Prospective long-term study of vagus nerve stimulation for the treatment of refractory seizures.

PURPOSE: To determine the long-term efficacy of vagus nerve stimulation (VNS) for refractory seizures. VNS is a new treatment for refractory epilepsy. Two short-term double-blind trials have demonstrated its safety and efficacy, and one long-term study in 114 patients has demonstrated a cumulative improvement in efficacy at 1 year. We report the largest prospective long-term study of VNS to date. METHODS: Patients with six or more complex partial or generalized tonic-clonic seizures enrolled in the pivotal EO5 study were prospectively evaluated for 12 months. The primary outcome variable was the percentage reduction in total seizure frequency at 3 and 12 months after completion of the acute EO5 trial, compared with the preimplantation baseline. Subjects originally randomized to low stimulation (active-control group) were crossed over to therapeutic stimulation settings for the first time. Subjects initially randomized to high settings were maintained on high settings throughout the 12-month study. RESULTS: The median reduction at 12 months after completion of the initial double-blind study was 45%. At 12 months, 35% of 195 subjects had a >50% reduction in seizures, and 20% of 195 had a >75% reduction in seizures. CONCLUSIONS: The efficacy of VNS improves during 12 months, and many subjects sustain >75% reductions in seizures.

Intrathecal baclofen for management of spastic cerebral palsy: multicenter trial.

Intrathecal baclofen infusion has demonstrated effectiveness in decreasing spasticity of spinal origin. Oral antispasticity medication is minimally effective or not well tolerated in cerebral palsy. This study assessed the effectiveness of intrathecal baclofen in reducing spasticity in cerebral palsy. Candidates were screened by randomized, double-blind, intrathecal injections of baclofen and placebo. Responders were defined as those who experienced an average reduction of 1.0 in the lower extremities on the Ashworth Scale for spasticity. Responders received intrathecal baclofen via the SynchroMed System and were followed for up to 43 months. Fifty-one patients completed screening and 44 entered open-label trials. Lower-extremity spasticity decreased from an average baseline score of 3.64 to 1.90 at 39 months. A decrease in upper extremity spasticity was evidenced over the same study period. Forty-two patients reported adverse events. Most common reports were hypotonia, seizures (no new onset), somnolence, and nausea or vomiting. Fifty-nine percent of the patients experienced procedural or system-related events. Spasticity in patients with cerebral palsy can be treated effectively by continuous intrathecal baclofen. Adverse events, although common, were manageable.

Vagus nerve stimulation therapy for partial-onset seizures: a randomized active-control trial.

OBJECTIVE: The purpose of this multicenter, add-on, double-blind, randomized, active-control study was to compare the efficacy and safety of presumably therapeutic (high) vagus nerve stimulation with less (low) stimulation. BACKGROUND: Chronic intermittent left vagus nerve stimulation has been shown in animal models and in preliminary clinical trials to suppress the occurrence of seizures. METHODS: Patients had at least six partial-onset seizures over 30 days involving complex partial or secondarily generalized seizures. Concurrent antiepileptic drugs were unaltered. After a 3-month baseline, patients were surgically implanted with stimulating leads coiled around the left vagus nerve and connected to an infraclavicular subcutaneous programmable pacemaker-like generator. After randomization, device initiation, and a 2-week ramp-up period, patients were assessed for seizure counts and safety over 3 months. The primary efficacy variable was the percentage change in total seizure frequency compared with baseline. RESULTS: Patients receiving high stimulation (94 patients, ages 13 to 54 years) had an average 28% reduction in total seizure frequency compared with a 15% reduction in the low stimulation group (102 patients, ages 15 to 60 year; p = 0.04). The high-stimulation group also had greater improvements on global evaluation scores, as rated by a blinded interviewer and the patient. High stimulation was associated with more voice alteration and dyspnea. No changes in physiologic indicators of gastric, cardiac, or pulmonary functions occurred. CONCLUSIONS: Vagus nerve stimulation is an effective and safe adjunctive treatment for patients with refractory partial-onset seizures. It represents the advent of a new, nonpharmacologic treatment for epilepsy.

Detection of a soluble form of B7-1 (CD80) in synovial fluid from patients with arthritis using monoclonal antibodies against distinct epitopes of human B7-1.

