Viral Meningitis By Dr Bashir Ahmed Dar Associate Professor Medicine Sopore Kashmir

MENINGITIS    

By Dr Bashir Ahmed Dar Associate Professor Medicine Chinkipora Sopore Kashmir Email- [email protected]

What is meningitis?

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Meningitis is an infection of the pia-arachanoid and the CSF fluid that surrounds the brain. Meningitis is usually caused by an infection with a virus, with a bacterium or even with fungi.

How is Meningitis Caused Colonization of nasopharynx by bacteria or viruses  Is an important way of spreading meningitis by way of cribriform fossa or viremia or bacteriaemia and can spread to others by coughing etc. 

How is Meningitis Caused 

contagious, spread via tiny drops of fluid from the throat and nose of someone who is infected. The drops may become airborne when the person coughs, laughs, talks, or sneezes. They then can infect others when people breathe them in or touch the drops and then touch their own noses or mouths.

How is Meningitis Caused 

Sharing food, drinking glasses, eating utensils, tissues, or towels .

How is Meningitis Caused 

spread between people who are in close contact, such as those who live together or people who are exposed by kissing

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N. meningitidis cause epidemics of meningitis. In particular in a crowded day-care situation or a military recruit in a crowded training camp,schools,colleges has fallen ill with meningococcal meningitis

How is Meningitis Caused 

Meningococcus is the bacteria that has caused outbreaks across North America over the last 8 - 10 years including most recently. Understandably the presence of a meningitis epidemic in a community is very scary to parents

How is Meningitis Caused 

Most of the viruses that cause meningitis live in the intestines and tend to be passed on as a result of poor hygiene. Many different viruses can cause viral meningitis, most commonly enteroviruses that normally live harmlessly in people's bowels

How is Meningitis Caused 

L. monocytogenes has been associated with such foods as raw milk, pasteurized fluid milk,cheeses (particularly soft-ripened varieties), ice cream, raw vegetables, fermented raw-meat sausages, raw and cooked poultry, raw meats (of all types), and raw and smoked fish. Its ability to grow at temperatures as low as 0°C permits multiplication in refrigerated foods. In refrigeration temperature such as 4°C the amount of ferric iron promotes the growth of L. monocytogenes.

How is Meningitis Caused 

through a person's stool, and someone who comes in contact with the stool — such as a child in day care .

How is Meningitis Caused Hematogenous  Many of the bacteria and viruses that cause meningitis are fairly common and are typically associated with other routine illnesses.  infection of the skin, urinary system, gastrointestinal or respiratory tract can spread by the bloodstream 

How is Meningitis Caused 

A person may have another type of infection (of the lungs, throat, or tissues of the heart) caused by an organism that can also cause meningitis

How is Meningitis Caused  

Direct infection skull fractures possess abnormal openings to the sinuses, nasal passages, and middle ears. Organisms can pass through openings and cause infection. surgical procedures or who have had foreign bodies surgically placed within their skulls (such as tubes to drain abnormal amounts of accumulated CSF) have an increased risk of meningitis.

How is Meningitis Caused        

otitis media mastoiditis Osteomyelitic foci in the skull sinusitis Penetrating cranial injuries Brain or spine surgery Ventriculoperitoneal shun lumbar puncture.

How is Meningitis Caused skull fractures  Extradural abscess  Subdural empyaema  Spinal epidural abscess.  Pachymeningitis 

How is Meningitis Caused  

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Neurotropic also via an uncommon but interesting method called intraneural spread. This involves an organism invading the body at a considerable distance away from the head, spreading along a nerve, and using that nerve as a kind of ladder into the skull, where the organism can multiply and cause meningitis. Herpes simplex virus is known to use this type of spread, as is the rabies virus. Rabies HSV

How is Meningitis Caused RISKS  Asplenia  drugs that suppress immune system  Immunocompromised  HIV, malignancy  malignancy  alcholism 

How is Meningitis Caused 

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Patients with cardiac and pulmonary anomalies may spread septic foci,bronchiectasis, occasionally pneumonia). Common with pulmonary AV fistulae and R to L cardiac defect T-cell defects (HIV) Neural tube defects- Staph aureus, enteric organisms Terminal compliment deficiency- Neisseria septic foci from thrombophibitis iv drug abusers

How is Meningitis Caused Immune-compromised Patients are also prone for fungal infections and the fungal infections that can result in meningitis are  Aspergillus  Candida  Mucor  Protozoal,Ameba infections,Toxoplasma 

Organisms Causing Meningitis Bacterial  Viral  Fungal  Ricketsial  Parasitic/Protozoal 

Organisms Causing Meningitis      

Purulent bacterial meningitis etiology newborns Group B Strep ,E. coli children - H. influenzae , Str. pneumoniae HIB vaccine has reduced incidence of H influnza infection adults - meningococccal (small epidemies - army, holiday camps,school going students),pneumococcal

Organisms Causing Meningitis 

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Streptococcus agalactiae (also known as Group B streptococcus) is a beta-hemolytic gram-positive streptococcus. S. agalactiae is a species of the normal flora of the female urogenital tract and rectum. Its chief clinical importance is that it can be transferred to a neonate passing through the birth canal and can cause serious group B streptococcal infection.

