Multiple sclerosis II

Published on 10/04/2015 by admin

Last modified 22/04/2025

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Multiple sclerosis II

Differential diagnosis

The diagnosis of MS depends on identification of multiple episodes of demyelination separated in space and time. The occurrence of a single episode does not lead to a diagnosis of MS. The differential diagnosis for the most characteristic episodes will be considered individually. The differential diagnosis of multiple episodes will then be considered.

Single episodes

Optic neuritis

The most important differential is with optic nerve compression. This is usually more insidious in onset and is progressive. This can be ruled out by MRI scan. Between 25 and 60% of patients first presenting with optic neuritis go on to develop MS.

The most important differential diagnosis is spinal cord compression (Fig. 1a). In more insidious spinal cord syndromes, the differential diagnosis includes rarer spinal cord disease such as vitamin B12 deficiency, HTLV-1 myelopathy and familial spastic paraparesis. In patients lacking sensory signs, consider amyotrophic lateral sclerosis; associated lower motor neurone signs allow a distinction. After first presentation with complete transverse myelitis, patients later develop MS; those with partial spinal cord syndromes more often progress (70%).

Fig. 1 MRI in multiple sclerosis. (a) A T2-weighted scan of the cervical spine showing intrinsic high-signal changes; (b) a proton-weighted axial scale scan showing periventricular high-signal changes.

Brain stem syndromes

The differential diagnosis is wide, including tumours, brain stem encephalitis, cranial polyneuritis, an Arnold–Chiari malformation or vascular disease, the last being the most common alternative in older patients. MRI may clarify this differential; CSF examination and other investigations may be needed.

Multifocal CNS disease

The relapsing remitting form of MS can be mimicked by other inflammatory diseases such as systemic lupus erythematosus, sarcoid, Behçet’s disease and polyarteritis nodosa, and infectious diseases such as Lyme disease and syphilis. These are all rare. A monophasic illness characterized by widespread multifocal demyelination can occur either in isolation (acute disseminated encephalomyelitis) or after an infection (post-infectious encephalomyelitis). In these conditions, there are multiple areas of demyelination separated in space but not in time.

Investigations

The investigation of a patient with suspected MS can be divided into:

excluding other causes for the clinical syndrome

finding abnormalities characteristic of MS.

Excluding other causes

Some of the most common presentations and their investigations are discussed above. The investigation of any first presentation is more intensive than the investigation of a relapse. However, even patients with an established diagnosis of MS can develop unrelated neurological complications.

Finding characteristic abnormalities

Demonstrating clinically silent lesions

MRI is particularly powerful at detecting clinically silent lesions in MS. These tend to occur in characteristic sites within the white matter: the periventricular region and corpus callosum (see Fig. 1). Similar changes can be seen in the spinal cord, though these are more commonly found when symptomatic. If a scan is enhanced with gadolinium, then active lesions can be seen; the enhancement persists for 6–8 weeks.

Abnormalities on the MRI scan of the brain are found in over 90% of patients with clinically definite MS. There is a loose correlation between the changes on MRI and disability; occasionally patients with severe disability can have almost normal MRI scans while some patients who are clinically normal have marked abnormalities on MRI.

Not all patients with MRI abnormalities of this type have MS. Over age 50 years, T2-weighted abnormalities are seen in a normal population. Similar lesions occur in cerebral ischaemia, sarcoidosis, Behçet’s syndrome and other vasculitic illnesses. In patients who present with a single episode of demyelination, the finding of MRI abnormalities substantially increases the risk of developing MS.

Neurophysiological tests can also be used to show that there has been unrecognized demyelination. This is usually done in the visual pathways using visual evoked responses (VERs), which will be delayed if there has been demyelination, or in the sensory pathways with somatosensory evoked responses. They are not diagnostic of MS and will be abnormal in the symptomatic eye if the optic nerve is being compressed. VERs are abnormal in about 80% of cases of clinically definite MS.

Finding characteristic CSF changes

Routine analysis of the CSF usually produces a normal result: the white cell count may be slightly elevated (<15 cells/ml). Protein electrophoresis, using isoelectric focusing, may find oligoclonal bands (OBs) in the CSF but not in serum. This indicates intrathecal immunoglobulin synthesis and is present in 95% of patients with clinically definite MS. OBs occur in other diseases, infections (e.g. neurosyphilis, Lyme disease) and in inflammatory diseases (e.g. Behçet’s syndrome and systemic lupus erythematosus), but in these systemic illnesses the same bands are usually also found in serum.

Complications

The complications of MS have much in common with other disabling neurological conditions. Common medical problems seen in MS are summarized in Table 1. The social impact of the disease can include loss of job, divorce or social isolation. Depression is common and suicide can occur.

Table 1 Treatment of complications

Problem	Treatments	Comment
Spasticity	Baclofen, dantrolene, tizanidine, physiotherapy, botulinum toxin in selected muscles	Reducing the tone with drugs must be balanced against the increased weakness
Fatigue	Amantadine, pemoline, modafinil	N.B. Fatigue may be a symptom of depression
Ataxia	Isoniazid (with pyridoxine)	Usually there is little response
Bladder problems
Unstable bladder Uncoordinated bladder	Oxybutynin, tolterodineIntermittent self-catheterization ± oxybutynin	Consider urinary infection and treat
Erectile failure	Sildenafil
Constipation	Bulking agents and stool softeners	May need manual evacuation

Prognosis

The prognosis is variable and any comments about long-term prognosis are complicated by the improved diagnostic methods that allow milder disease to be recognized. On the basis of currently available studies, life expectancy is reduced by between 10 and 20 years. Half the patients have moved into the progressive phase of the disease by 10 years and half require aids to walk by 17 years. About 15% have a very benign form of the disease with only a few relapses and minor, if any, disability. Where disease is mild after 5 years, severe disease develops infrequently. Several factors influence prognosis. Relapsing remitting disease has a better prognosis than primary progressive. Men tend to do worse than women. Sensory symptoms or optic neuritis at onset tend to indicate a better prognosis.

Management and treatment

Specific symptoms can be helped. The most common problems are summarized in Table 1. Pain may occur and usually responds to pain-modulating drugs such as amitriptyline or gabapentin. Carbamazepine may also help some paroxysmal symptoms such as Lhermitte’s or trigeminal neuralgia. Tremor is usually difficult to treat; occasionally stereotactic thalamotomy may be helpful. Depression is common and needs to be treated with appropriate support and antidepressants. Physiotherapy is helpful at optimizing the level of function of the patient and occupational therapy optimizes the patient’s environment to minimize the impact of disabilities. Speech therapy may be helpful in some patients.