Post-infectious neurological conditions: Odd but real ... · Post-infectious neurological...
Transcript of Post-infectious neurological conditions: Odd but real ... · Post-infectious neurological...
Post-infectious neurological conditions:
Odd but real pathologies!
Ronald van Toorn [email protected]
Benign regressive post infectious
neurological disorders
Post-infectious encephalomyelitis (ADEM)
Post-infectious cerebellitis
Post-infectious transverse myelitis
Optic neuritis in children
Neuromyelitis optica
Guillain-Barre syndrome
Characteristics
Post-infectious or post vaccination in origin. Develop within 5 days to 3-5 weeks
after infection or vaccination.
Inflammatory demyelinating white matter disease characterized pathologically
by autoimmune demyleination, breakdown of blood brain barrier with development
of vasogenic oedema and contrast enhancement in the acute stage.
They commonly have an acute onset and a regressive course
They commonly have a benign course with good prognosis and full functional
recovery should be expected in most cases.
Clinical features ADEM Infectious
Encephalitis
Most common age Children Any age
Recent vaccination Common uncommon
Prodromal illness Usually Occasionally
Fever May occur Common
Visual loss (one or both eyes) May occur Uncommon
Spinal cord signs May occur Rare
ADEM vs. infectious encephalitis
ADEM
Diagnosis based upon a combination of clinical and radiological features.
Exclusion of diseases that resemble ADEM.
No evidence-based prospective clinical trial data for the Rx of ADEM.
Intravenous methylprednisolone 20-30mg/kg/day (max 1g/day) for 3-5 days,
followed by an oral corticosteroid taper of 4-6 weeks.
Insufficient response: IVIG 2g/kg divided over 2-5 days
Post-infectious cerebellitis
Peak incidence 2-4 years.
Most commonly presenting as truncal, rather than extremity, ataxia.
Most commonly identified cause: Varicella
More than 90% of children recover, and treatment is supportive.
Cerebellar swelling can result in fatal or near-fatal outcome.
Optic neuritis
Most cases > 85% immune-mediated in children.
Bilateral involvement.
Young children may not notice unilateral visual loss.
They may not report bilateral visual loss until their behaviour indicates visual loss
to parents or teachers.
Headache is common in children with optic neuritis.
Periorbital and pain on eye movements.
Afferent pupil defect.
Fundus examination.
CSF opening pressure
CSF analysis.
Aquaporin antibodies
Treatment: Methylprednisolone 1-2 mgkgday for 3-5 days, tapering dose of
prednisone over 2-4 weeks.
Low probability of recurrent demyelinating events and a diagnosis of MS
An approach to diagnostics: the
challenge Child with encephalitis
MRI
CSF (PCR)
Serology
MRI non-diagnostic
CSF PCR negative
What next ?
Auto immune encephalitis
Antibodies against intracellular antigens
Onconeural antibodies: Hu, Yo, Ri, CV2, amphipycin, Ma2
GAD (glutamic acid decarboxilase)
Antibodies against neuronal surface receptors
NMDAR, GABA, VGKC, AMPA, Glycine receptors
Relative % of encephalitis etiologies 2011
Etiology USA n=76 children Australia n=163 children
Herpes simplex 1 22% 6%
Enterovirus 2% 12%
Other infections 19% 18%
ADEM 14% 20%
NMDAR encephalitis 9% 6%
VGKC encephalitis 7%
Unknown 37% 31%
Clinical syndromes
Limbic encephalitis
Movement disorder
Encephalitis Lethargica
Neuropsychiatric
Seizures
Catastrophic type
Specific type
Less specific
Disturbance in memory
Temporal lobe seizures
Affective disturbance
Anti-NMDAR encephalitis
Features
Clinical phenotype Psychosis, hallucinations,
catatonia
Cognitive, memory change,
aphasia
Seizures (~70%)
Movement disorder
Autonomic features
MRI Normal in ~50-80%
Mesial temporal lobe
enhancement
CSF Usually pleocytosis
Oligoclonal bands (~50%)
NMDAR encephalitis
Diagnosis,
investigation
Antibodies against NMDAR in
serum and /or CSF.
Females- investigate for ovarian
teratoma
1ml serum or 0.5ml CSF Turnover time 1-2 weeks
Ampath/Euroimmun
Outcome of anti-NMDAR encephalitis
About 75% of patients with NMDAR antibodies recover or have mild
sequelae; all other patients remain severely disabled or die.
Full recovery possible.
Deficits when present, usually cognitive and psychiatric
Voltage Gated Potassium Channel
Complex encephalitis
Features
Clinical phenotype Less well defined in children
Seizures, status epilepticus
Cognitive and behavioural change
MRI Often normal
‘Limbic encephalitis’ or non-
specific
CSF Rarely pleocytosis
Voltage Gated Potassium Channel
complex encephalitis
Features
Diagnosis, investigation
Antibodies against VGKC-complex in serum Not paraneoplastic syndrome.
Treatment First line: Steroids, IVIG or plasma exchange No reports of use of second line
Outcome Untreated, ~50% chance of epilepsy or cognitive/executive dysfunction Therapy improves outcome in adults
Adjunctive corticosteroids in all
children with encephalitis?
Viral load does not correlate with the severity of disease or with the extent of cranial
MRI abnormalities. Viral load is not influenced by treatment with corticosteroids
(No increase in viral load or decrease in viral clearance.)
Experimental animal research & recent retrospective clinical observations indicate
that a substantial benefit in outcome can be expected in patients with HSVE who are
treated with adjuvant dexamethazone.
Currently, the available evidence is insufficient to support the routine use of
corticosteroids in patients with HSVE.
GACHE trial (German trial of Acyclovir and corticosteroids in HSV encephalitis)
Refractory Seizures
Febrile seizures with no preceding condition.
Negative lab investigations including CSF analysis.
Status epilepsy refractory to conventional pharmacotherapy.
Long-term developmental delay.
Idiopathic catastrophic epilepsy
(Baxter et al 2003 Seizure)
Devastating epileptic encephalopathy in school age children (DESC)
(Mikaeloff et al 2006 Epilepsy Res)
Acute encephalitis with refractory, repetitive partial seizures (AERRPS)
Sakuma et al 2010 Acta Neurol Scand)
Febrile infection related epilepsy syndrome (FIRES)
(Baalen et al Epilepsia 2010)
It may be that therapeutic trials of corticosteroids may be useful is certain epileptic disorders.
Post-infectious & autoimmune encephalitides are not uncommon.
Commercial testing is now available for some of the disorders.
Clinical spectrum is not confined to only encephalitis.
The different syndromes have characteristic clinical features.
Early recognition is important: Responsive to immunotherapy.
Conclusion