Outcome measures for clinical trials in multiple sclerosis.
Explore the source record for details and available documents.
Clinical Trials as Topic↗
Biomedical subjects
H S Panitch
Publications and source records attributed to H S Panitch.
The association of cervical spondylosis and multiple sclerosis.
The diagnostic and therapeutic considerations produced by the coexistence of cervical spondylosis and multiple sclerosis are complex. We have encountered six patients, affected by both multiple sclerosis and cervical spondylosis, in whom neurosurgical procedures were performed. The diagnosis of multiple sclerosis was confirmed by a combination of clinical, neuroimmunologic, electrophysiologic, and neuroradiologic findings. The diagnosis of spondylosis with spinal cord compromise was confirmed by myelography and computed tomographic scan in all cases, and by magnetic resonance imaging in four. Surgery was followed by lasting clinical improvement in two patients, transient improvement in one, and no change in the other three. Our experience confirms that multiple sclerosis and cervical spondylosis can coexist and suggests that this coexistence may result in an interaction that compounds the deleterious effect on the nervous system. Diagnostic evaluations of patients, particularly young patients, with symptoms of cervical spondylosis should include consideration of the possible coexistence of multiple sclerosis. The evaluation of a patient with known multiple sclerosis who develops new signs of cervical spinal cord dysfunction should always include spinal neuroimaging studies. When progression of symptoms coincides with documented progression of anatomic compression, surgical intervention can yield good results.
Adult↗
Demyelinating disease after neurologically complicated primary Epstein-Barr virus infection.
This report describes five patients who, following a neurologically complicated primary Epstein-Barr virus infection, developed progressive or relapsing neurologic deficits. The sequelae in four patients followed 4 to 12 years led to the diagnosis of multiple sclerosis (MS). The fifth patient presented with acute disseminated sclerosis and exhibits diffuse neurologic deficits that have persisted for 2 years. We suggest that the diagnosis of an unexplained acute neurologic or psychiatric syndrome should raise the question of a primary EBV etiology. A precisely timed serologic and hematologic study of the blood is imperative to capture the essential evidence. The data presented represent a clinical association between a neurologically complicated primary EBV infection and both chronic and acute demyelinating disease. The evidence does not justify a conclusion that EBV virus causes MS.
Adolescent↗
Interferons in multiple sclerosis. A review of the evidence.
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system, characterised clinically by relapses and remissions, and leading eventually to chronic disability. Despite an enormous amount of research, the cause of MS remains unknown; however, pathological, genetic, and immunological features have been identified that suggest the disease has an autoimmune basis. Accordingly, current therapy of MS includes corticotrophin or corticosteroids for acute exacerbations, and more potent immunosuppressive drugs for severe cases unresponsive to steroids. All of these agents can cause serious adverse reactions. There is an urgent need for immunotherapy that is less toxic, that can be given early and perhaps indefinitely, and that will prevent relapses and progression of the disease. Our current knowledge of the effects of interferons (IFNs) in MS is based on the results of laboratory research and clinical therapeutic trials carried out over the past decade. Existing evidence points to the conclusion that the effects of the IFNs in MS are mediated by immunoregulatory rather than antiviral or nonspecific mechanisms. Administration of IFN gamma increases the exacerbation rate, and IFN gamma as well as other cytokines may be involved in the pathogenesis of MS lesions. In contrast, studies of IFN beta show that it tends to inhibit the activity of IFN gamma and appears to prevent disease activity. Intrathecal administration of IFN beta, although effective, is cumbersome and potentially hazardous. A large multicentre placebo-controlled trial of systemic recombinant IFN beta was recently conducted in the US, and the results of the first 2 years of treatment were considered sufficiently encouraging that an application for licensing was submitted to the Food and Drug Administration in June 1992. If approved, it will be the first new agent licensed for clinical use in MS in over 20 years. The study will continue under double-blind conditions for at least another year, and a second trial of systemic recombinant IFN beta therapy is also in progress. These studies should provide definitive answers to questions about the role of IFNs in the pathogenesis of MS, as well as the place of recombinant IFN beta as an effective therapeutic agent.
