RESUMO
Remyelination, albeit incomplete, has been demonstrated in human central nervous system (CNS). However, information about the initial stage and the final extent of such remyelination is not available. We describe the morphologic findings of a demyelinating lesion with evidence of early remyelination in a biopsy obtained from a 15-year-old boy about two weeks after the onset of neurologic symptoms. The demyelinated area appeared hypercellular with a relatively large number of oligodendrocytes frequently seen in the process of new myelin formation. In addition to the usual reactive changes, the astrocytes were often seen to contain otherwise normal-looking oligodendrocytes within their cytoplasm. In the ensuing months, the patient made apparently total functional recovery accompanied by nearly complete resolution of the white matter lesions demonstrated by the subsequent magnetic resonance studies. These observations suggested that the initial remyelination seen in the biopsy eventually succeeded in producing extensive remyelination in the lesion. Although the exact nature of the demyelinating disorder in our patient remains undetermined, this study indicates that clinically significant remyelination is possible in human CNS. Also, our findings appeared strikingly similar to those described in certain experimental animal models in which widespread remyelination is known to occur.
Assuntos
Encéfalo/crescimento & desenvolvimento , Doenças Desmielinizantes/fisiopatologia , Bainha de Mielina/fisiologia , Adolescente , Biópsia por Agulha , Encéfalo/patologia , Doenças Desmielinizantes/diagnóstico , Doenças Desmielinizantes/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Bainha de Mielina/ultraestruturaRESUMO
OBJECTIVES: To determine whether intra-abdominal pressure (as estimated from urinary bladder pressure) is elevated in patients with central obesity (as measured by sagittal abdominal diameter) and pseudotumor cerebri and whether this increased intra-abdominal pressure is associated with increased pleural pressure and cardiac filling pressure, implying a resistance to venous return from the brain. DESIGN: Nonrandomized, prospective. SETTING: University hospital, operating room. MAIN OUTCOME MEASUREMENTS: Intracranial pressure, urinary bladder pressure, sagittal abdominal diameter, transesophageal pleural pressure, central venous pressure, pulmonary artery pressure, and pulmonary artery occlusion pressure. SUBJECTS: Six women with pseudotumor cerebri (one with CSF leak, one with lumboperitoneal shunt). RESULTS: Urinary bladder pressure (22 +/- 3 cm H2O) and sagittal abdominal diameter (29 +/- 3 cm) were significantly elevated in these patients with elevated intracranial pressure (293 +/- 80 mm H2O) compared with a previously reported group of nonobese control patients. The transesophageal pleural pressure (15 +/- 10 mm Hg), central venous pressure (20 +/- 6 mm Hg), mean pulmonary artery pressure (31 +/- 6 mm Hg), and pulmonary artery occlusion pressure (21 +/- 7 mm Hg) were all markedly elevated compared with published normal values and with previous data from obese patients without pseudotumor cerebri. CONCLUSIONS: These data support the hypothesis that central obesity raises intra-abdominal pressure, which increases pleural pressure and cardiac filling pressure, which impede venous return from the brain, leading to increased intracranial venous pressure and increased intracranial pressure associated with pseudotumor cerebri.
Assuntos
Abdome/fisiopatologia , Circulação Coronária , Coração/fisiopatologia , Obesidade/complicações , Pseudotumor Cerebral/etiologia , Pseudotumor Cerebral/fisiopatologia , Adulto , Feminino , Derivação Gástrica , Cefaleia/etiologia , Humanos , Obesidade/cirurgia , Pressão , Estudos Prospectivos , Zumbido/etiologiaRESUMO
BACKGROUND: The effect on CSF pressures and symptoms of weight loss induced by gastric surgery was studied in morbidly obese patients with idiopathic intracranial hypertension (IIH). METHODS: Gastric weight reduction surgery was performed in eight morbidly obese women (49 +/- 3 kg/m2 body mass index) who had IIH and elevated CSF pressures. Each had been treated medically for IIH. Two had ventriculoperitoneal shunts, with occlusion in both and hemorrhage and hemiparesis in one. Post--weight-reduction measurement of CSF pressures, signs and symptoms of IIH, and obesity co-morbidity were evaluated. RESULTS: CSF pressures decreased in all eight patients, from a mean of 353 +/- 35 to a mean of 168 +/- 12 mm H2O (p < 0.001), following mean weight loss of 57 +/- 5 kg (p < 0.001) when measured at 34 +/- 8 months after surgery. At follow-up no patient had papilledema, all eight patients had resolution or marked reduction of headache, and resolution of tinnitus occurred in all six patients with this symptom. Neuroimaging was unchanged at 27 +/- 6 months after surgery in six patients. There was also resolution or clinical improvement of additional obesity-related co-morbidity, including diabetes, hypertension, sleep apnea, obesity hypoventilation, joint pains, stress urinary incontinence, and gastroesophageal reflux. CONCLUSIONS: Although several complications occurred following obesity surgery over the 11 years of this study, the current low morbidity and mortality with gastric bypass make this a primary option in the severely obese patient with IIH.
