Post-infectious neurological conditions:

Odd but real pathologies!

Ronald van Toorn vtoorn@sun.ac.za

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.

ADEM

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%)

Medial temporal lobe enhancement

Pathogenesis

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

Treatment algorithm

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

Patients with tumours do better. Early treatment improves outcome

VGKC-complex encephalitis

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