Multiple sclerosis

Multiple sclerosis is the most common autoimmune inflammatory demyelinating disease of the central nervous system. It tends to affect women of the Northern European descent in their 20-40s. The pathologic feature of MS is multifocal areas of demyelination with loss of oligodendrocytes and astroglial scarring as well as axonal injury.

Diagnosis - MS is a clinical diagnosis. The typical patient is a young adult with either focal or multifocal neurologic deficit that often follow a relapsing remitting pattern. There are no distinct symptoms that are only seen with MS but there are classic clinical findings listed below.

Optic neuritis - is the most common type of involvement of the visual pathways. It usually presents as acute or subacute unilateral eye pain that is accentuated by movement of the eye. This is followed by a variable degree of visual loss affecting mainly central vision. Physical examination of patients with Optic Neuritis reveals a relative afferent pupillary defect (Marcus Gunn pupil). Desaturation of color (particularily red) is a common finding as well.

Internuclear ophthalmoplegia -  Internuclear ophthalmoplegia refers to abnormal horizontal ocular movements with lost or delayed adduction and horizontal nystagmus of the abducting eye. It is caused by a lesion of the medial longitudinal fasciculus on the side of diminished adduction. Convergence is preserved.

Sensory symptoms - Sensory symptoms are a common in MS. Symptoms are commonly described as numbness, tingling, pins-and-needles, tightness, coldness, or swelling of the limbs or trunk. Radicular pains also can be present, particularly in the low thoracic and abdominal regions. An intensely itching sensation, especially in the cervical dermatomes and usually unilateral, is suggestive of MS.

Lehermitte Phenomenon - Described as transient sensory/pain symptom that can be described as radiating down the spine or into the limbs with flexion of the neck and is commonly seen in MS

Vertigo - Vertigo is a reported symptom in 30 to 50 percent of patients with MS.

Motor symptoms - Paraparesis or paraplegia is more common than significant upper extremity weakness in patients with MS due to the lesions in the descending motor tracts of the spinal cord. Severe spasticity can occur when attempts to move the extremities occurs such as getting out of bed or a chair.

Coordination - Gait imbalance, difficulty in performing coordinated actions with the arms, and slurred speech may occur as a result of impairment of cerebellar pathways. Physical examination typically reveals dysmetria, decomposition of complex movements, and hypotonia, most often observed in the upper extremities. An intention tremor may be noted in the limbs and in the head. Walking is impaired by truncal ataxia.

Bowel/bladder/sexual function - Bowel, bladder, and sexual dysfunction are common in MS. The extent of sphincter and sexual dysfunction often parallels the degree of motor impairment in the lower extremities. The most common urinary complaint is urgency. Urinary incontinence becomes more common as the disease progresses, and an atonic dilated bladder that empties by overflow can be the end result.

Fatigue - Fatigue is a characteristic finding in MS, usually described as physical exhaustion that is unrelated to the amount of activity performed. Many patients complain of feeling exhausted on waking, even if they have slept soundly. Fatigue can also occur during the day but may be partially or completely relieved by rest. In addition, there appears to be a correlation between fatigue and disrupted sleep in MS patients.

Depression - depression is the most affective disturbance in MS. Depression may be more common in patients with MS than in others with chronic medical conditions. It is not known whether depression in MS patients reflects a comorbid association with bipolar illness or an effect of frontal or subcortical white matter disease.

Epilepsy - Epilepsy is more common in patients with MS than in the general population, occurring in 2 to 3 percent of patients. Convulsions may be either tonic-clonic in nature or partial complex.


McDonald criteria - The McDonald criteria can only be applied after careful clinical evaluation of the patient. The core requirement of the diagnosis is the objective demonstration of dissemination of central nervous system (CNS) lesions in both space and time, based upon either clinical findings alone or a combination of clinical and MRI findings.

• Dissemination in space - demonstrated on MRI by one or more T2 lesions in at least two of four MS-typical regions of the CNS (periventricular, juxtacortical, infratentorial, or spinal cord) or by the development of a further clinical attack implicating a different central nervous system site. For patients with brainstem or spinal cord syndromes, symptomatic MRI lesions are excluded from the criteria and do not contribute to lesion count.

• Dissemination in time - demonstrated on MRI by the simultaneous presence of gadolinium-enhancing and nonenhancing lesions at any time, or a new T2 and/or gadolinium-enhancing lesion on follow-up MRI, irrespective of its timing with reference to a baseline scan, or by the development of a second clinical attack.

Lesion characteristics - The characteristic lesion demonstrated on MRI is the cerebral or spinal plaque. Histological examination of active plaques reveals perivascular infiltration of lymphocytes and macrophages.

Cerebrospinal fluid analysis -  Qualitative assessment of cerebrospinal fluid for oligoclonal IgG bands using electrophoresis is an important diagnostic CSF study when determining a diagnosis of MS. The immunoglobulin increase is predominantly IgG.

Treatment - A number of medications are available as disease modifying therapy which includes interferon beta drugs, glatiramer acetate, fingolimod, teriflunomide, mitoxantrone. Natalizumab  is approved as monotherapy only.