Organisms Causing Meningitis 

In the western world, S. agalactiae is a major cause of bacterial septicemia of the newborn, which can lead to death or longterm sequelae such as hearing loss. S. agalactiae can also cause neonatal meningitis, which does not present with the hallmark sign of adult meningitis, a stiff neck

Organisms Causing Meningitis 

rather, it presents with nonspecific symptoms such as fever, vomiting and irritability and can consequently go undiagnosed until it is too late. Somewhat more rarely, S. agalactiae can also cause invasive group B streptococcal disease of the adult in the pregnant, elderly, or immunosuppressed.

Organisms Causing Meningitis 

Viral  

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HSV especially in infants Enterovirus (coxsackie, echovirus)

HIV Lymphocytic choriomeningitis virus Arbovirus Mumps CMV EBV VZV Adenovirus Measles

Organisms Causing Meningitis Rubella  Rotavirus  Influenza and parainfluenza 

Organisms Causing Meningitis 

Fungal  Cryptococcus  Coccidiodes  Histoplasmosis  Mucormycosis  Aspergilosis  Candidasis  With a particular prone settings etc

Organisms Causing Meningitis 

Parasitic/protozoal  Angiostrongylus  Toxoplamosis  Hydatid  Amoeba  Malaria  Cysticercosis

Organisms Causing Meningitis Rickettsial  Rocky mountain spotted fever 

Organisms Causing Meningitis Others  Tuberculosis  Borrelia burgdorferi  Treponema pallidum  Mycoplasma pneumoniae  brucella  Chlamydia 

Organisms Causing Meningitis viral meningitis  fairly common disease but rarely fatal  lymphocytic predominance ie mononuclear cells (but may see neutrophils if CSF sampled early in course - up to 48hrs  glucose not reduced 

Organisms Causing Meningitis 

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may follow Temporary, flu-like symptoms with running nose sneezing etc., headache, low grade fever and stiff neck. Goes away on its own usually within three to 10 days Bed rest, paracetamol Enteroviruses, the most common type of viral meningitis Strict isolation is not necessary

Organisms Causing Meningitis 

Since most cases are due to enteroviruses that may be passed in the stool, people diagnosed with viral meningitis should be instructed to thoroughly wash their hands after using the toilet.

Organisms Causing Meningitis  

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The incidence of viral meningitis drops with age. Neonates are at greatest risk and have the most significant risk of morbidity and mortality. The incidence during the first year of life is 20 times higher than in older children and adults.

Organisms Causing Meningitis 

CRP much more elevated in bacterial than in viral meningitis (ie, 50-150 in bacterial meningitis group vs <20 in viral meningitis group).

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Treatment for viral meningitis is mostly supportive.

Neisseria meningitidis

Hemophilus influenza (H flu)

Strep pneumoniae

CSF-Gram stain: 

Low power view showing many neutrophi ls.

CSF-Gram stain: 

High power shows clusters of bacteria.

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Neutrophil s

CSF-Gram stain: 

High power shows clusters of bacteria.

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Neutrophil

CSF-Gram stain: 

High power shows clusters of bacteria.

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Neutrophil

CSF-Gram stain: Observe Paired rounded bacteria – (diplococci) staining pink (gram negative)

Pathogenesis of Meningitis 

The virus or bacteria replicates in the initial organ system (ie, respiratory or gastrointestinal mucosa) and gains access to the bloodstream. Primary viremia or bacteremia introduces the virus or bacteria to the reticuloendothelial organs (liver, spleen, and lymph nodes.)

Pathogenesis of Meningitis 

If the replication persists despite immunologic defenses, secondary bacteremia or viremia occurs, which is thought to be responsible for seeding of the CNS. Rapid viral replication likely plays a major role in overcoming the host defenses.

