RESUMEN
BACKGROUND: Charcot-Marie-Tooth type 1A (CMT1A) is an autosomal dominant polyneuropathy due to a 1.5 Mb tandem duplication in chromosome 17p11.2, containing the PMP22 gene. This mutation is not modified during inheritance. OBJECTIVES: We set forth to test the hypothesis that in a subgroup of CMT1A patients there is clinical anticipation, namely an increase in disease severity over generations. METHODS: Thirty-nine CMT1A mutation-positive patients in 16 families and 23 parent-offspring pairs were evaluated. This included 14 families with 2 generations and 2 families with 3 generations. Age of presentation was assessed by interviewing the patients and clinical severity was measured using the CMT neuropathy score (CMTNS). RESULTS: In 21/23 parent-child pairs and 14/16 families, there was an earlier age of presentation in children of genetically affected parents. The mean age of onset in the progeny was 12.61 years compared to 41.22 years in the parent generation, (p < 0.001). Mean severity in the younger generation was slightly higher than that of the parent generation. When corrected for the age difference, the trend for a worse phenotype in the younger generation became statistically significant (p < 0.02,Wilcoxon signed rank test). CONCLUSIONS: Our findings suggest that in a subgroup of CMT1A patients there is an increase in clinical severity over generations. The mechanism responsible for this observation remains unknown. Our findings should be validated on a larger cohort of CMT1A families.
Asunto(s)
Anticipación Genética , Enfermedad de Charcot-Marie-Tooth/genética , Enfermedad de Charcot-Marie-Tooth/fisiopatología , Predisposición Genética a la Enfermedad/genética , Mutación/genética , Proteínas de la Mielina/genética , Adolescente , Adulto , Factores de Edad , Edad de Inicio , Anciano , Anciano de 80 o más Años , Enfermedad de Charcot-Marie-Tooth/etnología , Niño , Cromosomas Humanos Par 17/genética , Estudios de Cohortes , Análisis Mutacional de ADN , Evaluación de la Discapacidad , Etnicidad/genética , Familia , Femenino , Marcadores Genéticos/genética , Predisposición Genética a la Enfermedad/etnología , Pruebas Genéticas , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Nervios Periféricos/metabolismo , Nervios Periféricos/fisiopatología , Fenotipo , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVE: Since cardiac surgery is now performed on patients with high risk for cerebrovascular disease, we studied the clinical findings and medium term outcome of patients with acute stroke/transient ischemic attack (TIA) after cardiac surgery. METHODS: All consecutive patients with acute stroke/TIA after cardiac surgery were prospectively observed during a 19 month period. Follow-up was between 3 months and 21 months. Risk factors, type of stroke, anatomic localization, initial neurological deficit and followup outcome were evaluated, using standard assessment scores. RESULTS: Among 406 patients operated (mean age 64.3 +/- 12.7 years, 284 males), 18 developed stroke and 2 TIAs (mean age 65.7 years, 13 males). There were no cases of intracerebral hemorrhage. Most of the strokes happened shortly after valve surgery (mean 1.3 days post operatively) and were right hemispheric (right = 11, left = 3; p = 0.034). Vertebrobasilar stroke appearance was delayed (mean: 8.25 days post operatively); they were attributed mostly to cardiac arrhythmias. Stroke/TIA patients did not have a higher preoperative risk than those without, but their cardiac functional score was worse (p = 0.01), and the average cardiopulmonary bypass time during surgery was longer (p = 0.009). Two patients died in hospital, both with vertebrobasilar stroke. Most of the hemispheric stroke patients became functionally independent (mean modified Rankin Scale < 2), even those with initial severe deficit. CONCLUSION: Strokes after cardiac surgery are mostly right hemispheric and exclusively ischemic. Outcome is relatively fair. We suggest an embolic injury to the right hemisphere, procedure related, as a possible mechanism.
Asunto(s)
Procedimientos Quirúrgicos Cardíacos/efectos adversos , Lateralidad Funcional , Ataque Isquémico Transitorio/etiología , Complicaciones Posoperatorias , Accidente Cerebrovascular/etiología , Anciano , Femenino , Cardiopatías/cirugía , Humanos , Ataque Isquémico Transitorio/epidemiología , Ataque Isquémico Transitorio/patología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Observación , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Factores de TiempoAsunto(s)
Esclerosis Amiotrófica Lateral/inmunología , Autoanticuerpos/sangre , Gangliósido G(M1)/inmunología , Anciano , Esclerosis Amiotrófica Lateral/genética , Especificidad de Anticuerpos , Autoanticuerpos/biosíntesis , Autoanticuerpos/inmunología , Progresión de la Enfermedad , Femenino , Humanos , Inmunoglobulina M/sangre , Inmunoglobulina M/inmunología , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
We prospectively evaluated herpes zoster patients during the acute phase of the disease for central nervous system involvement. Of 24 patients with spinal zoster, 13 (54%) had spinal cord abnormality, which was asymptomatic in 12 of the 13. Age but not lack of acyclovir treatment was associated with such involvement. In all but 2, neurological involvement resolved within 6 months. Although the mechanism responsible for the neurological abnormalities is unknown, findings may support the hypothesis that zoster is associated with spread of viral infection into the spinal cord and therefore support the possibility that zoster is due to active viral replication in the ganglion.
Asunto(s)
Tronco Encefálico/inmunología , Herpes Zóster/fisiopatología , Médula Espinal/anomalías , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Ganglios Espinales/inmunología , Herpes Zóster/inmunología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Médula Espinal/inmunologíaRESUMEN
BACKGROUND: Acute disseminated encephalomyelitis (ADEM) is a usually monophasic demyelinating disorder of the central nervous system. Recurrences pose a diagnostic challenge because they can be overlooked or suggest an alternative diagnosis. OBJECTIVE: To examine the frequency, nature, and outcome of recurrent ADEM. DESIGN: Review of the medical records of patients diagnosed in our institution as having ADEM between January 1, 1983, and May 31, 1998. Recurrences were defined as appearance of new symptoms and signs at least 1 month after the previous episode. RESULTS: Five (24%) of 21 patients with ADEM developed recurrent disease episodes. In all, diagnosis was confirmed by brain biopsy. One patient had 4 disease episodes, 2 had 3, and the other 2 each had 2. Recurrence appeared 1.5 to 32 months after initial presentation and involved the same brain territory in 6 of 9 recurrences in 3 of 5 patients. In 2 patients, recurrences included neuropsychiatric signs. A good response to corticosteroid therapy was observed in 10 of 13 of treated ADEM attacks: in 3 of the 4 treated initial events and in 7 of 9 recurrences. CONCLUSIONS: Recurrent ADEM may be more prevalent than previously recognized. Patients who relapse tend to have more than 1 recurrence that usually involves, clinically and radiologically, a brain territory that was affected before and can simulate a space-occupying lesion that requires histologic diagnosis. Neuropsychiatric features may be the main presentation of a relapse. Since recurrent ADEM is a corticosteroid-responsive condition, awareness and early diagnosis are mandatory.