Lymphocyte subset differences in patients with chronic fatigue syndrome, multiple sclerosis and major depression.

Chronic fatigue syndrome (CFS) is a heterogeneous disorder of unknown aetiology characterized by debilitating fatigue, along with other symptoms, for at least 6 months. Many studies demonstrate probable involvement of the central and autonomic nervous system, as well as a state of generalized immune activation and selective immune dysfunction in patients with CFS. The aim of this study was to compare the lymphocyte subsets of patients with chronic fatigue syndrome to those of patients with major depression and multiple sclerosis as well as those of healthy control subjects. No differences were found in total numbers of T cells, B cells or natural killer (NK) cells. However, differences were found in T, B and NK cell subsets. Patients with major depression had significantly fewer resting T (CD3(+)/CD25(-)) cells than the other groups. Patients with major depression also had significantly more CD20(+)/CD5(+) B cells, a subset associated with the production of autoantibodies. Compared to patients with multiple sclerosis, patients with CFS had greater numbers of CD16(+)/CD3(-) NK cells. Further study will be required to determine whether these alterations in lymphocyte subsets are directly involved in the pathophysiology of these disorders, or are secondary effects of the causal agent(s).

Restoring hand function in patients with severe polyneuropathy: the role of electromyography before tendon transfer surgery.

Electromyography (EMG) was evaluated as a supplement to clinical examination and biomechanical considerations to optimize forearm donor muscle selection before tendon transfers to 4 functionless hands in 3 patients with slowly progressive polyneuropathies. Two patients had unusually severe Charcot-Marie-Tooth disease; the third patient had idiopathic mononeuropathy multiplex. Standard EMG parameters were used to devise an intuitive muscle grading system, including most importantly interference patterns and motor control, plus motor unit morphology and stability. Given our objective of restoring survivable function despite ongoing polyneuropathy, we found that EMG reveals prognostically important differences among partially denervated candidate muscles that cannot be detected by experienced clinical examiners. Opposition transfer was performed on one hand of each patient. After 39-, 39-, and 51-month follow-up durations, restored opposition was graded as good in these 3 hands. We conclude that EMG provides meaningful guidance in selecting optimal forearm muscles for tendon transfers to hands in the setting of slowly progressive polyneuropathies.

Optimizing care of patients with ALS. Steps to early detection and improved quality of life.

Primary care physicians should be alert for early, purely motor neurologic signs and symptoms of ALS, a progressive and ultimately fatal motor neuron disease. Because many neuromuscular disorders mimic ALS, careful differential diagnosis is essential. All patients with signs of motor neuron dysfunction need prompt referral to a neurologist at a regional ALS care center to ensure that they receive an accurate diagnosis and disease-specific multidisciplinary care. Once the diagnosis is confirmed, primary care physicians should work closely with the ALS center to ensure continuity of care and provide emotional support for both patient and family. Patients may also benefit from enrollment in treatment trials and the ALS CARE database. Riluzole, the only medication approved for treatment of ALS, has been shown to slow disease progression and prolong survival. Such benefits have provided new hope to patients and have spurred investigators to search for other, more effective medications for use alone or in combination.

Serial neuropsychological assessment and magnetic resonance imaging analysis in multiple sclerosis.

OBJECTIVE: To assess the correlation between cognitive dysfunction and disease burden in multiple sclerosis (MS) during a 1-year period. DESIGN: The Brief, Repeatable Battery of Neuropsychological Tests in Multiple Sclerosis was performed at entrance and 1 year. Patients underwent at least 20 proton density (range, 20-24) and T2-weighted axial magnetic resonance imaging (MRI) brain scans except for stable patients who were scanned monthly. Magnetic resonance imaging was evaluated using computer-automated, 3-dimensional volumetric analysis. SETTING: A research clinic of a university hospital. PATIENTS: Forty-four patients with MS of the following disease categories: relapsing-remitting (14), relapsing-remitting progressive (12), chronic progressive (13), and stable (5). MAIN OUTCOME MEASURES: The relationships between scores on the Brief, Repeatable Battery of Neuropsychological Tests in Multiple Sclerosis and 2 MRI measures (total lesion volume and brain to intracranial cavity volume ratio) were assessed using linear regression. These MRI measures were also compared with cognitive status at 1 year using analysis of variance. RESULTS: Overall, there was no decline in mean cognitive test performance during 1 year. Significant correlations were found between baseline neuropsychological test scores of nonverbal memory, information-processing speed, and attention and both MRI measures. Patients with chronic progressive MS demonstrated the strongest correlations. At 1 year, change in information-processing speed and attention correlated with change in total lesion volume. The mean increase in total lesion volume was 5.7 mL for 4 patients whose cognitive status worsened compared with 0.4 mL for 19 patients who improved and 0.5 mL for 21 patients who remained stable. CONCLUSIONS: During a 1-year period mean cognitive performance did not worsen. Automated volumetric MRI measures of total lesion volume and brain to intracranial cavity volume ratio correlated with neuropsychological performance, especially in patients with chronic progressive MS. Worsening MRI lesion burden correlated with cognitive decline.