Pathogenesis of Meningitis There occurs local immune response to bacteria or virus  Increased vascular permeability  oozing of fluid exudate,inflammatory cells  Neutrophils migrate from capillaries and release toxins  TNF-a and IL-B1 produced by activated macrophages and endothelial cells 

Pathogenesis of Meningitis Ensuing inflammatory response increases blood-brain permeability  Cerebral edema  Increased ICP 

Pathogenesis of Meningitis 

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cellular damage and loss of cellular homeostasis and worsen cerebral edema damage to vessels lead to vasculitis and bleed or thrombose leading to infaraction or haemorrahage exudate formation etc can obstruct CSF flow and lead to hydrocephalous ICP lead to herniation

Pathogenesis of Meningitis 

exudative pus of dead cells ,fluid,fibrin and leucocytes (pus) cause thick whitish grey layer that covers the leptomeninges over the surface of brain and filling sulci and basal cisterns with swollen edematous brain.

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damage to neurons can take place if extending to brain cells resulting in their degeneration.

The white appearance of this calf brain is caused by neutrophils within the meninges – a condition known as meningitis. This is usually due to a bacterial infection.

This calf brain shows similar pathology. If a glass slide is pressed to the surface of the brain and stained it would show high numbers of neutrophils.

This brain shows irregular red spots which are areas of hemorrhage Bovine and necrosis caused by the bacteria, Histophilus somni.

Brain: meningitis.

Pathogenesis of Meningitis 

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if infection becomes localised in brain then can lead to abcess formation especially in case of direct infections. immune system tries to confine this localised infection therefore may develop fibrous wall around it with perivascular chronic inflamatory cells around it,leading to brain abcess with central suppuration and liqufication due to death of cells .healing may occur with fibrous scar.

The Evolution of the Abscess is as follows An area of cerebritis begins, in which Polymorphonuclear leukocytes are attracted to the invading bacteria.  Liquefaction of brain tissue rapidly ensues, and at the periphery, a thin rim of granulation tissue composed of new capillaries and fibroblasts is formed. 

Evolution of the Abscess 

With time, a connective tissue capsule is formed by collagen laid down by infiltrating fibroblasts. Often this is more perfectly formed on the outer aspect of the abscess, presumably due to the contribution of the reservoir of potential in the adjacent meninges.

Evolution of the Abscess 

Due to the poor encapsulation of the medial aspect of an abscess, which abuts upon or is located within the cerebral white matter, the infection tends to form daughter or satellite abscesses medially which may eventually rupture into the ventricular system

Evolution of the Abscess 

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Such rupture may lead to rapid death, and in any event, is usually followed by severe ventriculitis and massive meningitis as infected CSF pours into the subarachnoid space. Antibiotic therapy greatly decelerates the growth of an abscess, and may allow time for a complete capsule to form after which the abscess may be removed surgically.

Evolution of the Abscess

Evolution of the Abscess 

The image above shows a large abscess in the brain. The purulent center is surrounded by a capsule. Often a zone of hyperemia is present adjacent to the wall and there is marked swelling of the adjacent brain tissue

Evolution of the Abscess

Evolution of the Abscess

Evolution of the Abscess Abscess-Cerebral Gross:

Abscess-Cerebral MRI

Meningial enhancement Meningial enhancement in a Bacterial meningitis - CT Scan Image

Meningial enhancement

Signs & symptoms of Meningitis Acute (<1 day)- common with S. pneumoniae and N. meningitides  Subacute (2-3 days)- preceding URI like symptoms, more common with H. flu and other pathogens. 

Signs & symptoms of Meningitis 

Non-specific complaints  Fever  Headache  Nausea and vomiting --Nuchal rigidity  Lethargy  Irritability  Restlessness  Poor feeding  Back pain  Altered mental status (seizure, coma)

Signs & symptoms of Meningitis Febrile  stiff neck causing may causearched position Opisthotonos  Focal neurologic signs  Petechia/purpura- DIC with N. menigitidis  Positive Kernig’s and Brudniski’s i.e. ,

Meningismus (stiff neck + Brudzinski + Kernig signs)

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Shock Disseminated intravascular coagulation (DIC) Cerebral edema

Kernig’s Sign Patient placed supine with hips flexed 90 degrees. Examiner attempts to extend the leg at the knee  Positive test elicited when there is resistance to knee extension, or pain in the lower back or thigh with knee extension 

Signs & symptoms of Meningitis

Brudzinski’s Sign Patient placed in supine position and neck is passively flexed towards the chest  Positive test is elicited when flexion of neck causes flexion at knees and/or hips of the patient 

Normal fundus

Increased intracranial pressure (ICP)  

