Neurovirology

1. Neurovirology Acute viral infections Rabies, Enteroviridae, Mumps, Arenaviridae, Arboviruses Herpes viral infections HSV, VZV, CMV Chronic viral infections JC-virus (PML), Measles (SSPE)

2. Acute viral infections Forms of acute neurological disease Meningitis, Panencephalitis, Leukoencephalitis and Poliomyelitis Uncommon complications of common systemic infections Clinical Features: Depend on which cells are infected Meningitis headache, fever, stiff neck, CSF pleocytosis Most common cause of viral meningitis: enteroviruses, HSV2, mumps, HIV LCMV

3. Acute viral infections: Clinical features Encephalitis Increased intracranial pressure common Altered consciousness, focal neurological signs, accentuated tendon reflexes, seizures, tremors, Involvement of hypothalamus can lead to hypothermia diabetes insipidus, SIADH Spinal cord involvement - flaccid paralysis, bowel and bladder symptoms. With the exception of HSV, the topography of lesions is of little help in diagnosis

4. Encephalitis: Histopathology / Etiology Panencephalitis (involving both gray and white matter) Necrotizing HSV-1 or -2, VZV, Arbo Non-necrotizing HIV, CMV, HTLV-1, measles Polioencephalitis (predominantly involving gray matter) Polys followed by lymphs, neuronophagia and microglial nodules Enteroviruses, rabies, arboviruses Leukoencephalitis (predominantly involving white matter) PML, HIV, Post-infectious

5. Rabies: Virus One of the rhabdoviruses, a group of negative-single-strand RNA viruses with a distinct bullet shape Receptor: NCAM (CD56), Acetylcholine receptor Can grow in a wide variety of cell cultures generally noncytopathic, in curious contrast to the fatal outcome of infection in vivo in virtually all warm blooded animals. Susceptibility is variable as are periods of latency and infectivity and salivary excretion

6. Rabies: Epidemiology Virus is sustained in wild carnivores and insectivorous bats Sylvatic reservoirs: foxes, skunks raccoons and bats Skunk now the commonest reservoir of wildlife rabies in US. Airborne transmission in bat caves Transmission from man to man has not been documented (except for corneal transplants)

7. Rabies: Epidemiology 50% of dogs with proven rabies do not have virus in saliva. Overall transmission through bite is 15%. Dog excretes virus up to 5 to 7 days prior to clinical symptoms other carnivores viral secretion not known, therefore quarantine and observation of no use except for dogs (e.g. bats frequently without clinical symptoms).

8. Rabies: Clinical Incubation period in man 15 days to 1 year (?) Half of patients in US with no history of bite. Half develop hydrophobia. Ascending paralysis with pleocytosis in 25% and elevation of protein

9. Rabies: Pathology Bland pathologic findings - Grossly normal diagnosis in dogs used to be made by examining stomachs Microscopic Perivascular inflammation Without tissue necrosis Neuronophagia uncommon Pathognomonic feature is Negri body 1 to 7 micron inclusions mostly in neurons Found in ammon's horn and Purkinje cells of cerebellum

10. Rabies