex inputs  Prosopagnosia: inability to recognize faces (damage to visual association area) Gerstmann’s Syndrome Rare syndrome of agraphia, acalculia, right-left confusion, and finger agnosia  Caused by dominant side inferior parietal lobe lesion (angular gyrus) Neglect Lack of attention given to one hemispace causing decreased/loss of awareness to that side of the body/world  Due to non-dominant side lesions of frontal/parietal lobes  Not due to lack of ability to sense that side of the body/world; the brain simply ignores it Diagnosis  Basically the ignored side (often the left) is omitted from activities o Pt will only groom the right side of body, eat the right half of food, or draw the right half of a picture they’re asked to draw  Extinction of double, spontaneous stimulation – pt will only recognize the non-neglected side when given some sensory stimulus to both sides of the body  Left side may be used with encouragement

Other non-dominant hemisphere syndromes  Prosody – failure to understand/execute proper inflection of speech; speech is fine (right-side lesion)  Anosognosia – failure to recognize deficits (right-side); left-side lesions are often aware of deficits Ch.12 Dementia Dementia in a nutshell Dementia patients typically have memory loss, speech abnormalities, difficulty with problems solving/abstract thinking, impaired judgement, personality changes, and emotional lability Pseudodementia: term describing depression that mimics dementia; typically, these pts will have dementialike features but will often show a lack of impairment with prodding. Classically, a patient who brings themselves into your clinic complaining of dementia symptoms is depressed. Dementia pts are unaware of their deficits. Specific Types of Dementia Alzheimer’s Disease: the most common dementia; present in 4% of pts >65 years old  Histology: neurofibrally tangles and senile plaques in cortex/hippocampus  Risk factors: o Old age, female sex, history of head trauma, Down’s syndrome o ApoE4 (chrom. 19), Amyloid Precursor Protein (chrom. 21), Presenilin 1 (chrom. 14), Presenilin 2 (chrom. 1), a2-microglobulin mutation (chrom. 12)  Manifestation: o Early: language/reasoning/behavior normal with minor “slip ups” o Late: significant impairment of language/reasoning/cognitive function, loss of independence o Very Late: impairment of motor function, personality changes, hallucinations, delusions o “Sundowning” is a phenomenon where symptoms become worse at night.  Diagnosis o Clinical signs/symptoms and progressive worsening o Elevated tau protein or low AB-42 levels in CSF o MRI showing shrinkage of amygdala, hippocampus, and thalamus o PET/SPECT showing bilateral tempo-parietal hypometabolism o Truly can only be diagnosed with pathologic brain samples showing plaques/NFTs  Therapy: o Goal is to delay progression and maximize function; disease course lasts approximately 12 years o Donepezil: cholinesterase inhibitor | Diarrhea, abdominal cramps, hepatic toxicity o Rivastigmine: cholinesterase inhibitor | Diarrhea, abdominal cramps, hepatic toxicity o Memantine: NMDA-receptor antagonist | dizziness, headache, confusion o Galantamine: cholinesterase inhibitor | Diarrhea, abdominal cramps, weight loss  Disease course lasts 9-12 years before death Vascular Dementia: dementia resulting from cerebrovascular disease  Subtypes o Macrovascular: disease from infarction of major brain vessels o Microvascular: disease from subcortical ischemia (lacunar strokes/deep white matter damage)  Risk factors: HTN, diabetes, advanced age, embolic sources, atherosclerosis  Diagnosis: o Dementia + two or more of additional symptoms: o Focal neurologic signs | abrupt, step-wise, or stroke-related onset | brain imaging showing multiple strokes, lacunes, or extensive white matter damage  Treatment: prevent further vascular disease and treat risk factors

Dementia with Lewy Bodies: 2nd most common dementia; difficult to differentiate from Parkinson’s/AD  Classic description is a Parkinsonian Dementia syndrome with visual hallucinations featuring o Cognitive impairment: typical description of a dementia patient o Fluctuations of alertness: can go from normal to completely impaired at any time; may be severe or subtle depending on the patient o Prominent Visual Hallucinations: the hallmark feature (80%), presence of this is often a clincher for the diagnosis; may be amusing or troubling to the patient o Delusions: not weird considering they have hallucinations o Parkinsonism: may be confused for PD; but will not respond to Levodopa o Neuroleptic sensitivity: often will get worse with these drugs (giving pt with hallucination haloperidol and they get worse!); may precipitate extreme reactions like NMS  Pathology: Lewy Bodies (eosinophilic intracellular inclusions of alpha-synuclein) are found in the substantia nigra and cortical neurons  Tx: complex due to inability to tolerate anti-psychotics; similar to AD, but low doses of atypical antipsychotics can be a good strategy  Disease course lasts 10-15 years before death

Progressive Supranuclear Palsy (Steele-Richardson-Olszewski syndrome)  Manifestation: o Impaired vertical gaze, dysarthria, dysphagia, extrapyramidal rigidity, gait ataxia, dementia o Early: ataxia and falls prominent with dementia features o Late: dementia becomes prominent with hallmark of overwhelming apathy  Diagnosis o Clinical with atrophy of dorsal midbrain, globus pallidus, and STN o NFTs/atrophy/damage to subcortical structure are common  Disease course lasts 6-10 years before death Huntington’s Disease: autosomal dominant neurodegenerative disorder of basal ganglia  Manifestation: o Onset around age 40 o Triad: chorea, behavioral/personality changes, dementia o May develop obsessive-compulsive disorder (intrusive thoughts with relieving compulsions) o Suicide is common and may occur very early in disease  Diagnosis: o Clinical manifestations or family history of disease o Genetic testing (>40 CAG repeats on the HD gene on chrom. 4) o Atrophy of caudate nucleus on imaging  Pathology: destruction of caudate/putamen (GABA producing neurons of striatum) with loss of layer 3 of the cerebral cortex due to aberrant protein folding causing neuronal death  Tx: Difficult to treat; better to prevent in further generations with genetic counseling  Disease course lasts 10-20 years before death Parkinson’s Disease: causes dementia but really more of a movement disorder. Covered in Ch.15

Frontotempotal Lobe Dementia  Manifestations: o Impaired executive function (poor social function, decision making, trouble with organization or sequencing, etc.) o Hallmark Personality changes, often with disinhibition o Atrophy of the frontal/temporal lobes  Associated with abnormal tau protein TDP-43 Prion-Related Dementias (transmissible spongiform encephalopathies)  Creutzfeldt-Jakob Disease (CJD): rapidly progressive dementia (weeks) with pyramidal signs, ataxia, exaggerated startle reflex, and myoclonus o EEG: periodic sharp waves o MRI with DWI: basal ganglionic abnormalities o CSF: normal with presence of 14-3-3 protein o No therapy; death occurs in about a year of onset  Variant CJD (mad cow disease), Gerstmann-Sträussler-Scheinker syndrome, Fatal Familial Insomnia, and Kuru are all other forms of Prion diseases  Disease results in the brain to become “sponge-like” with holes due to cell death from abnormal folding of proteins based off a prion template. HIV-associated Dementia Complex: progressive cognitive function deterioration ether caused primarily by the disease or by other infectious diseases due to immune-deficiency  Memory problems, poor concentration/attention are common complaints  More common in pts with low CD4+ counts  Tx: with HAART should prevent this from happening due to preventing HIV progression Vitamin B12 deficiency  Presents as a progressive dementia with spinal cord/PNS dysfunction o Paresthesia in hands/feet, sensory ataxia, visual loss, and orthostatic hypotension o Memory loss is also common  Megaloblastic anemia and sore tongue (beefy red) are common systemic symtpoms  Tx: replenish B12 *Note that Wilson’s Disease, Hypothyroidism, Hypercalcemia, and Addison’s disease can all cause Dementias

