Demyelinating Disease

Symptoms of demyelinating disorders are variable and depend on the neurologic deficits in the affected portion of the nervous system. Primary demyelinating disorders should be considered in patients presenting with diffuse or multifocal neurologic deficits of acute onset that wax and wane; in particular those that onset shortly after a vaccination or infection. The most common presenting symptom of demyelinating diseases are sensory disturbances of the limbs, vision loss, and subacute motor symptoms (e.g, weakness, spasticity, hyperreflexia, gait and balance disturbance) [1].

Common demyelinating disorders and presenting symptoms include:

• Multiple sclerosis - Common presenting features of multiple sclerosis include weakness, paraesthesia or focal sensory loss, diplopia, optic neuritis, ataxia, dizziness, muscle spasms, trigeminal neuralgia, depression, weakness, fatigue, seizures, and/or mild cognitive impairment. Bladder, bowel, and sexual dysfunction often occur as well [2].
• Acute disseminated encephalomyelitis - Patients with acute disseminated encephalomyelitis commonly have ataxia, headache, weakness, slurring of words, speech impairment, cranial nerve palsies, seizures, lethargy, delirium, stupor, and/or vomiting [3] [4].
• Progressive multifocal leukoencephalopathy - Common symptoms of progressive multifocal leukoencephalopathy include insidious onset of neurological deficits related to speech, vision, motor function, personality, and cognition [5] [6].
• Central pontine and extrapontine myelinolysis is characterized by acute onset of confusion, weakness of the extremities, and/or mutism. Other symptoms may include ataxia, difficulty swallowing, and low blood pressure. Some patients may also complain of movement disorders (e.g., dystonia, choreoathetosis, shuffling).

The diagnosis of demyelinating disease consists of a history of present illness, physical exam, laboratory, neuromuscular and imaging tests. A history of any recent infections and/or vaccinations should be noted.

Laboratory tests that should be done include complete blood count, syphilis test (e.g., RPR), antinuclear antibodies, fluorescent treponemal antibody test, lyme titer, sedimentation rate, and angiotensin converting enzyme level [7].

A cerebrospinal fluid (CSF) exam may demonstrate pleocytosis (slight elevation of mononuclear white blood cells), oligoclonal immunoglobulin G (IgG) bands, and an elevated globulin to albumin ratio [8]. Patients with myelin damage will have elevated CSF myelin protein levels, which is indicative of myelin damage.

A magnetic resonance imaging (MRI) scan may show subclinical demyelinated lesions and/or enhancement of nerve roots with the use of gadolinium [9].

The "hot bath test" works by elevating the body's temperature, which leads to exacerbation of symptoms and worsened deficits in persons with demyelinating disease.

Neuromuscular testing including an electromyography (EMG) can be used to help determine presence of peripheral neuropathy and demyelination [10].

A sural nerve biopsy can be performed to add to the evidence for the diagnosis of a demyelinating disease.

1. Olek, 2005 - adapted from Paty et al., 1994 and Studney D et al., 1993, MS COSTAR: A computerized patient record adapted for clinical research purposes. J Neurol Rehab; 7:145.
2. McAlpine D, Lamsden CE, Acheson ED. Multiple Sclerosis - A Reappraisal, ed. 2, Edinburgh, Churchill and Livingstone, 1972.
3. Gupte G, Stonehouse M, Wassmer E, et al. Acute disseminated encephalomyelitis: a review of 18 cases in childhood. J Paediatr Child Health. 2003;39:336–42
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5. Sugimoto C, Ito D, Tanaka K, et al. Amplification of JC virus regulatory DNA sequences from cerebrospinal fluid: diagnostic value for progressive multifocal leukoencephalopathy. Arch Virol 1998;143:249–62.
6. Hammarin AL, Bogdanovic G, Svedhem V, et al. Analysis of PCR as a tool for detection of JC virus DNA in cerebrospinal fluid for diagnosis of progressive multifocal leukoencephalopathy. J Clin Microbiol 1996;34:2929–32.
7. Jones CT. Childhood autoimmune neurologic diseases of the central nervous system. Neurol Clin. 2003;21:745–64.
8. Park SJ, Jeong IH, Kong BS, et al. Disease Type- and Status-Specific Alteration of CSF Metabolome Coordinated with Clinical Parameters in Inflammatory Demyelinating Diseases of CNS. PLoS One. 2016;11:e0166277.
9. Balashov K. Imaging of Central Nervous System Demyelinating Disorders. Continuum (Minneap Minn). 2016 Oct;22(5, Neuroimaging):1613-35.
10. Hanewinckel R, Ikram MA, Van Doorn PA. Peripheral neuropathies. Handb Clin Neurol. 2016;138:263-82.