The costimulatory molecule B7-1 (CD80) has been shown to be an important component for T cell immune responses. We have generated several monoclonal antibodies (PSRM-1, -2, -3, -6, and -7) against B7-1 using a human glycosylphosphatidylinositol-anchored B7-1 (GPI-B7-1) as an antigen. These monoclonal antibodies are able to detect B7-1 by flow cytometry, ELISA, and Western blotting. One antibody in particular, PSRM-3, blocks the CD28/CTLA-4 interaction with B7-1 and consequently blocks costimulation of T cells. The other PSRM monoclonal antibodies did not compete with PSRM-3 for recognition of B7-1 and also failed to block B7-1 interaction with CTLA-4 and CD28, indicating that these antibodies bind to different epitopes. PSRM-3 and -7 detect phosphatidylinositol-specific phospholipase C-released soluble GPI-B7-1 in a sandwich ELISA. We used this sandwich ELISA to assay for the presence of a soluble form of B7-1 in synovial fluids of arthritis patients. By sandwich ELISA, B7-1 was detected in the synovial fluid of 5/11 patients with rheumatoid arthritis, 5/5 patients with osteoarthritis, and 2/6 patients with other forms, including crystalline-induced arthritis. The presence of soluble B7-1 was confirmed by immunoprecipitation using PSRM-3-coupled Sepharose beads. The source and function of soluble B7-1 are unknown at present; it is possible, however, that the soluble form of B7-1 molecule may play a local immunoregulatory role which may suppress or induce inflammation depending upon whether it interacts with the T cell costimulatory CD28 molecule or the negative signaling CTLA-4 molecule.

Cerebral arteritis and bacterial meningitis.

Twelve cases of large- and medium-sized cerebral artery stenosis and/or occlusion associated with bacterial meningitis occurred. Neurological complication due to arterial involvement developed in seven patients on the third and fourth days of illness; in one patient, it developed on the fifth day, and in another it developed on the 14th day. In three cases, this could not be determined. Arterial stenosis is considered primarily to result from arterial spasm due to humoral factors that may be elaborated within the CSF or arterial wall, as in the cases of ruptured aneurysm; and secondarily, from to inflammatory involvement of major vessels at the base of the brain and from irritation by angiographic contrast material.

Mitral valve prolapse syndrome in children with Duchenne's progressive muscular dystrophy.

Myocardial function was evaluated prospectively by noninvasive methods in 20 boys with clinical, biochemical, muscle biopsy, and electromyographic evidence of Duchenne's progressive muscular dystrophy. Auscultatory evidence of a nonejection systolic click suggested mitral valve prolapse (MVP) syndrome in seven patients. Phonocardiography disclosed that the click was mid-systolic in four patients and early in three. Echocardiographic features consistent with this diagnosis were identified in all seven patients and in an additional four. One of these had an apical pansystolic murmur, suggestive of mitral regurgitation, whereas in the other three, prolapse of the mitral valve was "silent". Echocardiographic findings included an abrupt midsystolic, posterior motion (greater than 3 mm beyond the CD line) in five patients, multiple sequence echoes in six, and posterior coaptation of the mitral valve near the left atrial wall in six. The features most characteristic of MVP syndrome was a smooth, pansystolic, anteriorly concave (hammock-like) posterior motion deviating more than 3 mm beyond the CD line. Among the remaining nine patients who did not have echocardiographic evidence of prolapsing mitral valve, none had an early, middle or late nonejection systolic click or a heart murmur, although four patients in this group had moderate to severe scoliosis. These observations document of occurrence of MVP syndrome in children with Duchenne's muscular dystrophy and indicate that its prevalence is high. We speculate that prolapse of the mitral valve in these patients is an expression of the underlying cardiomyopathy characteristic of Duchenne's muscular dystrophy rather than an isolated, dystrophic involvement of the mitral valve leaflets.

Guillain-Barré syndrome with hydrocephalus in early infancy.

Guillain-Barré syndrome (GBS) is a self-limited and uncommon acquired neurologic syndrome in childhood. It is not thought of as a problem of infancy and is not always included in the differential diagnosis of the floppy infant. This case report describes GBS ina 1-month-old infant. In addition this infant developed hydrocephalus concurrent with the appareance of high CSF protein levels. This patient is described to demonstrate that GBS can occur at all ages and that hydrocephalus may occur particularly when the CSF protein is at an unusually high level.