Ch.13 Sleep Disorders Sleep Physiology Four Major Stages of Sleep:  N1: transition from awake to asleep characterized my minimal ECG activity  N2: intermediate sleep characterized by sleep spindles and K-complexes  N3: deep (slow wave) characterized by delta (0.5 to 2Hz) waves  REM: characterized by alpha waves and rapid eye movements; adults spend 20-25% of sleep in REM Circadian Rhythm:  Sleep is on a 24 hour cycle coordinated by the suprachiasmatic nucleus (hypothalamus)  When light comes in, some impulses from the optic chiasm can shut down this nucleus  Without light this nucleus releases orexin to stimulate the pineal gland to release melatonin causing sleepiness! Polysomnography  Special testing for suspected sleep disorders. Uses EEG, ECG, EMG, eye monitoring, airflow monitoring, and pulse oximetry to measure a TON of things on a person sleeping  Usually a good test to parse out exactly what’s going on in someone’s sleep Sleep Disorders Circadian Rhythm Disorders: screwing up your circadian rhythm will cause these.  Advanced sleep-phase disorder: you’re falling asleep or awakening earlier than you want  Delayed sleep-phase disorder: same thing but you’re falling/awakening later than wanted  Tx: light therapy to re-establish circadian rhythm and melatonin to aid sleeping Restless Leg Syndrome: disorder where pts are compelled to move their legs or feel unpleasant sensations when they lay down to go to bed, resulting in difficulty falling asleep  Movements may occur when they are asleep waking them or bed-partner  Commonly runs in families and is autosomal dominant in nature  Dx: clinical history and severity that it’s causing disruption; often these pts are anemic thus ferritin levels should be taken  Tx: DA stimulatory agents (ropinirole/primipexole) and iron repletion o Refractory cases may receive other medications (benzos, anticonvulsants, etc.) Narcolespy/Cataplexy: first episodes typically occur around age 20  Excessive daytime sleepiness with narcolepsy – irresistible urge to sleep with refreshed awakening  Cataplexy – sudden loss of muscular tone in response to emotion (surprise, fear, etc.)  Sleep paralysis – feelings of not being able to move during dreaming/early sleeping or awakening  Hypnagogic/hypnapompic hallucinations – hallucinations upon going to sleep/waking up  Pathophys: Loss of hypocretin (orexin) secreting cells in the hypothalamus o CSF with hypocretin (orexin) level <110 pg/mL is diagnostic with symptoms  Multiple Sleep Latency Test: special testing where pt is asked to fall asleep 5 times during a day and latency of falling asleep is measured o Average sleep latency of <8 minutes with >2REM episodes at sleep onset is diagnostic  Tx: o Nacrolepsy: modafinil or methylphenidate/dextroamphetamine o Cataplexy: sodium oxybate or TCAs

Parasomnias/Dyssomnias: weird behaviors while you sleep. They’re weird!  Sleep terrors: NREM sleep actives often of screaming/autonomic hyperactivity. Pts WILL NOT remember the events and it’s best to just let them do their thing and not hurt themselves  Somnambulism: walking around or more complex behaviors in NREM sleep. Not remembered  Nightmares: scary dreams. These ARE remembered as we remember REM sleep.  Sleep paralysis: sensation of being paralyzed usually upon awakening from sleep  REM behavior disorder: failure of normal sleep paralysis in REM sleep causing pt to act out their dreams…possibly hurting themselves or others. Clonazepam (benzo) can suppress this  Nocturnal Cramps: usually deep cramps in the legs/feet during sleep that can disrupt sleeping  Somniolquy: talking in sleep, may be provoked by talking to the sleeping patient  Hypnic Jerks: sudden spasms occuring with sleep onset  Enuresis: peeing the bed! Sleep Apnea: sudden awakenings due to lack of O2 saturation from either mechanical obstruction (obstructive sleep apnea) or failure of effort in ventilation (central sleep apnea).  Apnea: cessation of airflow >10 seconds or more  Hypoapnea: pauses with 50% reduction in airflow  Dx: polysomnography showing >5 apneas/hypoapneas/or respiratory related arousals  Tx: CPAP/sleep hygiene/eliminating risk factors is the typical treatment of choice of OSA o Surgery may be needed if obstruction is the problem o Central sleep apnea is more complicated and needs a further work-up to determine cuase Insomnia: inability to fall asleep or maintain sleep; the most common sleep disorder  Tx: o ID and treat any underlying causes of insomnia o Maintain good sleep hygiene o Sedatives (refractory insomnia) like melatonin, antihistamines, benzos, zolpidem/zaleplon

Ch.14 Vascular Disorders Anterior Circulation  cerebrum Innominate artery -> Right common carotid (CCA) | Aorta -> Left common carotid (CCA)  Both CCAs -> internal carotid (ICA) and external carotid arteries (ECA)  ICA o Runs behind the pharynx; enters the skull; forms the carotid siphon (S-shaped curve)  Carotid siphon gives off the Ophthalmic Artery o Penetrates the Dura Mater giving off the 1anterior choroidal/2posterior communicating arteries, then Bifurcates into the anterior cerebral artery (ACA) and Middle Cerebral Artery (MCA)  ACAs are connected by the anterior communicating artery  MCA gives off the lenticulostriate arteries then trifucates into anterior temporal, large superior, and large inferior branches  ECA will supply the meninges and external structures Supplies  ACA – anterio-medial cerebral hemispheres, caudate, and bottom of frontal lobes  Lenticulostriate arteries – basal ganglia and internal capsule  MCA large superior branch – lateral cerebral hemispheres above sylvian fissure  MCA large inferior branch – temporal and inferior parietal lobes  Anterior Choroidal artery – courses with optic tract supplying globus pallidus, posterior limb of internal capsule, medial temporal love, and lateral geniculate body (LGN) Posterior Circulation  brainstem, cerebellum, visual cortex Subclavian artery -> vertebral artery (VA)  VAs enter the vertebrae transverse foramina at C5-C6; courses up the intravertebral foramina, and exit to course behind the atlas before piercing the dura to enter the foramen magnum  Intracranial VAs o Give off 1anterior spinal artery, 2posterior spinal artery, 3posterior inferior cerebellar artery (PICA) before joining to form the basilar artery  Basilar Artery o Give off 1Anterior inferior cerebellar arteries (AICA), 2Pontine branches, 3Superior cerebral artery (SCA) then divide at the pontomesencephalic junction into the posterior cerebral arteries (PCA)  Brainstem vascular supply is through smaller branches coming off the posterior circulation Brain Ischemia – 80% of strokes are ischmic! Thombosis: localized occlusive processes causing blood flow obstruction  Atherosclerosis is most common; often occurring in the large vessels in the head/neck  Primary hematologic problems (polycythemia, thrombocytosis, hypercoagulable states) may cause platelet clotting within the vessels  Vasoconstriction/fibromuscular dysplasia/arterial dissection can occur  Hypertension (medial vascular hypertrophy) commonly affects penetrating intracranial arteries Embolism: clot forms somewhere in the body and breaks off to lodge/occlude bloodflow somewhere else  Stroke emboli most commonly come from the heart (atrial fibrillation!) or other major vessels  Arterial dissection can result in clot formation with embolization

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Paradoxical emboli form in veins (usually DVT) and travel through a heart septal defect of A-V malformation in the lungs to hit the brain Air, fat, cholesterol, bacteria (mycotic), foreign bodies, or placental material have a chance of entering the vessels, acting as an embolus

