CNS inflammatory diseases

Question 1

NMDA receptor encephalitis

Answer 1

Antibodies directed against GluN1 subunit of NMDA receptor. More common in girls.
Infectious or paraneoplastic syndrome (underlying ovarian teratoma). Risk after HSV encephalitis.

Behavioural change - psychiatric.
Dyskinesia (orofacial, oculogyral)
Perseverative/repetitive movements
Seizures

Rx: steroids 30mg/kg, IVIG, plasma exchange. Rituximab. Caution with use of antipsychotics with risk of dystonia and neuroleptic malignant syndrome

Question 2

Overlapping Guillain-Barre and encephalitis

Answer 2

Anti-GQ1b autibodies may be found in:

• Bickerstaff encephalitis (brainstem encephalitis); impaired consciousness with reflexes brisk instead of absent
• Miller-Fisher syndrome: tends to present with ataxia, areflexia, ophthalmoplegia and other CN abnormalities and then descends.

Question 3

Acute disseminated

encephalomyelitis (ADEM)

Answer 3

Monophasic inflammatory demyelinating disease of the CNS with mean age 5-8 years.
Preceding systemic infection
Viral like prodrome
Encephalopathy (behavioural change) + focal neurological findings, seizures and pyramidal signs (upgoing plantars).

Multifocal areas of T2 hypertensity with sparing of periventricular white matter and corpus collosum (unlike MS)
CSF - no oligoclonal bands

Ddx: viral encephalitis (HSV), metabolic disease, autoimmune, HLH, MS, cancer
10% will relapse

Question 4

Causes of relapsing demyelinating disease

Answer 4

Neuromyelitis optica (NMO) involving severe attacks of optic neuritis and transverse myelitis. Associated with increase CSF protein and oligoclonal bands.
Antibodies to Aquaporin 4 channel on the surface of astrocytes. 

Myelin oligodendrocyte glycoprotein (MOG) antibody disease presents with a similar but less severe phenotype.

Question 5

Opsoclonus mycolonus ataxia syndrome with neuroblastoma

Answer 5

Multi-directional eye flickering movements.
Opsoclonus (dancing eyes), myoclonic jerks, behavioural disturbances and ataxia.

Autoimmune, inflammatory reaction targeting the CNS, triggered by either a paraneoplastic or infectious event.
Peak onset 1-3 years with half having occult neuroblastoma

Question 6

Transverse myelitis

Answer 6

Spinal cord inflammation damages nerve fibers, and causes them to lose their myelin coating leading to decreased electrical conductivity in the central nervous system.
Most common location is a thoracic lesion producing UMN signs in lower limbs and spastic diplegia. Symptoms include weakness and numbness of the limbs, deficits in sensation and motor skills, dysfunctional sphincter activities, and dysfunction of the autonomic nervous system.

Causes: bacterial, viral infections, vaccinations, MS, paraneoplastic syndromes, vascular cause.

Treatment is with plasmapheresis - 1/3 recover fully, 1/3 improve, 1/3 no change

Question 7

Tay Sachs disease

Answer 7

Tay-Sachs disease is a rare AR disorder that progressively destroys nerve cells (neurons) in the brain and spinal cord. Caused by mutations in the HEXA gene which in lysosomes codes for an enzyme that breaks down GM2 ganglioside.

Usually presents 3-6 months of age, with loss of motor skills and exaggerated startle reaction. Vision and hearing loss, intellectual disability, and paralysis ensues. An eye abnormality called a cherry-red spot, which can be identified with an eye examination, is characteristic of this disorder.

Question 8

Zellweger spectrum disorder

Answer 8

AR disorder with signs of adrenoleukodystrophy. Associated with characteristic dysmorphism including frontal bossing, large anterior fontanelle, flattened occiput, abnormal ears, hypotonia with absent reflexes. Hepatomegaly and renal cortical cysts can be seen on USS. There is characteristic stippled calcification of the patella and greater trochanter. Infants typically have hearing impairments and opthamological abnormalities (cataracts/corneal clouding/glaucoma/pigmentary retinopathy). Fatal within 6-12 months.