Multiple Sclerosis Flashcards
Epidemiology of MS
-Young (20-40)
-2F:1M
-1 in 500 Scotland- common in higher latitudes
-30% monozygotic twin concordance, 2% dizygotic
Chronic cell-mediated autoimmune disorder characterised by demyelination in CNS (type 4 hypersensitivity)
What structures are involved in MS?
-Disease of the brain and spinal cord myelin
-Axons= oligodendrocytes provide metabolic support and saltatory conduction for underlying axon
Why is myelin important?
-Development- increasing physical and mental skills, learning throughout life
What causes MS?
-Genes (identical twins 30%)
-Immune system (latitude and vitamin D)
-Infections (EBV)
-Vitamin D deficiency?
Pathology of MS
-Demyelinating disease
-Inflammatory lesions
-Immune attack- T cells into brain- demyelination
=Oligodendrocyte precursor cells to remyelinate (nerve protection) but shorter and thinner than original
MS disease course
-Alternating remission and relapsing course (most common, 85%): acute attacks 1-2 months followed by periods of remission
-Inflammation then neurodegeneration
-LATER=less back to normal, progressive (worsens over time, developed neurological signs and symptoms between relapses, 65% relapsing-remitting disease within 15 years diagnosis, gait and bladder disorders)
-If progressive proceeded by relapsing remitting MS called secondary progressive MS vs always getting worse primary progressive (primary: 10%, progressive deterioration from onset, older people)
MS Investigations
LESIONS DISSEMINATED IN TIME AND SPACE
McDonald criteria
-Routine blood tests (electrolyte imbalance)
-CT (tumour)
-MR brain (inflammation, periventricular plaques, Dawson’s fingers, lesions disseminated in time and space, high signal T2 lesions)
-CSF= oligoclonal bands, increased intrathecal synthesis of IgG
-Delayed visual evoked potentials delayed but well preserved waveform)
establishing progressive neurological deterioration over 1 year or more for a diagnosis of primary progressive MS
Typical presentation of relapsing-remitting MS
Patient’s with multiple sclerosis (MS) may present with non-specific features, for example around 75% of patients have significant lethargy.
Diagnosis can be made on the basis of two or more relapses and either objective clinical evidence of two or more lesions or objective clinical evidence of one lesion together with reasonable historical evidence of a previous relapse.
Visual
optic atrophy
Uhthoff’s phenomenon: worsening of vision following rise in body temperature
internuclear ophthalmoplegia
-Blurred vision in one eye (optic neuritis- pale optic disk, optic atrophy), painful eye movements
-Double vision
Sensory
pins/needles, ascending
numbness
trigeminal neuralgia
Lhermitte’s syndrome: paraesthesia in back/ limbs on neck flexion
-Gradual onset of central neurological problem (days)
Motor
spastic weakness: most commonly seen in the legs
-Numbness/ weakness down half of the body (hemiparesis) or both legs (paraparesis)
Cerebellar
ataxia: more often seen during an acute relapse than as a presenting symptom
tremor
-Cerebellar syndrome: urinary incontinence, ataxia, tremor, sexual dysfunction, intellectual deterioration, transverse myelitis
-Fatigue/ lethargy
-Progressive difficulties with balance or gait
Others
urinary incontinence
sexual dysfunction
intellectual deterioration
Charcot’s neurologic triad: dysarthria (difficult or unclear speech, plaques in brainstem, eating talking swallowing), nystagmus (plaques in nerves in eyes, optic neuritis, painful eye movements), intention tremor plaques in motor pathways in spinal cord, weakness spasm tremor ataxia)
Treatments for relapsing-remitting MS
A number of drugs have been shown to reduce the risk of relapse in patients with MS. Typical indications for disease-modifying drugs include:
=relapsing-remitting disease + 2 relapses in past 2 years + able to walk 100m unaided
=secondary progressive disease + 2 relapses in past 2 years + able to walk 10m (aided or unaided)
30% reduction
-Beta-interferon
-Glatiramer acetate
-Teriflunomide
50% reduction
-Dimethylfumerate
-Fingolimod
-Cladribine
70% reduction
-Ocrelizumab
-Natalizumab
-Alemtuzumab
-Haematopoietic stem cell transplant
Side effects of relapsing-remitting MS treatments
-Dimethylfumerate= some cases of PML (progressive multifocal leukocephalopathy very often fatal)
-Fingolimod= prevents lymphocytes from leaving lymph node, HSV encephalitis
-Natalizumab= monoclonal antibody targeting leucocytes, often first line, IV, PML
-Alemtuzumab= 2% of ITP, 30% thyroid disease
-Ocrelizumab= anti-CD2 monoclonal antibody, IV, first line, infection
-Beta-interferon= subcut/IM, not as effective
Role of stem cells in progressive MS
-Reduce immune attack?
-Ensure oligodendrocytes repair myelin quickly?
-Stops nerves dying back/ regrow nerves with correct connections?
-IPS person specific= compatibility/ disease lines
-Ethically easier
-How do we get them in?
-Can they migrate?
-How will they know what connections to make?
Other pharmacological management of MS
-IV methylprednisolone in acute relapse, 5 days to shorten length but not degree of recovery
-Baclofen and gabapentin for spasticity
Fatigue
once other problems (e.g. anaemia, thyroid or depression) have been excluded NICE recommend a trial of amantadine
other options include mindfulness training and CBT
Spasticity
baclofen and gabapentin are first-line. Other options include diazepam, dantrolene and tizanidine
physiotherapy is important
cannabis and botox are undergoing evaluation
Bladder dysfunction
may take the form of urgency, incontinence, overflow etc
guidelines stress the importance of getting an ultrasound first to assess bladder emptying - anticholinergics may worsen symptoms in some patients
if significant residual volume → intermittent self-catheterisation
if no significant residual volume → anticholinergics may improve urinary frequency
Oscillopsia (visual fields appear to oscillate)
gabapentin is first-line