Systemic Hypoperfusion: not enough blood pressure means not enough perfusion!  Heart Failure (infarction or arrhythmia) or systemic hypotension (blood loss, hypovolemia, overwhelming infection) are the two more common causes  Watershed regions (regions last to receive blood supply) are the periphery of perfusion zones will be greatly/diffusely affected Stroke Syndromes These are simply outlined on pg. 106; see if you can’t name off the syndrome with these prompts! Anterior Circulation Stroke Syndromes: carotid artery occlusion, MCA embolism, or hemorrhage in basal ganglia  Left cerebral hemisphere stroke (in book)  Right cerebral hemisphere stroke (in book) Posterior Circulation Stroke Syndromes  Lateral Medullary Stroke (Wallenberg Syndrome; intracranial VA occlusion) o Ipsilateral: increased or reduced facial pain/temp sense, Horner’s Syndrome o Contralateral: reduced body pain/temp sense; arm discoordination o Bilateral: nystagmus, ataxia; possible dysphagia/hoarseness if severe  Bilateral Pontine Base/Medial Tegmentum Stroke (Basilar Artery) o Quadriparesis | conjugate gaze paresis, intranuclear aphthalmoplegia, or CN VI nerve palsy o Coma may occur if severe  Cerebellar infarction (PICA or SCA) o Gait ataxia; dysarthria; ipsilateral dysmetria  Left PCA infarction o Right homonymous hemianopia o Sometimes amnesia o Alexia without agraphia if splenium of corpus callosum involved  Right PCA infarction o Left homonymous hemianopia o Sometimes left-sided visual neglect Lacunar Strokes: may be anterior or posterior circulation, but will affect penetrating arteries  Pure Motor Stroke: contralateral face/arm/leg weakness with no sensory/behavioral losses  Pure Sensory Stroke: contralateral face/arm/leg paresthesia without motor/visual/behavior losses  Dysarthria-Clumsy hand syndrome: slurred speech and a clumsy hand  Ataxic hemiparesis: weakness/ataxia of contralateral body (leg>arm)

Arterial Dissection Ischemic stroke: dissection diverts blood supply causing ischemia (typically anterior circulation) Embolic stroke: Virchow’s triad occurs within the new lumen causing a clot to form Carotid Artery dissection may feature ipsilateral Horner’s syndrome  Ascending oculo-sympathetic neurons are damaged -> ptosis/miosis  Sudomotor fibers (ascending with external carotids) are preserved -> sweating intact! Vertebral artery dissection: ipsilateral neck pain/posterior circulation stroke (neck manipulation!) Treating Acute Stroke…to give or not give tPA Some major points when considering tPA thrombolytic therapy  Timeframe: Pt is >4.5 hours away from symptom onset -> no tPA  Hemorrhage/bleeding: hemorrhagic infarction, tendency to bleed/anti-coagulant meds, recent surgery, thrombocytopenia, or recent bleeding episode -> no tPA  Sugars: hypo/hyperglycemia may mimic signs/symptoms of stroke  Blood pressure: lowering blood pressure causes less brain perfusion, worsening an ischemic stroke! Don’t lower BP unless there’s signs of end-organ damage from HTN After acute event, you must anti-coagulate!  Heparin, Warfarin, Aspirin, or newer Factor Xa inhibitors (Dabigatran, etc.) can all be of use  Anti-arrythmatics can be helpful if atrial fibrillation is present! A-fib can easily cause clots to be formed and thrown, thus stopping the arrhythmia may aid in preventing future events  Control risk factors (HTN, lipid abnormalities, obesity, smoking, drinking, etc.) with medication and lifestyle changes Intracranial Hemorrhage Subarachnoid Hemorrhage: sudden onset severe headache; is nauseating/disabling  Death may ensue quickly with increased intracranial pressure from brainstem herniation  Tx: prevent intracerebral vasoconstriction/rebleeding with vascular clips, vascular coiling (cut off bleed) or nimodipine (Ca2+ channel blocker; minimize vasoconstriction) Intracerebral Hemorrhage: early signs are related to location of bleed  Typically caused by hypertension in the smaller penetrating arteries (cerebellum, basal ganglia, internal capsule, caudate nucleus)  Cerebral amyloid angiopathy is most frequent in the elderly as a cause; affect parietal/occipital lobes  Trauma/A-V malformation/bleeding diatheses can all be causes Vascular malformations Types  Ateriovenous Malformation (AVM) – artery going straight into a vein. Can cause undue pressure resulting in hemorrhage  Cavernous angioma – compact mass of vessels without brain tissue interspersed  Developmental venous anomalies (DVA) - mass of vessels with brain tissue interspersed  Telangiectasia – spider-like dilated capillaries with intervening brain Typically managed with obliteration or medical management of symptoms

Ch.15 Seizure Seizure Classification New onset seizures typically occur in children and elderly folks  ALWAYS get head imaging on a new onset seizure to rule out an organic cause  EEG may be useful to catch ongoing seizure or identify a seizure disorder through EEG waves Epilepsy: a tendency to have recurrent, unprovoked seizures  Lennox Gastaut Syndrome: childhood seizures + retardation (1-2Hz spike-and-wave) o Tx: Valproate; lamotrigine; felbamate; rufinamide  Benign rolandic epilepsy: childhood seizures often happening at night (centro-temporal spikes) o Tx: Carbamazepine (may not be treated)  Absence epilepsy: childhood/teen absence seizures; triggered by hyperventilation (3Hz spike-n-wave) o Tx: Ethosuximide; valproate  Juvenile myoclonic epilepsy: teen seizures often happening in the morning (4-6Hz spike-n-wave) o Tx: Valproate; lamotrigine; levetiracetam Simple Partial: seizure that is confined to one part of the brain where pt stays conscious  Focal Motor Seizure (motor cortex): stiffening/jerking of a specific body part  Jacksonian March (motor cortex): spread from fingertips to body as seizure activity moves along the motor homunculus to involve a general side of the body  Sensory hallucination: visual (occipital), tactile (parietal), gustatory/olfactory/déjà vu/jamais vu (temporal) Complex Partial: seizure is confined to one hemisphere and pt loses consciousness  Arise in parietal or temporal lobes  Automatisms (repetitive, purposeless motor movements) are a common feature  Pt will not respond properly to their environment due to impaired consciousness Generalized Tonic-clonic (Grand Mal): generalized, intense seizure with three major phases  Tonic phase: whole body tenses up, sometimes with a “epipeltic cry” from pharynx muscle tension  Clonic phase: rhythmic jerking movements for 1-2 minutes, typically petering out after that  Post-ictal phase: confusion/somnolence following clonic phase Absence: generalized seizure featuring unresponsiveness  Typically occurs in children  Consists of staring period with immediate recovery; these spells are often not noticed by the patient, but they are not aware of what’s going on around them during the spell  May be thought to be learning disability or look like daydreaming on initial presentation  3Hz generalized spike-and-wave on EEG is characteristic  Hyperventillation is a common trigger Febrile: generalized seizures occurring within context of infection  Only affect children 6 months – 5 years of age  No major risk for epilepsy in the future if you get these

Psychogenic Non-epileptic: seizure that doe not follow any recognized EEG pattern, often seen in pts with psychiatric history (often abuse). Continuous EEG monitoring may help in figuring out these seizures from epileptic events Treatment of Seizure With new onset seizure:  First attempt to find the cause (MRI, CT, LP, EEG, etc.) then treat the cause  If no cause is found and patient is asymptomatic, AED drugs are typically not initiated With second seizure:  First attempt to find the cause (MRI, CT, LP, EEG, etc.) then treat the cause  If no cause is found, then AED treatment should be considered  Monotherapy dose is increased until symptoms are controlled or side effects kick in  Another drug can be added with the ultimate goal of tapering the first drug to eventually have the second one as monotherapy Make flashcards of Table 15-3 for Anti-epileptic Drugs Vagal Nerve Stimulation: apparently these devices are implanted and stimulate the vagus nerve in timed pulses to limit epileptic activity Surgery: resection of the epileptogenic area of the brain (found via continuous video-EEG + neuroimaging) Status Epilepticus While most seizure activity is acute, some may take a prolonged course giving significant risks to the patient cause in seizure. It’s called status epilepticus. Here’s the algorithm to approach this event: 1. Give normal first aid and protect the patient 2. If pt continues to seize for more than a few minutes assess ABCs, check glucose levels, and establish IV access 3. Send blood lab studies; give 100mg thiamine IV, followed by 50% dextrose (may be B1 deficient alcoholic) 4. Administer Lorazepam 0.1 mg/kg IV – benzo to chill them out 5. [if seizure persists] Phenytoin/fosphenytoin 20mg/kg IV – anti-epileptics 6. [if seizure persists] Intubate and give phenobarbital 20mg/kg IV – old school anti-epileptics 7. [if seizure persists] Induce coma (barbiturates, midazolam, or propofol) and begin continuous EEG monitoring

