Cns Infection Paper1 2006

Infections Of The Central Nervous System(CNS)

Ⅰ. Pathogen: virus, bacterial, fungal, spirochetal, parasitic organisms, etc.

Ⅱ. Category: 1. Depending on the pathogen: 2. Depending on duration: (1)acute infection (2)subacute infection (3)chronic infection

3. Depending on the position of foci: (1) Parenchymatitis: encephalitis, myelitis, myelencephalitis, etc. (2)Pia-arachnitis: meningitis, spinal meningitis,etc. (3)Meningoencephalitis:

Ⅲ Pathway of infection 1. Respiratory pathway 2. Blood circulation pathway 3. Direct pathway 4. Reverse infection via nervous stem

Major Routes of CNS Invasion • Hematogenous spread is the most common route of CNS invasion. • Seeding of blood with agents may come from – Superficial or deep abscesses – GI / GU tracts – Respiratory system - especially lung abscess – Bacterial endocarditis

Diagnostic test for meningitis : lumbar puncture…. A lumbar puncture collects cerebrospinal fluid to check for the presence of disease or injury. A spinal needle is inserted, usually between the 3rd and 4th lumbar vertebrae in the lower spine.

Permits the urgent distinction of bacterial meningitis from viral meningitis and examination of the CSF allows precise diagnosis.

CSF Changes in CNS Infections • CSF composition is maintained within very narrow limits. • CSF composition changes in CNS infections – Often diagnostic in meningitis – Unreliable in brain abscess

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Key Normal CSF Values Pressure: 80-180 mmH2O Cells: <5/ cubic mm. All mononuclear Protein: <40 mg/dl – May rise slightly with age Glucose: about 2/3 of blood glucose. <50% of blood glucose is abnormal

Diagnosis of CNS Infection 

Standard neurodiagnostic procedures include: • • •

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CSF examination EEG scanning

These can be normal in early stages of the disease Other diagnostic evaluations should be initiated immediately

Herpes simplex Virus encephalitis (HSE)

This is the commonest and gravest form of acute viral encephalitis. The incidence is 0.2-0.5/100,000 population in U.S. Between 30 and 70 percent of these are fatal, and majority of patients survivals are left with serious neurological abnormality. HSE occurs sporadically throughout the year and in patients of all ages and in all the part of the world.

Ⅰ. Etiology and Mechanism Herpes simplex viruses (HSV-1and HSV2) are belong to DNA virus. HSE is due almost always to HSV-1, which is also the cause of common herpetic lesions of the oral mucosa. HSV-2 may also cause acute encephalitis, usually in the neonate and in relation to genial herpetic infection in the mother .

Ⅱ. Pathology The lesions take the form of an intense hemorrhagic necrosis of the inferior and medial parts of the temporal lobes and the medial-orbital parts of the frontal lobes and the limbic lobes.

These lesions are usually bilateral but not symmetrical, which is so characteristic that the diagnosis can be made by gross inspection or by their location and appearance on image studies. In the acute stages of the disease, intranuclear eosinophilic inclusions are found in neurons and glial cell, characteristically.

Ⅲ. Clinical feature: 1. Acute onset: symptoms evolved over several days. 2. Acute encephalitis: fever, headache, seizures, confusion, stupor and coma.

3. Symptoms and findings about impairments of intermedial parts of the frontal and temporal lobes: olfactory or gustatory hallucinations, anosmia, temporal lobe seizures, personality change, bizarre or psychotic behavior or delirium, aphasia and hemiparalysis.

4. Aseptic meningitis: signs of meningeal irritation such as rigidity neck, Kernig’s sign(+). 5. Some patients have the history of herpetic lesions of the oral mucosa.

Ⅳ. Assistant test: 1. CSF: increased pressure, a pleocytosis (range 10 to 500 cells/mm3 usually less than 200). Mainly the cells are lymphocytes, but occasionally there is a significant number of neutrophils. The protein content is increased in most case. Rarely, the CSF glucose levels maybe reduced to slightly less than 40 ㎎ /dL.

Increased ICP is transmitted through the subarachnoid space to the optic nerve sheath, blocking axoplasmic flow and venous return in the optic nerve causing engorgement and elevation (swelling) of the optic disk. This classic sign of ICP takes several hours to days to develop and is often not present in the early hours of ICP increasing. Normal ICP in adults is less than 200 mm H2O. Normal Papilledema

2. CT or MRI scans: showing hypodensity of the affected areas, among them scattered with many small hyperdensity shadows. 3. PCR: The detection of HSV antigen in the CSF by the application of PCR is useful in diagnosis, which is suitable for the early stage diagnosis.

MRI scans of HSE

Ⅴ.Diagnosis: Principle: 1. Clinical manifestation: acute onset; encephalitis syndrome; the change of mental; meningitis syndrome. 2. Assistant test: abnormal change of CSF and CT/MRI scans, and detection of HSV-Ag(+).

