Detecting Multiple Sclerosis Mimics Early

Divya Singhal; Joseph R Berger

Future Neurology. 2012;7(5):547-555.

Future Perspective

For the immediate future, the diagnosis of MS will remain dependent on the clinical examination, MRI findings, laboratory results and electrophysiological data.

MS will remain a clinical diagnosis heavily dependent on prudent interpretation of clinical, MRI, laboratory and electrophysiological data for the foreseeable future. In that sense, the disorder is like many other neurological conditions. It is quite unlikely that a specific biomarker will become available that will permit the diagnosis of MS with any degree of sensitivity or specificity. A better understanding of the pathogenesis of the disorder, however, may alter that prediction. For instance, if a unique infectious etiology is unexpectedly discovered to underlie MS akin to the recent report of a monkey γ-herpes virus causing an animal model of relapsing and remitting demyelinating disease in Japanese macaque monkeys,^[33] a single laboratory diagnostic study may be conceivable.

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Next Section

Abstract and Introduction
Establishing the Diagnosis of MS & Considering Alternative Disorders
Discussion of Some Commonly Mistaken Diagnoses
Conclusion
Future Perspective
References
Sidebar

Box 1. The importance of detecting multiple sclerosis mimics early.
Treating a multiple sclerosis mimic appropriately may avoid significant morbidity or mortality that may occur in the absence of appropriate treatment Minimizing overdiagnosis of multiple sclerosis decreases or eliminates the potentially pernicious impact on a patient's psyche, social situation and employment Avoiding the side effects of platform disease-modifying medications, such as flu-like symptoms and skin reactions Avoiding the use of costly medications and the expense of laboratory monitoring Avoiding the use of potentially harmful multiple sclerosis therapies

Box 2. Dictums for diagnosing multiple sclerosis.
Uncommon manifestations of common disorders are far more common than common manifestations of uncommon conditions It is important to remain open minded and question one's established diagnosis when there are atypical features of the disease Multiple sclerosis (MS) can manifest in a wide variety of fashions, but so do its mimickers MS remains a clinical diagnosis. Careful history, physical examination and ancillary studies are fundamental to diagnosing MS A careful and comprehensive review of systems and general physical examination rather than ancillary studies may correctly suggest an MS mimicker; specific tests for these disorders are often simply confirmatory. Features that suggest an alternative diagnosis include fever, skin rash, arthralgias and headache Avoid an over-reliance on MRI interpretations

Box 3. Different diagnoses of multiple sclerosis.
*Inflammatory/autoimmune* Neuromyelitis optica Acute disseminated encephalomyelitis Sarcoidosis Systemic lupus erythematosus Sjogren's syndrome Polyarteritis nodosa Behçet's disease Giant cell arteritis Primary CNS angiitis CNS vasculitis Susac's syndrome Sneddon's syndrome (antiphospholipid antibody syndrome) Chronic inflammatory demyelinating polyneuropathy Bickerstaff's brainstem encephalitis Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids Eale syndrome Cogan's syndrome
*Vascular* Migraine variants Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy Moyamoya disease Binswangers disease Small vessel disease of hypertension and diabetes mellitus Cerebroretinal vasculopathy Degos disease
*Infectious* Lyme disease Neurosyphilis Toxoplasmosis Human T-lymphotropic virus 1 myelopathy Progressive multifocal leukoencephalopathy Subacute sclerosing panencephalitis HIV Brucellosis Encephalitis
*Neoplastic* Metastatic brain disease Glioma and gliomatosis cerebri Primary CNS lymphoma Intravascular lymphoma Paraneoplastic syndromes
*Mitcohondrial disorders* Leigh's disease Mitochondrial neurogastrointestinal encephalopathy Mitochondrial encephalopathy with lactic acidosis syndrome
*Metabolic disorders* Vitamin B12 deficiency Vitamin E deficiency Copper deficiency Porphyria Leigh's disease Wilson's disease Adrenoleukodystrophy Adrenomyeloneuropathy Metachromatic leukodystrophy Fabry's disease Krabbe's disease Leukoencephalopathy with neuroaxonal spheroids Adult polyglucosan body disorder Organic methylmalonic acidemia Autosomal dominant partial lipodystrophy with congenital cataracts Griscelli sydrome (hemophagocytic lymphohistiocytosis) Neuropathy, ataxia and retinitis pigmentosa
*Neurodegenerative conditions* Spinocerebellar ataxia Amyotrophic lateral sclerosis and primary lateral sclerosis Olivopontocerebellar degeneration
*Mechanical* Cervical spondylosis Arnold–Chiari malformation Spinal arterio-venous malformation and dural fistula Syringomyelia Arachnoiditis Lesion of foramen magnum and clivus
*Miscellaneous disorders* Environmental toxins Posterior reversible encephalopathy syndrome Central pontinemyelinolysis Eosinophilia–myalgia syndrome Primary systemic sclerosis Postradiation and postchemotherapy leukoencephalopathy Drugs and toxins, such as toluene and cyclosporin
*Ophthalmological* Neuroretinitis Central serous chorioretinopathy Inflammatory ocular disorders
*Psychiatric* Conversion disorder Somatization Hypochondriasis

Adapted from. [11,34]

Box 4. Features that raise concerns about the diagnosis of multiple sclerosis.
*Clinical features* Onset after the age of 50 years or prior to adolescence Family history of a similar disease – suspect genetic conditions Monophasic event Continually progressive course Lack of dissemination in space – that is, focal symptomatology Presence of gray matter features – aphasia, dementia and seizures Presence of systemic symptoms attributable to another condition Presence of peripheral complaints – for example, multiple neuropathies Presence of systemic features that are unexplained by multiple sclerosis
*MRI features* Symmetric lesions Peripheral white matter lesions (as opposed to periventricular lesions) Lack of ovoid lesions and/or 'black holes' Large white matter lesions Lack of involvement of the inner corpus callosum Mass effect with vasogenic edema Gray matter involvement, particularly large infiltrating brainstem lesions Longitudinally extensive spinal cord lesions (involving over three spinal cord segments) Unremarkable cranial and spinal MRI Persistently enhancing lesions Simultaneous enhancement of all lesions Microhemorrhagic foci
*Laboratory test abnormalities* Cerebrospinal fluid pleocytosis exceeding 50 white blood cells/cm ³ Cerebrospinal fluid protein exceeding 1 g/l Absence of oligoclonal bands and/or elevated IgG index or synthesis rate Significantly elevated sedimentation rate and C-reactive protein