Ch. 16 Movement Disorders Idiopathic Parkinson’s Disease Spontaneous neurodegenerative disorder, but has some genetic risk factors: SNCA (a-synuclein), PARK2 (E3 ubiquitin ligase), UCHL1 (ubiquitin carboxy-terminal esterase L1), PINK1 (PTEN-induced putative kinase 1), LRRK2 (leucine0rich repeat kinase 2) are prominent ones Pathology: brain-wide neurodegeneration with specific concern of dopaminergic neuron loss in the vental substantia nigra pars compacta being a main driver of disease motor manifestations Symptoms: Four major symptoms with one less common symptom are characteristic of PD  Pill rolling tremor: slow (3-5 Hz); evident at rest  Cogwheel rigidity: arm passively moves in a “chunking” cogwheel fashion  Bradykinesia (slow movement)/bradyphrenia (slow thinking)  Postural instability: failed postural muscle reflexes needed to maintain balance  Dementia: less common (20-30%) but recognized as a result of primary disease Tx: There are a TON of drugs for PD, [look at your flashcards to review them individually]; but below are some common vignette situations where you’d choose specific drugs:  Initial treatment: Levodopa-Carbidopa or dopamine agonist  Little response to initial Tx: increase dose, workup for alternative diagnoses  Tremor predominates: Anti-cholinergic or amantadine (NMDA antagonist)  Early-morning stiffness: controlled release L-dopa for more precise dosing  L-dopa hallucinations: discontinue concurrent therapy to L-dopa; decrease L-dopa dose; low-dose antipsychotic  “Wearing off”: add concurrent drugs to enhance L-DOPA effect or have smaller more frequent doses  Dyskinesia (late state): consider adding/switching/augmenting dopamine therapy; consider surgery Parkinson Syndromes: some syndromes share “Parkinsonism” as a feature but are not PD.  Progressive supranuclear palsy: parkinsonism with characteristic ophthalmoplegia (limited vertical gaze > limited horizontal gaze); difficulty looking down makes it hard to walk  Cortico-basal ganglionic degeneration: parkinsonism with apraxia (difficulty in executing motor/other actions despite normal strength/sensory function) and alien-hand syndrome  Diffuse Lewy Body disease: parkinsonism with early dementia, hallucinations, and extreme sensitivity to neuroleptic drugs  Vascular Parkinsonism: parkinsonism that affects mainly the lower limb accompanied by vascular disease  Multiple systems Atrophy: parkinsonism with early autonomic/corticospinal/cerebellar dysfunction and sometimes myoclonus or vocal cord paresis

Drug-Induced Movement Disorders Often treatment of psychotic disorders incudes D2 DA-receptor blockage, thus it should be no surprise that these drugs may result in movement disorders. Some big ones are below:  Akathisia – inability to sit still (ants in the pants); Tx: anti-cholinergics, beta-blockers, decrease neuroleptic  Neuroleptic Malignant Syndrome – muscle rigidity (^CK levels), fever, leukocytosis, autonomic instability, and altered consciousness. Tx: discontinue neuroleptic, antipyretics, rehydration, bromocriptine/dantrolene, physical cooling  Tardive Dyskinesia – uncontrollable lip smacking/tongue rolling/chewing in the context of neuroleptic use (often typical antipsychotics); Tx: discontinue drug, DA depletion may aid in limiting symptoms but often this is irreversible Stiff-Person Syndrome Rare autoimmune/paraneoplastic disorder of progressive muscle rigidity with painful spasm  Tin man gait: Stiffness in trunk/axial muscles, lumbar hyperlordosis, and restricted hip/spine mobility  Painful spasms occurring suddenly and sometimes in response to startle Dx: clinical symptoms and continuous NMJ stimulation without evidence of other disease  Anti-glutamic acid decarboxylase (GAD) or Anti-amphiphysin antibodies may be found  CSF is often normal Tx: benzodiazepine and baclofen for muscle relaxation to stop spasms  If autoantibodies present, immunosuppressive therapy (steroids, plasmapheresis, IVIG) are useful Tremor Involuntary rhythmic movement of the body. Resting (when pt at rest), postural (when pt maintains a posture for a prolonged time), action (appears with voluntary movement), or intention (appears when action has nearly completed)  Action/intension tremors are a feature of cerebellar disease  Resting tremor is characteristic of Parkinsonism Essential Tremor: isolated postural tremor that occurs spontaneously and progresses insidiously  Most common cause of tremor  Often involves hands, but could involve any part of the body  Bilateral  Improves with alcohol consumption is chacteristic  Tx: primidone (barbiturate) or propranolol (B-blocker) are proven therapy Chorea Involuntary dance-like movements, often with clumsiness and discoordination. Some other features include:  Motor Impersistence: failure to sustain a motor contraction  Serpentine Tongue: cannot keep the tongue protruded, thus it writhes like a snake  Milkmaid grip: cannot maintain grip thus the pt hand slides down like it’s milking what their gripping Causes: There’s a huge list of causes of chorea but some major ones include Huntington’s Disease, Poststreptococcal infection (Syndenham chorea), SLE, thyrotoxicosis, and pregnancy Tx: haloperidol (D2 antagonist) has had success

Ballism Poorly controlled flinging/flailing movements of the limb (arm goes ballis-tic)  Hemiballismus: unilateral ballism; typically, from contralateral basal-ganglia lesions or hyperglycemia  Tx: DA depletion/blockaid is typical therapy | thalamotomy/pallidotomy may help in severe cases Dystonia Sustained muscle contraction often resulting in abnormal twisting or posturing  Classically relieved by “sensory tricks” like gently touching the contracted muscles  Exacerbated by stress/fatigue/intense emotions/specific motor movements (Action Dystonia)  Minimized by relaxation/sleep Primary Dystonia: occurs as a single entity without underlying disease  May be focal (one muscle), segmental (one muscle group), or generalized  Often result of an autosomal dominant disorder from mutations in the gene for torsin A chrom. 9)  Tx: Botulinum Toxin to paralyze the muscles Secondary Dystonia: occurs as a result of underlying disease  Early onset or presence of other neurologic findings are classic for secondary dystonia  Hemidystonia is often secondary in nature  Caused by a myriad of neurodegenerative and non-degenerative diseases Myoclonus Sudden “lightning-like” movements from brief, intense muscle contraction (positive) or inhibition (negative) that can occur in 4 different contexts:  Physiologic (hiccups, hypnic jerks) – occur due to come physiologic process  Essential – no underlying etiology can be found; often improves with alcohol  Epileptic – occurs in context of epileptic seizures  Symptomatic – occurs as a symptom of primary pathologic process Tx: clonazepam or valproic acid (both anti-consultants) are used successfully Tics Abrupt, stereotyped, coordinated movements or vocalizations as a result of an “inner urge” or tension that is relieved by engaging in the tic Tourette’s syndrome is the classic tic disorder characterized by at least 1 motor and 1 vocal tic for >6 months causing significant distress/impairment to the patient  Often prominent in teenage years but can diminish into adulthood  Associated with Obsessive-Compulsive Disorder Pediatric Autoimmune Neurologic Disorders Associated with Streptococcal-Infection (PANDAS)  Tic/OCD exacerbation following a Group A B-hemolytic streptococcal infection  Strep-autoantibody formation after the infection affects the basal ganglia (unproved theory) Tx: DA-antagonists are most effective but Clonazepam/clonidine have more favorable side-effect profiles, and are often first-line

