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Biomedical subjects

I Sarova-Pinhas

Publications and source records attributed to I Sarova-Pinhas.

At least 19 recordsLinked to original sources

T cell vaccination in multiple sclerosis relapsing-remitting nonresponders patients.

Myelin autoreactive T cells are involved in the pathogenesis of multiple sclerosis (MS) and lead to propagation of the disease. We evaluated the efficacy of T cell vaccination (TCV) therapy for patients with aggressive relapsing-remitting MS who failed to respond to immunomodulatory treatments. Twenty nonresponders relapsing-remitting MS patients were immunized with autologous attenuated T cell lines after activation with synthetic myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG) encephalitogenic peptides. Each patient received three vaccinations in 6- to 8-week intervals. Annual relapse rate decreased from 2.6 to 1.1, P = 0.026. Neurological disability stabilized as compared with the 2- and 1-year pretreatment progression rates. Significant reduction in the number and volume of active lesions, as well as reduction in T2 lesion burden, was demonstrated by quantitative MRI analysis. No serious adverse events were observed. Our findings suggest that TCV has beneficial clinical effects in MS patients who, in spite of immunomodulatory treatments, continue to deteriorate. TCV could serve as a potential alternative therapy for this subgroup of nonresponders patients.

Adult↗

Multiple sclerosis in childhood and adolescence: clinical features and management.

The presentation of multiple sclerosis (MS) in childhood has traditionally been thought to be rare. However, more paediatric cases are now being reported, as a result of progress in diagnostic techniques with the use of sensitive imaging modalities of the brain and spinal cord. Management from an early age and the availability of new treatment options have changed the outcome of paediatric MS. Drugs currently available for treatment, such as beta-interferons, copolymer-1 and intravenous immunoglobulin G, have been found to reduce relapse rate, disease severity and progression to disability in adults, but have not been investigated in children and adolescents. The overall outcome of MS in children is apparently no worse than in adults and the disease may even be less aggressive in children. In juvenile MS, disease progression does not appear to be related to age of onset, severity of neurological involvement or mono/polysymptomatic involvement at presentation. The potential to treat MS has significantly changed the prognosis. Early diagnosis is important, as early treatment can prevent or delay the development of disability.

Adolescent↗

Immunoglobulin treatment in refractory Myasthenia gravis.

Failure to induce and maintain remission in severe exacerbations of myasthenia gravis (MG), despite optimal care, is a common problem. We evaluated the efficacy and safety of high-dose intravenous immunoglobulin (IVIg) therapy in an open-label study of 10 patients with severe generalized myasthenia and an acute deterioration unresponsive to conventional therapy including high-dose corticosteroids, cyclosporine, and azathioprine. Intravenous Ig at a loading dose of 400 mg/kg was administered daily for 5 consecutive days, with maintenance IVIg treatment at a dose of 400 mg/kg, once every 6 weeks. Significant improvement occurred in all patients, beginning at 6 +/- 2 days of treatment as measured by the Osserman scale, fatigue variables, muscle strength, and respiratory function tests. No side effects were observed during induction of remission. Further IVIg treatments were highly efficacious in maintaining the remission. The severity of the disease decreased by 2.5 +/- 0.8 grades of the Osserman scale over a period of 1 year (P <0.001), in parallel with reduction of immunosuppressive therapy as well as a decrease in acetylcholine receptor antibody titers (P < 0.01). Intravenous Ig therapy seems to be highly potent for inducing rapid improvement in refractory myasthenia during acute deterioration as well as for maintaining remission.

Adult↗

Cerebrospinal fluid magnesium level as a prognostic factor in ischaemic stroke.

