Examine this patient's eyes.
Remissions and relapses: visual loss, diplopia.
· Optic atrophy.
· Internuclear ophthalmoplegia.
· Look for features of cerebellar syndrome (see pp 1434).
Proceed as follows:
Tell the examiner that you would like to do a full neurological examination.
Examine this patient's legs.
Remissions and relapses: weakness, incoordination, pain, paraesthesias, urinary urgency, impotence. Steinberg's triad is history of
incontinence of bladder, impotence and constipation.
* Spastic paraparesis (increased tone, upgoing plantars, weakness, brisk reflexes and ankle or patellar clonus). Spasticity is
quantified using the Ashworth Scale, which scores muscle tone on a scale of 04 with 0 representing normal tone and 4 severe
· Impaired coordination on heel-shin test (if there is marked weakness, this test may be unreliable).
Proceed as follows:
· Check abdominal reflexes (absent or diminished in over 80% of cases).
· Tell the examiner that you would like to do the lbllowing:
-Look for optic atrophy and cerebellar signs.
In such patients, remember that spinal cord compression should be ruled out before making a diagnosis of multiple sclerosis.
Some examiners may consider it insensitive to use the term 'multiple sclerosis' in front of the patient and may prefer that the
candidate uses the term 'demyelinating disorder' instead.
This patient has optic atrophy and spastic paraparesis (lesion) due to multiple sclerosis, and is wheelchair bound (functional status).
What investigations would you consider?
· Spinal radiography, including both cervical and thoracic regions.
· Lumbar puncture: total protein concentration may be raised (in 60% of cases), with an increase in the level of immunoglobulin
G (in 40%) and oligoclonal bands (in 80%) on electrophoresis.
· Visual evoked potentials: despite normal visual function there may be prolonged latency in cortical response to a pattern
stimulus. This indicates a delay in conduction in the visual pathways.
· MRI scan of the brain: about 50% of patients with early multiple sclerosis in the spinal cord show abnormal areas in the
periventricular white matter.
· Serum vitamin B ~2 - to exclude subacute degeneration of the spinal cord.
Mention a few causes of bilateral pyramidal lesions affecting the lower limbs.
· Cord compression.
· Multiple sclerosis.
· Cervical spondylosis.
· Transverse myelitis.
· Motor neuron disease.
· Vitamin Bi2 deficiency.
· Cerebrovascular disease.
How common is multiple sclerosis?
The prevalence is about 1 in 800 people, with an annual incidence of 2-10 per 100 000. The age of onset varies but peaks between
20 and 40 years of age (Brain 1980; 112: 13346).
What are the main ways in which multiple sclerosis can present?
· Optic neuritis (in 40% of cases) resulting in partial loss of vision.
· Weakness of one or more limbs.
· Tingling in the extremities due to posterior column involvement.
· Nystagmus, cerebellar ataxia.
What is the natural history of multiple sclerosis?
The course of the disease is extremely variable and patients with multiple sclerosis tace enormous prognostic uncertainty. The onset
may be acute, subacute or insidious. The course may be rapidly downhill, or may spontaneously remit for periods lasting from days
to years before a second exacerbation (N Engl J Med 2000; 343:938 52).
What are the clinical categories of multiple sclerosis?
· Relapsing-remitting: episodes of acute worsening with recovery and a stable course between relapses.
· Secondary progressive: gradual neurological deterioration with or without super-imposed acute relapses in a patient who
previously had relapsing-remitting multiple sclerosis.
· Primary progressive: gradual, almost continuous neurological deterioration from the onset of symptoms.
· Progressive relapsing: gradual neurological deterioration from the onset of symptoms but with subsequent superimposed
What is Lhermitte's sign?
A tingling or electric shock-like sensation which radiates to the arms, down the back or into the legs on flexion of the patient's neck.
It has also been called the barber's chair sign. It indicates disease near the dorsal column nuclei of the higher cervical cord. Causes
include multiple sclerosis, cervical stenosis, subacute combined degeneration of the cord.
What is Uhthoff's symptom?
The exacerbation of symptoms of multiple sclerosis during a hot bath.
Do you know of any criteria for the diagnosis of multiple sclerosis?
Poser's criteria: a history of two episodes of neurological deficit and objective clinical signs of lesions at more than one site within
the central nervous system establishes the diagnosis of definite multiple sclerosis. In the presence of only one clinical sign, the
demonstration of an additional lesion by laboratory tests - such as evoked potentials, MRI, CT or urological studies - also fulfils the
A diagnosis of probable multiple sclerosis is defined as either two attacks with clinical evidence of one lesion, or one attack with
clinical evidence of two lesions.
Which conditions may be considered formes fruste of multiple sclerosis?
· Optic neuritis.
· Single episode of transverse myelitis with optic neuritis.
What is the role of steroids in acute optic neuritis and the development of multiple sclerosis?
In acute optic neuritis, treatment with a 3-day course of high-dose intravenous methylprednisolone (followed by a short course of
prednisone) reduces the rate of development of multiple sclerosis over a 2-year period (N Engl J Med 1993; 326: 581-8; N Engl J
Med 1993; 329:1764-9).