Ⅵ. Treatment: 1. Treatment to pathogen Acyclovir: 30 ㎎ / ㎏ , intravenously daily (continued for 10 to14 days). 2. Treatment to symptoms Lower the temperature and control the seizures and decrease the ICP, etc.

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3. General treatment. Cortical hormone: early enough and short stage use. Nervous cells nutrient, Supportive treatment and recovering treatment.

Tuberculous Meningitis

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Usually subacute – may be fulminant Affects all ages – Classically: a disease of the young – Increasingly affects older adults Alcoholics, indigent Immigrants (3rd world countries) Increased in AIDS

Pathogenesis 1 tuberculosis 

Inhalation of organisms

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Replication in regional lymphatics

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Spread to hilar nodes

Systemic infection

Activation of cell-mediated Granuloma formation immunity (6 weeks) Eradication /containment Reactivation at < 1% of cases per year

• Classically a complication of miliary TB – Onset within months of primary infection – More common in children  Now is usually a disease of older adults – Due to reactivated infection – Usually pulmonary – Can also be extrapulmonary – May begin by reactivation within brain TBC meningitis without signs of systemic infection

Pathogenesis 2 tuberculous meningitis 

Granuloma adjacent to ventricle or meninges

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Rupture

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Seeding of CSF

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Ventriculitis Basilar Meningitis

Basilar Meningitis in Tuberculosis • Hydrocephalus  Cranial nerve palsies  Involvement of vessels within inflamed meninges ( vasculitis ) – Arterial and venous thrombosis – Brain infarction

MRI scans of TBM

Tuberculous Meningitis: CSF 

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Differs from bacterial meningitis – Mixed pleocytosis with lymphocytic predominance – Low glucose – High protein Organisms may hard to find – <30% yield by AFB stain – 70% by culture (takes up to 6 weeks) – PCR is major means of rapid diagnosis

Treatment: comprehensive 

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Antituberculosis drugs :key treatment early, alliance , full dose , long time, draught are principle of drug use . Treatment to symptoms. Supporting treatment

Fungal Infection Of CNS

General Feature 1. Fungal infection of the CSF may arise without obvious predisposing cause, but frequently they complicated some other disease process, such as AIDS, organ transplantation, severe burns.

2. Fungal meningitis develops insidiously over a period of several days or weeks. They have the similar symptoms and signs, such as involvement of several cranial nerves, arteries with thrombosis and infarction of brain, multiple cortical or subcortical microabscesses, and hydrocephalus complicated with meningitis. Often the patient is a febrile or has only intermittent fever.

3. CSF: increased pressure; moderate pleocytosis ( usually <1000 cells/ ㎜ 3, lymphocytes predominate); in the acute case, a pleocytosis above 1000 cells/ ㎜ 3 and a predominant polymorphonuclear; subnormal glucose; elevated protein.

Cryptococcosis Meningitis

Ⅰ. Pathology: A granulomatous meningitis is present, in addition, there may be small granulomas and cysts within the cerebral cortex. The cortical cysts contain a gelatinous material and large numbers of organism; the solid granulomatous nodules are composed of fibroblasts grail cells, aggregates of organisms, and areas of necrosis.

Ⅱ. Clinical Feature

1. Subacute onset. 2. In the majority case, early complaints are headache, nausea, and vomiting. 3. Half patients with mental changes. 4.Some case present with symptoms of increasing intracranial pressure due to hydrocephalus ( papilledema in half such patients).

5. Some patients are present with a confused state, dementia, cerebellar ataxia or spastic, usually without other focal neurologic deficit. 6. Meningovascular lesion may be superimposed on the clinical feature. 7. A pure motor hemiplegia (likely due to hypertensive lacune infarct ) is present.

Ⅲ. Assistant test. 1. CSF: increased pressure, a variable lymphocytic pleocytosis (usually<15 cells/mm3); the initial CSF formula may display polymorphonuclear cells, but it rapidly changes to a lymphocytic predominance; the reduced glucose; high level protein ;special diagnosis depends on finding cryptococcus neoformans in the CSF: India-ink preparation are distinctive and diagnostic in experienced hands. 2. CT scan: may find out large sick foci.

Ⅳ.Treatment

1. Treatment to the fungal organisms. (1). Amphotericin B: 0.5-0.7mg/kg, intravenous daily. (2). Flucytosine: 150mg/kg/day oral. These two drugs can be used together to increase the effect and to reduce the side-effect.

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2. Treatment to symptoms. Decrease ICP by dehydration, relieve pain, protect the optic nerve and prevent cerebral rupture are more importent. 3. Supporting treatment.

Attention: Vitamin B1 、 B6 and B12 are forbidden, because they are helpful for Cryptococcus growing.

CNS INFECTION OF HIV

Epidemiology Leading cause of death in the world  In 1998, 2.3 million AIDS related deaths accounting for 4.2% of all deaths in the world  Fourth leading cause of disability adjusted life years lost, a measure that assesses the impact of the disease on both length and quality of life  Tuberculosis (TB), the former leading microbial killer, was estimated to have killed 1.8 million people in 1998, but 400,000 of these deaths were in HIVinfected individuals  HIV infection is now responsible for more than 20% of all deaths in people with TB.

