CNS infection 2

VIRAL INFECTIONS OF THE CNS

Spread to CNS BY: 1- Haematogenous 2- Direct Spread

VIRAL (aseptic) MENINGITIS

Is viral infection of the leptomeninges & the subarachnoid space leading to inflammatory exudative reaction.
Common viruses causing meningitis:
- Enteroviruses 80% of cases which include ( coxachiev., echov & poliov. )
- Herpes simplex virus - HIV - Arthropod borne virus
Less commonly: - VZV - EPV - LCM
Clinical Features:
Acute onset of headache, fever and neck stiffness which appear to be less severe than acute bacterial meningitis and photophobia, nausea and vomiting.
Investigations:
In addition to basic investigation mentioned,
CSF Study should be done, which shows (ASEPTIC CSF PROFILE)
– predominantly lymphocytic meningitis 10-500%
Normal sugar 2/3 rbs - slight protein elevation - -ve Gram Stain & Culture
CSF-PCR for viral DNA & specific viral culture media
Treatment:
Directed symptomatically.


ACUTE VIRAL ENCEPHALITIS
Virus induced infective inflammation of brain parenchyma, with characteristic clinically of headache, fever and disturbed level of conscious and focal neurological deficits, associated with CSF changes, diffuse EEG slowing and contrast MRI changes. DDx:

HERPES SIMPLEX ENCEPHALITIS

Is the most common cause of acute sporadic encephalitis.
Pathogenesis:
HSV1 almost all cases of HSE & oral herpes by respiratory & salivary contact.
HSV2 venereal disease & haematogenous dissemination may cause encephalitis in newborns or aseptic meningitis in adults.
Virus reaches the brain through branches of trigeminal nerve to basal meninges, resulting in localized encephalitis in orbitfrontal & temporal lobes, suggesting endogenous reactivation rather primary infection which is suggested to be about 25%.
Encephalitis varies from inflammation with Cowdry A eaosinophilic inclusion bodies, necrosis and haemorrhage; brain oedema might be so severe leading to Brain Coning.
Clinical Presentation:
Although there is no age or sex predilection, >50% of pts are older than 20yr.
The most common early features are abrupt:
- Fever - headache - altered conscious - aphasia & neurological defecit
- Personality changes but may be ushered motor or focal fits.
The Encephalitis may evolve more slowly with:
Aphasia - Mental changes - Preceding more severe neurological defecits.
Signs of meningeal irritation are often present.
Investigations:
Basic Blood & Biochemcal investigations
CSF study like viral: ASEPTIC + (RBC) + PCR
Contrast MRI >80% shows focal fronto-temporal lesion bilaterally which is usually asymmetrical, associated with variable oedema and possible haemorrhage.
EEG >80% shows diffuse or focal slowing with periodic complex discharges.
Treatment:
The aim is to catch the pt early in the course of the disease, and start specific antiviral therapy as soon as possible:
Acyclovir (Zovirax) 30mg/kg/day in three divided daily doses as slow IV infusion .
Other Antivirals may be used:
- Gancyclovir - Cidofovir - Vidarabine - Ribavirin
- Foscarnet
- Dexamethazone IV: for increased ICP
- AntiEpileptic Drugs: for epileptic attacks.


Complications & Prognosis:
Cognitive deficits: mainly memory deficits in about 70%.
Epilepsy.
Speech deficits.
Variable neurological deficits’: ex hemiparesis.
The condition was 70% fatal before the era of the antiviral drug, which drop it to 30% fatality.

ACUTE DISSEMINATING ENCEPHALOMYELITIS (ADEM)

Acute, Monophasic, Multifocal, Post or Para Infectious, or Post vaccinal, Demyelination reaction affecting the white mater of brain, brain stem, cerebellum & spinal cord, no infectious agent could be isolated hisopathologically.
Expressed more fully in children than adults.
Encephalitic Form: Headache, Confusion, Convulsions, deficits.
Cerebellitic Form: Ataxia, Dysarthria......
Myelitic form: Para or quadriparesis, sensory deficits, sphincter dysfunction......
CSF mimics viral infection.
Contrast CT or MRI shows same aged multiple white matter lesions.
EEG shows diffuse slowing.
TREATMENT:
Pulse IV Methylprednisolone 1gm/day Infusion for 5 days.
If failed: - Plasmapharesis
-IV Immunoglobulin 2gm/kg over 5 days.
PROGNOSIS:
Mortality Rate 20%, about 90% who recover, recovers completely.
Complications:
Epilepsy - Mental Retardation - Variable neurological Deficits.


SLOW VIRAL INFECTIONS
1-Subacute Sclerosing Pan Encephalitis (SSPE):
A disease affecting adolescents and children many years after Primary measles virus infection, rarely after vaccination.
Boys> girls, incidence 5-10/106 measles infections.
Clinical Presentation: ( without fever )
-Intellectual and scholar decline with forgetfulness.
- MYOCLONIC JERKS (Hang Up Myoclonus)
- Apathy & clumsiness.
- Retinal changes.
- Dementia & rigidity.
Investigations:
- EEG shows abnormal background activity with Burst Suppression.
- Brain MRI shows cortical atrophy & periventricular white matter T2 c hyperintense changes.
-Elevated Serum Measles Antibody Level.
- Elevated CSF Ig levels & CSF-PCR for Measles.
TREATMENT & PROGNOSIS:
Inosine Pranobex: 100mg/kg/day.
Interferon Alpha
Ribavirin
The course is prolonged over months, occasionally up to 10 years leading to death, Spontaneous improvement or stabilisation occurs in only 10% of patients.


2- PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML)
Occurs due to opportunistic infection of Oligodendrocytes with the Papovavirus (Polyomavirus JC) in patients with defective cell mediated immunity, e.g. AIDS patients 5% & Reticuloendothelial System tumors, Sarcoidosis & MS patients on Natalizumab.
CLINICAL PRESENTATION:
Hemiparesis - Hemianopia - Aphasia - Dementia

INVESTIGATION:
Serology usually not beneficial.
CSF-JCV-PCR
Brain Biopsy
Brain CT / MRI
TREATMENT:
By improving immune function & treating underlying disorder. THE COURSE in 80% usually the patient dies in months, rarely the course may last several years.

3-PRION DISEASES –

TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY (TSE):
Are either: Infectious, Genetic, or Sporadic. Prion PrPSC is abnormal protein, transmissible like viruses, but they don’t have nucleic acids. Transmission occurs via tissue like, neurosurgical, corneal transplant, hormone donation, eating human brain as in KURU, occasionally by beef meat as in Variant CFJ or rarely blood.
Creutzfeldt-Jacob Disease (CJD):
2-VARIANT CJD:
3-KURU:
4-FATAL FAMILIAL INSOMNIA:
5-GERSTMANN-STRAUSSLER SCHEINKER (GSS):