Papilledema Cushing’s triad  Bradycardia  Hypertension  Irregular respiration  Severe headache  herniation  vomitting

Meningococcemia - Petechiae

Signs & symptoms of Meningitis         

Is due to small skin bleed All parts of the body are affeced The rashes do not fade under pressure Pathogenesis: a. Septicemia b. wide spread endothelial damage c. activation of coagulation d. thrombosis and platelets aggregation

Signs & symptoms of Meningitis e. reduction of platelets (cosumption )  f. BLEEDING 1.skin rashes  2.adrenal hemorrhage  Arenal hemorrhage is called WaterhouseFriderichsen Syndrome.It cause acute adrenal insufficiency and is uaually fatal 

Meningococcemia - Purpura fulminans

Signs & symptoms of Meningitis 

May also look like bruises,echymosis .

Complications and Outcome of Meningitis Infection can spreading to  Dura – pachymeningitis  Leptomeninges - leptomeningitis  Brain – encephalitis  Spinal cord – myelitis  Ventricles - ventriculitis 

Complications and Outcome of Meningitis 

Disseminated intravascular coagulation (DIC) Cerebral edema

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Adrenal hemorrhage is called WaterhouseFriderichsen Syndrome.It cause acute adrenal insufficiency and is uaually fatal septicaemia and infection spreading to other organs motor and neurological deficits

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Complications and Outcome of Meningitis       

Seizures SIADH Subdural effusions & empyema Septic sinus or cortical vein thrombosis Arterial ischemia / infarction (inflammatory vasculitis) CNs Palsies (esp deafness) Septic shock / multi-organ failure from bacteremia (esp meningococcus & pneumococcus)

Complications and Outcome of Meningitis 

risk of adrenal hemorrhage with hypoadrenalism (Waterhouse-Friderichsen syndrome)

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Serum sodium level may be abnormal because of dehydration or the rare occurrence of syndrome of inappropriate antidiuretic hormone secretion (SIADH).

Complications and Outcome of Meningitis 

Serum amylase level may be elevated in cases caused by mumps even in the absence of parotitis.

Focal infarctions/microinfarcts due to endarteritis oblitrerans  Formation of intracranial mass  Cranial nerve palsies 

Increased intracranial pressure Headache Vomiting Decreased Level of Consciousness Papilledema Herniation

TYPES OF HERNIATION 1. 2. 3.

4.

Subfalcine (cingulate) Transtentorial (uncal) Tonsillar (foramen magnum) Extracranial

TRANSTENTORIAL (UNCAL) HERNIATION SHIFT OF THE BRAIN FROM THE MIDDLE TO THE POSTERIOR FOSSA THROUGH THE TENTORIAL INCISURA MAY BE UNILATERAL OR “CENTRAL” SECONDARY EFFECTS INCLUDE: Compression of the third cranial nerve(s) Duret hemorrhages in midline rostral brainstem Compression of the contralateral cerebral peduncle (Kernohan’s notch) Compression of the posterior cerebral artery with infarction of the medial occipital lobe

HYDROCEPHALUS DILATATION OF THE VENTRICULAR SYSTEM NONCOMMUNICATING: Due to obstruction within the ventricular system, e.g., tumor, aqueductal stenosis COMMUNICATING: Due to obstruction of CSF flow in the subarachnoid space with decreased reabsorption

Complications and Outcome of Meningitis 

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Consequences of meningitis can be mild, moderate or severe, with many survivors being left with permanent disability Septicaemia and shock can lead to skin grafting and scarring, amputations and in severe cases neurological deficits Meningitis can lead to damage in various areas of the brain resulting in loss of sight, hearing and neurodevelopmental deficits

Complications and Outcome of Meningitis Scarring  amputation of digits and limbs  Neurological damage 

Complications and Outcome of Meningitis      

Visual impairment and blindness Auditory impairment and deafness Neuromotor disabilities Seizure disorders Behaviour problems Learning difficulties

Complications and Outcome of Meningitis 

The complications associated with septic shock can result in irreversible tissue damage and gangrene

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Tissue damage occurs as a result of inadequate tissue perfusion and oxygenation from hypotension and coagulopathy

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Skin grafting and amputation may be necessary

Complications and Outcome of Meningitis 

Damage to various areas of the brain as a consequence of inflammation in the subarachnoid space

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This appears as exudate covering the surface of the brain

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Many complications are due to cranial nerve damage

Complications and Outcome of Meningitis 

Psychosocial and emotional problems - low self esteem and difficulties coping

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Subtle complications - poor concentration, clumsiness and mood swings

