RESUMO
Three years after the introduction of natalizumab (NA) therapy for the second line treatment of relapsing-remitting multiple sclerosis (MS), Italian MS centers critically reviewed the scientific literature and their own clinical experience. Natalizumab was shown to be highly efficacious in the treatment of MS. However, the risk of progressive multifocal leukoencephalopathy was confirmed and defined better. This article summarizes the MS-SIN Study Group recommendations on the use of NA in MS, with particular reference to the appropriate selection and monitoring of patients as well as to the management of adverse events.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Anticorpos Monoclonais Humanizados , Humanos , Leucoencefalopatia Multifocal Progressiva/induzido quimicamente , NatalizumabRESUMO
OBJECTIVE: To prospectively validate MRI activity and neutralising anti-interferon antibody (NAb) during the first 6 months of interferon beta treatment as response indicators in multiple sclerosis (MS). METHODS: Patients with relapsing-remitting MS were followed during the first 2 years of treatment. Neurological assessments were performed every 3 months or when a relapse was suspected. MRI scans performed at baseline and at 3, 4, 5 and 6 months after the start of treatment were assessed centrally for disease activity: new T2 or gadolinium enhancing T1 lesions. NAb were assessed using the MxA protein assay; positivity was defined as two consecutive titres >or=20 NU/ml. We evaluated the predictivity of an active scan, NAb positivity, or both, during the first 6 months of treatment, on the occurrence of clinical disease activity in the following 18 months. RESULTS: 147 patients were assessed at 16 centres. Predictivity parameters (with confidence intervals) were as follows: active scan, sensitivity (SN) 52% (34-69%), specificity (SP) 80% (65-91%), negative predictive value (NPV) 73% (58-77%), positive predictive value (PPV) 62% (42-79%), p = 0.002; NAb positivity, SN 71% (45-88%), SP 66% (55-76%), NPV 92% (82-97%), PPV 29% (16-45%), p = 0.01; active scan and NAb positivity, SN 71% (38-91%), SP 86% (73-94%), NPV 94% (86-98%), PPV 50% (29-70%), p = 0.0003. CONCLUSIONS: MRI activity and NAb occurrence during the first 6 months of interferon beta treatment were reliable predictors of long term clinical response, particularly when combined. Patients with negative predictors showed a less than 10% risk of developing clinical activity. Patients with positive predictors showed a 50% risk of further clinical activity. These patients need to be followed carefully with further MRI and NAb tests.
Assuntos
Adjuvantes Imunológicos/uso terapêutico , Interferon beta/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Exame Neurológico/efeitos dos fármacos , Testes de Neutralização , Adulto , Anticorpos/sangue , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Esquema de Medicação , Feminino , Seguimentos , Humanos , Injeções Subcutâneas , Interferon beta-1b , Interferon beta/imunologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/imunologia , Estudos Prospectivos , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Immunomodulatory drugs have been shown to be only modestly effective in clinically definite relapsing remitting multiple sclerosis (RRMS). It has been hypothesized that their efficacy could be higher if used at the first appearance of symptoms, that is in the clinically isolated syndromes (CIS) suggestive of demyelinating events, a pathology which carries a high risk to convert to clinically definite MS (CDMS). OBJECTIVES: The objective of this review was to assess the effects of immunomodulatory drugs compared to placebo in adults in preventing conversion from CIS to CDMS which means the prevention of a second attack. SEARCH STRATEGY: We searched the Cochrane MS Group Trials Register (June 2007), Cochrane Central Register of Controlled Trials (CENTRAL)The Cochrane Library Issue 3, 2007, MEDLINE (January 1966 to June 2007), EMBASE (January 1974 to June 2007) and reference lists of articles. We also contacted manufacturers and researchers in the field. SELECTION CRITERIA: The trials selected were double-blind, placebo-controlled, randomised trials of CIS patients treated with immunomodulatory drugs. DATA COLLECTION AND ANALYSIS: Study selection have been independently done by two reviewers. Two further reviewers independently assessed trial quality and extracted and analysed data. Study authors were contacted for additional informations. Adverse effects information was collected from the trials. MAIN RESULTS: Only three trials tested the efficacy of interferon (IFN) beta including a total of 1160 participants (639 treatment, 521 placebo); no trial tested the efficacy of glatiramer acetate (GA). The metanalyses showed that the proportion of patients converting to CDMS was significantly lower in IFN beta-treated than in placebo-treated patients both after one year (pooled OR 0.53; 95% CI, 0.40 to 0.71; p <0.0001) as well as after two years of follow-up (pooled OR 0.52; 95% CI, 0.38 to 0.70; p <0.0001). Early treatment with IFN beta was associated with the side effect profile reported by the randomised controlled trials with this drug. Since side effects were reported with some heterogeneity in the three studies the metanalysis was possible only for the frequency of serious adverse events, not significantly different in IFN beta-treated or placebo-treated patients. AUTHORS' CONCLUSIONS: The efficacy of IFN beta treatment on preventing the conversion from CIS to CDMS was confirmed over two years of follow-up. Since patients had some clinical heterogeneity (length of follow-up, clinical findings of initial attack), it could be useful for the clinical practice to further analyse the efficacy of IFN beta treatment in different patient subgroups.