Wilson’s Disease Autosomal recessive disorder due to copper-binding protein mutation  Mutation  impaired copper-ceruloplasmin conjugation  copper entry to biliary excretory pathway  Copper accumulates in the liver (liver damage) and spills into the blood (deposition into tissue) Symptoms  Parkinsonism: due to basal ganglia deposition; rigidity, tremor, dyskinesia  Cognitive Dysfunction: due to cortical deposition; cognitive slowing, difficulty with processing  Mood/Personality changes from cortical frontal-lobe deposition  Kayser-Fleischer ring: golden/brown/greenish discoloration in the cornea due to deposition in Descemet’s membrane Dx:  Increased serum copper, decreased ceruloplasmin are expected, not 100%  Increased 24-hr urine copper excretion is most sensitive screening  Kayser-fleshcer rings in the eye are helpful clue  Liver biopsy with copper deposition is diagnostic Tx: lifelong copper chelation with D-penicillimine or newer zinc chelators; screening for family members Paroxysmal Dyskinesias Rare disorders causing recurrent attacks of hyperkinesis with preserved consciousness  Kinesigenic: short and abrupt; often triggered by sudden movements  Non-kinesigenic: longer lasting; often triggered by alcohol, fatigue, and stress  Exercise-induced dystonia (occurs with exercise) may last for hours Tx: carbamazepine (anti-convulsants)

Ch.17 Head Trauma Epidural Hematoma: bleeding between the skull and the dura mater  Result of trauma to the middle meningeal artery, dural venous sinuses, or middle meningeal vein  Presentation: Trauma (may get knocked out)  lucid interval  pass out (herniation) with rapid progression to coma if left untreated  Dx: CT angiography shows hyperdense, lens-shaped lesion between skull and dura mater  Tx: timely surgical evacuation and decompression Subdural Hematoma: bleeding between the dura mater and the brain  Result of torn bridging veins (connect surface of brain with dural sinuses) often in elderly or in infants  Presentation: headache with a variety of neurologic symptoms (contralateral hemiparesis, seizure, cortical dysfunction) and possible herniation if large  Dx: CT shows sickle-shaped bleed that crosses skull-suture lines  Tx: may need surgical drainage or may resolve on its own depending on severity with discontinuation of anticoagulant medications to minimize bleeding Concussion: alteration/loss of consciousness from head trauma without structural alteration to the brain  Presentation: head trauma with altered consciousness, amnesia; sometimes headaches, dizziness, vertigo, nausea, and cortical blindness (partial vision loss with normal appearing eye)  Dx: symptoms in the presence of all normal CT/MRI imaging (More of a functional loss)  Tx: rule out bleed/structural injury…if not present, then rest/relaxation  Note that these often occur to athletes and guidelines have been set for returning to the field o No loss of consciousness or symptoms can allow player to return to the field; if a second blow to the head occurs then they must wait 1 week before returning o LOC >15 min must be followed/evaluated for 1 week. If symptoms resolve they may return o If symptoms persist for a prolonged time, they must be taken to a hospital Post-concussion Syndrome: sleep disturbance, cognitive impairment, behavioral problems, headache, dizziness in the setting of post-mild TBI and normal MRI. Often pending litigation, workers’ compensation issues, and depression prolong the course (I.E. the patient is full of shit) Diffuse Axonal Injury: diagnosis made with CT showing multiple, diffuse areas of punctate hemorrhage in deep white matter/corpus callosum. Associated with poor prognosis. Post-traumatic Seizure/Epilepsy: seizures develop in about 2% of pt with TBI (high chance with higher severity) with 25% of those pts with seizure developing epilepsy  Seizure is treated with anti-epileptic drugs but does not reduce the chance of later development of epilepsy! Often this develops within a year after the TBI Central (Transtentorial) Herniation: herniation of the diencephalon centrally through the trans-tentorial notch due to increased ICP (bleed, mass, etc.) resulting in compression and symptoms:  1. Decreased alertness (cortical compression  2. Small, reactive pupils (hypothalamic sympathetic tract compression)  3. Decorate posturing (cutting off cortical input, brainstem takes over)  4. Fixed, midposition pupils with decerebrate posturing (brainstem damage)  5. Motionless, unresponsive coma proceeding to death (brainstem damage with brain death)

Uncal Herniation: unilateral herniation of the temporal lobe uncus (often a unilateral mass) resulting in rapid compression of both underlying and surrounding structures  1. Mass effects (hemiparesis or focal deficits) may be the first sign of abnormality  2. Ipsilateral CN III palsy (dilated pupil + motor weakness) is an early sign as it runs just beneath the uncus) followed by impaired consciousness  3. Kernohan’s notch phenomenon: ipsilateral hemiparesis from the contralateral cerebellar peduncle becoming compressed against this notch  4. PCA compression causing occipital/temporal lobe compression, and eventually death Subfalcine Herniation: frontal lobe mass may result in unilateral herniation of the cingulate gyrus under the falx cerebri; which honestly may not change the clinical picture that much as they have a friggin brain tumor.  May result in ACA compression by the cingulate gyrus resulting in lower extremity weakness Assessment and Treatment of Head Trauma Head trauma: ABCs, CT/MRI, Glasgow coma scale are best initial steps  GCS: measures eye opening, verbal, and motor movements as a quick gauge for impairment o Eye: spontaneous, to speech, to pain, non o Verbal: oriented, confused, inappropriate, incomprehensible, none o Motor: obeys command, localizes pain, withdraws to pain, decorticate, decerebrate, none o Scoring: 3-7 (severe), 8-12 (moderate), 13-15 (mild) Increased ICP (>15 mmHg in adults)  If it gets too high, it can compromise cerebral perfusion pressure and the brain will fail to get blood  CPP = mean arterial pressure – intracranial pressure; should be between 60-75mmHg; too high means HTN encephalopathy but too low means hypoxia  Definitive Tx: Correct the abnormality causing the ICP (bleed, tumor, etc.) is definitive  Short term Tx: o Elevate head to 30o (improves venous drainage) o Hyperventillation (PCO2 to 25-30 mmHg) results in cerebral vasodilation because O2 levels are good and it feels that it doesn’t need as much blood o Mannitol or hypertonic saline will not cross the BBB and pull fluid into the systemic circulation (do not use mannitol in pts with renal failure!) o Pentobarbital reduces cerebral metabolism  less bloodflow  less ICP o CSF drainage gets some CSF off the brain

Ch. 18 Systemic and Metabolic Disorders Toxic Metabolic Encephalopathy: clinical state of global cerebral dysfunction caused by some underlying pathology; the most common reason for neuro consult!  Characterized by waxing and waning level of arousal (may also be delirious)  The goal of Dx/Tx is to find the underlying pathology and treat it. Simple as that.  Because hepatic encephalopathy is common, asterixis may be a finding that you see often when dealing with this. Can be a great clue as to how to treat. Neurosarcoidosis: multi-system inflammatory disease that rare affects the CNS alone, but more likely affects the CNS in the context of other systemic manifestations (typically lung)  Symptoms: totally pleomorphic; may manifest in ANY part of nervous system causing symptoms  Pathology: affected tissue shows characteristic non-caseating granulomas  Dx: definitive diagnosis requires brain biopsy showing non-caseating granulomas o Typically, CNS dysfunction + systemic sarcoidosis = suspected CNS sarcoid o CSF often has elevated protein/lymphocytes but could be normal o Serum ACE is often elevated with possible hypercalcemia (the granulomas produce ACE) o MRI may show non-specific soft-tissue lesions  Tx: steroids or (rarely) autoimmune suppressing agents (methotrexate/azathioprine) Diabetes Mellitus: impairment of sugar management within the body  Sugar levels can affect the nervous system in a huge number of ways (vascular damage, neural damage at any level, hyper/hypoglycemic states, etc.) and it would be criminal to try and memorize them all  Most common: peripheral polyneuropathy of distal limbs  Hyperglycemia can produce lethargy, drowsiness, seizure (focal or generalized), and uncommonly dystonia/chorea (reversible damage to basal ganglia). o Diabetic ketoacidosis may cause swelling and herniation of the brain o Hyperglycemic non-ketotic Coma can also occur in severe situations  Hypoglycemia: headache, blurry vision, dysarthria, confusion, seizure, and coma can all result  Due to vascular involvement, stroke is more common in diabetic patients Alcohol and Nutrition Disorders: while there are MANY ways to for alcohol and vitamin deficiencies to affect the CNS, there are two major ones to be well aware of. 

