Sensory abnormalities such as numbness, paresthesias, and altered sensations of pain or temperature are common in MS. Using phenomenologic methodology, patient interviews were conducted to assess the occurrence of sensory abnormalities termed “macrosomatic illusions” in MS. These were defined as sensations of “largeness” accompanied by banding and/or tightness in specific body regions. These sensations were reported by 72 MS patients with mean disease duration of 4.7 years and mean EDSS score of 2.9. The phenomena usually affected more than one site: lower extremity (58 reports), torso (36 reports), upper extremity (26 reports), face (9 reports), and entire side of the body (4 reports). The sensations were variously described as “toes are like sausages,” “feels like I'm wearing clown shoes,” “like I have a tight corset on,” or “fingers feel swollen.” In five of seven patients for whom cervical MRI was available at the time of symptoms, lesions were identified in the spinal cord that correlated anatomically with the macrosomatic illusions. Longitudinal prospective studies are warranted to further characterize the prevalence and cause of these phenomena, their impact on disability and quality of life, and association with spinal cord disease.

Since there is a need for cost-effective screening techniques to identify neuropsychological impairment in multiple sclerosis (MS) patients, and because existing methods require cognitive testing with subsequent interpretation by a neuropsychologist, a brief self-report procedure was developed to screen for neuropsychological impairment in MS. In the first phase of the study, a pool of 80 items was generated based on a literature review and consultation with healthcare professionals. The set was reduced to 15 via Rasch analysis. Using these items, a brief (five minute) MS Neuropsychological Screening Q uestionnaire (MSNQ), including patient- and informant-report forms, was composed. In phase II, 50 MS patients and their caregivers completed the MSNQ. A comprehensive neuropsychological test battery was also administered. A nalyses covered the reliability of the MSNQ and correlations between both patient- and informant-report scores and objective neuropsychological testing. C ronbach’s a coefficients were 0.93 and 0.94 for the patient- and informant-report forms, respectively, and both forms of the test were strongly correlated with a more general cognitive complaints questionnaire. The patient MSNQ form correlated significantly with measures of depression but not with objective tests of cognitive function. In contrast, the informant form was correlated with patient cognitive performance but not depression. A cut-off score of 27 on the informant form of the MSNQ optimally separated patients based on a neuropsychological summary score encompassing measures of processing speed and memory. There were two false-negatives and one false-positive, giving the test a sensitivity of 0.83 and a specificity of 0.97. It is concluded, therefore, that this self-administered neuropsychological screening test is reliable and predicts neuropsychological impairment in MS patients with a reasonable degree of accuracy.

Abstract The registry of Multiple Sclerosis Treatment and Care (MSTRAC) is an ongoing US research project that was initiated in April 1998. This article reports the characteristics of 2,590 relapsing multiple sclerosis (MS) patients and 483 physicians enrolled as of July 31, 1999. The mean age of the MSTRAC patients was 44 years; 92% were white; and 83% were women. The majority had some college education, and 50% were employed. Eighty-one percent of patients had relapsing-remitting MS, 17% had secondary progressive MS with relapses, and 3% had progressive relapsing MS. Mean age at symptom onset was 34 years, and mean duration of illness was nine years; mean time between disease onset and diagnosis was two years. Most patients (84%) experienced either no or slow disability progression that varied significantly by the type of relapsing MS (P < .001). MSTRAC physicians had practiced medicine for a mean of 15 years and had spent 84% of their time in patient care. Physicians were distributed across the United States and saw their MS patients in various settings.

Multiple sclerosis (MS) is considered an autoimmune disease associated with immune activity directed against central nervous system antigens. Based on this concept, immunosuppression and immunomodualtion have been the mainstays of therapeutic strategies in MS. During the last decade new therapies have been shown to significantly improve MS disease course. The effective therapies have led to a better understanding of MS pathogenesis and further development of even more efficient therapeutic interventions.

Background: T1 hypointense lesions (T1 black holes) are focal areas of relatively severe CNS tissue damage detected by MRI in patients with MS. Objective: To determine the natural history of T1 hypointense lesions in relapsing MS and the utility of T1 hypointense lesions as outcome measures in MS clinical trials. Methods: MR studies were from the Multiple Sclerosis Collaborative Research Group trial. Longitudinal results are reported in 80 placebo- and 80 interferon beta-1a (IFN beta-1a)-treated patients with mild to moderate disability relapsing-remitting MS. Results: There was a small but significant correlation between T1 hypointense lesion volume and disability at baseline and on trial (r = 0.22, r = 0.28). In placebo patients there was a 29.2% increase in the mean volume of T1 hypointense lesions (median 124.5 mm(3)) over 2 years (p < 0.001 for change from baseline), as compared to an 11.8% increase (median 40 mm(3)) in the IFN beta-1a-treated patients (change from baseline not significant). These treatment group comparisons did not quite reach significance. The most significant contributor to change in T1 hypointense lesions was the baseline number of enhancing lesions (model r(2) = 0.554). Placebo patients with more active disease, defined by enhancing lesions at baseline, were the only group to show a significant increase in T1 hypointense lesion volume from baseline. Conclusion: The development of T1 hypointense lesions is strongly influenced by prior inflammatory disease activity, as indicated by enhancing lesions. These results suggest that treatment with once weekly IM IFN beta-1a (30 meg) slows the 2-year accumulation of these lesions in the brain.