Assuntos
Imunossupressores/uso terapêutico , Interferon Tipo I/uso terapêutico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla/prevenção & controle , Peptídeos/uso terapêutico , Acetato de Glatiramer , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Proteínas RecombinantesRESUMO
Thyroid dysfunction and autoimmunity have been reported during type I interferon therapy, namely interferon-alpha for chronic hepatitis or interferon-beta for multiple sclerosis. To define the frequency of thyroid dysfunction and autoimmunity during interferon-beta treatment, 156 multiple sclerosis patients were prospectively followed up by 18 centers for 1 yr after starting interferon-beta-1b treatment. Serial clinical assessments and tests of thyroid and liver function and antithyroid autoantibodies (all performed by the same centralized laboratory) were conducted every 3 months. TSH and antithyroid autoantibodies against human TG or thyroid microsomal antigens were measured by immunoradiometric methods; free T3 and T4 were measured by chromatographic assays. Longitudinal occurrence of thyroid or liver alterations or of autoantibodies was analyzed with the generalized estimating equations method, correcting for the correlation of repeated measurements of the same subject over time. Pretreatment comparison with a control group of 437 healthy blood donors did not show significant differences in the frequency of thyroid dysfunction or antithyroid autoantibody positivity. During interferon-beta treatment, the de novo frequency of thyroid alteration was 8.3%, that of liver alteration was 37.5%, and that of antithyroid autoantibody was 4.5%. Generalized estimating equations analysis demonstrated that the frequency of liver alteration significantly increased during treatment compared with the baseline value (odds ratio, 7.03; confidence interval, 2.49-19.9), whereas that of thyroid alteration or of antithyroid autoantibodies did not. The frequency of thyroid dysfunction during interferon-beta treatment showed random, nonsignificant changes over time and, in addition, was not correlated to antithyroid autoantibody positivity.
Assuntos
Autoanticorpos/sangue , Interferon beta/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/fisiopatologia , Glândula Tireoide/efeitos dos fármacos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Interferon beta-1a , Interferon beta-1b , Itália , Testes de Função Hepática , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/imunologia , Proteínas Recombinantes/uso terapêutico , Valores de Referência , Doenças da Glândula Tireoide/genética , Doenças da Glândula Tireoide/imunologia , Testes de Função Tireóidea , Glândula Tireoide/imunologia , Tireotropina/sangue , Tiroxina/sangue , Fatores de Tempo , Tri-Iodotironina/sangueRESUMO
Three patients with dystrophia myotonica and echocardiographic signs of subclinical cardiopathy had cardiac side effects during oral treatment with phenytoin sodium or carbamazepine. These side effects were dose related: ventricular tachycardia appeared at a toxic serum phenytoin level in one patient and disappeared as the concentration fell within the therapeutic range, and atrioventricular block grade 1 developed in two patients at low serum carbamazepine levels, its severity increasing with the drug level. Given the risk of dangerous side effects, cardiac status needs to be carefully assessed before administration of phenytoin or carbamazepine in the treatment of dystrophia myotonica.