Medical and pharmacologic management of upper extremity neuropathic pain syndromes.

Written from a neurologic and therapeutically conservative perspective, this review advocates fundamentally medical and pharmacologic management of upper extremity neuropathic pain syndromes, including chronic regional pain syndromes, formerly classified reflex sympathetic dystrophy (RSD) and causalgia. Mandatory steps include, first, a prompt serious attempt to localize the nerve lesion whenever possible using complete, sophisticated neurologic examinations, then thoughtfully selected conventional neurophysiologic and radiologic tests. Strongly discouraged are promiscuous use of "RSD" to describe all neuropathic pains, and diagnostic reliance upon thermography and uncontrolled sympathetic blocks. Conservative multidisciplinary diagnostic and treatment teams should often possess a nucleus of neurologist and hand therapist, plus additional consultants including psychiatric. Every physician and therapist managing neuropathic pain must consider psychologic and wellness issues within their responsibilities. Prompt referral to an experienced surgeon is crucial for decompression or repair of relevant, significant, objectively proven (ideally neurophysiologically) nerve and root lesions. Ambiguous professional colloquialisms, "central pain" and "central sensitization," unfortunately provide value-laden pretexts for premature invasive treatments, and animate the truly dreadful concept "central RSD". Various classes of conventional oral non-narcotic adjuvant analgesics are reviewed, and the inevitability of their empiric, non-formulaic administration. No patient-specific, rationally-identifiable molecular receptor/switch can be deduced clinically or tripped mechanistically to terminate chronic pain. Two promising new non-narcotic centrally-active medications, gabapentin and tramadol, are highlighted as harbingers of future progress. The neglected subtle art of prescription writing is stressed, particularly for medication-sensitive patients. Medical cost containment should promote critical, long overdue outcomes studies comparing conservative and invasive pain treatments.

Another case of virologically confirmed zoster sine herpete, with electrophysiologic correlation.

A third virologically-confirmed case of thoracic-distribution zoster sine herpete is reported. Electromyography (EMG) of paraspinal muscles demonstrated frequent fibrillation potentials restricted to chronically painful thoracic root segments. Treatment with intravenous acyclovir and oral famciclovir were ineffective. These findings suggest the usefulness of EMG of muscles corresponding to painful dermatomes, combined with virologic studies, to support the diagnosis of zoster sine herpete.

Longitudinal MRI in multiple sclerosis: correlation between disability and lesion burden.

We followed 18 multiple sclerosis patients clinically and with repeated brain MRIs with and without gadolinium for over 1 year. Clinical evaluations included scoring on the Kurtzke Expanded Disability Status Scale (EDSS) and the Ambulation Index (AI) scale. There was a significant correlation between the change in EDSS or AI and the change in number of lesions on MRI and between cumulative number of lesions on MRI and cumulative change in EDSS or AI. Our findings support the validity of MRI as a measure of clinical activity and potentially as an objective quantitative outcome measure for assessing response to therapy.

Diagnosis of patients with peripheral nerve disease.

Podiatrists have a unique opportunity to detect neuropathies at stages where specific treatment and measures to limit progression may be most beneficial. This article reviews neuropathic symptoms and signs that call for timely neurologic evaluation and intervention and outlines the essentials of a focused evaluation. The detailed clinical history and examination are still the mainstays for determining the specific diagnosis of most neuropathies and for distinguishing other neurologic disorders that may mimic neuropathies. Whenever the cause, severity, or very presence of a neuropathy remains uncertain, electromyography and nerve conduction studies performed by a well-trained physician experienced with neuromuscular diseases should be the mandatory next steps. Clinicians should expect electrophysiologic studies to define the specific pattern of neuropathy (fiber-length dependent versus multifocal) and the predominant pathologic process (axon loss versus demyelination), enabling them to restrict diagnostic tests to a rational, necessary, cost-effective, and productive minimum.