Wernicke Encephalopathy (WE)-Korsakoff Syndrome (KS): continuous pathologic process resulting from vitamin B1 (thiamine) deficiency, typically in the context of chronic alcoholism o WE: confusion, truncal ataxia, ophthalmoplegia (impaired pupillary light response, muscular weakness) that develops over days-weeks. o KS: anterograde/retrograde amnesias with confabulation resulting from untreated WE. High mortality rate; best to stop process before it gets here o Tx: IV Vit B1 (thiamine) BEFORE ADMINISTERING GLUCOSE

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Subacute Combine Degeneration of Spinal Cord: posterior/lateral white matter tract degeneration due to Vit. B12 (pyridoxine) deficiency o Presentation: stocking-glove paresthesia, macrocytic anemia, sometimes in the setting of low B12 or folate levels, or elevated methylmalonic acid/homocysteine (precursors of B12)

Systemic Lupus Erythematosus (SLE): a classic pleomorphic systemic autoimmune inflammatory disease  Common CNS manifestations: o Neuropsychiatric: psychoses and mood disorders o Stroke: more common with SLE featuring Anti-phospholipid antibodies or Anti-cardiolipin antibodies (Lupus Anticoagulant) o Chorea/transverse myelitis: more common with Anti-phospholipid antibodies  Common PNS manifestations: o Distal symmetric polyneuropathy  Dx: systemic manifestations of Lupus, ANA/anti-cardiolipin/anti-phospholipid/anti-histone (drug induced) antibody titers  Tx: Symptomatic treatment with steroids (decrease inflammation) and cyclophosphamide (immunosuppression) Anti-phospholipid Syndrome: syndrome featuring Anti-phospholipid antibodies either outside or within the context of SLE  Presentation: arterial/venous thromboses, recurrent fetal loss, thrombocytopenia o Sneddon’s syndrome: add on cerebral ischemia and livedo reticularis o Increased risk for stroke due to hypercoagulable state; classically a young woman who has a unexplained stroke  Dx: high titer IgG Anti-phospholipid antibodies on two occasions 6 weeks apart  Tx: long-term anticoagulation (INR of 3-4) Central Pontine Myelinolysis: rare demyelinating disorder due to too rapid correction of hypo/hypernatremia  Classic pt is an alcoholic who has been vomiting; doctor does proper protocol but brings Na+ levels back to normal too quickly. The next day, the pt is a locked-in syndrome (quadreparesis with only vertical movement of the eyes)  Pons, basal ganglia, thalamus, and subcortical white matter can all be affected

Ch.19 CNS Tumors Background on CNS Tumors The most common CNS tumor is a metastasis (can’t emphasize that enough) Primary Brain Tumors (PBTs) are fairly heterogeneous and cn have a LOT of presentations depending on the type, location, and age of the patient.  Adults: most tumors are supratentorial and are meningiomas/gliomas  Kids: most tumors are infratentorial; CNS Tumors are #1 cancer in children and the #2 cancer killer. o Do not give kids <3 years of age radiation; they will likely get side effects later at any age, but they’re particularly susceptible below age 3 Genetics play a massive role in CNS tumors with specific mutations being responsible for some:  Neurofibromatosis 1 (NF1; chrom. 17) – optic nerve glioma and ependymoma  Neurofibromatosis 2 (NF2; chrom. 22q12) – bilateral acoustic neuroma  Von Hippel-Lindau (VHL, chrom 3p25) – Hemangioblastoma  Li-Fraumeni syndrome (p53, 17p13.1) – glioma/medulloblastoma Clinical manifestations can be wide-ranging and it strongly depends on type/location of the tumor  Adults: Persistent headache, new onset seizure, altered mental status are most common  Kids: often posterior fossa (infratentorial) with loss of appetite/weight loss, reduced school performance, dizziness/ataxic gait, neck pain, or eye abnormalities Dx of a brain tumor relies on CT/MRI to show abnormal tissue growth in the context of persistent symtpoms  Ring enhancing lesions: may be a tumor that has disrupted the blood brain barrier (MRI contrast exits the vasculature and surrounds the tumor. But may be from many other types of pathology (abcess, infarction, hematoma, etc.)  Hydrocephalus, midline shift, hemorrhage, edema, meningeal enhancement, and changes on MR spectroscopy are all things that can be seen on imaging  Definitive diagnosis is tissue histologic examination via biopsy or open surgery sampling The book does a GREAT job of breaking down different tumor types. Look at pgs. 152-158 and try to recall the following tumor types:  Glioblastoma Multiform (Grade IV astrocytoma) – most common primary CNS tumor in adults (poor prognosis with 3-5 year survival); typically solitary lesion with ring-enhancement. o Necrosis and neovascular proliferation set this apart from lower grades o Often presents late in the course of growth, thus the poor prognosis o May span white matter tracts of corpus callosum (“butterfly lesion”)  Low-grade Glioma (Grade I/II astrocytoma) – slow growing tumor often presenting with seizure. Resected if possible. Median survival is 7 yearss  Oligodendroglioma – slow growing with calcifications. “Fried egg appearance” on histology o 1p with 19p co-deletion considered genetic signature of these o Good prognosis with long median survival, but often recurs  Ependymoma – tumor of ependymal cells often appearing within the CSF space o Kids – typically in the cerebral ventricles o Adults – typically in the spine CSF o Hydrocephalus with high ICP (papilledema, cranial nerve palsy, etc.) and cauda equine syndrome can occur as presentation due to location

