Detecting Multiple Sclerosis Mimics Early

Divya Singhal; Joseph R Berger


Future Neurology. 2012;7(5):547-555. 

In This Article

Discussion of Some Commonly Mistaken Diagnoses


Until the recognition of an antibody directed against aquaporin 4,[12] NMO or Devic's disease was regarded as a variant of MS. However, not only are its pathogenesis and clinical manifestations different than MS, its response to treatment is different as well. The NMO patient tends to be a decade older at the time of onset and is more commonly female (9:1 vs 3:1 for MS).[21] Unlike MS, it is not infrequently observed in non-Caucasians. At the time of disease onset, cranial MRI is often normal. When MRI abnormalities of the brain develop, the lesions may be seen in the hypothalamus, corpus callosum, brainstem and periventricular regions corresponding to areas expressing high levels of aquaporin 4.[22] Spinal cord involvement typically extends over ≥3 segments and involves the central cord, whereas spinal cord involvement in MS is less than three segments and the lesions are generally peripherally located. The CSF in NMO occasionally shows a prominent pleocytosis in which either polymorphonuclear or mononuclear cells may predominate. CSF oligoclonal bands are found much less frequently with NMO than MS.

Acute Disseminated Encephalomyelitis

Acute disseminated encephalomyelitis (ADEM) can occur at any age, but is most commonly seen in the pediatric population (especially in children that are 5–8 years of age) with a male predominance in contradistinction to MS.[23] It is a distinct entity traditionally diagnosed on the basis of monophasic course and presence of encephalopathy coupled with multifocal symptoms attributable to acquired demyelination. There is often a history of an antecedent viral infection. Although a form of recurrent ADEM is now well recognized, in addition to the classic monophasic ADEM, features that help in distinguishing ADEM from MS include the presence of encephalopathy (as evidenced by seizures, behavioral changes, impaired cognition or even coma), multifocal location of lesions and the development of new symptoms within a 3-month period. New symptoms that develop beyond 3 months should raise the suspicion for MS.[24,25] The presence of oligoclonal bands in the CSF and both enhancing and nonenhancing lesions on gadiolinium-enhanced MRI (indicating temporal dissemination) lean towards a diagnosis of MS.

Systemic Lupus Erythematosus

The nervous system involvement is involved in 25–75% of affected individuals and may result in a myriad of neurological disorders, including behavioral and cognitive disturbances, seizures, meningitis, optic neuritis, internuclear ophthalmoplegia, myelopathy, stroke and occasionally movement disorders.[26] Behavioral abnormalities are the most common among these findings and include visual and auditory hallucinations, paranoid delusions and affective disorders.[27] Systemic lupus erythematosus can affect any portion of the nervous system and neurologic sequelae of lupus are the second leading cause of death in patients with systemic lupus erythematosus following lupus nephritis. Although neurolupus and MS have several overlapping findings in terms of MRI changes, serology (positive antinuclear antibodies) and CSF abnormalities (elevated IgG and the presence of oligoclonal bands), neurolupus is clinically distinct due to stereotypic clinical presentation with systemic manifestations – classically a combination of arthralgias, rash, alopecia, fever, renal failure and other stigmata of systemic lupus erythematosus as outlined in the American Rheumatology Association criteria.


Lyme disease is regarded by some as the great mimicker of the CNS. The incidence of neurological complications ranges from 10 to 40% and may be the presenting manifestations of Lyme.[28,29] Common manifestations include encephalomyelopathy, cranial neuropathies, depression and radiculoneuritis. Up to 50% of patients may not recall a tick bite, symptoms may be relapsing and remitting, and white matter changes may be observed on cranial MRI, it is important to consider neuroborreliosis in the differential diagnosis of MS.[30]


Sarcoidosis is an idiopathic granulomatous multisystem disorder that affects the nervous system in 10–40% of patients. This disorder has a predilection for African–American patients and serum ACE level and chest x-ray should be obtained when the disease is suspected; however, diagnosis is dependent on histopathological confirmation. A clue to diagnosis of neurosarcoidosis is the presence of meningeal enhancement.


Of the numerous leukodystrophies, adrenoleukodystrophy and metachromatic dystrophy are the two disorders that most commonly tend to resemble progressive forms of MS. Less often, Krabbe globoid cell leukodystrophy, Fabry's disease and adult-onset autosomal-dominant leukodystrophy are considered in the differential diagnoses.[31] Clinical features that aid the search for underlying leukodystrophy include the presence of pertinent family history, abdominal complaints, Addisonian features, classic skin findings (such as angiokeratomas in Fabry's disease), hearing loss and/or peripheral neuropathy.[32] Oligoclonal bands are usually absent in these inherited disorders and relevant ancillary testing (e.g., electrophysiological studies, presence of very long-chain fatty acids in adrenoleukodystrophy or arylsulfatase A in metachromatic leukodystrophy) help to clinch the correct diagnosis.