Adult↗
Interferon therapy for multiple sclerosis.
Laboratory findings that suppressor cell function is improved with beta interferon therapy and that gamma interferon activity is inhibited by beta interferon provide support for the hypothesis that beta interferon will have a significant therapeutic effect on relapse rates in multiple sclerosis.
Humans↗
Myelopathic neurosarcoidosis: diagnostic value of enhanced MRI.
Neurosarcoidosis is an underdiagnosed variant of the systemic disease. We report a case of myelopathic neurosarcoidosis, noting the contribution made by MRI in establishing the diagnosis, and we discuss the possibility that the disease is differentially responsive to various steroid formulations.
Adult↗
Relapsing transverse myelitis.
Acute transverse myelitis is a monophasic disorder, the recurrence of which raises the question of multiple sclerosis (MS) or other multifocal CNS disease. We now report three patients with a previously undescribed syndrome of relapsing isolated acute transverse myelitis. Each had two to five attacks over periods of 3 to 8 years, characterized by ascending paresthesias, urinary retention, sensory loss with a thoracic or cervical level, paraparesis, hyperreflexia, and bilateral Babinski signs. MRI demonstrated areas of increased signal intensity on T2- and proton density-weighted scans and decreased signal intensity on T1-weighed scans of the cervical or thoracic spinal cord consistent with an inflammatory or demyelinating process. All patients had normal complete myelograms, oligoclonal IgG bands were consistently absent from the cerebrospinal fluid, cranial MRIs were normal, and there was no other clinical or laboratory evidence of MS, collagen-vascular disease, or active viral infection. They were treated with high doses of intravenous corticosteroids, stabilized between episodes, and had partial or complete recovery. The recognition of these three patients at a single medical center in a 1-year period suggests that relapses of acute transverse myelitis may not be rare.
Adolescent↗
Gamma-interferon induction in patients with chronic progressive MS.
Although gamma interferon (gamma-IFN) may be involved in the pathogenesis of exacerbations of multiple sclerosis (MS), whether it plays a role in chronic progressive MS is not known. To investigate this, we retrospectively analyzed serum samples from nine chronic progressive MS patients who were treated with monthly intravenous infusions of the interferon inducer polyinosinic acid polycytidylic acid polylysine in carboxymethylcellulose (poly ICLC). Using a bioassay we found that the mean peak total interferon level was 177 U/ml 12 hours after infusion, and using a radioimmunoassay we found that the mean peak gamma-IFN level was 15.9 U/ml 12 hours after infusion, so that gamma-IFN made up approximately 10% of the total. Greater gamma-IFN induction did not correlate with clinical worsening; induced gamma-IFN levels were not higher in two patients who worsened on treatment, and the highest levels were found in a patient who remained stable. Either chronic progressive MS is not sensitive to gamma-IFN or the effects of gamma-IFN are masked by other mediators induced by poly ICLC.
Antigens, CD↗
Preliminary trial of 3,4-diaminopyridine in patients with multiple sclerosis.
Ten patients with multiple sclerosis (MS) were enrolled in a preliminary trial of the potassium channel blocker, 3,4-diaminopyridine, to evaluate drug toxicity and pharmacokinetics. The patients were treated with oral 3,4-diaminopyridine, first with increasing single doses up to 100 mg and then with divided dosage for up to 3 weeks. Paresthesias were reported by all patients and abdominal pain was dose limiting in 6 patients. 3,4-Diaminopyridine levels and half-life varied widely from patient to patient. Cerebrospinal fluid levels of 3,4-diaminopyridine were about 10% of those in serum. Neither seizures nor epileptiform changes on electroencephalographic examination occurred. Small reversible improvements in specific neurological deficits were seen on examination in all patients and reversible improvement in visual evoked response latencies were found in 2 patients. These results suggest that further study of 3,4-diaminopyridine in patients with MS is warranted.
4-Aminopyridine↗
Effects of experimental recombinant interferons on multiple sclerosis.
Explore the source record for details and available documents.
Clinical Trials as Topic↗
Indomethacin, interferons, and multiple sclerosis.
Explore the source record for details and available documents.