Magnesium has been reported to have a dilatatory effect on cerebral arteries. Reduction of extracellular Mg+2 has been shown to be directly correlated with the intensity of cerebral spasm. A neuroprotective effect of magnesium in stroke has also been hypothesized. The aim of our study was to examine the Mg+2 levels in serum and cerebrospinal fluid (CSF) in the early stage of stroke and to evaluate the correlation between Mg+2 levels and the development of neurological deficits. Between 1986 and 1994, 96 patients who had a stroke of 24- to 48-h duration were enrolled in the study. Serum and CSF levels of magnesium were checked on admission, 2448 h after the onset of stroke. Using a neurological score, the neurological deficit was assessed on the 1st day, 1 and 4 weeks later. Computed tomography (CT) was performed after 1 week, and the volume and location of infarction were calculated and measured. Statistical analysis was performed for cortical and subcortical patients separately, using Spearman correlation and multiple linear and logistic regression analyses. Significant correlation was found between CSF Mg+2 and the size of the infarct (P < 0.0001). There was no correlation between serum Mg+2 and CSF Mg+2 levels. Regression analysis demonstrated an increase in the values of the Mathew Neurological Score with higher CSF Mg+2 levels. This association remained true after other factors such as age, associated heart disease, diabetes and infarction size had been taken into account by the regression model. The results confirm that there is a relationship between a low Mg+2 concentration in CSF during the first 48 h after onset of ischaemic stroke and the intensity of the neurological deficit. The therapeutic consequence of this finding may have some importance.

Adult↗

Intravenous immunoglobulin treatment in multiple sclerosis. Effect on relapses.

We conducted a double-blind, placebo-controlled study of 40 patients (aged 19 to 60 years) with clinical definite relapsing remitting (RR) MS and brain MRI confirmed. Patients were randomly assigned to receive a loading dose of immunoglobulin IgG (0.4 g/kg/body weight per day for 5 consecutive days), followed by single booster doses (0.4 g/kg/body weight) or placebo once every 2 months for 2 years. The primary outcome measures were change in the yearly exacerbation rate (YER), proportion of exacerbation-free patients, and time until first exacerbation. Neurologic disability, exacerbation severity, and changes in brain MRI lesion score were the secondary outcome measures, all determined at baseline, 1 year, and on completion. Treated patients showed a reduction in YER from 1.85 to 0.75 after 1 year and 0.42 after 2 years versus 1.55 to 1.8 after 1 year and to 1.4 after 2 years in the placebo group (p = 0.0006, overall), reflecting a 38.6% reduction in relapse rate. Six patients in the IVIg group were exacerbation free throughout the 2-year period of the study, whereas none were exacerbation free in the placebo group. The median time to first exacerbation was 233 days in the IVIg group versus 82 days in the placebo group (p = 0.003). Neurologic disability as measured by the Expanded Disability Status Scale (EDSS score) decreased by 0.3 in the IVIg group and increased by 0.15 in the placebo group. Total lesion score evaluated by brain MRI did not show a significant difference between groups. Side effects were minor and occurred in only 19 of 630 (3.0%) infusions administered in both groups. Our results suggest that IVIg may be safe and effective in reducing the frequency of exacerbations in RR-MS.

Adult↗

Familial dyslexia associated with cavum vergae.

Three members of one family, diagnosed as dyslexic, are described. All of them have variations of midline cavity: cavum vergae or cavum septum pellucidum, diagnosed by neuroradiological examination. In contrast, the non dyslexic members of the same family have no neuroanatomical congenital variations. We raise the possibility of a functional correlation between the dyslexia and the anatomical findings in the affected members of this family.

Adolescent↗

Cerebrospinal fluid soluble interleukin-2 receptor in cerebral lupus.

Cerebrospinal fluid (CSF) and serum samples of 20 young adults (mean age 41 +/- 3.4 yr) with a first episode of stroke were tested for interleukin-2 (IL-2), soluble interleukin-2 receptor (SIL-2R), tumour necrosis factor-alpha (TNF-alpha) and interleukin-1-beta (IL-1 beta) levels. The results were compared to 20 patients who had neurological symptoms without evidence of a neurological disease. Three subgroups were formed according to the aetiological source of the stroke, determined by the neurological examination and evaluation. In 13 patients, the presence of atheromatous carotid plaque or cardiac disease was found. In five of the patients, stroke was the presenting symptom of systemic lupus erythematosus (SLE), which developed during the follow-up period. In two patients, no obvious aetiology could be demonstrated. The SIL-2R level was significantly higher in the CSF of patients who later developed definite SLE (P = 0.001). Other CSF interleukins and all serum interleukin levels were not significantly different in any of the groups. No correlation between albumin quotient and CSF SIL-2R was found. The SIL-2R level in the CSF may be used as a diagnostic tool to differentiate immunologically mediated vascular processes in the CNS from stroke of other origin.