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In 2003 the number of newly affected individuals are about 5 million 4.2 million adults and 700,000 children under the age of 15 In 2003 approximately 3 million deaths due to AIDS globally 2.5 million adults and 500,000 children under the age of 15

AIDS 

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Neurologic symptoms and signs present in more than one half of AIDS patients during course of disease and can be the presenting manifestation in 10% Result from direct effects of HIV, opportunistic infections and from treatment toxicity Pathogen of opportunistic infections: Brain: Listeria, CMV , toxoplasmosis , PML, VZV, aspergillosis Meninges: Cryptococcosis, syphilis, TB, Herpes 1 and 2 Spinal Cord: VZV, syphilis, HSV, CMV ,etc. multiplex

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Neurologic infectious disease are important cause of morbidity and mortality. Underrecognition of infectious etiologies in setting of increasing populations of immunocompromised hosts, drug resistance, international travel all contribute to morbidity. Bacterial meningitis most commonly caused by S. pneumonia and N. meningitidis in <50 yrs. Ceftriaxone resistance has been reported. Controversy remains about use of steroids. Encephalitis is divided into sporadic and epidemic.

NEUROPATHOLOGY OF HIV INFECTION

1.Central Nervous System Mechanism of CNS infection is unclear, but HIV seems unable to cross blood-brain barrier alone. It probably crosses in macrophages and T cells and most directly affects subcortical structures (basal ganglia, thalamus, brain stem). AIDS dementia complex (ADC), a subcortical dementia,is different from cortical dementia such as Alzheimer's disease.

Toxoplasma gondii toxoplasmosis results in CNS dysfunction - altered cognition - Headache - focal neurological deficits - Encephalitis - Seizures The best prevention is away from pet (such as cat).

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Cerebellar disorders� cerebellar lesions always result from opportunistic infections such as toxoplasmosis and progressive multifocal leukoencephalopathy or primary CNS lymphoma Recently, the relationship between stroke and AIDS was reported. The most common cause of cerebral infarction in both clinical and autopsy series was nonbacterial thrombotic endocarditis. Intracerebral hemorrhages were usually associated with thrombocytopenia, primary CNS lymphoma, and metastatic KS.

2.spinal cord pathology - HIV myelitis - opportunistic infections - lymphomas - vacuolar myelopathy� affect the dorsolateral white matter tracts.

3.Neuromuscular disturbances Neuromuscular disturbances may first appear as movement disorders.  A neurological examination can be performed to provide a diagnosis and prognosis. This may include the level of the lesion, neuromuscular deficits, need for assistive devices, ADL （ aids to daily living ） and functional abilities.  Various quality of life assessments can be used with the HIV population 

4.Peripheral Nervous System  

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Sensory early and middle stages: - distal lower extremities are largely involved - paresthesia and decreased temperature sensitivity advanced stages: - patient has decreased ankle and knee reflexes - diminished temperature and vibration sensitivity and proprioception, and hyperesthesia Motor resembles Guillain-Barreá syndrome (progressive muscle weakness paralysis, decreased deep tendon reflexes). splints and ankle-foot orthoses may prevent deformities

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Distal symmetrical polyneuropathy (DSP) most common form of neuropathy in HIV infection signs & symptoms Numbness Burning paresthesias in the feet symptoms are typically symmetrical and so severe that patients have contact hypersensitivity and gait disturbances upper extremity involvement and distal weakness may occur later in the course of DSP

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Neurological Examination will show - sensory loss to pain and temperature in a stocking-glove distribution - increased vibratory thresholds, - diminished ankle reflexes compared with knee reflexes. - concurrent CNS disorders and neuropathy, characterized by hyperactive knee reflexes and depressed ankle reflexes.

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Distal symmetrical polyneuropathy (DSP) - Incidences of DSP increases with advancing immunosuppression, in parallel with decreased CD4 counts - Thirty-five percent of patients with AIDS may present with electrophysiological or clinical abnormalities. - Pathological evidence of DSP is present in almost all patients who die of AIDS.

5.Autonomic Nervous System  

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arrhythmias ��especially tachycardia abnormal blood pressure �� orthostasis and with isometric exercises dementia myelopathy peripheral sensory neuropathies

Treatment 

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Treatment for CNS impairments include an eclectic blend of rehabilitation strategies. No special and effective treatment, so that prevention is the most important treatment.

Kaposi’s sarcoma

CSF Changes in Meningitis Viral

Tuberculous

Fungal

Cells

Lymphs (+ poly’s)

Lymphs + poly’s

Lymphs

Protein

Mildly Elevated

Midrange Elevated

elevated

Glucose

Normal

<50% blood

<50% blood

Specific Diagnosis

PCR (Serology)

Culture (20 ml) Culture (20ml)

Thanks