Inflammations of the nervous system

Dynamics acute monophasic biphasic subacute fluctuating chronic intermittent progressive Localization meningitis encephalitis abscess epidural empyema sinus thrombophlebitis

Pathology 1. Meningeal infiltration 2. Blood-brain barrier damage perivascular cellular infiltration extracellular edema 3. Glial proliferation 4. Damage of the nervous tissue
(neuron, axon, oligodendroglia, myelin sheath)

The routes of infection 1. Hematogen (abscess) 2. Paranasal sinuses (meningitis) 3. Respiratory tract (nose, lung) (meningoencephalitis) 4. Scull fracture (abscess, epidural
empyema, meningitis)

5. Peripheral nerve (rabies, HSV, VZV)

MENINGITIS Pathology Cellular infiltration of the meningxes Brain parenchyma is intact, except edema and radicular/cranial nerve lesions

Clinical picture: ("Meningeal syndrome) general symptoms (fever, weakness) signs of meningeal irritation (nuchal rigidity, Kernig-, Brudzinsky signs, headache, hyperirritability) changes in mental status (apathy, somnolence, delirium) focal neurological signs are absent "CSF syndrome" (increased cell&protein)

Acute aseptic meningitis Pathogens: virus HERPES (HSV, HZV, EBV, CMV), ENTERO (echo, coxaci, polio, etc.), ARBO (tick-bite encephalitis virus), ADENO, LCMV, HIV, etc. spirochete (leptospira, borrelia, treponema) Clinical picture Incubation 7-10 day, "dromedary" course CSF: cell count 50-1000/ul, lymphocytes protein level moderately elevated (0.4-lg/1) sugar: normal microbiol. culture: negative Dg: serology (repeated) Others: EEG, neuroimaging: usually normal Therapy: supportive

Subacute/chronic meningitis Pathogens: mycobacterium, mycoplasma fungus (candida, cryptococcus, aspergillus) spirochete (leptospira, borrelia) virus (LCMV) toxoplasma non-infective (leukemia, SLE, tumour cells) Clinical picture (weeks-months) intermittent febrile states slowly progressive mental changes, mild (or absent) meningeal signs, progressive cranial nerve palsies CSF: 50-100/ul cells, lymphocytes high protein level - 1-3 g/1 (severe BBB damage) low sugar level (>2 mmol/l) Dg: need special culture technique, serology Therapy: for tbc: Isonicid, Rifampycin, Dexamethason. for fungus: Amphotericin B

Purulent meningitis Pathogens: adult: Pnemococcus, N. meningitidis, child: Hemophylus, Enterobacteria Clinical picture: primary extracranial manifestation (lung, paranasal) severe condition, high fever, prominent meningeal signs, confusion (high mortality !) residual signs (hydrocephalus, hypacusis, ment. retard., epileptic seizures) CSF: green-like 1000 to several 10,000 cells/ul, granulocytes high protein level (1-3 g/1) low sugar Dg: microbiol. culture Other: eradication of the (respiratory) source EEG: generalized slowing CT/MRI: look for "pus-cap, brain abscess, hydrocephalus Therapy: based on the culture. Before: Penicillin + Ampicillin + Ceftriaxon iv., in severe cases + Dexamethason (Steptokinaze)

Covered syndrome (pretreated/masked form of purulent meningitis) Clinical picture headache, intermittent febrile state, but no prominent meningeal signs antibiotic therapy in the recent history CSF no more than 1000 cells, granulocytes/mixed protein elevated >1 g/l sugar: decreased negative culture result Diagnosis based on CSF findings Therapy should be the same as in acute purulent meningitis (combined antibiotics) Brain abscess Etiol.: direct or haematogenic spreading Clinical picture: focal signs, seizures, rised intracranial pressure Dg: CT, MRI TH: antibiotics, surgical

ENCEPHALITIS Pathology: Blood-brain barrier damage + Central nervous system damage Clinically: "Encephalitis syndrome" meningeal syndrome + neurological signs (focal signs of motor-, sensory, autonomic systems, sings of inreased intracranial pressure) seizures altered mental state EEG, MRI, CSF alterations

Polio- leuko- panencephalitis

Polioencephalitis: Herpes simplex encephalitis Clinical: primary [subclinical] infection with HSV-1, endogenous reactivation, flu-like phase followed by encephalitis located to temporal lobe (aphasia, paresis, seizures, psychoorganic syndrome). Dg: CSF, EEG, MRI, biopsy (PCR), serology. Treatment with Acyclovir 30mg/bwkg a day for weeks Tick-born encephalitis Clinical: tick bite, flu-like illness followed by meningitis or encephalitis syndrome, predilection for cervical spinal cord motoneurons and temporal lobe Dg: typical CSF findings, serology TH: supportive