Assuntos
Carbamazepina/efeitos adversos , Bloqueio Cardíaco/induzido quimicamente , Fenitoína/efeitos adversos , Taquicardia/induzido quimicamente , Adulto , Carbamazepina/sangue , Carbamazepina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenitoína/sangue , Fenitoína/uso terapêuticoRESUMO
Autoimmune side effects, namely autoantibody (autoAb) occurrence and thyroid function alteration, have been described during interferon-beta (IFN-beta) treatment for multiple sclerosis (MS). AutoAb occurrence and autoimmune thyroid diseases are also frequently detected in MS patients free of any treatment. The aim of this study was to evaluate the relationship between IFN-beta 1b treatment, autoAb occurrence, and autoimmune diseases in MS. Thyroid and liver function and serum autoAb (antithyroid, antinuclear, anti-liver, anti-kidney microsomes, anti-smooth muscle and parietal cell antigens) occurrence were evaluated in 156 relapsing-remitting MS (RRMS) patients before and every 3 months after starting IFN-beta 1b treatment (8 MIU subcutaneously [s.c.] on alternate days). The probability of having liver or thyroid function alteration or autoAb occurrence was analyzed longitudinally with the generalized estimating equations (GEE) approach. At baseline, 16.1% of patients had autoAb. During treatment, autoAb occurred de novo in 7.2% of patients. GEE analysis showed that the probability of having autoAb at any time during IFN-beta 1b treatment did not change significantly compared with baseline. AutoAb occurring de novo rarely persisted during treatment and significantly less than those already present at baseline. Positivity for autoAb at baseline or during treatment was not correlated with the development of thyroid or liver function alteration during IFN-beta 1b treatment. Our study indicates that IFN-beta treatment is a safe treatment for MS patients, free of risk of autoimmunity and of associated liver or thyroid function alteration.
Assuntos
Autoanticorpos/sangue , Autoanticorpos/efeitos dos fármacos , Doenças Autoimunes/imunologia , Interferon beta/efeitos adversos , Interferon beta/uso terapêutico , Esclerose Múltipla/sangue , Esclerose Múltipla/tratamento farmacológico , Adjuvantes Imunológicos/efeitos adversos , Adjuvantes Imunológicos/uso terapêutico , Adolescente , Adulto , Idade de Início , Autoanticorpos/biossíntese , Feminino , Seguimentos , Humanos , Interferon beta-1a , Interferon beta-1b , Hepatopatias/epidemiologia , Hepatopatias/imunologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/epidemiologia , Estudos Prospectivos , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Valores de ReferênciaRESUMO
A double-blind, single crossover study of chronic oral taurine administration versus placebo was conducted on nine patients with dystrophia myotonica. The severity of myotonia was assessed by clinical and electromyographic criteria and by testing the sensitivity of myotonic muscles to the intra-arterial infusion of potassium chloride. Confirming the antimyotonic effect of acute parenteral taurine, chronic treatment induced significant improvement of myotonia and a decreased sensitivity to the arterial potassium load as well as an enhancement of electrolyte movements across the membrane of the studied muscles. No significant side effects were noted.
Assuntos
Miotonia/tratamento farmacológico , Taurina/administração & dosagem , Administração Oral , Ensaios Clínicos como Assunto , Método Duplo-Cego , Eletromiografia , Feminino , Humanos , Injeções Intra-Arteriais , Masculino , Miotonia/fisiopatologia , Cloreto de Potássio/administração & dosagem , Cloreto de Potássio/uso terapêutico , Taurina/uso terapêuticoRESUMO
Total body irradiation (TBI) produces prolonged immunosuppression with rare side effects. We studied 12 thymectomized patients affected with chronic generalized severe myasthenia gravis. All patients had been totally or partially refractory to prolonged oral treatment with immunosuppressive drugs, and most had contra-indications for these drugs. Low-dose (1.8- to 2.3-Gy total dose) TBI was administered in single, 0.1-Gy doses, two to three times per week. TBI was well tolerated and was associated with objective clinical improvement in six patients, lasting more than 2 years in five. In addition, TBI produced a long-lasting lymphopenia with a pronounced decrease of T CD4+ lymphocytes; T CD8+ lymphocytes were almost unchanged over the 2 years of the study. CD16+ and CD20+ lymphocytes, after an initial decrease, increased above baseline. TBI was also associated with decreased anti-AChR antibody titer. The decrease of lymphocyte count and of anti-AChR antibody titer was more pronounced in the patients who improved, suggesting that lymphopenia and immunosuppression may have contributed to clinical improvement.