Humans↗
Serial immunological studies in multiple sclerosis patients treated systemically with human alpha interferon.
A battery of immunological functions was studied over a 2-year period in conjunction with a placebo-controlled trial of natural human alpha interferon in patients with multiple sclerosis. IgG synthesis was increased both systemically and intrathecally by administration of interferon; however, there were only minor changes in cerebrospinal fluid oligoclonal bands. Levels of helper and suppressor T lymphocytes fluctuated independently of clinical exacerbations, although mean helper/suppressor ratios were higher in multiple sclerosis patients than in controls and increased further during interferon treatment. Cerebrospinal fluid myelin basic protein and antibodies to basic protein were not affected by exacerbations or by interferon administration. Circulating IgG antibodies induced by interferon treatment appeared to be directed at a non-interferon contaminant of the preparation. None of the assays was a consistent indicator of disease activity or of clinical response to interferon.
Adult↗
Leukocytes from multiple sclerosis patients respond to alpha- and gamma-interferons.
Blood mononuclear leukocytes from multiple sclerosis (MS) patients were evaluated for reactivity to alpha- or gamma-interferon (IFN), using a response whereby IFN-treated (primed) cells synthesize higher levels of IFN than untreated cells. Leukocytes were treated in vitro with natural alpha-IFN, recombinant alpha-IFN, recombinant gamma-IFN, or no IFN, then exposed to measles virus to induce IFN synthesis. With no IFN treatment, IFN production by cells from the MS patients was significantly less than normal (P less than or equal to 0.025). However, with IFN treatment, cells from MS patients were primed as well as cells from normal controls: IFN synthesis for the MS patients' cells was increased 10-11-fold with either alpha-IFN preparation and 3.6-fold with gamma-IFN. These findings verify the presence of leukocyte reactivity to alpha-IFN and provide the first demonstration of responsiveness to gamma-IFN in MS.
Humans↗
Experimental allergic encephalomyelitis: enhancement of cell-mediated transfer by concanavalin A.
Adoptive transfer of experimental allergic encephalomyelitis (EAE) with splenic lymphocytes from Lewis rats sensitized to myelin basic protein (BP) was potentiated by incubation of the cells in vitro with concanavalin A (Con A). Spleen cells of donors which had recovered from EAE also transferred the disease readily after activation by this procedure. In contrast, the transfer of activity of lymph node cells was not altered. We conclude that during the course of EAE a population of T cells with immunologic memory for BP is generated and persists in the spleen. Incubation with Con A activates these cells and results in marked enhancement of their ability to transfer the disease.
Animals↗
Progressive rubella panencephalitis. Late onset after congenital rubella.
In children with congenital rubella infection the deficits remain stable; neurologic deterioration after the first few years of life is not believed to occur. We have encountered three patients with a definite or presumptive diagnosis of congenital rubella, in whom a progressive neurologic illness developed that began in the second decade and was characterized by spasticity, ataxia, intellectual deterioration, and seizures. High antibody titers to rubella virus in serum and spinal fluid were present in two, and all had increased cerebrospinal-fluid protein and gamma globulin. Extensive attempts to recover a virus from brain and body fluids were unsuccessful. The brains of two patients showed a widespread, progressive, subacute panencephalitis mainly affecting white matter. These data suggest that rubella virus may be a cause of progressive panencephalitis.
Adolescent↗
Reflex epilepsy evoked by decision making.
A patient had seizures while playing chess or cards or when filling out complex forms, doing complex mathematical problems, and during certain parts of the neuropsychological testing. Seizures were myoclonic and accompanied and electroencephalographic dysrhythmia of the atypical spike and wave type. Evoked seizures were not related to visual, tactile, or auditory stimuli or clues. In chess, seizures occurred when he was on the defense and threatened. Simple decision making or physiologic stress did not evoke seizures nor did nonsequential decision making under verbal pressure. Evoking factors were complex decision making in a sequential fashion and with an element of stress or concern regarding the outcome of the decision making. Stimulus was usually nonverbal. Three major factors--decision complexity, sequential factor, and related stress or concern--may have some reciprocal relationships.
Adult↗