10.12 Immune-mediated CNS Disorders

Question 1

What produces myelin in PNS & CNS?

Answer 1

PNS - Schwann cell
CNS (+optic nerve) - Oligodendrocyte

Question 2

Clinical features of Multiple sclerosis
Optic nerve
Brainstem, cerebellum
Cerebral hemisphere
Spinal cord

Answer 2

Optic nerve
- Inflammation of Optic Nerve = Optic Neuritis
- Symptoms:
• Rapidly developing impairment of vision in one eye, associated with change incolour perception
• Retro-orbital or ocular pain exacerbated by eye movement
- Signs:
• Decreased pupillary light reaction
• Varying degrees of vision reduction
• Abnormal colour vision
• Central scotoma

Brainstem
Signs which point to a lesion within the brainstem (intrinsic)
• INO (internuclear opthalmoplegia)
• Gaze Palsy
• Nystagmus
• Individual Cranial nerve deficits, e.g. facial sensory loss

Cerebellum - white matter involvement
Signs of Cerebellar Hemispheric Dysfunction
- Ataxia
- Ataxic Speech: called staccato: “with each sound or note sharply detached or separated from the others”
- Tremor

Cerebral Hemispheres - no cortical dysfunc
- Signs of Hemispheric Dysfunction (unilateral)
• Hemiparesis
• Hemisensory loss/change in sensation
- Both Hemispheres
• Cognitive decline → dementia
• Pseudobulbar palsy

Question 3

Clinical subtypes of multiple sclerosis

Answer 3

1. Relapsing- remitting MS
- 70%
- unpredictable attacks of dysfunction followed by remission in between
- frequency varies
- may or may not leave permanent deficits

2. Primary progressive MS
- clinical signs and symptoms of MS without history of attacks in between
- steady increase in disability

3. Secondary progressive MS
- follow on relapsing-remitting MS

Question 4

MS: After 15 years

Answer 4

• Half of the patients will need assistance in walking or will be wheelchair bound
• Frequency of death by suicide 8 times higher among patients with MS compared to the general population
• 7-year decreased life expectancy

Question 5

Neuromyelitis optica spectrum disorders (NMOSD)
Spectrum disorder
Pathogenesis

Answer 5

Spectrum disorder
- Optic: should be bilateral / recurrent (optic neuropathy)
- Spinal cord: Longitudinally extensive transverse myelitis (area of inflammation in spinal cord spans a length of 3 or more vertebral segments)

• Autoimmunedisease
• Previously thought to be part of MS spectrum
• Associated with AQP-4 (aquaporin 4) or MOG (myelin oligodendrocyte glycoprotein) antibodies
• in SA: seen with active PTB

Question 6

NMO disease course / prognosis

Answer 6

75% have recurrent episodes of ON/LETM/both
- More aggressive than MS
- >50% are non-ambulatory or have severe visual impairment in one or both eyes at 5 years
- 32% 5-year mortality
- Requires long term immunosuppression
- AQP-4 antibodies

25% have monophasic illness
- MOG antibodies or seronegative

Question 7

Acute disseminated encephalomyelitis (ADEM)
General

Answer 7

• Acute demyelination of CNS
• Often after febrile illness
• Common in children
• More common in HIV+
• Suspect in otherwise healthy young person with acute CNS illness

Question 8

ADEM clinical features

Answer 8

Similar to MS; just more acute and more severe

Brain
- Confusion
- Seizures
- Hemiparesis
- Ataxia
- Brainstem signs

Cord
- Paraparesis / quadriparesis

Optic nerve
- Optic neuropathy

Question 9

ADEM course or prognosis

Answer 9

• Rapid recovery – weeks rather than months
• Majority recover fully, some with cognitive deficits
• Mortality rate 1-3%

Question 10

Autoimmune encephalitis
General
Common Type

Answer 10

• Group of disorders in which the host immune system targets self- antigens expressed in the CNS
• Consider as alternative diagnosis to viral encephalitis
• More common than viral encephalitis
• Common clinical features:
  • Confusion / amnestic syndromes
  • Seizures
  • Movement disorders, e.g. dystonia, myoclonus
  • Psychiatric manifestations
• Commonest and most important = anti-NMDA receptor encephalitis

Question 11

Anti-NMDA receptor encephalitis
General
Prognosis / course

Answer 11

• Most frequently young women
  • Underlying ovarian teratoma in 50%
• Psychiatric manifestations (anxiety, agitation, psychosis, bizarre behaviour), memory deficits and insomnia
• Seizures
• Dyskinesias, often orofacial
• Language dysfunction
• Alteration of consciousness → coma

Prognosis
- 1⁄2 improve in 4 weeks with 1st line immunotherapy
- Another 3⁄4 of remainder improve with 2nd line immunotherapy
- However: many patients have protracted course with slow improvement over 2 years
- 10-15% relapse