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Multiple Sclerosis: Differential Diagnoses & Workup
Updated: Jul 17, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Differential Diagnoses
Other Problems to Be Considered
Acute disseminated encephalomyelitis
Acquired immunodeficiency syndrome myelopathy
Arachnoiditis
Cerebrovascular disease
Chronic fatigue syndrome
Clinically isolated syndrome
Degenerative diseases (eg, hereditary spastic paraparesis, spinocerebellar degeneration, olivopontocerebellar atrophy)
Herpes zoster myelitis
Human T-cell lymphotropic virus type 1 associated myelopathy
Inflammatory CNS disorders (eg, Lyme disease, Behçet syndrome, Sjögren syndrome, neurosarcoidosis)
Leukodystrophy
Metabolic disorders (eg, vitamin B12 deficiency, vitamin E deficiency)
Myasthenia gravis
Neoplasms
Neuromyelitis optica (Devic disease)
Neurosarcoidosis
Psychiatric disorders
Progressive multifocal leukoencephalitis
Subacute combined degeneration of the spinal cord (vitamin B12 deficiency)
Workup
Laboratory Studies
- Perform blood work to exclude collagen vascular disease, infections (ie, Lyme disease, syphilis), endocrine abnormalities, vitamin B-12 deficiency, sarcoidosis, and vasculitis. These test results are within the reference range with multiple sclerosis (MS).
- Draw cerebrospinal fluid and examine for infection, oligoclonal bands (OCBs), and intrathecal immunoglobulin G (IgG) production. OCBs are found in 90-95% of MS patients and intrathecal IgG production in 70-90%; however, these findings are not specific for MS.
Imaging Studies
- MRI remains the imaging procedure of choice for diagnosing and monitoring disease progression in the brain and spinal cord. This test can show brain abnormalities in 90-95% of patients and spinal cord lesions in up to 75% of cases, especially in elderly patients. MRI alone cannot be used to diagnose multiple sclerosis (MS). The brain shows a characteristic pattern of lesions, usually periventricular. (See images below and Images 3-4.)
Multiple areas of increased fluid-attenuated inversion recovery (FLAIR) signal in a periventricular pattern suggesting Dawson fingers.
Same patient as in Image 3. Gadolinium contrast shows enhancement of the left frontal lesion, suggesting active demyelination.
- New or newly active lesions in the CNS can be enhanced with gadolinium as a result of the breakdown of the blood brain barrier. They may be enhanced from days to several weeks. These enhancing lesions have been seen even without clinical signs of disease activity. This finding is significant because it demonstrates that not all lesions result in neurologic deficits; however, it does demonstrate that the disease is widespread and present even during the periods previously believed to be silent.
- The T2-weighted images on MRI show edema and more chronic lesions. The T1-weighted images demonstrate cerebral atrophy and "black holes." These black holes represent areas of axonal death.
- With MRI, the lesion (plaque) burden, a measure of disease severity, can be determined. Unfortunately, the lesion burden is not well correlated with impairment or disability. MRI can help to determine cerebral and spinal cord atrophy, even early in the disease. This atrophy signifies widespread axonal loss in the brain and spinal cord even when active lesions are not identified. Atrophy in the spinal cord, cerebellum, and cerebral cortex has been correlated with disability.
- In 2001, an international expert panel was convened and produced recommended diagnostic criteria for MS. These have become known as the McDonald 2001 criteria and consist of a combination of clinical, imaging, and paraclinical tests.4 For MRI, 3 of 4 of the following findings should be present: (1) 1 gadolinium-enhancing lesion or 9 T2-weighted hyperintensities, (2) at least 1 infratentorial lesion, (3) at least 1 juxtacortical lesion, and (4) at least 3 periventricular lesions. Dissemination over time (by either waiting for a second attack or by serial MRIs) and space (MRI/cerebrospinal fluid analysis) must be proven.
- An unusual but clinically important MRI presentation of MS is tumefactive demyelinating lesions.5 These are large tumorlike lesions typically found in younger individuals with rapidly progressive neurological deficits. Tumor is the most critical differential in these cases. These tumefactive MS lesions typically demonstrate incomplete ring enhancement on post-gadolinium MRIs. (See images below and Images 5-6.) Hydrogen 1 magnetic resonance (1H-MR) spectroscopy can be helpful in differentiating these lesions from neoplasms; however, brain biopsy is sometimes needed for confirmation.
Magnetic resonance imaging (MRI) scan showing multiple areas of increased T2 signal.
Same patient as in Image 5; no phase wrap with postgadolinium contrast. These lesions enhance in a ringlike fashion. This is typical of tumefactive multiple sclerosis.