Multiple sclerosis (MS), a chronic inflammatory demyelinating disease of the central nervous system, is the most common crippling neurological disease of young adults in the US. The 2 basic clinical forms of the disease (relapsing and progressive), which can occur singly or in combination, encompass a wide range of clinical severities are usually established between 18 and 35 years of age and can persist an entire lifetime. Life expectancy of 20 years is 85% of normal.

Objective: To determine if progressive brain atrophy could be detected over 1- and 2-year intervals in relapsing MS, based on annual MR studies from the Multiple Sclerosis Collaborative Research Group (MSCRG) trial of interferon β-1a (Avonex). Methods: All subjects had mild to moderate disability, with baseline expanded disability status scores ranging from 1.0 to 3.5, and at least two relapses in the 3 years before study entry. Atrophy measures included third and lateral ventricle width, brain width, and corpus callosum area. Results: Significant increases were detected in third ventricle width at year 2 and lateral ventricle width at 1 and 2 years. Significant decreases in corpus callosum area and brain width were also observed at 1 and 2 years. Multiple regression analyses suggested that the number of gadolinium-enhancing lesions at baseline was the single significant contributor to change in third ventricle width. Atrophy over 1 and 2 years as indicated by enlargement of the third and lateral ventricle and shrinkage of the corpus callosum was greater for patients entering the trial with enhancing lesions. Greater disability increments over 1 and 2 years were associated with more severe third ventricle enlargement. Conclusion: In patients with relapsing MS and only mild to moderate disability, significant cerebral atrophy is already developing that can be measured over periods of only 1 to 2 years. The course of cerebral atrophy in MS appears to be influenced by prior inflammatory disease activity as indicated by the presence of enhancing lesions. Brain atrophy measures are important markers of MS disease progression because they likely reflect destructive and irreversible pathologic processes.

The cytokines, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-αrpar;, and interleukin-2 (IL-2) are important endogenous proinflammatory proteins and have been linked to disease activity in multiple sclerosis. In this study, we use flow cytometric methodology to compare the secretion of IFN-γ, IL-2, and TNF-α from peripheral blood-derived T cells of multiple sclerosis patients to the secretion in healthy controls. The percentages of IFN-γ, IL-2, and TNF-α secreting cells are not significantly different between multiple sclerosis patients and controls. However, the TNF-α secreting CDS cell percentage is correlated with the IFN-γ and IL-2 secreting CD3 cell percentages in multiple sclerosis patients. In the controls, only the TNF-α secreting CD3 cell percentage is correlated with IFN-γ. These findings show that correlated secretion of cytokines occurs in multiple sclerosis and suggest that concerted intercytokine interactions may play an important role in the disease.

In the classical corneomandibular reflex (CMR), corneal stimulation elicits a bilateral eyelid blink and a brisk anterolateral jaw movement. We here describe 14 patients with a spontaneous palpebromandibular (eyelid-jaw) synkinesia (SPMS) in whom jaw movements, similar to those in CMR, regularly accompanied spontaneous eye blinks without an external corneal stimulus. Eleven of the patients with SPMS also had CMRs on corneal stimulation. Four patients had clinical and imaging evidence of brainstem lesions above the mid-pons, 5 patients had autopsy or imaging evidence of both bilateral cerebral and upper brainstem lesions, and 5 patients had clinical or imaging evidence of bilateral cerebral dysfunction. Topical corneal anesthesia administered to patients who had both CMR and SPMS blocked the CMR but had no effect on the SPMS. In patients with both SPMS and CMR, measurements of latency from onset of orbicularis oculi electromyographic activity to onset of lateral pterygoid EMG activity, and mandibular kinesiography of jaw velocity and direction showed that the eyelid-jaw synkinesias of CMR and SPMS had similar characteristics. We conclude that SPMS is pathophysiologically the same as the eyelid-jaw synkinesia of CMR and both synkinesias originate centrally, probably in the pons. In CMR, the jaw movement is primarily related to the blink rather than the corneal stimulus, but corneal stimulation may be necessary to overcome a higher threshold for expression of the synkinesia than in patients with SPMS. Like CMR, SPMS emerges in patients with upper brainstem or bilateral cerebral lesions and SPMS may therefore be a useful localizing clinical sign.

