Multiple sclerosis

Question 1

Definition of multiple sclerosis

Answer 1

A chronic inflammatory condition of the CNS characterised by multiple plaques of demyelination disseminated in time and space.

Question 2

Epidemiology of multiple sclerosis

Answer 2

Lifetime risk: 1/1000.
Mean age of onset = 30 years.
Sex F>M = 3:1.
Race: more common in caucasians.

Question 3

Associations of multiple sclerosis

Answer 3

Genetic: HLA-DRB1

Viral (EBV). Minor viral infections often precede relapses.

Question 4

Pathophysiology of multiple sclerosis

Answer 4

CD4 cell-mediated destruction of oligodendrocytes leading to demyelination and eventual neuronal death. Initial viral inflammation primes humeral antibody responses versus myelin basic protein (MBP). Hallmark plaques of demyelination.

Question 5

Classification of multiple sclerosis

Answer 5

1. Relapsing-remitting: 80%. Symptoms come and go with periods of good health.
2. Secondary progressive: follows relapsing-remitting (gradually more or worse symptoms with fewer remissions)
3. Primary progressive (10%) - symptoms gradually worsen with no remission.

Question 6

Rate of progression of multiple sclerosis

Answer 6

About 50% of those with relapsing-remitting MS develop secondary progressive MS during the first ten years of their illness

Question 7

Presentation of multiple sclerosis

Answer 7

TEAM
Tingling
Eye: optic neuritis (reduced central vision + pain on eye movement)
Ataxia & other cerebellar signs
Motor: usually spastic paraparesis

Question 8

Clinical features of multiple sclerosis

Answer 8

Sensory: dys/paraesthesia, reduced vibration sense, trigeminal neuralgia
Motor: spastic weakness, tranverse myelitis
Eye: dyplopia, visual phenomena, bilateral INO, optic neuritis then atrophy.
Cerebellum: trunk and limb ataxia, scanning dysarthria, falls.
GI: swallowing disorders, constipation.
Sexual/GU: Erectile dysfunction + anorgasmia, retention, incontinence.
Lhermitte’s sign.

Question 9

What is Lhermitte’s sign

Answer 9

Neck flexion causes electric shock sensation in trunk/limbs. Sign suggests lesion or compression of upper cervical cord or brainstem, classically MS.

Question 10

Describe optic neuritis

Answer 10

Presenting complaint is pain on eye movement, and rapid decrease in central vision.
Uhthoff’s phenomenon: vision worse with heat e.g. hot bath.
On examination: reduced acuity, reduced colour vision, white disc, central scotoma, RAPD.

Question 11

What is Uhthoff’s phenomenon

Answer 11

The worsening of neurological symptoms in MS and other demyelinating conditions.

Question 12

Describe internuclear ophthalmoplegia

Answer 12

Disruption of MLF (medial longitudinal fasciculus) connecting CN6 to CN3.
Weak adduction of ipsilateral eye + nystagmus of contralateral eye. Convergence preserved.

Question 13

Investigations for multiple sclerosis

Answer 13

MRI: Gadolinium-enhancing or T2 hyper-intense plaques. Gd-enhancement = active inflammation. Typically located in periventricular white matter.
Lumbar puncture: IgG oligoclonal bands (not present in serum).
Antibodies: anti-MBP, NMO-IgG (highly specific for Devic’s syndrome).
Evoked potentials: delayed auditory, visual and sensory.

Question 14

Diagnostic criteria for multiple sclerosis

Answer 14

Diagnosis is clinical, by demonstration of lesions disseminated in time and space
May use McDonald criteria

Question 15

Differential Dx for multiple sclerosis

Answer 15

Inflammatory conditions that may mimic multiple sclerosis plaques:
CNS sarcoidosis
SLE
Devic’s (neuromyelitis optica NMO): MS variant with transverse myelitis and optic atrophy, distinguished by presence of NMO-IgG antibodies

Question 16

General features of management for multiple sclerosis

Answer 16

Good communication + providing written information
Inform the patient of their legal obligation to inform the DVLA
Encourage autonomy
Support family/carers
Close communication between members of MDT

Question 17

Medical management of multiple sclerosis relapses

Answer 17

Any episode of sudden increase (=12-24h) of distressing symptoms or activity limitation.
Exclude UTI before starting steroids.
Methylprednisolone IV or PO 500mg/day for 5 days (warn of SE of metallic taste).
Avoid giving steroids >3 times a year or >3 weeks in one go, no tapering needed. Gastric protection with omeprazole 20mg QD or ranitidine 150mg QD.

Question 18

Disease-modifying therapy in multiple sclerosis

Answer 18

Interferon beta licensed for relapsing-remitting MS in patients who can walk 100m. Most common SE is flu-like episode 24h after dose, but easy to control with ibuprofen.
Glatiramer: daily subcutaneous injection.
Injection site reactions for IFN beta and glatiramer, but decrease with longer use.
Also: Dimethyl fumarate (oral, daily), teriflunomide, alemtuzumab.
Natalizumab (but 1 in 600 PML), fingolimod, mitoxantrone (risk of systolic dysfunction and leukaemias).

Question 19

Precautions in women taking disease-modyfing therapy for multiple sclerosis

Answer 19

Avoid any disease-modifying drugs for 12 months before conception

Question 20

Medical treatment of pain in multiple sclerosis

Answer 20

Can be neuropathic or muskuloskeletal in origin (d/t reduced mobility).
Analgesia, then TENS if analgesia not sufficient.
CBT may help.
Neuropathic pain - anticonvulsants e.g. carbamazepine or gabapentin, or antidepressants e.g. amitriptyline.

Question 21

Treatment of spasticity in multiple sclerosis

Answer 21

Passive stretching.
First line: gabapentin, baclofen
Second line: dantrolene, botulinum injections

Question 22

Treatment of urological complications in multiple sclerosis

Answer 22

Offer condom catheter for men or pad for women, or intermittent self-catheterisation if high residual volume.
Anticholinergics (oxybutinin, tolterodine).
Desmopressin for night problems or daytime frequency but never more than once in 24h.

Question 23

Factors for poor prognosis in multiple sclerosis

Answer 23

Older female
Motor signs at onset
Many relapses early on
Many lesions on MRI