Makindo Medical Notes.com

Related Subjects: |Neurological History taking |Motor Neuron Disease (MND-ALS) |Miller-Fisher syndrome |Guillain Barre Syndrome |Multifocal Motor Neuropathy with Conduction block | Multiple Sclerosis (MS) Demyelination | Transverse myelitis | Acute Disseminated Encephalomyelitis | Progressive Multifocal Leukoencephalopathy (PML) | Inclusion Body Myositis |Cervical spondylosis |Anterior Spinal Cord syndrome |Central Spinal Cord syndrome |Brown-Sequard Spinal Cord syndrome |Spinal Cord Compression |Spinal Cord Haematoma |Spinal Cord Infarction

Epidemiology

• Chronic neurological disease that affects approx 100,000 people in UK.
• Commonest cause of serious physical disability in adults of working age.
• MS affects one in every 500 persons, women twice as frequently as men.
• Commoner higher latitude. Vitamin D levels

Pathology

• Brain parenchyma shows well-defined lesions plaques with loss of myelin which show CD8 B and T-lymphocytes, microglia, and macrophages, plasma cells, immunoglobulins, and complement.
• Apoptosis and gliosis found in the white matter of the brain and cord. Affects periventricular white matter, optic nerves, cervical spinal cord, brainstem, cerebellar peduncles.
• Myelin sheaths destroyed. Cell bodies intact. Poor saltatory conduction.

Clinical

• MS diagnosis needs 2 or more clinically distinct episodes in different brain site at different times
• Clinically Isolated syndrome: Single episode of demyelination. Some progress to MS
• Optic neuritis. 25%. Monocular sight loss. Lesion in the nerve behind the disc so fundus looks normal, but acuity reduced. Eventual pallor at the disc. Eye can be painful eye. Only 50% go on to have MS.
• Severe fatigue is common. Worsened by meds
• Transverse Myelitis: comes on over days. Sensory level, spastic weakness, sphincter (bladder/rectal) dysfunction, flexor spasms, Spastic diplegia scissor gait. Lhermitte's signs electric shock sensations on flexing neck suggests cervical cord disease. Can also be seen with cervical spondylosis
• Cerebellum + connections: Cerebellar ataxia, nystagmus, diplopia, past pointing, wide based gait
• Brainstem syndromes - ataxia, internuclear ophthalmoplegia (see below) , dysarthria, INO, diplopia, facial numbness (V), rubral tremor
• Sensory: any sensory signs as ascending fibres affected by plaques - altered temperature, paraesthesia, patchy sensory loss, tic doloreux
• Uhthoff's phenomenon neurology worsens in warm environment e.g. bath, warm days.
• Cerebral symptoms - memory loss, dysphasia, disinhibition.
• Dementia may be a late finding

Different Forms

• Relapsing remitting (85%) acute attacks which resolve completely or partially with no progression between attacks. May be treated with interferon
• Primary progressive (10-20%) :steady progression from outset with little recovery or improvement
• Secondarily progressive: starts as RRMS but then steadily worsens and follows on from relapsing remitting type. Progressive disability probably due to axonal loss by repeated attacks of demyelination
• Fulminant form < 10% which causes accumulating severe disease and disability over months

Diagnostic criteria

• Neurologist to assess clinical and MRI findings to establish 2 or more episodes disseminated in time (DIT) and space (anatomy) in the CNS (DIS)

Locations

• CNS: periventricular, juxtacortical, infratentorial, or spinal cord.
• Gadolinium enhanced. Formal diagnosis uses McDonald Clinical Criteria.

Investigations

• FBC, ESR, C-reactive protein, LFT, U&E, calcium, glucose, TFT, vitamin B12, HIV serology.
• CSF: increased protein and oligoclonal bands indicate IgG antibodies to specific antigens.
• Visually evoked potentials abnormal in 95%
• MRI with FLAIR Brain and spine. T2 imaging for plaques. Assess disease burden. T1 images also show "black holes," areas of permanent axonal damage. Gadolinium can enhance the sensitivity of the T1-weighted MRI scan. Silent plaques-usually around the lateral ventricles and corpus callosum. An MRI scan (specifically, a T2W scan) is strongly suggestive of MS if it shows at least 4 lesions in the brain, or if 3 lesions are present but one of them is located in the regions surrounding the ventricles in the brain, the periventricular region.

Management

• Acute attack : Oral methylprednisolone 0.5 g OD x 5 days shortens flare. Does not reduce long term disability. Supervised exercise program
• Disease modifying treatments are mainly for relapsing remitting pattern
• Interferon: Interferon beta-1a and Interferon beta-1b. From human cytokines. High cost. Flu like side-effects. Reduces relapses by 1/3rd. Ineffective in primary or secondary progressive disease.
• Glatiramer acetate: (Copaxone), a mixture of polypeptides. May protect myelin from immune system attack. Reduces relapses by 1/3rd.
• Mitoxantrone most effective of them all but is limited by cardiac toxicity.
• Natalizumab risk of PML. For rapidly evolving severe relapsing-remitting MS (RES)

Other MS complications

• Fatigue: Amantadine. Aerobic, balance, stretching exercises including yoga may be helpful in treating MS-related fatigue.
• Spasticity: Typical agents or botulinum toxin for focal spasm. Intrathecal baclofen in very severe disease
• Oscillopsia: gabapentin or memantine
• Overactive bladder/Detrusor hyperreflexia. Start tolterodine 2-4 mg/day or equivalent
• Emotional lability: amitriptyline
• Detrusor and sphincter dysynergia, retention, urgency. Consider intermittent self-catheterization
• Nocturnal enuresis nasal desmopressin

Prognosis

• Better prognosis: Onset adult life < 40, Women, Optic neuritis/sensory onset, Complete recovery from early first attacks
• Worse prognosis: Male, Truncal ataxia, Action tremor, Pyramidal symptoms, Progressive disease

References