HSV

Acute anterior poliomyelitis Clinical: gastrointestinal infection, viraemia followed by asymmetric flaccid paresis, predilection for large motoneurons in spinal cord and brainstem, Dg: typical CSF findings, Treatment : supportive, prevention with peroral immunization) Lyssa, rabies Clinical: transmitted by bite of an rabid animal {small predators}, week to months of incubation period, Stages: 1. Prodrome (fever, fatigue) 2. Excitation (restlessness, hyperirritability, convulsions, 3. Paralytic phase (widespread paresis, death) Dg. Pathology (Negri-body in hippocampus), CSF, preventive immunization)

CMV

Negri

Leukoencephalitis Pathology: immune demyelination Clinical picture: acute/subacute, monophasic disease with widespread white matter lesion, typical CSF (BBB damage +OB)

parainfectious encephalomyelitis (measles, rubella, varicella, smallpox, mumps, infectious mononucleosis)

postvaccination encephalomyelitis (vaccination against smallpox, measles, rabies, tetanus)

Panencephalitis (slow virus diseases, progressive course) SSPE (subacute sclerotising panencephalitis) CJD (Kreutzfeld-Jakob disease) PML (progressive multifocal leuko-encephalopathy)

SSPE

Pathogenesis: childhood infection with measles virus reactivation of "defective" virus (5-10y), Clinical picture no general signs, young patients, progressive dementia (impaired cognitive performance in school), ataxia, myoclonic jerks, decerebration, death EEG: generalized slow waves (Rademecker complex) in every 3-10 sec. CSF: OB, high anti-measles Ab's Th: symptomatic

CJD

Etiology: Prion (sporadic, iatrogenic, familial) Clinical picture Onset: 35-65 y, personality changes, progressive dementia within few months, extrapyramidal signs, ataxia, dysarthria, myoclonus, death within a years EEG: triphasic slow complexes, 1-2 cps CSF: unremarcable Dg: clinical picture, (brain biopsy) Th: symptomatic

GSS (Gertsmann-Straussler-Scheinker disease) AD inheritance Onset: 40-50 y, duration 1-10 y Clin.: spinocerebellar degen. + dementia

FFI (Fatal familial insomnia) Degen. of the medial nucleus of thalamus Clin: lack of sleep + vegetative disturbances Dg: clinical + EEG/polysomnography

PML (progressive multifocal leukoencephalopathy)

Immunsuppression (HIV, cytostatics, leukemia, malignancies) Mechanism: JC papova virus causes oligodendroglia degeneration Clinical picture: subacute onset, changing in personality, pramidal signs, ataxia, dementia, death within a few months CSF: unremarkable MRI: demyelination (confluent, no enhancement) Dg: brain biopsy Th: stop immunsuppression, symptomatic

Neurosyphilis

Pathogen: treponema pallidum Primer genital infection followed by hematogenous spreading

Forms: 1. Luetic meningitis (early) 2. Meningovascular syphilis (months) 3. Paralysis progressiva (dementia, psychosis, several years) 4. Tabes dorsalis (spinal ataxia)

Dg: CSF, serology, MRI Th: penicillin

NEUROBORRELIOSIS Etiology Spirochetal (Borrelia burgdorferi) infection by bite of a vector insect (tick borne) Symptoms and signs Relapsing-remitting course with multiple organ affection: skin- ECM, heart-carditis, joints- mono-, polyarthritis, and CNS/PNS neuroborreliosis Stages (acute) flu-Iike symptoms (headache, myalgia, ECM) (subacute) meningitis, meningoradiculitis, mono-, polyneuritis (+arthritis, and sometimes carditis) (chronic) meningo-encephalo-myelitis

NEUROBORRELIOSIS Characteristic neurological forms: Diplegia facialis-most common form of neuritis caused by BB. (1-3 weeks) Bannwarth-Sy. (meningo-polyradiculitis, 1-3 months) Encephalomyelitis (ataxia, memory disturbances, fatigue, progressive pyramidal signs, disturbances of bladder functions, neuritis retrobulbaris, peripheral neuritis, tetraparesis, dementia) MRI: focal white matter lesions CSF: OB Dg: Based on clinical picture + serology Th: Prolonged course with high doses of antibiotics (Doxycyclin, Penicillin,Rocephin )

NEUROLOGICAL COMPLICATIONS OF AIDS 1. DISEASES WITH DIRECT RELATIONS TO HIV-1 Meningitis (acute, or chronic form) Encephalopatia (= AIDS-dementia complex) Myelopathy Neuropathy -symmetric polyneuropathy -mononeuritis multiplex Myopathy (direct or due to treatment) 2. SECONDARY COMPLICATIONS Opportunistic infections (CMV; Toxopl., Cryptococcus, PML, HSV, TBC) Neoplasms (lymphoma, metastases, etc) Cerebrovascular diseases (vasculitis) Metabolic disorders (Wernicke, vitamin deficyency)

HIV