Assuntos
Obesidade Mórbida/cirurgia , Pseudotumor Cerebral/fisiopatologia , Redução de Peso , Adulto , Feminino , Humanos , Pressão Intracraniana/fisiologia , Obesidade Mórbida/fisiopatologiaAssuntos
Síndrome de Hipoventilação por Obesidade/diagnóstico , Obesidade Mórbida/cirurgia , Papiledema/diagnóstico , Redução de Peso , Feminino , Humanos , Pessoa de Meia-Idade , Síndrome de Hipoventilação por Obesidade/complicações , Obesidade Mórbida/dietoterapia , Pseudotumor Cerebral/diagnósticoRESUMO
OBJECTIVE: To assess the safety, tolerability, and efficacy of interferon beta-1a (IFNbeta-1a) combined with methotrexate (MTX), i.v. methylprednisolone (IVMP), or both in patients with relapsing-remitting multiple sclerosis (RRMS) with continued disease activity on IFNbeta-1a monotherapy. METHODS: Eligibility criteria included RRMS, Expanded Disability Status Scale score 0-5.5, and > or = 1 relapse or gadolinium-enhancing MRI lesion in the prior year on IFNbeta-1a monotherapy. Participants continued weekly IFNbeta-1a 30 microg i.m. and were randomized in a 2 x 2 factorial design to adjunctive weekly placebo or MTX 20 mg p.o., with or without bimonthly IVMP 1,000 mg/day for 3 days. The primary endpoint was new or enlarged T2 lesion number at month 12 vs baseline. The study was industry-supported, collaboratively designed, and governed by an investigator Steering Committee with independent Advisory and Data Safety Monitoring committees. Study operations, MRI analyses, and aggregated data were managed by an academic coordinating center. RESULTS: The 313 participants had clinical and MRI characteristics typical of RRMS. Combinations of IFNbeta-1a with MTX or IVMP were generally safe and well tolerated. Although trends suggesting modest benefit were seen for some outcomes for IVMP, the results did not demonstrate significant benefit for either adjunctive therapy. The data suggested IVMP reduced anti-IFNbeta neutralizing antibody titers. CONCLUSIONS: This trial did not demonstrate benefit of adding low-dose oral methotrexate or every other month IV methylprednisolone to interferon beta-1a in relapsing-remitting multiple sclerosis.
Assuntos
Adjuvantes Imunológicos/administração & dosagem , Interferon beta/administração & dosagem , Metotrexato/administração & dosagem , Metilprednisolona/administração & dosagem , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Adolescente , Adulto , Anti-Inflamatórios/administração & dosagem , Comportamento Cooperativo , Interpretação Estatística de Dados , Avaliação da Deficiência , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/administração & dosagem , Interferon beta-1a , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/patologia , Seleção de Pacientes , Resultado do TratamentoRESUMO
OBJECTIVE: To review the rationale, design and baseline data of the Avonex Combination Trial (ACT), an investigator-run study of intramuscular interferon beta-1a (IM IFNbeta-1a) combined with methotrexate (MTX) and/or IV methylprednisolone (IVMP) in relapsing-remitting multiple sclerosis (RRMS) patients with continued disease activity on IM IFNbeta-1a monotherapy. METHODS: Eligibility criteria included RRMS, Expanded Disability Status Scale score 0-5.5, and >or=1 relapse or gadolinium-enhancing MRI lesion in the prior year while on IM IFNbeta-1a monotherapy. Subjects continued IFNbeta-1a 30 mcg IM weekly and were randomized in a 2 x 2 factorial design to adjunctive weekly placebo or MTX 20 mg PO, with or without IVMP 1,000 mg/day for three days every other month. ACT was industry-supported, and collaboratively designed and governed by an Investigator Steering Committee with independent Advisory and Data Safety Monitoring Committees. Study operations, MRI analysis and aggregated data were managed by the Cleveland Clinic MS Academic Coordinating Center. RESULTS: In total 313 subjects were enrolled with clinical and MRI characteristics typical of RRMS. Most subjects (86.9%) qualified with a clinical relapse, with or without an enhancing MRI lesion, in the preceding year. At baseline, 21.4% had enhancing lesions, and 5.1% had anti-IFNbeta neutralizing antibodies. ACT's management and operational structures functioned well. CONCLUSION: This study provides an innovative model for academic-industry collaborative MS research and will enhance understanding of the utility of combination therapy for RRMS patients with continued disease activity on an established first-line treatment.