Objective: To attempt to identify the site of the lesion causing continuous facial myokymia (CFM) in multiple sclerosis (MS) through the use of magnetic resonance imaging (MRI). Design: A case series was employed. Setting: The Baird Multiple Sclerosis Center, Millard Fillmore Hospital, and the Neurology Department, Buffalo General Hospital, Buffalo, NY. Participants and Measures: Twelve patients with MS and CFM were examined by MRI of the brain while the CFM was present. The MRI examinations were also performed before the CFM had developed and after it had ceased in eight of the patients. Another 57 patients with MS who never had CFM but who had similar disabilities to those who did were also examined by MRI. Results: In 11 of the 12 patients with MS and CFM, the causative lesion was demonstrated to involve the postnuclear, postgenu portion of the facial nerve intra-axially in the dorsolateral pontine tegmentum ipsilateral to the CFM. In the majority of patients who were studied after the CFM had stopped clinically, the lesion was observed to resolve on MRI. Seventeen percent of the patients with MS but without CFM were found to have the typical pontine tegmental lesion. Conclusions: Continuous facial myokymia in MS is caused by a pontine tegmental lesion involving the postnuclear, postgenu portion of the facial nerve. The lesion is identified by MRI in approximately 90% of patients with MS who have CFM clinically. The typical MRI lesion may also be found in a minority of patients with MS who do not have CFM clinically.

Triple-antibody flow cytometry was used to search for distinctive populations of peripheral blood lymphocyte immunophenotypes in multiple sclerosis (MS). Using monoclonal antibodies to the cell surface markers CD3, CD4, and CD8, T cell subsets were quantified on a cohort of 31 MS patients (not treated with corticosteroids for at least 6 months), 30 healthy donors, and 14 patients with other autoimmune diseases (also corticosteroid treatment-free for at least 6 months). Untreated MS patients displayed a significantly greater population of CD3+CD4+CD8+ circulating T cells than healthy donors (P = 0.023). Patients with other autoimmune diseases displayed mean populations of CD3+CD4+CD8+ cells greater than normal donors and less than MS, but not significantly different from either. An additional 45 MS patients who had received corticosteroid therapy within the previous 6 months were phenotyped. Treatment of symptomatic MS with corticosteroids was associated with a smaller population of circulating CD3+CD4+CD8+ cells. Some MS patients have significantly greater numbers of peripheral blood T lymphocytes simultaneously expressing CD3, CD4, and CD8 surface markers than healthy donors and this population of cells may be reduced by corticosteroids treatment. This triple positive phenotype may be a manifestation of a systemic immune abnormality in MS.

We found 23 of 48 patients (48%) with isolated monosymptomatic optic neuritis (ON) to have 1 to several brain lesions by MRI. All the brain lesions were clinically silent and had characteristics consistent with multiple sclerosis (MS). During 4 years of follow-up, 9 patients (19%) developed definite MS on clinical grounds. Six of the converting patients had abnormal MRIs; the other 3 had MRIs that were normal both initially (when they had ON only) and when repeated after they had developed MS. The other 17 patients with abnormal MRIs have not developed symptoms or signs of MS during follow-up. Thus, an abnormal MRI does not auger development of clinical MS within a mean of 4 years, nor does a normal MRI protect against development of disseminated disease. It is not prudent to give a patient with isolated monosymptomatic ON the diagnosis of MS (probable or definite) because of an abnormal MRI (with or without other laboratory abnormalities).

This report reviews the current applications of magnetic resonance imaging of the central nervous system. Since its introduction into the clinical environment in the early 1980s, this technology has had a major impact on the practice of neurology. It has proved to be superior to computed tomography for imaging many diseases of the brain and spine. In some instances it has clearly replaced computed tomography. It is likely that it will replace myelography for the assessment of cervicomedullary junction and spinal regions. The magnetic field strengths currently used appear to be entirely safe for clinical application in neurology, except in patients with cardiac pacemakers or vascular metallic clips. Some shortcomings of magnetic resonance imaging include its expense, the time required for scanning, and poor visualization of cortical bone.

Intrathecally Administered Natural Human Fibroblast Interferon Reduces Exacerbations of Multiple Sclerosis: 11:00 AM 3 L. Jacobs;A. Salazar;R. Herndon;P. Reese;A. Freeman;R. Josefowicz;A. Cuetter;F. Husain;W. Smith;R. Ekes;J. O'Malley; Neurology