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May be age-specific

Complications and Outcome of Meningitis 

Tiredness

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Recurring headaches

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Memory loss, which may be severe

Difficulties in concentration  Anger outbursts  Clumsiness 

Differential Diagnosis of Meningitis   

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Brain abscess Encephalitis Tumor like ASTROCYTOMAS,OLIGODENDROGLIOMAS ,EPENDYMOMAS MIXED GLIOMAS Metastatic tumor Subdural and epidural empyema subdural subarachnoid

Differential Diagnosis of Meningitis Chemical meningitis: Rupture of tumor  intracranial haemorrage like  Epidural  subdural  Subarachnoid  intraparenchymal 

Differential Diagnosis of Meningitis metabolic encephalopathy  hyperglycaemic coma  uremia  hepatic encephalopathy  vit B deficiencies  vascular diseases (amyloid angiopathy, vasculitis, berry aneurysms, A-V malformations 

CSF & LUMBER PUNCTURE 

It is produced in the brain by modified ependymal cells in the choroid plexus (approx. 50-70%), and the remainder is formed around blood vessels and along ventricular walls. It circulates from the choroid plexus through the interventricular foramina (foramen of Monro) into the third ventricle, and then through the cerebral aqueduct (aqueduct of Sylvius) into the fourth ventricle, where it exits through two lateral apertures (foramina of Luschka) and one median aperture (foramen of Magendie).

CSF & LUMBER PUNCTURE 

It then flows through the cerebellomedullary cistern down the spinal cord and over the cerebral hemispheres.

CSF & LUMBER PUNCTURE 

The cerebrospinal fluid is produced at a rate of 500 ml/day. Since the brain can only contain from 135-150 ml, large amounts are drained primarily into the blood through arachnoid granulations in the superior sagittal sinus. Thus the CSF turns over about 3.7 times a day.

CSF & LUMBER PUNCTURE 

Direct cranial measurement of ICP. ICP monitoring requires admission to the hospital. A small pressure monitor is inserted through the skull into the brain or ventricles to measure the ICP. pressure monitoring (either by lumbar catheter or the intracranial method) can detect an abnormal pattern of pressure waves.

CSF & LUMBER PUNCTURE 

Ventricular puncture for the relief of increased ICP is one of the oldest practices in neurosurgery.

CSF & LUMBER PUNCTURE 

The "gold standard" technique for ICP monitoring is a catheter inserted into the lateral ventricle, usually via a small right frontal burr hole. This can be connected to a standard pressure transducer via a fluidfilled catheter in neurosurgery.

CSF & LUMBER PUNCTURE  

Indirect measurement of ICP by lumber puncture. The two principal objections to lumbar puncture in the diagnosis of intracranial hypertension have been the danger of inducing brain-stem compression through tentorial or tonsillar herniation and the contention that spinal fluid pressure is not always an accurate reflection of ICP.

CSF & LUMBER PUNCTURE 

Indications

1. Diagnostic aid  2. Therapy for idiopathic intracranial hypertension  3. Infusion of anaesthetic (“spinal”), chemotherapy, or contrast agents (myelography) 

CSF & LUMBER PUNCTURE       

Contraindications - INR > 1.4 or other coagulopathy - platelets < 50 - infection at desired puncture site - obstructive / non-communicating hydrocephalus - intracranial mass - high intracranial pressure (ICP) / papilloedema

CSF & LUMBER PUNCTURE 

An LP may safely be performed without first doing a CT head in a young previously healthy patient with no history of seizures, a normal level of consciousness and a normal neurological exam.

CSF & LUMBER PUNCTURE 

Anatomy

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Intercristal line is an imaginary line that connects the superior border of the iliac crests

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- L4/5 interspace is the first interspace caudal to the intercristal line

CSF & LUMBER PUNCTURE   

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Materials sterile gloves and mask LP kit (contains: syringe, 25 and 22G needles, 1% lidocaine, sterile drapes, sponges and gauze, 22G LP needle, stopcock and manometer, 4 collection tubes and band-aid) - sterilization solution (chlorhexidine or proviodine)

CSF & LUMBER PUNCTURE      

Technique 1. Obtain patient consent 2. Position the patient,close to edge of bed as possible 3.Pillow under head and between legs 4.Head flexed and legs curled up towards chest,ask patient to bulge out lumbosacral spine 5.Carefully open LP kit and put cleaning solution in reservoir.

Positioning

INCORRECT

CORRECT

CSF & LUMBER PUNCTURE 6.Put on mask and sterile gloves.  7.Sterilize the field using the sterilizing solution and sponges provided. Clean a 6 inch area around the desired entry site, proceeding outward in concentric circles. Do this 3 separate times. Place sterile drape over the field. 