Intermittent cyclophosphamide pulse therapy in progressive multiple sclerosis: final report of the Northeast Cooperative Multiple Sclerosis Treatment Group.

Previous studies reported that a 2- to 3-week course of IV cyclophosphamide plus adrenocorticotropic hormone (ACTH) induction can temporarily halt progressive MS for a period of 12 months in the majority of patients treated, after which reprogression occurs. The Northeast Cooperative Multiple Sclerosis Treatment Group was formed to determine whether outpatient pulse cyclophosphamide therapy could affect reprogression and whether there were differences between a modified induction regimen and the previously published regimen. Two hundred fifty-six progressive MS patients were randomized into four groups to receive IV cyclophosphamide/ACTH via the previously published versus a modified induction regimen, with or without outpatient IV cyclophosphamide boosters (700 mg/m2 every other month for 2 years). There were blinded evaluations performed every 6 months. Results demonstrate that (1) there were no differences between the modified and the published induction regimens either in terms of initial stabilization or subsequent progression; (2) without boosters, the majority of patients continued to progress; and (3) in patients receiving boosters, there was a statistically significant benefit at 24 months and 30 months (p = 0.04). Time to treatment failure after 1 year was also significantly prolonged in the booster versus the nonbooster group (p = 0.03). Age was the most important variable that correlated with response to therapy in that amelioration of disease progression occurred primarily in patients 40 years of age or younger. Boosters had a significant benefit on time to treatment failure in patients ages 18 to 40, p = 0.003, but not in patients ages 41 to 55, p = 0.97.(ABSTRACT TRUNCATED AT 250 WORDS)

Double-blind pilot trial of oral tolerization with myelin antigens in multiple sclerosis.

Multiple sclerosis (MS) is thought to be an autoimmune disease mediated by T lymphocytes that recognize myelin components of the central nervous system. In a 1-year double-blind study, 30 individuals with relapsing-remitting MS received daily capsules of bovine myelin or a control protein to determine the effect of oral tolerization to myelin antigens on the disease. Six of 15 individuals in the myelin-treated group had at least one major exacerbation; 12 or 15 had an attack in the control group. T cells reactive with myelin basic protein were reduced in the myelin-treated group. No toxicity or side effects were noted. Although conclusions about efficacy cannot be drawn from these data, they open an area of investigation for MS and other autoimmune diseases.

Lower motor neuron dysfunction in patients with multiple sclerosis.

A patient in whom multiple sclerosis (MS) was ultimately diagnosed presented with a lower motor neuron syndrome involving 1 hand, with EMG evidence of denervation. Twelve other patients were subsequently identified with definite MS and asymmetric hand atrophy. These patients were studied clinically and electrophysiologically. Evidence of chronic and ongoing denervation was noted in the hands of 12 of the 13 patients; in only 3 patients could the EMG abnormalities be accounted for by peripheral nerve lesions. Thus, lesions resulting in lower motor neuron damage may occur in the central nervous system in MS patients. We suggest that demyelination in the region of the ventral root exit zone may account for these findings.

T-cell recognition of an immunodominant myelin basic protein epitope in multiple sclerosis.

Multiple sclerosis is thought to be an autoimmune disease of the central nervous system mediated by T cells specific for a myelin antigen. Myelin basic protein has been studied as a potential autoantigen in the disease because of its role as an encephalitogen in experimental autoimmune encephalomyelitis and post-viral encephalomyelitis and because of the presence in the blood of multiple sclerosis patients of in vivo-activated T cells reactive to myelin basic protein. Immune involvement in multiple sclerosis has been further suggested by the association with the major histocompatibility complex class II phenotype DR2, DQw1. To define the T-cell specificity toward myelin basic protein, 15,824 short-term T-cell lines were established from multiple sclerosis subjects, subjects with other neurological diseases, and normal controls. Here we report a higher frequency of T-cell lines reactive with a DR2-associated region of myelin basic protein between residues 84-102 in patients with multiple sclerosis compared with controls. A second region, identified between residues 143-168, was recognized equally in multiple sclerosis patients and controls and was associated with the DRw11 phenotype. These DR2 and DRw11 associations were also observed among T-cell lines generated from family members of a multiple sclerosis patient. The immunodominant 84-102 peptide from myelin basic protein was both DR2- and DQw1-restricted among different T-cell lines. These results raise the possibility that this immunodominant region may be encephalitogenic in some DR2+ individuals.