Adult↗

Endothelin in cerebrospinal fluid and plasma of patients in the early stage of ischemic stroke.

BACKGROUND AND PURPOSE: Endothelin 1 (ET-1), a highly potent endogenous vasoactive peptide, exerts a sustained vasoconstrictive effect on cerebral vessels. Elevation of ET-1 in plasma has been reported 1 to 3 days after ischemic stroke. Since we assumed that a much faster and more intense response may be observed in the cerebrospinal fluid (CSF) and since an increase in concentration of ET-1 in the CSF may cause constriction of cerebral vessels and eventually influence the neurological outcome, we measured ET-1 values in the CSF within 18 hours of stroke onset and compared the values with those in the plasma. METHODS: Twenty-six consecutive patients with acute stroke were clinically evaluated according to the modified Matthew Scale and underwent two repeat CT scans. Within 5 to 18 hours of stroke onset, lumbar puncture and blood samples were concomitantly obtained and tested; ET-1 levels in CSF and plasma of these patients were analyzed by radioimmunoassay and compared with the levels of a control group of patients with no neurological disease. RESULTS: The mean CSF concentration of ET-1 in the CSF of stroke patients was 16.06 +/- 4.9 pg/mL, compared with 5.51 +/- 1.47 pg/mL in the control group (P < .001). It was significantly higher in cortical infarcts (mean, 17.7 +/- 4.1 pg/mL) than in subcortical lesions (mean, 10.77 +/- 4.1 pg/mL) (P < .001) and significantly correlated with the volume of the lesion (P = .003). The correlation between ET-1 levels in the CSF and the Matthew Scale score was less significant (P = .05). Plasma ET-1 level was not elevated in any group. CONCLUSIONS: ET-1 is found to be significantly elevated in the CSF of stroke patients during the 18 hours after stroke. No elevation was demonstrated in plasma at this time period. ET-1 may be used as an additional indicator of ischemic vascular events in the early diagnosis of stroke. The dissimilarity between the CSF and plasma ET-1 concentrations may lead also to an hypothesis that there is a vasoconstrictive effect on the cerebral vessels or a neuronal effect caused by ET-1 in the mechanism of the progression of brain ischemia.

Adult↗

Anterior operculum syndrome localized by SPECT.

UNLABELLED: The aim of this case report was to present a patient with complete anarthria and orofacial apraxia without other relevant neurological deficit. The clinical features are compatible with anterior operculum syndrome. METHODS: A regional brain perfusion scan was done using 99mTc-HMPAO and a SPECT gamma camera. A brain CT scan and an MRI were also performed. RESULTS: Brain CT and MRI were not diagnostic. On brain SPECT, hypoperfusion of the left inferior area of the frontal lobe was noted. CONCLUSION: The patient studied showed an uncommon case of anterior operculum syndrome of focal degenerative origin localized by SPECT. SPECT may be a useful and effective method for diagnosis of this unusual neurological deficit.

Aged↗

Early treatment of a single generalized tonic-clonic seizure to prevent recurrence.

BACKGROUND: The question of whether to start antiepileptic treatment after a single unprovoked seizure remains controversial and has been the subject of much debate in the relevant literature. OBJECTIVES: To determine the rate of recurrence of a second attack after a single unprovoked epileptic seizure by using 2 study groups of treated and untreated patients and, thus, to establish a treatment policy for these patients. PATIENTS AND METHODS: A group of 91 patients with a single generalized tonic-clonic seizure were prospectively studied; 87 of these patients completed the study. The end point of the study was 36 months after the single attack or the occurrence of a subsequent epileptic attack. The patients were randomly divided into 2 groups; 45 patients who immediately received anticonvulsive treatment and 42 who remained untreated for the follow-up period. Patients in the treated group were given monotherapy with carbamazepine. The results of recurrences were statistically analyzed by using the Kaplan-Meier method. RESULTS: Results indicated a significantly higher percentage of seizure-free patients in the treated group compared with that in the untreated group (P = .001). The treated men were proved to be less at risk for recurrent seizures compared with treated women (P < .001 vs P = .03, respectively). CONCLUSION: Treatment after a single unprovoked seizure leads to a significant reduction in the risk of relapse of generalized tonic-clonic epilepsy.