- A newer neuroimaging technique, magnetic resonance spectroscopy, has been useful in following N -acetyl-aspartate (NAA) levels in patients with MS. NAA is an amino acid found in neurons and axons of the mature brain. In patients with relapsing-remitting MS, NAA levels are reduced, suggesting axonal loss; however, in patients with secondary progressive MS with more disability, the NAA levels are reduced more significantly. In fact, patients with MS had lower levels of NAA even in areas of the brain previously thought to be unaffected, when compared with levels in normal patients.
Other Tests
- Evoked potentials have been the most useful neurophysiologic studies for evaluation of MS. These tests include visual evoked potentials (VEPs), somatosensory evoked potentials (SSEPs), and brainstem auditory evoked potentials (BAEPs). These studies are used to identify subclinical lesions but are nonspecific for multiple sclerosis (MS).
- VEPs are performed by having a patient focus on a reversing black and white checkerboard pattern. Delays in latencies indicate demyelination in the anterior visual pathways.
- SSEPs evaluate the posterior column of the spinal cord, the brainstem, and the cerebral cortex. Delays in latencies of various peaks indicate demyelination in the correlated pathway of the spinal cord or brain.
- BAEPs are performed to evaluate ipsilateral asymptomatic MS lesions in the auditory pathways but are less sensitive than VEPs and SSEPs.
- EEG results have been found to be outside the reference range in some patients with MS, but the findings are nonspecific. Nonspecific EEG abnormalities can be seen in normal individuals in the general population.
Procedures
- Lumbar puncture is performed to evaluate cerebrospinal fluid for the presence of OCBs and intrathecal IgG production. Cerebrospinal fluid analysis is the only direct test capable of proving the patient has a chronic inflammatory condition.
Histologic Findings
Examination of demyelinating lesions, or plaques, in the spinal cord and brain of patients with multiple sclerosis shows myelin loss, destruction of oligodendrocytes, and reactive astrogliosis with relative sparing of the axon cylinder. These active lesions show breakdown of the blood brain barrier with penetration of leukocytes. A combination of T cells, B cells, and macrophages is believed to be responsible for attack on the myelin antigens.
More on Multiple Sclerosis |
| Overview: Multiple Sclerosis |
 Differential Diagnoses & Workup: Multiple Sclerosis |
| Treatment & Medication: Multiple Sclerosis |
| Follow-up: Multiple Sclerosis |
| Multimedia: Multiple Sclerosis |
| References |
| Further Reading |
| « Previous Page | Next Page » |
References
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Frohman EM, Racke MK, Raine CS. Multiple sclerosis--the plaque and its pathogenesis. N Engl J Med. Mar 2 2006;354(9):942-55. [Medline].
Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. Nov 1983;33(11):1444-52. [Medline].
[Best Evidence] Sormani MP, Tintore M, Rovaris M, et al. Will Rogers phenomenon in multiple sclerosis. Ann Neurol. Oct 2008;64(4):428-33. [Medline].
Selkirk SM, Shi J. Relapsing-remitting tumefactive multiple sclerosis. Mult Scler. Dec 2005;11(6):731-4. [Medline].
[Best Evidence] Nicholas RS, Friede T, Hollis S, et al. Anticholinergics for urinary symptoms in multiple sclerosis. Cochrane Database Syst Rev. Jan 21 2009;CD004193. [Medline].
[Best Evidence] Rojas JI, Romano M, Ciapponi A, et al. Interferon beta for primary progressive multiple sclerosis. Cochrane Database Syst Rev. Jan 21 2009;CD006643. [Medline].
[Best Evidence] Goodman AD, Brown TR, Krupp LB, et al. Sustained-release oral fampridine in multiple sclerosis: a randomised, double-blind, controlled trial. Lancet. Feb 28 2009;373(9665):732-8. [Medline].
[Best Evidence] Havrdova E, Galetta S, Hutchinson M, et al. Effect of natalizumab on clinical and radiological disease activity in multiple sclerosis: a retrospective analysis of the Natalizumab Safety and Efficacy in Relapsing-Remitting Multiple Sclerosis (AFFIRM) study. Lancet Neurol. Mar 2009;8(3):254-60. [Medline].
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European Study Group on interferon beta-1b in secondary progressive MS. Placebo-controlled multicentre randomised trial of interferon beta-1b in treatment of secondary progressive multiple sclerosis. Lancet. Nov 7 1998;352(9139):1491-7. [Medline].
Goodkin DE, Rudick RA, VanderBrug Medendorp S, et al. Low-dose (7.5 mg) oral methotrexate reduces the rate of progression in chronic progressive multiple sclerosis. Ann Neurol. Jan 1995;37(1):30-40. [Medline].
