CNS Viral Pathogens & Encephalitis 2024 - RCSI PDF

Leading the world to better health Viral Pathogens of the CNS/ Encephalitis Dr. James Donnelly Clinical Lecturer Dept. of Clinical Microbiology, RCSI  RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn SESSION ID: CNSML2...

Leading the world to better health Viral Pathogens of the CNS/ Encephalitis Dr. James Donnelly Clinical Lecturer Dept. of Clinical Microbiology, RCSI  RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn SESSION ID: CNSML2 Viral Pathogens of the CNS/ Encephalitis Class: Year 2 Semester 1 Course: Undergraduate Medicine Lecturer: Dr James Donnelly Date: 15th November 2024 LEARNING OUTCOMES 1. Describe the difference between meningitis and encephalitis 2. Describe the cause, route of infection, clinical presentation, diagnosis and management of - Viral meningitis: mostly enterovirus - Viral encephalitis: HSV, WNV, Tick borne Encephalitis, Japanese encephalitis, Polio and Rabies 3. Discuss other important viruses with CNS manifestations (polio, Zika, measles, JC, HIV) 4. Describe the aetiology of Transmissable Spongiform Encephalopathy (TSE) 5. Discuss the differences between sporadic and variant CJD, and the prevention of CJD DIFFERENCE BETWEEN MENINGITIS & ENCEPHALITIS Meningitis: Encephalitis: Inflammation of the Inflammation of the meninges brain parenchyma If occurs with meningitis, then referred to as meningoencephalitis DIFFERENCE BETWEEN MENINGITIS & ENCEPHALITIS Meningitis: Encephalitis: Fever Fever Meningism triad: Affects normal brain function – Headache – Altered mental status – Neck stiffness – Motor or sensory deficits – Photophobia – Behaviour or personality – May be non- changes specific in kids – Speech or movement Irritability (kids) disorders Vomiting – Seizures Less common: – Confusion, seizures VIRAL INFECTIONS OF THE CNS 1. Can be part of a generalised infection (e.g. polio) 2. May solely affect the CNS 3. May present some time after the initial presenting infection e.g. measles - Subacute sclerosing panencephalitis (SSPE) VIRUSES CAUSING CNS INFECTION Examples Clinical Presentation Meningitis Enteroviruses Usually self-limiting Herpes viruses (HSV, VZV, Symptoms of meningitis (see HHV6) previous slide) Mumps Encephalitis Herpes viruses (HSV, VZV, Symptoms of encephalitis (see HHV6) previous slide) Enteroviruses Mosquito borne: West Nile (WNV), Japanese encephalitis (JE) Tick borne: flaviviruses Rabies Paralysis Enteroviruses esp. polio virus, Flaccid paralysis (lower motor WNV, JE, Zika neurone +/- meningitis) Post- Measles (post-infectious Present after the acute illness infectious encephalitis, SSPE), VZV with neurological symptoms complication (vasculitis, arteritis, stroke) VIRAL MENINGITIS IN IRELAND Source: HPSC VIRAL ENCEPHALITIS IN IRELAND Source: HPSC CONGENITAL INFECTION AND CNS DAMAGE Viruses associated with congenital damage to the CNS: Rubella, Cytomegalovirus, Zika virus This topic will not be included here, and will be covered in Year 4/SC1; Obstetrics and Gynaecology, and Paediatrics rotations VIRAL MENINGITIS More common than bacterial causes of meningitis Many viral causes, including: – Enteroviruses: Echoviruses, Coxsackie B, Enterovirus 71 – Herpes viruses (e.g. Herpes simplex, VZV) – Mumps – Arboviruses (e.g. West Nile virus, Japanese encephalitis virus) Route of infection: After primary multiplication in other sites (e.g. GI tract for enterovirus) the virus may reach the CNS 1. Via the bloodstream (the usual route for enterovirus) 2. Along nerve pathways HSV Rabies 3. Through the olfactory mucosa HOW DO VIRUSES CAUSE DAMAGE IN THE CNS? The pathology in the CNS due to viral infection is multifactorial, caused by: – Virus multiplication & resultant cellular damage – Host immune response (cellular IR + cytokines) Clinical presentation: Classic symptoms: Fever, Headache, Neck stiffness, Vomiting, Photophobia Not usually as sick as patients with bacterial meningitis Symptoms usually evolve more slowly (several days) May be indistinguishable clinically from bacterial meningitis NON-POLIO ENTEROVIRUSES (SEE ALSO GIHEP LECTURE ON CLINICAL IMPLICATIONS OF VIRAL INFECTIONS OF THE BOWEL) Most common pathogens causing viral meningitis – Especially subtypes: Echoviruses, Coxsackie B, Enterovirus 71 Mainly affects infants and young children Usually mild and self-limiting – Can cause serious illness in neonates Peak activity in late spring to autumn Human only reservoir Transmission mostly via faecal-oral route – Multiply in GIT BUT only occasionally cause GI symptoms → Enter bloodstream (viraemia) → Leading to seeding of multiple organs, including the CNS  NON-POLIO ENTEROVIRUSES Other CNS manifestations: – Enterovirus 71: associated with encephalitis (esp. in East & SE Asia) – Enterovirus D68: possible association with acute flaccid paralysis following respiratory illness Enteroviral infections are very common and often cause other syndromes not involving the CNS, including: – Fever & rash – Myocarditis, pericarditis (Coxsackie viruses, echoviruses) – Hand, foot & mouth disease (Coxsackie viruses, enterovirus 71) DIAGNOSIS: CSF FINDINGS IN VIRAL MENINGITIS Protein Glucose Cells Microbiology Bacterial Very 12 weeks) Source: http://www.slideshare.net/tvelkov/cns-infections-lecture  3. RABIES Clinical presentation Diagnosis Prodrome: Fever, Clinical – patient history pain at bite site, Laboratory: salivation (ANS) – PCR from CSF or saliva CNS – Direct immunofluorescent – Restless, irritable, antibody staining of a skin aggressive biopsy from the nape of the May also be neck (above the hairline) disorientated and/or Remains a standard diagnostic have seizures test for human rabies. then – Serology and CSF (if no prior – Encephalitis / rabies vaccine or PEP) Paralysis  3. RABIES Treatment Prevention Wash the wound as Vaccination, including soon as possible post-exposure Preventive veterinary Post-exposure measures include prophylaxis as soon as vaccination of cats and possible (w/in 10 days dogs, as well as oral of exposure) vaccination of wild animal – Rabies immunoglobulin populations around the bite site and also IM – Rabies vaccine  4. WEST NILE VIRUS Belongs to a group of Epidemiology viruses known as Transmitted by the bite of an 'arboviruses’ infected mosquito – “ARthropod-BOrne” – Can infect humans, birds, horses and some other viruses: transmitted by mammals insects, ticks etc.) Temperate countries (e.g., Birds = usual host Northern North America) – Late summer or early autumn Tropical climates – Can be transmitted year-round 4. WEST NILE VIRUS Viruses 2013, 5(12), 3021- 3047; https://doi.org/10.3390/v512302 1  4. WEST NILE VIRUS Clinical presentation Asymptomatic (80%) Mild symptoms – Mild flu-like symptoms Fever, headache, generalised aches and pains – Usually make full recovery Severe neurological symptoms (