Assuntos
Miastenia Gravis/radioterapia , Irradiação Corporal Total , Adulto , Idoso , Autoanticorpos/sangue , Feminino , Imunofluorescência , Seguimentos , Humanos , Contagem de Leucócitos/efeitos da radiação , Subpopulações de Linfócitos/efeitos da radiação , Linfócitos/efeitos da radiação , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/imunologia , Receptores Colinérgicos/imunologia , Fatores de Tempo , Irradiação Corporal Total/efeitos adversosRESUMO
BACKGROUND: The occurrence or recurrence of autoimmune diseases or of autoantibodies (autoAb) has been reported during type I interferon (IFN) treatment. OBJECTIVE: To define the frequency of thyroid and liver dysfunction and of autoimmunity during IFN-beta 1b (IFNB) treatment of MS. METHODS: Prospective 1-year multicenter follow-up of 156 patients with MS recruited by 18 centers was conducted. Thyroid-stimulating hormone and anti-thyroid autoAb were measured by an immunoradiometric method, thyroid hormones by chromatographic assay, and non-organ-specific autoAb by indirect immunofluorescence. Tests were repeated every 3 months. The probability of having liver, thyroid, or autoAb alterations was analyzed longitudinally with the generalized estimating equations (GEE) method. RESULTS: Thyroid dysfunction was observed in 5.3% of cases at baseline and 8.3% de novo during IFNB treatment. GEE analysis showed that the probability of having thyroid alteration did not change significantly during treatment compared with baseline. Liver alteration was observed in 4.6% of cases at baseline and 37.5% de novo during IFNB treatment (p < 0.0001). GEE analysis showed that the probability of having liver alteration was higher (p < 0.002) at months 3 and 6 compared with baseline, returning to values similar to baseline by month 9. AutoAb were detected in 16.1% of patients at baseline and in 20% during IFNB. GEE analysis showed that the probability of having autoAb did not change significantly during treatment compared with baseline. Thyroid or liver alteration or autoAb occurring de novo during IFNB were usually transient. CONCLUSIONS: Differently from the frequency of liver function alteration (which significantly increased during the first months of IFNB treatment, suggesting a probable causal relationship with IFNB), the frequency of thyroid dysfunction or of autoimmunity showed random and insignificant changes over time, probably not related to IFNB treatment.
Assuntos
Adjuvantes Imunológicos/administração & dosagem , Interferon beta/administração & dosagem , Fígado/imunologia , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/imunologia , Glândula Tireoide/imunologia , Adolescente , Adulto , Autoanticorpos/sangue , Feminino , Humanos , Hipertireoidismo/imunologia , Hipotireoidismo/imunologia , Interferon beta-1a , Interferon beta-1b , Testes de Função Hepática , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Testes de Função Tireóidea , Tireotropina/sangueRESUMO
We conducted a double-blind trial of high-dose parenteral 6-methylprednisolone (MP) and placebo on 23 patients with acute MS. After the double-blind trial, the patients were given corticosteroids in gradually decreasing doses. The frequency of improvement was significantly higher and the bout duration significantly lower in the MP group than in the placebo group. The first signs of improvement (3 to 6 days after starting MP) were associated with a marked decrease in the rate of CNS IgG synthesis, but IgG CSF oligoclonal bands did not change. CNS IgG production slowly returned toward baseline despite progressive clinical improvement.