Assuntos
Adjuvantes Imunológicos/administração & dosagem , Interferon beta/administração & dosagem , Metotrexato/administração & dosagem , Metilprednisolona/administração & dosagem , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Adolescente , Adulto , Anti-Inflamatórios/administração & dosagem , Comportamento Cooperativo , Interpretação Estatística de Dados , Avaliação da Deficiência , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/administração & dosagem , Interferon beta-1a , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/patologia , Seleção de Pacientes , Resultado do TratamentoRESUMO
BACKGROUND: Stroke incidence and mortality are disproportionately higher among African Americans than among whites. OBJECTIVE: To describe the recurrent stroke characteristics and determine the predictability of known vascular risk factors for stroke recurrence in African Americans. METHODS: The authors followed 1,809 African Americans in the African-American Antiplatelet Stroke Prevention Study with recent noncardioembolic ischemic stroke for recurrent stroke, recurrent stroke subtype, and disability. RESULTS: Of the subjects, 10.6% experienced a recurrent stroke during follow-up. The mean interval between eligibility and recurrent stroke was 325 days (median 287 days, SD = 224 days). Stroke recurrence resulted in an average 1.5-point increase in the National Institute of Health Stroke Scale (p < 0.001) and a 3.5-point decrease in modified Barthel Index (p < 0.001). Of previously nondisabled subjects, 48% became disabled or died after stroke recurrence (p < 0.0001). Longitudinal analysis resulted in a hazard for recurrent stroke for each 10-mm Hg increase in systolic blood pressure of 1.103 (95% CI: 1.031 to 1.179, p = 0.004), pulse pressure 1.123 (95% CI: 1.041 to 1.213, p = 0.003), and mean arterial pressure 1.123 (95% CI: 1.001 to 1.260, p = 0.048). Multivariate analysis revealed increases in the recurrent stroke hazard for increases in baseline Glasgow Outcome Score (1.449, 95% CI: 1.071 to 1.961, p = 0.016) and increases in longitudinal pulse pressure (1.009, 95% CI: 1.001 to 1.017, p = 0.029). CONCLUSION: Recurrent stroke leads to disability and disability predicts recurrent stroke. Hypertension is the most predictive modifiable stroke risk factor.
Assuntos
Atividades Cotidianas , Negro ou Afro-Americano/estatística & dados numéricos , Avaliação de Resultados em Cuidados de Saúde/métodos , Medição de Risco/métodos , Acidente Vascular Cerebral/etnologia , Acidente Vascular Cerebral/mortalidade , Avaliação da Deficiência , Feminino , Humanos , Incidência , Masculino , Prognóstico , Recidiva , Fatores de Risco , Análise de Sobrevida , Taxa de Sobrevida , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Morbid obesity is increasing in the United States population. Morbidly obese patients may have disabling pulsatile tinnitus (PT) secondary to pseudotumor cerebri syndrome and often seek treatment from otolaryngologists because of this symptom. OBJECTIVE: To determine the effectiveness of weight reduction surgery (WRS) for relief of PT in patients with morbid obesity. STUDY DESIGN: Retrospective study of morbidly obese patients with associated PT. SETTING: Academic tertiary referral center. PATIENTS: Sixteen women with morbid obesity and associated PT who underwent WRS. RESULTS: Median age was 34 years (range 24-45 years). Average preoperative body mass index was 45 kg/m2 (range 33-70 kg/m2). Average weight loss was 45+/-17 kg (range 25-99 kg). Average postoperative weight was 75+/-14 kg (range 57-105 kg). The average preoperative cerebrospinal fluid pressure was 344+/-103 mm H2O (range 220-520 mm H2O). Postoperative measurements of cerebrospinal fluid, obtained on 4 patients, revealed an average decrease in pressure of 198 mm H2O (range 120-400 mm H2O). Thirteen patients experienced complete resolution of their PT (81%). Three patients continued to have PT despite significant weight reduction. CONCLUSIONS: Weight reduction surgery was effective in relieving PT in morbidly obese patients with associated pseudotumor cerebri syndrome and should be considered when conservative management has failed.