Skin Preparation 

Overlying skin cleaned with povidone-iodine

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Sterile drape placed with an opening over the LS

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Spinal Needle Insertion Local anesthesia infiltrated Local anesthesia infiltrated 20 or 22 gauge spinal needle with stylet Advance spinal needle slowly, angling slightly toward the head Flat surface of bevel of needle positioned to face patient’s

flanks

CSF & LUMBER PUNCTURE 

8. Ensure all items in LP tray are ready for use. E.g.. 1% or 2% lidocaine loaded into syringe, collection tubes open, test to see that the stylet slides in/out of LP needle easily, stopcock and manometer for opening pressure measurement ready

CSF & LUMBER PUNCTURE 

9.Local anaesthesia. Using a 25G needle, inject 1% or 2% lidocaine under the skin at the desired entry site. A small bleb under the skin is sufficient. Switch the needle tip to the 22G needle and anaesthetize deeper structures by inserting the needle further, injecting lidocaine while proceeding forward.

CSF & LUMBER PUNCTURE 

10.Insert LP needle. The bevel should be parallel to the spinal column. Always advance the needle with the stylet in place. Aim needle in the midline, slightly cephalad, towards the patient’s umbilicus. Advance needle slowly until it is inserted 2-3 cm, then withdraw the stylet to check for CSF return. Continue to advance the needle, periodically checking for CSF return. Often a "pop'' is appreciated as the needle pierces the dural membrane.

CSF & LUMBER PUNCTURE 

If the needle meets bone or if blood returns (hitting the venous plexus anterior or posterior to the spinal canal), withdraw the needle to the skin and redirect the needle

CSF & LUMBER PUNCTURE 

11.Once CSF flow is obtained, measure the opening pressure by attaching first the stopcock to the LP needle and then the manometer to the stopcock.

CSF & LUMBER PUNCTURE 12.Collect CSF fluid into sequential tubes. about 2 ml in each tube is sufficient for basic investigations. More fluid will need to be collected for special tests e.g. viral PCR, cytology etc  13.Reinsert stylet. Withdraw needle. Place band-aid over insertion site. 

CSF & LUMBER PUNCTURE

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What to order The basics Tube #1 Cell count and differential

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Tube #2 Chemistry (protein, glucose)

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Tube #3 Culture and Gram stain

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Tube #4 reserve with csf in it

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CSF & LUMBER PUNCTURE Other tests to consider  - Will need to collect extra fluid for these tests in tube #3 or #4.  India ink and / or Cryptococcal Ag (for Cryptococcus neoformans)  AFB and / or PCR for TB  Viral PCR (includes HSV, CMV, EBV)  arbovirus / WNV, echovirus 

CSF & LUMBER PUNCTURE 

VDRL

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fungal culture

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viral culture

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PCR and /or antibody titers for Lyme ds.

CSF & LUMBER PUNCTURE 

oligoclonal banding (3-4 ml)

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IgG index, IgG :albumin ratio

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cytology (must be collected in cytology fixative) (8-10ml)

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flow cytometry (3-4 ml) (NOT in fixative)

CSF & LUMBER PUNCTURE 

How much CSF to withdraw?

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- CSF is produced at a rate of 0.3 ml/min in adults or 450 ml/24h

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- CSF volume is approximately 150 ml in an adult

CSF & LUMBER PUNCTURE 

- For basic investigations, only require 4-8 ml

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- May require more volume for special tests. Maximum to be removed at one time should probably not exceed 20 ml.

CSF & LUMBER PUNCTURE Normal opening pressure ranges 50 to 200 mm H20 in adults and up to 250 mm H20 in obese women patients or 5-20 cm of H20.  2 Intracranial hypotension is defined as an opening pressure of less than 50 mm H20. 

CSF & LUMBER PUNCTURE 

Normal CSF is crystal clear. However, as few as 200 white blood cells (WBCs) per mm3 or 400 red blood cells (RBCs) per mm3 will cause CSF to appear turbid.

CSF & LUMBER PUNCTURE 

Glucose: 2/3rd or < 40% of concurrent serum glucose or less than 2/3rd of serum glucose (often absolute CSF glucose < 2.2 , (normal is 2.2 mmol to 4 mmol/l)

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cells <5/cmm mostly lymphocyte

CSF & LUMBER PUNCTURE Xanthochromia is a yellow, orange, or pink discoloration of the CSF, most often caused by the lysis of RBCs resulting in hemoglobin breakdown to oxyhemoglobin,  methemoglobin, and bilirubin. 