Assuntos
Metilprednisolona/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Adulto , Idoso , Albuminas/líquido cefalorraquidiano , Albuminas/imunologia , Ensaios Clínicos como Assunto , Método Duplo-Cego , Feminino , Humanos , Imunoglobulina G/biossíntese , Imunoglobulina G/líquido cefalorraquidiano , Imunoglobulina G/imunologia , Infusões Parenterais , Masculino , Metilprednisolona/administração & dosagem , Metilprednisolona/efeitos adversos , Pessoa de Meia-Idade , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Distribuição Aleatória , Albumina Sérica/imunologia , Fatores de TempoRESUMO
We report a randomized, double-blind, placebo-controlled pilot trial of systemic high-dose recombinant interferon alfa-2a (rIFNA) in 20 patients with relapsing-remitting (RR) multiple sclerosis (MS). Patients received 9 million IU rIFNA (n = 12) or placebo (n = 8) intramuscularly every other day for 6 months. Clinical exacerbations or new or enlarging lesions on serial MRI occurred in two of 12 rIFNA-treated and in seven of eight placebo-treated patients (p < 0.005). There was only one enlarging MRI lesion in the rIFNA group, whereas 27 new or enlarging lesions were present in the placebo group (p < 0.01). Baseline lymphocyte interferon gamma production of 19.10 +/- 7.12 IU/ml significantly decreased to 3.03 +/- 0.66 IU/ml (p < 0.04) in the rIFNA group, whereas production was unchanged in the placebo group. The rIFNA was tolerated without dropouts or serious side effects, but fever, malaise, fatigue (interfering with daily activities in two patients), and leukopenia occurred frequently. Neuropsychological tests excluded neurotoxicity. High-dose systemic rIFNA might reduce clinical and MRI signs of disease activity in RR MS and should be investigated in larger trials.
Assuntos
Interferon-alfa/administração & dosagem , Interferon gama/biossíntese , Linfócitos/imunologia , Esclerose Múltipla/tratamento farmacológico , Adolescente , Adulto , Método Duplo-Cego , Feminino , Humanos , Interferon alfa-2 , Interferon-alfa/efeitos adversos , Ativação Linfocitária/efeitos dos fármacos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/imunologia , Esclerose Múltipla/patologia , Proteínas Recombinantes , RecidivaRESUMO
We evaluated the long-lasting effects of systemic high-dose recombinant interferon alpha-2a (rIFNA) in relapsing-remitting (RR) MS after discontinuing treatment in a single-blind randomized placebo-controlled trial with 20 RR clinically definite MS patients using either nine million IU intramuscular rIFNA (n = 12) or placebo (n = 8) every other day for 6 months. Follow-up continued for a further 6 months without IFN treatment. In rIFNA-treated patients, main outcome measures, significantly different from placebo during treatment, returned, after discontinuing treatment, to values similar to placebo or baseline. Active MRI lesions per patient increased from 0.08 +/- 0.08 to 1.2 +/- 0.4 (p < 0.02), number of patients with clinical MRI signs of disease activity from 2 of 12 to 8 to 12 (P < 0.04), lymphocyte IFN gamma production from 3.0 +/- 0.7 to 12.4 +/- 2.2 IU/mL (p < 0.01), lymphocyte tumor necrosis factor alpha production from 5.8 +/- 0.9 to 18.9 +/- 6.3 pg/mL (p < 0.05). All side effects of rIFNA treatment disappeared after discontinuing the drug. The reduction of clinical MRI signs of disease activity and the immunologic effects were temporary and restricted to the period of rIFNA administration. The depression of many immunologic and clinical MRI responses during drug administration and their simultaneous return to baseline after discontinuing the drug strongly argue all observed changes were related to drug administration.