Assuntos
Obesidade Mórbida/complicações , Obesidade Mórbida/cirurgia , Zumbido/complicações , Redução de Peso , Adulto , Índice de Massa Corporal , Feminino , Seguimentos , Derivação Gástrica/métodos , Gastroplastia/métodos , Humanos , Pessoa de Meia-Idade , Pseudotumor Cerebral/complicações , Pseudotumor Cerebral/diagnóstico , Estudos Retrospectivos , Zumbido/diagnóstico , Zumbido/epidemiologia , Resultado do TratamentoRESUMO
OBJECTIVE: To study the efficacy of gastric surgery-induced weight loss for the treatment of pseudotumor cerebri (PTC). SUMMARY BACKGROUND DATA: Pseudotumor cerebri (also called idiopathic intracranial hypertension), a known complication of severe obesity, is associated with severe headaches, pulsatile tinnitus, elevated cerebrospinal fluid (CSF) pressures, and normal brain imaging. The authors have found in previous clinical and animal studies that PTC in obese persons is probably secondary to a chronic increase in intraabdominal pressure leading to increased intrathoracic pressure. CSF-peritoneal shunts have a high failure rate, probably because they involve shunting from a high-pressure system to another high-pressure zone. In an earlier study of gastric bypass surgery in eight patients, CSF pressure decreased from 353+/-35 to 168+/-12 mm H2O at 34+/-8 months after surgery, with resolution of headaches in all. METHODS: Twenty-four severely obese women underwent bariatric surgery--23 gastric bypasses and one laparoscopic adjustable gastric banding--62+/-52 months ago for the control of severe obesity associated with PTC. CSF pressures were 324+/-83 mm H2O. Additional PTC central nervous system and cranial nerve problems included peripheral visual field loss, trigeminal neuralgia, recurrent Bell's palsy, and pulsatile tinnitus. Spontaneous CSF rhinorrhea occurred in one patient, and hemiplegia with homonymous hemianopsia developed as a complication of ventriculoperitoneal shunt placement in another. There were two occluded lumboperitoneal shunts and another functional but ineffective lumboperitoneal shunt. Additional obesity comorbidity in these patients included degenerative joint disease, gastroesophageal reflux disease, hypertension, urinary stress incontinence, sleep apnea, obesity hypoventilation, and type II diabetes mellitus. RESULTS: At 1 year after bariatric surgery, 19 patients lost an average of 45+/-12 kg, which was 71+/-18% of their excess weight. Their body mass index and percentage of ideal body weight had fallen to 30+/-5 kg/m2 and 133+/-22%, respectively. In four patients, less than 1 year had elapsed since surgery. Five patients were lost to follow-up. Surgically induced weight loss was associated with resolution of headache and pulsatile tinnitus in all but one patient within 4 months of the procedure. The cranial nerve dysfunctions resolved in all patients. The patient with CSF rhinorrhea had resolution within 4 weeks of gastric bypass. Of the 19 patients not lost to follow-up, 2 regained weight, with recurrence of headache and pulsatile tinnitus. Additional resolved associated comorbidities were 6/14 degenerative joint disease, 9/10 gastroesophageal reflux disorder, 2/6 hypertension, and all with sleep apnea, hypoventilation, type II diabetes mellitus, and urinary incontinence. CONCLUSIONS: Bariatric surgery is the long-term procedure of choice for severely obese patients with PTC and is shown to have a much higher rate of success than CSF-peritoneal shunting reported in the literature, as well as providing resolution of additional obesity comorbidity. Increased intraabdominal pressure associated with central obesity is the probable etiology of PTC, a condition that should no longer be considered idiopathic.