Mechanism of colistin-induced neuromuscular depression.

The effect of a high concentration of the antibiotic colistin sulfate on neuromuscular transmission was examined by recording intracellularly from rat diaphragm blocked with tubocurarine chloride. The presynaptic effect of colistin was different from that of neomycin sulfate, which reduces the probability of acetylcholine release: Colistin reduced that the quantum content of the initial and the last 20 end-plate potentials of a train of 40 stimuli without altering the probability of acetylcholine release. The quantum size was reduced, while the frequency of miniature end-plate potentials was unchanged.

Correlation of electromyography with computed tomography in evaluation of lower back pain.

High-resolution computed tomography (CT) of the lumbar spine in 80 consecutive patients with lower back pain was correlated with electromyography (EMG) and with the clinical outcome at one-year follow-up. Forty-two patients had abnormal EMG findings that could be explained on the basis of anatomical defect(s) seen on CT. Nine had normal CT scans but abnormal EMGs, and five patients had normal EMGs but abnormal CT scans. Thirteen of the 80 patients were further investigated with myelography, 22 patients underwent surgical exploration, and the remainder received conservative therapy. In the majority of cases, surgery confirmed the abnormal CT and EMG findings; in some instances, however, myelography and/or surgery confirmed the abnormality only at the level demonstrated on EMG. The CT and EMG often agree. However, an abnormal EMG seems to correlate better with the demonstrated course of radiculopathy than CT.

Plasmapheresis with immunosuppressive drug therapy in progressive multiple sclerosis. A pilot study.

In light of encouraging preliminary data, 45 patients with severely progressive multiple sclerosis underwent long-term plasmapheresis in conjunction with low-dose cyclophosphamide and prednisone therapy. The disease progression was monitored by the Kurtzke disability status scale (DSS) and functional systems scale, neuro-ophthalmologic evaluations, evoked potentials, computed tomographic scans, and suppressor cell function assays. The conditions of 28 of the 45 patients improved significantly, the conditions of 14 patients showed limited improvement, and the conditions of three patients neither improved nor worsened. Improvement in other parameters correlated with the clinical results. Significant improvement in suppressor cell function was noted in those patients whose conditions had improved by one or more steps on the DSS.

Treatment of multiple sclerosis with hyperbaric oxygen. Results of a national registry.

Three hundred twelve patients were entered into a long-term study of effects of hyperbaric oxygen on multiple sclerosis. The protocol called for an initial 20 treatments in either the monoplace or multiplace chamber on a daily basis followed by monthly booster treatments for 2 years. One hundred seventy neurologists and 22 institutions provided data for this study. There was no control group, but the study was based on Schumacher's postulation that a scientifically valid study to test the efficacy of a new therapy was possible by choosing patients who were definitively diagnosed with multiple sclerosis and following them up for 2 years after the imposed treatment. If the overwhelming majority of the subjects failed to get worse over the 2-year observation period, the efficacy of the treatment would be manifest. The expanded Kurtzke Disability Status Scale (EDSS) was used to assess the severity of the disease state. The dropout rate was high with only 76% (237 of 312 patients) finishing the initial 20 treatments. Twenty-two percent (69 of 312) finished 1 year of booster therapy, and 9% (28 of 312) completed 2 years of monthly boosters. The mean deterioration on the Kurtzke EDSS score was 0.93 or almost a full step from the beginning of treatment until the last evaluation. There was no difference in outcome between those who had the shortest and longest periods of time between onset of symptoms and hyperbaric oxygen treatment. Treatment pressure made no difference in outcome. Changes in the Kurtzke EDSS score bore no relationship to the use of booster treatment. Patients who were reasonably well off at the onset of treatment with initial Kurtzke EDSS scores of 1 or 2 (n = 21) deteriorated by an average of 1.7 Kurtzke points. Those patients whose initial Kurtzke EDSS scores were greater than 2 (n = 164) deteriorated on an average of 0.82 points. Of interest was that 19.5% (39 of 200) of the patients reported a temporary improvement in bladder function, but improvement was maintained in only 11 patients (5.5%) at 2-year follow-up. Fifteen patients (7.5%) indicated long-term worsening. There was no significant change in the working status of the patients following hyperbaric oxygen treatment. Although this study treated the patients in accordance with protocols reported to produce a benefit in multiple sclerosis, we were unable to substantiate any useful long-term effect of hyperbaric oxygen therapy.

Memory disturbance in chronic progressive multiple sclerosis.

Forty-four patients with chronic progressive multiple sclerosis (MS) were compared with age- and education-matched control groups on a battery of clinical and experimental memory measures. Patients with MS performed substantially below the control groups on both immediate learning and delayed recall tasks, particularly in the retrieval of spatial information. The MS sample was subdivided into three groups using a cluster analytic procedure. One group (N = 9) performed well below expectations on memory tasks, exhibited signs of global cognitive disturbance, and had an atypical personality adjustment, characterized by irritability, social withdrawal, and apathy. A second group (N = 19) showed mild memory disturbance, associated with a greater use of psychotropic medications and a higher incidence of reactive depression. A third group (N = 16) performed normally on memory measures. The three groups of patients with MS did not differ in length or overall severity of illness.