Assuntos
Interferon-alfa/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Adulto , Feminino , Humanos , Interferon alfa-2 , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/patologia , Esclerose Múltipla/fisiopatologia , Estudos Prospectivos , Proteínas Recombinantes , Recidiva , Método Simples-CegoRESUMO
Plasma levels of carbamazepine, phenytoin and phenobarbital were monitored weekly over a period of 9 weeks in 20 epileptic patients unresponsive to treatment. No attempts were made to modify phenytoin and/or phenobarbital plasma levels; emphasis was on achieving carbamazepine plasma levels of 4 to 10 mug per milliliter. A remarkable drop in seizure frequency was attained within 2 to 3 weeks of monitoring, with carbamazepine plasma and concentrations within the desired range. Children disposed of the drug faster than adults. No effects of phenytoin and phenobarbital on carbamazepine plasma levels could be observed, while phenobarbital on carbamazepine plasma levels fluctuated remarkably without any relationship to carbamazepine levels. Transient leukopenia was present in most of the patients, while a significant reversible drop in red blood cells was observed in eight patients. The data reported confirm that with a careful monitoring of drug plasma levels, carbamazepine may exert a definite passive effect on seizure frequency in epileptic patients poorly responsive to therapy.
Assuntos
Carbamazepina/sangue , Epilepsia/tratamento farmacológico , Adulto , Fatores Etários , Carbamazepina/efeitos adversos , Carbamazepina/uso terapêutico , Criança , Quimioterapia Combinada , Eletroencefalografia , Epilepsia/fisiopatologia , Humanos , Masculino , Fenobarbital/uso terapêutico , Fenitoína/uso terapêuticoRESUMO
Using simultaneous dual direct immunofluorescence the effect of high dose intravenous methylprednisolone on the expression of T lymphocyte differentiation antigens in paired cerebrospinal fluid and peripheral blood samples of nine clinically active patients with multiple sclerosis was studied. Corticosteroid treatment was associated with a clinical improvement in eight out of the nine patients. In cerebrospinal fluid of all patients the treatment was associated with a decrease of CD3+, CD4+ and CD8+ T cells, and of intra-central nervous system IgG synthesis. CD8+ high CD11b+ low suppressor-effector T cells behaved differently in the eight patients who improved with treatment, where they significantly increased, and in the patient without clinical response, where they were almost unchanged. Similar phenotypic changes were found in peripheral blood, and all changes returned towards baseline after treatment. The lower sensitivity to corticosteroids of CD8+ high CD11b+ low T cells could change the balance between immunoregulatory T subsets. In this study the increased availability of a subpopulation mainly composed of T cells with a suppressor-effector function was associated with a clinical response to treatment.
Assuntos
Corticosteroides/uso terapêutico , Antígenos CD/análise , Antígenos de Diferenciação de Linfócitos T/análise , Antígeno de Macrófago 1/análise , Esclerose Múltipla/imunologia , Linfócitos T/imunologia , Adulto , Antígenos CD8 , Humanos , Imunoglobulinas/biossíntese , Pessoa de Meia-Idade , Esclerose Múltipla/líquido cefalorraquidiano , Esclerose Múltipla/tratamento farmacológico , Subpopulações de Linfócitos T/imunologiaRESUMO
In cats affected with cortical epileptogenic foci induced by penicillin application to and cobalt implantation into the pericruciate area, the brain amino acids contents were determined in the focus as well as in extrafocal areas. In different groups of animals, brain removal for biochemical determinations was performed at different times before, during and after epilepsy and the values compared to controls. The only amino acid to show a significant change before appearance of spikes in both types of epilepsy was taurine, which decreased. Cobalt epilepsy was accompanied by changes in a larger number of amino acids than penicillin epilepsy: in the former the brain content of taurine, GABA, aspartate, glutamate, serine, threonine, glycine and alanine was altered. The changes were proportional to the severity of epilepsy and more prominent in the focus area. After disappearance of spikes the levels of most amino acids returned to normal except for some amino acids, previously unaffected by penicillin epilepsy, which were decreased. It is proposed that the decrease in brain taurine, occurring before the appearance of penicillin and cobalt epilepsy, could increase the excitability of a certain neuronal population and thus, by potentiating the effects on neurons of penicillin and cobalt, contribute to the initiation of epilepsy.
