Patient presentation

1
Patient presentation

• M. Vlooswijk, 16-2-2005

2
Content

• Patient case and introduction
• Epidemiology
• Pathogenesis
• Clinical manifestations
• Diagnosis
• Treatment and prevention
• Prognosis
• Literature

3
Patient A.

• Man, 46 years. Medical history blank
• Symptoms sudden onset of myalgia, diffuse upper
  and lower limb weakness, skin rash
• During hospitalization respiratory failure,
  prolonged ventilation and tracheostomy placement
• Diagnostic tests CSF and blood titers WNV ,
  EMG widespread axonal loss of motor axons of
  upper and lower limb
• Source Marciniak et.al. 2004

4
Patient A (II)

• No improvement on intravenous immunoglobulin G
• Complications tracheobronchitis, pneumonia,
  Clostridium difficile infection and dysphagia
  requiring gastrostomy tube
• Total hospital stay 98 days
• Rest impairment after rehabilitation strength in
  upper limbs 2/3, lower limbs 2/2
• Source Marciniak et.al. 2004

5
Epidemiology

• West Nile Virus, arbovirus, family Flaviviridae
• First described in 1937
• Sporadic outbreaks in Israel and Africa
• Mid-1990s outbreaks with severe neurologic
  disease
• First outbreak in North-America NYC 99

6
Human cases of WNV infection in the USA, 19992003

• Source Lancet
• Infect Dis 2004

7
Bird-mosquito-bird cycle

• SourceCenter for Disease
• Control and Prevention

8

• Other ways of transmission transfusion, organ
  transplants, transplacental, breast milk,
  percutaneous exposure in laboratory
• 20 of infected persons develops mild illness
• One150 develops severe neurological illness
• Peak incidence August-September
• In temperate climates possibly all year

9
Pathogenesis

• Injection of virus-laden saliva
• Infection of fibroblasts, vascular endothelial
  cells or cells of the RES ? viremia ?
  inflammation BBB ? CNS infection
• Predilection within CNS posterior thalamus,
  basal ganglia, brainstem, spinal anterior horn
  cells
• Mechanisms of neuronal injury acute neuronal
  necrosis, neuronophagia

10
Clinical manifestations

• Source www.publichealthgreybruce.on.ca

11
Clinical manifestations (II)

• Febrile illness West Nile fever
• Self-limited with fever, headache, malaise, back
  pain, myalgia and anorexia. Rash in 50
• Neuro-invasive disease
• West Nile encephalitis
• West Nile meningitis
• Acute flaccid paralysis
• Complications
• Myocarditis, pancreatitis, hepatitis, ocular
  complications

12
Neuro-invasive disease

• West Nile encephalitis
• Encephalopathy, evidence of CNS inflammation,
  acute inflammation or demyelination on
  neuroimaging, focal neurological deficit, EEG
  consistent with encephalitis, seizures
• West Nile meningitis
• Clinical signs of meningeal inflammation, acute
  infection, acute meningeal inflammation on
  neuroimaging
• Acute flaccid paralysis
• Acute progressive limb weakness, asymmetry,
  hyporeflexia, no pain/paraesthesias or numbness,
  electrodiagnostic studies anterior-horn-cell
  process, increased signal in anterior spinal grey
  matter on MRI

13
Diagnosis

• To be considered in patients with unexplained
  febrile illness, encephalitis and/or meningitis,
  or flaccid paralysis, especially in summer or
  early fall. History of travelling to the US
• Lab
• White bloodcell count in serum normal or
  elevated
• CSF pleocytosis, predominance of lymphocytes,
  elevated protein concentration

14
Diagnosis (II)

• Neuro-imaging
• CT no evidence of acute disease
• MRI 30 enhancement of leptomeninges and/or
  periventricular areas, hyperintensity (T2) in
  basal ganglia, thalami, caudate nuclei,
  brainstem, spinal cord.
• EEG generalized continuous slowing
• Electrodiagnostic studies
• Normal SNAPs
• Normal to markedly decreased CMAPs

15
Diagnosis (III)

• Serologic testing
• Detection of IgM antibody to WNV in serum or CSF,
  eg with MAC-ELISA
• When IgM in CSF, CNS infection is highly probable
• False-positive results recent vaccination with
  yellow fever or Japanese encephalitis recent
  infection with a related flavivirus (eg dengue)

16
Treatment and prevention

• Supportive treatment
• Trials
• iv immunoglobulin containing anti-WNV Ab
• IFN alfa-n3
• Avoid exposure to mosquitoes (DEET)
• Drainage of standing water
• Blood donor screening for WNV
• No human vaccines yet available

17
Prognosis

• Mortality rates (associated with advanced age)
• Encephalitis 12
• Meningitis 2
• Functional impairment
• Acute flaccid paralysis some improvement, no
  recovery
• Encephalitis difficulty walking, muscle
  weakness, cognitive impairment

18
Literature

• Granwehr B.P. et.al. West Nile virus where are
  we now? Lancet Infect Dis 2004 4 547-56
• Marciniak C. et.al. Acute flaccid paralysis
  associated with West Nile virus  motor and
  functional improvement in 4 patients. Arch Phys
  Med Rehabil 2004 85 1933-8
• Labowitz Klee A. et.al. Long-term prognosis for
  clinical West Nile virus infection. Emerging
  Infectious Diseases 2004 10 1405-11
• Petersen L.R. West Nile virus infection. UpToDate
  2004