Chronic progressive multiple sclerosis. Relationship between cerebral ventricular size and neuropsychological impairment.

Forty-seven patients with chronic progressive multiple sclerosis were examined to assess the possible relationship between cerebral atrophy (by computed tomography [CT] ) and performance on neuropsychological tests of memory and verbal intelligence. Nineteen patients were found to have mildly dilated ventricles and another nine patients had moderate to severe ventricular enlargement. Performance on memory and intelligence testing was related to the degree of ventriculomegaly. Three linear CT measurements were also recorded. Using this method, the width of the third ventricle proved to be the best indicator of intellectual and memory dysfunction. Measures of cognition and ventricular size did not correlate with length of illness or overall disability as rated by the Kurtzke Disability Status Score.

The use of steroids in the treatment of idiopathic polyneuritis.

The efficacy of steroids in the treatment of acute idiopathic polyneuritis (Guillain-Barré syndrome) continues to be uncertain. Since 1965, 38 patients with idiopathic polyneuritis have been at the University of Kentucky Medical Center, and 16 of them were entered in a prospective double blind study designed to assess the effectiveness of steroid therapy. Seriously ill patients were excluded from the study and most of them received steroids. In both the double-blind group and the entire group of patients, the time from the onset of illness to recovery was significantly less in patients treated with steroids, although steroids did not alter the initial severity of illness or the duration of hospitalization.

Cranial magnetic resonance imaging in the evaluation of myelopathy of undetermined etiology.

The spinal form of MS is a clinical conundrum, the solution of which may yield many answers; to be certain that it is MS and not another disease causing the myelopathy is often difficult. We evaluated 20 patients with myelopathy of undetermined etiology (clinical findings limited to the spinal cord) using T2-weighted cranial magnetic resonance imaging (T2 MRI) and cranial computerized tomography (CT). Some patients were also studied with flash visual evoked responses (FVER) and spinal fluid analysis for myelin basic protein (MBP) and oligoclonal banding (OCB). Thirteen patients had T2 MRIs consistent with demyelinating disease (two or more areas of increased signal intensity, of appropriate size, in periventricular/subcortical white matter), while only one CT showed focal lesions. FVER were abnormal in 8 of 15 patients tested; spinal fluid OCB was present in 12 of 16 patients tested, only 1 of whom had elevated MBP. T2 MRI showed lesions typical of demyelination in the majority of study patients, was much more sensitive than CT, and was well correlated with evidence of demyelination by other tests. Although the specificity of T2 MRI in MS is unknown, it may be very high in this clinical setting.

Plasma exchange in chronic progressive multiple sclerosis: a long-term study.

Plasma exchange (PE) was shown in a previous double-blind randomized controlled study to confer significant additional benefit at 1 year upon patients with chronic progressive multiple sclerosis (CPMS) treated with immunosuppressive drug therapy (ISDT). Efficacy over an extended term, indications for retreatment, and long-term toxicity are dealt with in this analysis of a larger number of patients. During the past 7 years, 200 patients with CPMS have been treated with PE and low-dose ISDT at this center. Improvement on the Kurtzke Disability Status Scale by one or more steps post-therapy and at 3-year follow-up is significant by comparison with pre-PE disability status. Clinical improvement was maintained in the majority of patients, reaching as far as a 6-year follow-up. Major life-threatening complications attributable to this combined therapy were not observed.

Chronic progressive multiple sclerosis: double-blind controlled study of plasmapheresis in patients taking immunosuppressive drugs.

Fifty-four patients with chronic progressive multiple sclerosis received prednisone plus oral low-dose cyclophosphamide and either true plasmapheresis (PP) or "sham" PP weekly for 20 weeks in a double-blind controlled study. Immunosuppressive drug therapy alone (sham PP group, n = 29) was associated with improvement (greater than or equal to one step in Kurtzke Disability Status Scale [DSS]; mean change of 1.5) in 8 and stabilization of MS in 18 patients, with this status sustained in 23 patients at follow-up, 11 months after entry. In contrast, 14 of 26 patients who received "true" PP improved (greater than or equal to one step in DSS; mean change of 2.6), and 11 more were stable, with these changes sustained in 23 of 26 patients at follow-up. These differences, overall, between the PP and sham PP groups were significant at p less than 0.007.

Double-blind study of true vs. sham plasma exchange in patients treated with immunosuppression for acute attacks of multiple sclerosis.