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Meningioma: mesodermal origin, and almost always benign; 2nd most common primary CNS tumor o NF2 genetic mutations increases risk for this tumor o Histo: white, whorled sheets of uniform meningoepithelial cells o Often with progesterone receptors o Arises typically on the meninges, with calcifications (“hyperostosis”) which may represent invasion of bone tissue Medulloblastoma: PNET tumor classically arising from the medullary velum of the 4th ventricle (within the ventricular space) o Histo: small, round cells with high mitotic index o Fast growing often presenting with hydrocephalus (morning headache, unsteadiness, N/V) o Tendency to spread to CSF and bone  check CSF or do bone scans/bone marrow aspiration to ensure it has not spread anywhere else o Avoid lumbar puncture unless there is no obvious lesion; may cause herniation Schwannoma: Schwann cell tumor often entrapping/compressing certain cranial nerves o CN XIII (vestibulocochlear nerve; acoustic neuroma) – loss of hearing/dizziness; often unilateral; if bilateral, pt likely has NF2 genetic disease o CN V or CN VII – less commonly arises in cerebello-pontine angle. May compress these nerves causing presentation o Histo: uniform, palisading spindle cells called “Verocay bodies” Ganglioglioma: rare childhood tumor often consisting of both neurons and glial cells Hemangioblastoma: uncommon cerebellar cystic tumor (VHL gene mutation often present) Primary CNS Lymphoma: high grade non-Hodgkin B cell origin; can be primary but more often a lymphoma in the brain will be secondary thought to be due to Ebstein-Barr Virus o Ocular lymphoma may occur prior to CNS involvement in AIDS patients (may be able to determine immune function due to presence/absence) o Must rule out disseminated disease o Tx: cannot surgically remove, must use chemotherapy or radiation; may have dramatic, shortlived response to steroids but recurrence is almost inevitable Sellar/Supracellar Tumors o Pituitary Tumors: typically, presentation is related to functional production of a pituitary hormone and compression of the optic chiasm (bitemporal hemianopia) o Craniopharyngioma: slow growing tumor with benign cells but malignant behavior. Often invades neighboring structures presenting with headache, visual disturbance, and endocrine abnormalities  Suprasellar calcified cystic lesion is characteristic Metastatic (secondary) CNS tumors: the most common brain tumors o Lung, skin (melanoma), kidney (renal cell carcinoma), breast, and colon are common culprits entering the brain via systemic circulation or Batson’s venous plexus in the spine o Typically multiple focal lesions and poor prognosis o These can easily bleed, causing rapid worsening of symptoms due to mass effect

Note:  Anticoagulation is NOT contraindicated in patients with brain tumor  “Drop metastases” are commonly from ependymomas or medulloblastomas

Ch. 20 Demyelinating Diseases of the CNS Multiple Sclerosis Epidemiology: most common demyelinating disease (loss of myelin but preservation of axons)  Occurs in young (20-30), healthy, white, women most commonly  Oddly, it’s more common in northern latitudes, the risk of which is set around age 15 (if you move north before age 15 your risk increases, but afterwards to you retain the risk of your original home)  Genetic predisposition demonstrated epidemiologically Pathogenesis: unclear; thought to be result of a latent viral infection in early childhood Signs/Symptoms: can literally produce any neurologic symptom depending on where demyelination has occurred in the brain/spinal cord. Some classics are outlined below:  Optic neuritis: mildly painful loss of visual acuity/color vision (red-desaturation) in one eye. Pain often worse with moving the eye to look around. Severe events may cause blindness. Papilledema, optic disc pallor, and RAPD (Marcus Gunn pupil; constricts to consensual but not direct light).  Intranuclear Ophthalmoplegia: MLF damage causing lack of abduction in one eye and nystagmus in the other when attempting to look to one side. Convergence is preserved  Transverse Myelitis: patchy inflammatory damage to the spinal cord causing upper/lower motor motor neuron signs or sensation losses depending on where the lesion is. Tingling pain may be felt at the level of the lesions  Lhermitte’s sign: electric sensation shooting down the spine when the neck is flexed  Uhthoff’s phenomenon: worsening symptoms in the heat Disease Course: typical course is relapsing-remitting (symptoms occur then go away) with gradual permanent losses with each relapse of symptoms. However, the course can be variable:  Benign: attacks occur, but baseline function is fully retained after all attacks  Relapsing-Remitting: attacks occur, and baseline function only deteriorates after each one  Secondary Progressive: begins relapsing-remitting but permanent losses suddenly become progressive without attacks at a certain point  Primary progressive: no attacks, simply progressive permanent loss of function until death Dx: typically patient presents with a focal neurologic deficit and history reveals previous, similar episodes at different times in their life  MRI (FLAIR): shows demyelination lesions; these typically occur in periventricular white matter, juxtacortical regions, corpus callosum, or cerebellar peduncles.  CSF analysis: oligoclonal bands of IgG antibodies to myelin produced by proliferated plasma cells  Visual evoked potentials: may show evidence of old optic neuritis, demonstrating previous attack  To diagnose the patient must show multiple white matter lesions in the CNS separated by space (different parts of the brain) and time (occur at different time periods) Tx: treatment rests on three different approaches for the disease:  Acute attack Tx: IV methylprednisolone followed by oral prednisone taper (minimize inflammation)  Chronic Tx for disease process: immune modulating agents [flashcards p.165] to suppress the immune system via minimizing antibody production/demyelination. Drug-neutralizing antibodies may be produced resulting in failure of some of these drugs after time. They may also depress immune responses so check CBC/LFTs routinely  Chronic Tx for lasting deficits: typically specific treatment for specific symptoms: o Spasticity: baclofen (muscle relaxant), diazepam (benzo), tizanidine (muscle relaxant) o Bladder dysfunction: anti-cholinergic agents/self-catheterization o Tremor/ataxia: no effective treatment, often disabling

Acute Disseminated Encephalomyelitis An acute demyelinating disease following viral infection or vaccination. May present very similar to MS.  Monophasic disease (only one event with damage occurs)  Lesions are o Multiple, more confluent, and more patchy o Tend to hit the posterior cerebral hemisphere white matter o Will ALL appear acute (enhance with gadlinium  Often has behavioral/cognitive abnormalities early on, which is uncommon in MS Dx: imaging and clinical picture will reveal the diagnosis but to tell it apart from MS:  MRI may be fairly similar but still informative  CSF will have leukocytosis but rarely oligoclonal bands  No Hx of other past attacks (it still could be MS, but you’d need a second attack or newly appearing white matter lesions to diagnose MS) Tx: IV corticosteroids are often given to limit symptoms, but pt will completely recover in time. Neuromyelitis Optica (Devic Disease) Disease of onset of both transverse myelitis and optic neuritis either together or at different times  Can look similar to MS, but often pain is more prominent  Spine MRI more likely to show lesions spanning multiple confluent segments of cord  Poor prognosis with blindness and paralysis often occuring long term Dx: symptoms with aquaporin-4 antibodies Tx: corticosteroids, plasmapheresis, IVIG, and immunosuppressive chemotherapy are all used Leukoencephalopathies Progressive Multifocal Leukoencephalopathy (PML)  JC virus activation causing demyelination via oligodendrocyte infection  Seen only in immunosuppressed pts (AIDS, leukemia, pharmacologic) because JC virus is easily suppressed by the normal functioning immune system  Symptoms: dementia, focal cortical dysfunction, cerebellar abnormalities  MRI shows multiple foci of white matter with normal CSF analysis  Tx often doesn’t work, typically because pt is already very sick (50% mortality rate) Posterior reversible encephalopathy syndrome (PRES)  Symptoms: Acute confused state and cortical vision loss (blindness with normal pupils)  Occurs in two settings: o Rapidly developing HTN/eclampsia o Immunosuppression to prevent organ transplant rejection  MRI will show white matter abnormalities  Tx: depends on the underlying cause o Treat the HTN/eclampsia with appropriate measures o Decrease/alter immunosuppression regimen  Often reversible but can be fatal