Adult↗

Intravenous immune globulin in multiple sclerosis: clinical and neuroradiological results and implications for possible mechanisms of action.

Extensive evidence exists indicating that immunoregulatory mechanisms are involved in the pathogenesis of Multiple Sclerosis (MS). Several possible mechanisms by which intravenous immune globulin (IVIG) modulates the course of the disease are related to limiting the inflammatory process and repairing the damage by enhancing remyelination. Presently, the evidence for the effect of IVIG in MS is based on the results of small open trials, some of which have been encouraging. In the current study, the positive impact of IVIG treatment on arresting disease progression was evident by decreased brain Magnetic Resonance Imaging (MRI) scores of the lesion area. In an effort to extend these findings, the authors initiated a multicentre, prospective, randomized, double-blind, placebo-controlled study. The trial was designed to compare the efficacy of IVIG treatment with placebo in relapsing-remitting patients (ages 20-55 years) with definite MS, disease duration of 2-10 years and frequency of exacerbations 1-3/year during the 2 years prior to the study. Patients were examined monthly and brain MRI studies scheduled at entry, and after the first and second years of the trial. The primary endpoints included the number of acute exacerbations and neurological disability. The secondary endpoints included change in the MRI lesion burden, evaluated by the number and area of lesions. The trial ended in June 1995.

Adult↗

Sexual dysfunction in relapsing-remitting multiple sclerosis: magnetic resonance imaging, clinical, and psychological correlates.

The purpose of this study was to examine the sexual complaints and severity of sexual dysfunction in relapsing-remitting multiple sclerosis patients and to correlate them with psychological, neurological, and radiological variables. Frequency and characteristics of sexual disturbances were reported by 41 multiple sclerosis patients (32 females, 9 males; mean age 35.4 +/- 10.2 y). Clinical neurologic variables tested were disease duration, exacerbation rate, and disability; psychological variables tested were anxiety and depression. All patients underwent a brain magnetic resonance imaging (MRI) scan at the time of this study. The sexual dysfunction questionnaire included items based on the 3 phases of human sexual response: loss of libido, excitement (arousal difficulties, impotence, premature ejaculation), and anorgasmia. Five males (55.5%) and 16 females (50.0%) reported at least 1 sexual disturbance. The most frequent dysfunctions were loss of libido (26.8%) and arousal difficulties (19.5%). Females rated their difficulties as more severe. Sexual dysfunctions correlated with depression, (r = 0.68, P = 0.001). No correlation between MRI score and depression was found. Anorgasmia correlated with brain stem and pyramidal abnormalities (r = 0.56, P = 0.011; r = 0.56, P = 0.012, respectively). The total area of lesions (plaques) on the brain MRI scan also correlated with anorgasmia (r = 0.41, P = 0.02). Sexual dysfunctions in multiple sclerosis patients are frequent, are mild to moderate in severity, correlate with depression and in some cases central nervous system (CNS) demyelinating process, and thus may be related either to the psychological impact of this disease or to specific organic lesions in the brain.

Adult↗

Strokes mimicking peripheral nerve lesions.

Sensory-motor deficit in a peripheral nerve pattern due to brain lesion is rarely documented. We report on seven patients with a clinical manifestation of sensory-motor deficit, imitating peripheral nerve involvement, due to lacunar brain infarcts verified by brain computed tomography scan. Five of the patients had an ulnar nerve-like deficit and two median nerve-like deficits. The infarcts were located in the thalamus and the corona radiata. No clinical or electrophysiological evidence for peripheral nerve involvement was found. The unusual peripheral nerve pattern of lesions caused by lacunar brain infarcts can be defined as an additional lacunar syndrome and must be taken into consideration in the clinical evaluation of peripheral nerve deficits with normal nerve conduction velocity.

Aged↗

Peripheral neuropathy in multiple sclerosis: a clinical and electrophysiologic study.