We enrolled 116 patients in a multicenter, randomized, double-blind controlled trial of an 8-week course of 11 plasma exchange (PE) treatments in exacerbations of MS. The control group received sham PE, and both groups received identical treatment with IM ACTH and oral cyclophosphamide. Serum IgG decreased in the PE and sham treatment groups by 76% versus 22% by treatment 5, and by 64% versus 14% by treatment 11. PE also produced significant reductions in IgA, IgM, C3, and fibrinogen. PE patients had moderately enhanced improvement at 2 weeks relative to the sham group. PE patients with relapsing/remitting disease had significantly enhanced improvement at 4 weeks and there was also an increased improvement at 12 months, although this latter effect disappeared when we analyzed relapsing/remitting patients as a separate subgroup. Life table analysis showed the median time to recover preattack disability status was shorter in PE- than in sham-treated relapsing/remitting patients (4 vs. 13 weeks), a result confirmed by raw disability status scores in which there was recovery to their average preattack disability score by 3 months. PE given with ACTH plus cyclophosphamide enhances recovery from an exacerbation of disease in relapsing/remitting patients, although we observed no clear long-term benefits.

Cellular response to human acetylcholine receptor in patients with myasthenia gravis.

A preparation of human skeletal muscle acetylcholine receptor (AchR) was used in vitro as an antigen to stimulate lymphocytes from patients with myasthenia gravis (MG). Clinical data obtained from the patients included duration and severity of disease; history of steroid treatment or prior thymectomy; and the presence of thymoma. Lymphocytes from patients with MG showed a significantly higher response to human AchR antigen than did lymphocytes from control subjects. Previous studies of cellular response to AchR have used receptor prepared from eel or ray electric organs. By stimulating lymphocytes from MG patients with a preparation of human AchR, we have come one step closer to documenting a possible contribution of a cellular immune response to the pathogenesis of MG.

Scapuloperoneal syndrome. Report on two families with neurogenic muscular atrophy.

Scapuloperoneal syndrome is a more or less clinically distinct neurologic entity with predominant involvement of scapular and peroneal muscles. The disease shows a variable mode of inheritance. Electromyography and muscle biopsy has shown the presence of denervation and dystrophic changes, sometimes both in the same patient. Cardiac manifestations when present add a graver prognosis to an otherwise relatively benign disease. Study of two cases in this report, one with significant sensory changes and another with cardiopathy, showed degeneration of peripheral nerve and mixed features in muscle biopsy. It is postulated that the myopathic or dystrophic features in the muscle of these cases and other patients with scapuloperoneal syndrome is likely to be secondary to slow denervation and reinnervation.

Clinical electromyography: definition, application, and innovation.

Clinical EMG techniques, useful in the study of patients with neuromuscular disease, are defined. These include measurement of motor and sensory nerve conduction velocities; analysis of the size, shape, and latency of response of muscle and nerve action potentials after nerve stimulation; estimates of nerve excitability; study of the response to repetitive nerve stimulation as a measure of neuromuscular transmission; and observation of the electrical activity of muscle with needle recording electrodes (monopolar, bipolar, and multielectrodes). From a consideration of the application, limitations, and value of these various techniques, it can be concluded logically that to assure the highest probability of reliable information in regard to an individual patient, the choice of technique(s) and the part(s) to be studied should be intimately tied to a clinical analysis of that patient's problem. EMG as a fishing expedition is rarely fruitful; EMG as an exercise in clinical physiology is often exciting.

Successful medical treatment of a spinal histoplasmoma.

A woman with previously treated disseminated histoplasmosis was admitted with progressive paraparesis. Magnetic resonance imaging showed multifocal cerebritis and spinal histoplasmoma. She recovered following a second treatment with amphotericin B. This is the fourth reported patient with intramedullary spinal histoplasmoma, and the first demonstrating successful treatment of the lesion with medical therapy alone.

Neurologic complications of graft-versus-host disease.

BMT has become an important therapy for many hematologic disorders. Following BMT, the recipient may develop GVHD when it appears that immunocompetent donor lymphocytes react to host antigens. Acute and chronic GVHD represent two distinct syndromes. Acute GVHD has not been associated with primary neurologic involvement. Polymyositis has been reported in 12 patients with chronic GVHD, with the most common underlying illness being aplastic anemia. The clinical, serologic, and muscle biopsy features of the myositis in GVHD have been similar to those observed in idiopathic polymyositis. Weakness was moderate to severe and responded to prednisone, sometimes with the addition of azathioprine. Prognosis depended upon the underlying disease and not on the severity of the myositis. MG occurs rarely in chronic GVHD. Most patients with MG and GVHD have had aplastic anemia; those with aplastic anemia are more likely to have anti-AchR prior to BMT. The clinical manifestations of GVHD MG have not differed from classic autoimmune MG; each patient had elevated antiacetylcholine receptor antibodies titers. All patients have responded well to cholinesterase inhibitors but have received other immunosuppressants. These observations suggest that aplastic anemia is an important host factor in the development of the autoimmune disorders seen with chronic GVHD, certainly of myositis and MG. Herpes zoster peripheral nerve infections have occurred in patients with chronic GVHD. One patient had mononeuritis multiplex. In both acute and chronic GVHD, CNS impairment is usually caused by metabolic encephalopathy or infection. Primary CNS involvement has not been recognized.