Ch.21 Infections of the Nervous System Acute Bacterial Meningitis A true medical emergency. Every physician should know this disease. Presentation: headache, fever, neck stiffness (classic triad) but other symptoms are possible  Kernig’s Sign: pain with passive knee extension when the hip is flexed  Brudzinski’s Sign: involuntary hip flexion when neck is flexed Etiology: often not known without CSF testing or culture. Changes with age of the pt. Dx: based upon CSF sampling/testing; always do a CT before LP to rule out structural abnormalities so the pts brain won’t herniate when you take some CSF  CSF profile: elevated WBCs with PMN predominance; elevated protein; low glucose  Culture/gram stain can give specific etiology/antibiotic resistance profile Tx: empiric treatment is always initiated as soon as possible; once the specifics of the bug are known, treatment is changed only if it resists the current treatment.  Corticosteroids may also be used in children to prevent long-term damage like deafness Brain Abscess Presentation: headache, focal neurologic signs (depends on location), seizure, and possible increased ICP or fever. Typically, the causative organism correlated with how the abscess was seeded.  Invasion from sinuses = respiratory bugs  Trauma/penetrating wounds = skin bugs  Multiple abscesses = bacterial endocarditis bugs Dx: CT/MRI will show a “ring enhancing lesion” somewhere in the brain. While this isn’t diagnostic, often the clinical picture will point to abscess and imaging simply confirms.  SPECT may help differentiate neoplastic ring-enhancing lesions (increased signal in lesion) from abscess lesions (necrosis, thus no signal in the lesion) Tx: long-term antibiotics with neurosurgical drainage Spinal Epidural Abscess Presentation: neurologic deficits resulting from spinal compression. Depends on site of the lesion Dx: neurological signs with spine MRI to define the extent of the lesion are necessary  LP is contraindicated as you may pierce the abscess and seed the subarachnoid space Tx: prolonged antibiotics with surgical drainage Tuberculous Infection – Mycobacterium tuberculosis Tuberculous Meningitis: more often affects basal meninges (worry of hydrocephalus) with more insidious onset than normal bacteria (malaise before classic symptoms) and possible cranial nerve palsies  Leukocytosis with lymphocyte predominance, normal protein, very low glucose  Acid-fast bacilli on culture/gram stain (although very slow growing)  Spread from lung TB, so CXR and bronchioaveloar lavage may be useful if disease is not established  Tx: multiple anti-tubercular drugs for long-time. It SUCKS. Intracranial Tuberculoma: basically a big mass of TB in the brain. It’s rare in the US but common in the developing world. Basically, it’ll be just a mass in the brain like any other. Treat with anti-tubercular drugs Pott Disease: tuberculosis of the spine causing osteolytic lesions  Fever + lower back pain with damage spreading through disc spaces is classic for TB  Spinal compression symptoms vary and depend on the level of the lesio

Lyme Disease – Borrelia burgdorferi The spirochete is typically transmitted by the Ixodes Deer Tick (north eastern USA/Europe)  Stage 1: Bullseye rash (erythema chronicum migrans) with flu-like symptoms  Stage 2: Bilateral Bell’s Palsy and Heart-block (myocarditis)  Stage 3: Encephalopathy, migratory polyarthritis, painful radiculopathies Dx: history of tick bite with symptoms is always a good thing to note  Can be many signs but PCR for spirochetal antigen in CSF is probably the best test Tx: Doxycycline in early disease; IV ceftriaxone in later disease Viral CNS infections Viral Meningitis: Presents with typical signs of meningitis and CSF analysis is key in establishing diagnosis  Leukocytosis with lymphocytes, high protein, normal glucose  Gram stain/culture will show nothing; Viral PCR analysis is necessary Viral Encephalitis: presents as headache/fever with focal neurologic signs. Typically, you treat the symptoms as appropriate because the virus doesn’t have effective treatment…unless it’s HSV1 infection  Herpes Simplex Virus-1 (HSV-1): affect the medial temporal lobes/orbito-frontal cortex o Seizures, olfactory hallucinations, and profound amnesia are classic o CSF shows RBCs due to hemorrhagic damage and leukocytosis from infection o EEG can show epileptiform discharges (seizure activity) in temporal lobes o Tx: immediate administration of acyclovir pending CSF analysis and PCR for HSV-1 antigen Fungal CNS infections Cryptococcal Meningitis: the most common fungal meningitis, typically affecting immunocompromised hosts  Infection occurs with inhalation of fungus from soil or pigeon droppings  Symptoms: insidious neck pain, headache, and confusion possibly with fever  CSF: leukocytosis with lymphocytes, elevated protein, low glucose  Dx: india ink staining is classic, rapid latex agglutination assay (cryptococcal antigen) is more common  Tx: amphotericin B + flucytosine is a standard treatment Parasitic CNS infections Toxoplasmosis (Toxoplasma gondii): intracellular parasite usually acting as a TORCH infection or infection of an AIDS patient (either way pt has a crappy immune system)  Infection occurs with exposure to cat feces or eating undercooked meat  Presentation: headache, mental status change, focal neuologic deficits  Diagnosis: o Imaging: multiple ring-enhancing lesions in basal ganglia or grey-white matter junction o CSF analysis: PCR assays for toxo are positive o Biopsy of lesion with testing if typical treatments don’t work  Tx: may or may not be needed but often anti-malarials and other antibiotics are used Neurocysticercosis (Taenia Solium): the most common CNS parasite; endemic parasite of Central/South America (often seen in immigrants)  Common cause of new-onset seizure in newborns in developing world  Presentation: fever, headache, increased ICP, sometimes seizure  Dx: symptoms with multiple cystic lesions with surrounding edema (may be calcified or ring-enhancing)  Tx: albendazole (kill parasite) and steroids (control edema/swelling)

CNS/PNS complications of HIV infection HIV-associated Dementia: typically occurs as a end-stage manifestation of AIDS. Becoming less common with effective HAART treatments being available. If they have this, the pt is near death. Vacuolar myelopathy: another late stage manifestation with severe immunocompromised  Posterior column damage: loss of vibratory/position sense with sensory ataxia  Corticospinal tract dysfunction: upper motor neuron signs predominate  Urinary and sexual dysfunction: due to peripheral nerve/spinal damage  Tx: is just get the HAART cranked up and try to retain some immune function Progressive multifocal leukoencephalopathy (PML) (discussed Ch.20); Primary CNS lymphoma (discussed Ch.19); Opportunistic infections (discussed above) are all possible complications

Ch. 22 Disorders of the Spinal Cord Anatomy of the Spinal Cord Spinothalamic Tract – carries pain/temperature sensation from extremities to brain; runs in the anterior portion of the spinal cord (cross-section)  1st order: A-delta (fast) and C (slow) fibers for different sensory modalities which synapse at the dorsal (posterior) horn of the spinal cord  2nd order: cross over at the level of the spinal cord they entered in and ascend contralaterally to synapse at the VPL nucleus of the thalamus  3rd order: thalamus projects to the post-central gyrus (primary somatosensory cortex)  Note: this tract is somatotopically arranged so that they ascending fibers entering at the level of the sacrum are lateral and cervical spine are medial Dorsal Columns – carries light touch, proprioception, and vibratory sense from extremities to brain; runs in the posterior portion of the spinal cord (cross-section)  1st order: A-alpha and A-beta neurons run from the periphery ipsilaterally up to the medulla where they’ll synapse with the nucleus gracillis (lower extremity) or nucleus cuneatus (upper)  2nd order: cross over in the medulla and ascend to synapse at the VPL nucleus of the thalamus  3rd order: project from thalamus to the post-central gyrus (primary somatosensory cortex)  Note: somatoatopic arrangement is sacral medial/cervical lateral Corticospinal Tract – major tract that carries motor impulses from the brain to the muscles running the between the posterior columns and spinothalamic tract  Upper motor neuron: descends from the primary motor cortex, crossing over at the medulla to run in the contralateral spinal cord. These neurons synapse at an alpha-motor neuron in the anterior horn of the spinal cord at the level of the muscle they’ll innervate  Lower Motor neuron: run from the anterior horn and synapse at the muscle via the neuromuscular junction (NMJ) Exiting the spinal column  C1-C7 nerve roots exit above their respective vertebrae.  C8 exits below the C7 vertebrae (there is no C8 vertebra)  T1 and below exit below their respective vertebrae Spinal Cord Syndromes Spinal Cord Transection Spinal Cord Compression Hemi-cord syndromes Central Cord Lesions Multifocal/Diffuse Cord Dysfunction Cauda Equina and Conus Lesions Anterior Spinal Artery Syndrome Spinal Cord Trauma

Amylotrophic Lateral Sclerosis (ALS; Lou Gerhig’s Disease) Congenital/Degenerative Spinal Disease Diagnostic Tests for the Spinal Cord