Peripheral nerve abnormalities are uncommon in multiple sclerosis (MS). When present, they are usually attributed to factors associated with advanced disease, such as malnutrition or cytotoxic drugs. We prospectively evaluated 22 mildly disabled MS patients with sensory complaints for evidence of neuropathy using the Neuropathy Symptom Score (NSS), clinical examination, and electrophysiologic studies of peripheral nerves. Distal latency, F-wave response, and nerve conduction velocity (NCV) and amplitude in the ulnar, median, tibial, peroneal and sural nerves were examined. Neuropathy was recorded if electrophysiologic abnormalities were detected in at least two peripheral nerves in the same patient. The most frequent electrophysiologic abnormalities noted were prolonged F-wave response and low motor amplitude in the peroneal nerve, slow sensory conduction velocities of the ulnar and sural nerves, and prolonged distal latencies in the sensory ulnar and sural nerves. Electrophysiologic abnormalities were found in 33 of 244 nerves examined (14.7%) and occurred in 10 patients (45.5%). Neuropathic symptoms were mild and did not correlate with electrophysiologic abnormalities. Age, disease duration, disease course and neurologic disability as evaluated by the Kurtzke Expanded Disability Status Scale, were not associated with the presence of neuropathy. Our findings indicate a high frequency of sensory-motor neuropathy in a selected group of MS patients.

Adolescent↗

Neurological and functional outcome in patients with supratentorial hemorrhages. A prospective study.

BACKGROUND AND PURPOSE: A prospective study was performed to evaluate neurological and functional outcome after spontaneous supratentorial bleeding. The aim of the study was to determine whether clinical or neuroradiological parameters could predict the outcome of these patients during the first hours of hospitalization. METHODS: Two hundred seventy-nine patients--52 with thalamic, 87 with putaminal, and 140 with lobar hemorrhages--were followed prospectively and examined on admission and at 2 weeks, 3 months, and 6 months after onset. The patients underwent clinical (according to the Glasgow Coma Scale) and neuroradiological examinations on admission and were scored clinically and functionally (according to Stroke Severity score and Barthel Index) on the follow-up periods. Risk factors and the correlation between findings on admission and the latest clinical and functional results were calculated with the chi 2 test, Pearson correlation test, and Student's t test. Multivariate analysis was calculated with the stepwise regression test. RESULTS: In all of the bleeding locations, lethal outcome was significantly correlated with size of the hematoma (P < .001) and Glasgow Coma Scale score on admission (P < .001). Intraventricular blood expansion was found to have a better prognosis in thalamic bleeding (P < .007) and a worse prognosis in lobar hemorrhage (P < .01). The functional outcome after 6 months was directly correlated with the size of the bleeding area in lobar and putaminal hemorrhages. No correlation was found in thalamic bleeding. A worse functional outcome was found in putaminocapsular bleeding (P = .004) and in patients with ischemic heart disease. A limited better recovery prognosis was found in patients with lobar hematoma in the temporal lobe (P = .052). CONCLUSIONS: The probability of lethal outcome can be calculated on admission in all patients with supratentorial bleeding and in correlation with the location and size of the bleeding area and level of consciousness. Intraventricular expansion of blood is a better prognostic factor in thalamic bleeding and a worse one in lobar hematoma. Functional outcome is correlated with size of the bleeding area and level of consciousness on admission in putaminal and lobar hemorrhages but has no correlation to thalamic hemorrhage.

Age Factors↗

Fluoxetine induced weight loss: a pilot study in postpartum women.

Twelve women who developed an average postpartum weight gain of 18.3kgs (SD +/- 6.09) entered an open trial, for three months, of fluoxetine 20 mg daily. The weight gain during their pregnancies was nearly twice that recommended by the treating gynecologists. Seventy-five percent success rate was achieved -8/12 were +/- 5% of their pre-pregnancy weights upon completion of the trial. Mean weight upon entering the trial was 82.25kgs (SD +/- 13.39), and at termination, 65.75kgs (SD +/- 8.59), P < 0.001. Anorexia and weight loss (more than 5% of body weight) have been reported in the literature in 9% and 13%, respectively, of depressed patients treated with fluoxetine. The use of this drug to promote weight loss is here reported in a selected population of women without signs or symptoms of depression, whose weight gain during pregnancy was excessive.

Adult↗