CSF & LUMBER PUNCTURE 

Discoloration begins after RBCs have been in spinal fluid for about two hours, and remains for two to four weeks.

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Xanthochromia is present in more than 90 percent of patients within 12 hours of subarachnoid hemorrhage

CSF & LUMBER PUNCTURE 

CSF protein levels (normal 15 to 45 mg/dL ) or < 1.5 g per L.

CSF & LUMBER PUNCTURE 

Culture provides definitive diagnosis as well as identificaiton of pathogenic organism and antibiotic susceptibilities

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blood culture positive in 50% cases

CSF & LUMBER PUNCTURE 

The Xpert EV test, approved for use in March 2007, can rapidly test for enteroviral meningitis. The test uses a reverse-transcription PCR disposable cartridge on which CSF is applied, and enteroviral genetic material is identified if present. Results are ready in 2.5 hours, as opposed to days to weeks in traditional PCR studies.

CSF & LUMBER PUNCTURE 

CT scan with contrast helps in ruling out intracranial pathology. Contrasted scans should be obtained to evaluate for any enhancement along the meninges.

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ct scan also excludes intracranial abscess, subdural empyema, or other lesions. Alternatively, and if readily available, an MRI of the brain should be done.

CSF & LUMBER PUNCTURE 

MRI with contrast is the criterion standard in visualizing intracranial pathology in viral encephalitis HSV-1 commonly affects basal frontal and temporal lobes with a typical picture of diffusely enhancing bilateral lesions.

CSF & LUMBER PUNCTURE 

All patients whose condition is not improving clinically within 24-48 hours should have more extensive work-up to discern the cause of meningitis.

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Blood, feces, and throat swabs may be sent for viral serology and cultures.

CSF & LUMBER PUNCTURE 

Acid-fast staining of CSF should be performed and the remaining fluid should be sent for PCR testing for HIV and CMV.

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Serum titers of antibodies against HIV and toxoplasma should be obtained.

CSF & LUMBER PUNCTURE 

EEG may be performed if encephalitis or subclinical seizures are suspected in the altered patient. Periodic lateralized epileptiform discharges (PLEDs) are often seen in herpetic encephalitis.

CSF & LUMBER PUNCTURE 

CSF Lactate Concentration

normally 14 mg/dl  in bacterial meningitis is usually <25 mg/dl  PCR for microbial DNA may become sensitive and specific method for bacterial identification 

CSF & LUMBER PUNCTURE 

CT Scanning sould be done and preferred choice before Lumbar Puncture in Suspected Meningitis

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Acid-fast staining of CSF should be performed and the remaining fluid should be sent for PCR testing for HIV and CMV. Serum titers of antibodies against HIV and toxoplasma should be obtained.

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CSF & LUMBER PUNCTURE 

Additional serum collection 10-21 days later may aid in discerning rising titers in the antibodies against specific viral pathogens; a 4-fold increase in viral antibodies confirms the diagnosis. This is particularly useful for arboviral and LCMV cases, but also is helpful in ruling out toxoplasmosis, leptospirosis, borreliosis, and rickettsial infections. Although some of these studies do not yield an immediate result for clinical decision making, they may be useful for prognostication.

CSF PRESSURE 

Opening pressure: 5-20 cm water (only valid in lateral decubitus position) or 50200 mm of H20.

CSF PRESSURE 

ICP is measured in millimeters of mercury (mmHg) and, at rest, is normally 5–20 mmHg for a supine adult, and becomes negative (averaging -10 mmHg) in the vertical position.

CSF PRESSURE Normal CSF pressure in the lower back is between 50-200 mm water.  Normal Intracranial pressure(within the cranium) however is between 5-20 mmHg or 50-200 mm H2O in adults. 

Investigations & Diagnosis of Meningitis Repeat CSF analysis 24 to 36 hours (minimum of 24 hours) after initiation of therapy  Changes in therapy/concomitant therapy as needed  Evaluation of drug concentrations in CSF 

Investigations & Diagnosis of Meningitis 5-7 weeks after completion of all therapy  Lumbar puncture repeated only if clinically indicated 

Investigations & Diagnosis of Meningitis LATE POST-THERAPY VISIT  5-6 months after completion of therapy  Emphasis on hearing/ development/ neurological findings  Behavioral difficulties should be documented as well 

Investigations & Diagnosis of Meningitis 

Persistence of pathogen at 24-36 hr. tap leading to additional therapy or change in therapy.