Halper J, Holland NJ. Comprehensive nursing care in multiple sclerosis. New York, NY:. Demos Vermande;1997:chap 2, 5.
Lechtenberg R. Multiple Sclerosis Fact Book. 2nd ed. Philadelphia, Pa:. FA Davis Co;1995:29-66.
Miller AE. Diagnosis, classification and prognosis. Multiple sclerosis: clinical issues and decisions. Paper presented at: Western Regional Conference. February 1996.
Paty DW, Noseworthy JH, Ebers GC. Multiple Sclerosis. Philadelphia, Pa:. FA Davis Co;1998:48-134.
Rice GP, Filippi M, Comi G. Cladribine and progressive MS: clinical and MRI outcomes of a multicenter controlled trial. Cladribine MRI Study Group. Neurology. Mar 14 2000;54(5):1145-55. [Medline].
Schapiro RT. Symptom Management in Multiple Sclerosis. 3rd ed. New York, NY: Demos Medical Publishing;. 1998:25-124.
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Simon JH. From enhancing lesions to brain atrophy in relapsing MS. J Neuroimmunol. Jul 1 1999;98(1):7-15. [Medline].
Talbot PJ, Paquette JS, Ciurli C, et al. Myelin basic protein and human coronavirus 229E cross-reactive T cells in multiple sclerosis. Ann Neurol. Feb 1996;39(2):233-40. [Medline].
The Canadian Cooperative Multiple Sclerosis Study Group. The Canadian cooperative trial of cyclophosphamide and plasma exchange in progressive multiple sclerosis. Lancet. Feb 23 1991;337(8739):441-6. [Medline].
Trapp BD, Peterson J, Ransohoff RM, et al. Axonal transection in the lesions of multiple sclerosis. N Engl J Med. Jan 29 1998;338(5):278-85. [Medline]. [Full Text].
Trapp BD, Ransohoff RM, Fisher E. Neurodegeneration in multiple sclerosis: relationship to neurological disability. Neuroscientist. 1999;5(1):48-57.
Further Reading
Related eMedicine topics:
Acute Disseminated Encephalomyelitis
Brain, Multiple Sclerosis
Diffuse Sclerosis
Mental Disorders Secondary to General Medical Conditions
Multiple Sclerosis [Emergency Medicine]
Multiple Sclerosis [Neurology]
Multiple Sclerosis [Ophthalmology]
Multiple Sclerosis, Spine
Optic Neuritis
Optic Neuritis, Adult
Optic Neuritis, Childhood
Spasticity [Neurology]
Spasticity [Physical Medicine and Rehabilitation]
Clinical guidelines:
Assessment: the use of natalizumab (Tysabri) for the treatment of multiple sclerosis (an evidence-based review). Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. American Academy of Neurology - Medical Specialty Society. 2008 Sep 2. 8 pages. NGC:006705
Disease modifying therapies in multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. American Academy of Neurology - Medical Specialty Society
Multiple Sclerosis Council - Disease Specific Society. 2002 Jan 22 (reviewed 2003 Oct). 10 pages. NGC:003144
EFNS guideline on treatment of multiple sclerosis relapses: report of an EFNS task force on treatment of multiple sclerosis relapses. European Federation of Neurological Societies - Medical Specialty Society. 2005 Dec. 8 pages. NGC:005169
Natalizumab for the treatment of adults with highly active relapsing-remitting multiple sclerosis. National Institute for Health and Clinical Excellence (NICE) - National Government Agency [Non-U.S.]. 2007 Aug. 21 pages. NGC:005899
The utility of MRI in suspected MS: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. American Academy of Neurology - Medical Specialty Society
Child Neurology Society - Medical Specialty Society. 2003 Sep 9. 10 pages. NGC:003154
Clinical trials:
A Safety Study of Combination Treatment With Avonex and Placebo-Controlled Dosing of Topamax in Relapsing-Remitting Multiple Sclerosis
Gene Expression Profiles in Multiple Sclerosis (MS)
Safety/Effectiveness of Adding Monthly Dexamethasone to Weekly Avonex for MS
Study to Evaluate Intravenous and Oral Steroids for Multiple Sclerosis Attacks
Trial of Memantine for Cognitive Impairment in Multiple Sclerosis
Keywords
multiple sclerosis, sclerosis, MS symptoms, MS Society, multiple sclerosis symptoms, demyelinating, demyelination, multiple sclerosis treatment, multiple sclerosis diagnosis, multiple sclerosis pain, multiple sclerosis MRI, multiple sclerosis therapy, multiple sclerosis research, MS early symptoms, disseminated sclerosis, insular sclerosis, Marburg's disease, Balo's concentric sclerosis