Does pregnancy affect the clinical features of multiple sclerosis?
Pregnancy itself may have a mildly protective effect but there is an increased risk of relapse during the puerperium; overall, the
effect on the course of the disease is probably negligible.
What is the role of exercise in the treatment of such patients?
Patients should be encouraged to keep active during remission and to avoid excessive physical exercise during relapses.
What is the role of MRI in multiple sclerosis?
MRI can identify up to 80% of patients with multiple sclerosis. T2-weighted images show hyperintense focal periventricular lesions.
Although periventricular white matter lesions are typical of multiple sclerosis, they are not pathognomonic. Small infarcts,
disseminated metastases, maya-maya disease and inflammatory diseases can produce a similar picture. High-resolution MRI may
provide useful prognostic information in patients who present with an acute, clinically isolated syndrome suggestive of multiple
sclerosis. On 5-year follow-up, over half the patients who had asymptomatic white matter lesions at presentation had developed
clinically definite multiple sclerosis, compared with 3% of patients who had normal results at presentation. The disease progressed
rapidly if the scan showed four or more lesions at presentation, and a greater number of lesions also correlated with the
development of moderate or severe disability (N Engl J Med 1993; 116: 135-46; Brain 1998; 121: 495-503).
Mention some other demyelinating disorders.
· Devic's disease: myelitis with optic neuritis. There has been debate as to whether this is a form of multiple sclerosis or a
· Tuberous sclerosis (patchy demyelination; see pp 511-13).
· Schilder's disease (diffuse cerebral sclerosis; may present with cortical blindness when the occipital cortex is involved).
What are the prognostic markers that predict more severe multiple sclerosis ?
· Progressive disease from the onset of symptoms.
· Frequent relapses in the first two years.
· Motor and cerebellar signs at presentation to neurologist.
· Short interval between the first two relapses.
· Male gender.
· Poor recovery from relapse.
· Multiple cranial lesions on T2-weighted MRI at presentation.
Note, Women and patients with predominantly sensory symptoms and optic neuritis have a more favourable prognosis.
Is there any treatment for multiple sclerosis?
· Two forms of interferon [3 (i.e. lb, Betaferon, and la, Avonex, Rebit) have been shown to reduce the relapse rate in
relapsing-remitting (non-progressive) neuro-logical deficit by one third (Neurology1993; 43:655 67; Lancet 1998; 352: 1491-7).
Whether reduction in relapse rate reduces or prevents later disability is not known; some evidence has been presented in
favour. The Association of British Neurologists recommends interferon [3 be prescribed for ambulant patients with at least two
definite relapses in the previous two years followed by recovery, which may or may not be complete.
· Interferon [3-lb has been reported to delay progression (for 9-12 months) in a study period of 2-3 years) in secondary
progressive multiple sclerosis of moderate severity (minimum walking distance of 20 metres with assistance) and has been
licensed for this indication. However, the SPECTRIMS study, which was a large trial, showed no significant benefit of interferon
beta-lb therapy in delaying disability in secondary progressive multiple sclerosis. Mitoxantrone hydrochloride has been shown
to reduce the rate of clinical relapse and delay progression of disability in secondary progressive multiple sclerosis.
· Copolymer-I (Neurology 1995; 45: 1268-76), glatiramer acetate (Copaxone) and pulsed intravenous immunoglobulin
(Lancet 1997; 349: 589-93), like the interferon betas, reduce the relapse rate. However, the role of immunomodulatory agents
needs to be defined.
· Intravenous methylprednisolone may hasten recovery from acute relapses but has no effect in the long term. A recent trial
suggested that intravenous methyl-prednisolone is no better than equivalent oral doses of methylprednisolone for acute
relapses (Lancet 1997; 349: 902-6).
· Plasma exchange enhances recovery of relapse-related neurological deficits in patients with no response to high-dose
· Fatigue is modestly reduced by amantadine (Neurology 1995; 45: 1956-61).
· Bladder dysfunction usually consists of combined detrusor hyper-reflexia and incomplete emptying. Volumes of less than 100
ml of urine remaining in the bladder after micturition are managed with oxybutinin or detrusitol; volumes greater than 100 ml
require clean, intermittent self-catheterization (J Neurol Neurosurg Psychiatry 1996; 60: 6-13).
· Sexual dysfunction (erectile failure) may be helped with the phosphodiesterase inhibitor sildenafil citrate (Viagra), or yohimbine
or other alpha-adrenergic blockers.
· Limb spasticity requires a multidisciplinary approach to ensure correct posture, prevention of skin ulceration from pressure, and
management of bladder and bowel dysfunction as well as medications such as tizanidine (an alpha2-adrenoreceptor
antagonist), an antispastic agent (Neurology 1994; 44 (suppl 9): 70-78S). Tizanidine reduces spasticity but there is no
beneficial effect on mobility.
Remember that there is no evidence to suggest that any treatment alters the long-term outcome in multiple sclerosis.
J.L. Lhermitte (1877-1959), a French neurologist and neuropsychiatrist, wrote on spinal
injuries, myoclonus, internuclear ophthalmoplegia and chorea.