CSF evaluation Condition

Normal Bacterial, acute Viral TB Fungal

WBC

Protein (mg/dL)

Glucose (mg/dL)

>50 (2.2 <5 , lymphocytes mainly 5-45 mmol to 4 mmol/l) 100-500 or <2.2 m >1000K PMN’s >1.5gm/l mol/l <1000

increased

Low to normal

<500 < 500

increased increased

decreased decreased

CSF Diagnosis Normal

WBC <5 (lymphocytes)

Glucose Protein 2/3rd of serum 15 to 45 glucose mg/dl

Bacterial >1000 PMN’s Meningitis predominate

Low

Elevated (>100 mg)

Aseptic Elevated Meningitis (PMN’s early, lymphocytes late) TB Elevated Meningitis (PMN’s early,

Normal to low

Normal or slightly elevated

Low

Elevated (>100 mg)

CSF evaluation Condition

WBC

Normal

<5, lymph's mainly

Bacterial, acute

>1000 PMN’s

TB

<500

Fungal Viral

<500 <1000

Protein (mg/dL)

Glucose (mg/dL)

5-45 >50 Increased> more than Low 100 mg/d Increased low upto 500 mg/dl Upto 500 Upto 100

low Normal

Summary of Typical CSF Findings Normal 0-5 0 5 60-80 66%

Bacterial >1000

Viral <1000

TB <500

Predominate

Early

+/- increased

Late

Predominate

Increased

Decreased

Normal

Decreased

<40%

Normal

< 30%

Protein

5-40

Increased

+/- Increased

Increased

Culture

Negative

Positive

Negative

+TB

Cells Polymorphs Lymphocytes Glucose CSF plasma: Glucose ratio

TREATMENT of MENINGITIS   

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Empiric Antibiotics: Cefotaxime 2g IV 6 hrly add Vancomycin 1-2 g IV 8-12 hrly in all patients (till possibility of Penicillin-resistant Strep pneumoniae has been ruled out) add Ampicllin 2g IV 6 hrly in elderly or immunocompromised patients (for Listeria infections)

TREATMENT of MENINGITIS 

for patients with serious penicillin allergies, Meropenem 1-2g IV 8hrly as alternative

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Ceftazidime (2g IV 8 hrly or BD) + Vancomycin for neurosurgical patients, those with shunts or CSF leaks May consider adjunctive Acyclovir (10 mg/kg IV 8 hrly if normal renal function) in case of viral infection.

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TREATMENT of MENINGITIS 

Therapy can be modified as the results of Gram stain, cultures, and PCR testing become available. Patients in unstable condition need critical care unit admission for airway protection, neurologic checks, and prevention of secondary complications.

TREATMENT of MENINGITIS 

since SIADH has been reported. Fluid restriction, diuretics, and rarely hypertonic saline infusion may be used to correct the hyponatremia

TREATMENT of MENINGITIS 

Cerebral edema does occur in cases of severe encephalitis and may require intracranial pressure control by infusion of mannitol (1 g/kg initial dose followed by 0.25-0.5 g/kg 6 hrly), IV dexamethasone, or intubation and mild hyperventilation, with arterial PCO2 around 28-30 mm Hg

TREATMENT of MENINGITIS 

Use of adjunctive corticosteroids:



- prior to or along with initial antibiotics, administer Dexamethasone 10 mg IV for suspected bacterial meningitis (based on cloudy CSF, CSF WBC counts > 1000 or + Gram stain)



- continue 10 mg IV 8 hrly x 4 days

TREATMENT of MENINGITIS 

Isolation & Contact Prophylaxis:



- Generally isolate cases of bacterial meningitis for up to 48 hours of appropriate antibiotics

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- Concern is to reduce transmission of meningococcal infections

TREATMENT of MENINGITIS 

can be taken out of isolation after this time or if alternative pathogen identified



- department of health should be notified of pathogens in pyogenic meningitis

TREATMENT of MENINGITIS Close contacts (family members, partners, co-workers or school children) should receive prophylaxis if meningococcal or haemophilus influenzae type B (if not vaccinated):  - rifampin 600 mg PO bid x 2d  - ciprofloxacin 500 mg PO single dose 

TREATMENT of MENINGITIS dexamethasone 0.6 mg/kg/day IV 6-8 hrly for 4 days  reduces incidence of neurologic sequelae, i.e., hearing loss 

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electrolyte abnormalities - SIADH

Prognostic Factors 1. Age  2. Level of Consciousness (50% mortality if unresponsive or minimally responsive on admission)  3. Seizures early in course  4. Strep. pneumoniae meningitis  5. CSF results (lower glucose & WBC counts, higher protein)