Assuntos
Aminoácidos/metabolismo , Córtex Cerebral/metabolismo , Convulsões/metabolismo , Animais , Gatos , Cobalto , Penicilina G , Convulsões/induzido quimicamente , Taurina/metabolismo , Ácido gama-Aminobutírico/metabolismoRESUMO
A woman, aged 30, experienced attacks of pathological laughter which began during the first months of life; they meet the qualifying criteria of epileptic laughter. Several attacks were recorded by polygraphy and cinefilm. The attack begins with a feeling of unreality associated with a forced, involuntary smile progressing to full laughter. The patient tried to mask the laughter which was not accompanied by euphoria but was followed by loss of consciousness and automatisms. Only during the latter phase of the previously normal EEG did an ictal discharge appear over the right hemisphere. On the basis of the electroclinical pattern and of a review of the literature, the seizure is tentatively explained in terms of a progressive ictal involvement of temporodiencephalic structures.
Assuntos
Epilepsia/diagnóstico , Riso , Adulto , Eletroencefalografia , Feminino , Humanos , SíndromeRESUMO
A patient, suffering from an oat-cell bronchial carcinoma, presented with complex partial seizures, complete loss of recent memory, mild disorientation and confabulation. There was no complaint of anxiety. The rest of the neurological examination and four computed tomographic scans of the head were normal. Repeated EEG recordings were abnormal. Antiepileptic and antipsychotic treatment led to full remission within 10 days. Post-mortem examination of the brain revealed no pathological changes.
Assuntos
Carcinoma Broncogênico/diagnóstico , Encefalite/patologia , Sistema Límbico , Neoplasias Pulmonares/diagnóstico , Carcinoma Broncogênico/complicações , Encefalite/complicações , Feminino , Humanos , Sistema Límbico/patologia , Neoplasias Pulmonares/complicações , Pessoa de Meia-Idade , SíndromeRESUMO
The effect of taurine administration upon potassium-induced muscular hyperexcitability was studied in patients affected with dystrophic myotonia and in normal volunteers. Intra-arterial infusions of increasing concentrations of potassium chloride were given and venous potassium levels simultaneously monitored. Taurine prevented or remarkably reduced the electric signs of muscular hyperexcitability. Potassium chloride and taurine effects upon muscular excitability are discussed in terms of changes of membrane conductance, particularly for potassium ions.
Assuntos
Músculos/fisiopatologia , Distrofia Miotônica/tratamento farmacológico , Potássio , Taurina/uso terapêutico , Potenciais de Ação , Permeabilidade da Membrana Celular , Humanos , Distrofia Miotônica/fisiopatologiaRESUMO
Progressively increasing concentrations of potassium chloride were administered intra-arterially to patients affected with dystrophia myotonica (Steinert's disease) and to healthy volunteers before and after parenteral taurine treatment. Changes in the excitability of thenar eminence muscles were related to plasma potassium concentrations. A rise in the plasma potassium brought about a parallel increase of muscular excitability in normal individuals whilst in dystrophic myotonic patients it was associated with a two-phase phenomenon: the severity of myotonia first decreased and then, at higher plasma potassium levels, greatly worsened with the occurrence of spontaneous myotonic discharges. The administration of taurine, a membrane-stabilizing drug, considerably lowered the excitability of both normal and dystrophic myotonic muscles. The effects of potassium and taurine on muscular membrane conductance may explain the observed changes in muscular excitability.
Assuntos
Músculos/fisiopatologia , Distrofia Miotônica/fisiopatologia , Cloreto de Potássio , Permeabilidade da Membrana Celular , Humanos , Injeções Intra-Arteriais , Distrofia Miotônica/tratamento farmacológico , Potássio/metabolismo , Cloreto de Potássio/administração & dosagem , Sarcolema/fisiologia , Taurina/uso terapêuticoRESUMO
The evaluation of an antimyotonic drug is often difficult since the severity of myotonia is itself hard to assess. The rise in arterial potassium level produced by the infusion of increasing concentrations of potassium chloride brought about reproducible changes in the excitability level of myotonic muscles proportional to the plasma potassium concentration. The excitability changes were assessed by three methods commonly used for evaluating antimyotonic drugs. The duration of the electromyographic relaxation time after maximal voluntary effort proved to be the only test which reliably assessed the variations of muscular excitability proportional to the increased plasma potassium. By contrast, the duration of percussion- or electrically-induced myotonic after-discharges was extremely variable and independent of plasma potassium.