Neurologic safety event rates in the SENTIS trial control population.

BACKGROUND: Adverse event (AE) rates for interventional stroke trials are not well established. AIMS: We prospectively evaluated control arm AEs from a randomized stroke trial to establish expected rates of neurologic AEs. METHODS: Control data from the Safety and Efficacy of NeuroFlo Technology in Ischemic Stroke (SENTIS) Trial were evaluated. Patients were ≥ 18 years with National Institutes of Health Stroke Scale (NIHSS) scores 5-18 within 14 h of stroke onset. Follow-up was 90 days. Neurological AEs and serious AEs (SAEs) were adjudicated and the following defined times used to determine treatment relatedness: 24-h imaging for intracranial hemorrhage (ICnH) including hemorrhagic transformation, 7 days each for cerebral edema and neurologic worsening/stroke progression, and 30 days for new ischemic strokes. RESULTS: The control group included 257 patients, 49.4% female, mean age of 68.3 years, and median NIHSS of 10. Neurologic AEs occurred at the following rates: ICnH 27.6%, cerebral edema 6.6%, neurologic worsening 18.3%, and new stroke 4.7%. Most of these events occurred within the defined times: ICnH 74.6%, cerebral edema 94.1%, neurologic worsening 87.2%, and new stroke 83.3%. CONCLUSIONS: SENTIS Trial control arm neurologic events provide estimates of expected AE rates and defined times that can be used for future stroke trial's safety assessments.

Combining beta interferon and atorvastatin may increase disease activity in multiple sclerosis.

OBJECTIVE: To explore whether high-dose atorvastatin can be administered safely to persons with relapsing-remitting multiple sclerosis (MS) taking thrice weekly, 44 microg dose subcutaneous interferon beta-1a. METHODS: Persons with clinically stable, relapsing-remitting MS, on standard high-dose subcutaneous interferon beta-1a, were randomized in a double-blind fashion to receive either placebo or atorvastatin at dosages of 40 or 80 mg/day for 6 months. Blinded neurologic examinations and brain MRI readings were obtained at months 0, 3, 6, and 9. Laboratory blood testing was performed monthly. Main outcome measures were the determination of drug toxicity using blood tests and ECG and determination of MS-related disease activity, either clinical relapses or new or contrast-enhancing lesions on MRI. RESULTS: Twenty-six subjects received at least one dose of study drug. Ten of 17 subjects on either 80 mg or 40 mg of atorvastatin per day had either new or enhancing T2 lesions on MRI or clinical relapses. One of the nine subjects on placebo had a relapse with active lesions on MRI. The subjects receiving atorvastatin were at greater risk for either clinical or MRI disease activity compared to placebo (p = 0.019). Significant changes in blood tests were noted only for lower cholesterol levels in subjects receiving atorvastatin. CONCLUSION: The combination of 40 or 80 mg atorvastatin with thrice weekly, 44 microg interferon beta-1a in persons with multiple sclerosis resulted in increased MRI and clinical disease activity. Caution is suggested in administering this combination.

Role of thymectomy in myasthenia gravis.

Thirteen patients with myasthenia gravis underwent total thymectomy between January, 1988 and December, 1991. The duration of symptoms prior to surgery varied from 2 months to 20 years. In a follow-up ranging from 2 months to 4 years, 11 patients showed a significant improvement with either complete discontinuation of medication or a marked reduction in doses. One patient with a small benign thymoma showed some improvement but subsequently required stepping up of anticholinesterase medication and addition of steroids and immunosuppressants; another patient with atrophic thymic tissue had complete remission after thymectomy but developed myasthenic symptoms six months later requiring medication again. Thymectomy is recommended for all patients with generalised myasthenia gravis with or without thymoma regardless of the duration of disease unless the patient is a very high risk candidate for surgery. It is not recommended for isolated ocular myasthenia gravis.

Status epilepticus: clinical experience with two special devices for continuous cerebral monitoring.

Continuous cerebral monitoring (CCM) was performed on 34 patients in status epilepticus (SE), using changes in amplitude detected by the cerebral function monitor (CFM) and changes in frequency detected by compressed spectral array (CSA). The EEG was used intermittently to help identify seizure patterns obtained with these methods. Seventeen patients in clinically manifest SE also had non-convulsive seizures. In 17 patients, SE was refractory to conventional anticonvulsants, requiring treatment with pentobarbital or paraldehyde. In these patients, CCM provided dynamic electroencephalographic monitoring of burst-suppression and prompt detection of breakthrough seizures. Patients in SE should undergo CCM to differentiate between non-convulsive seizures and post-ictal state both of which may produce prolonged unresponsiveness following clinical seizures. CCM after data reduction with the two special devices used is a viable and practical alternative to continuous conventional EEG monitoring during SE. However, in order to evaluate the sensitivity and specificity of these methods, it will be necessary to design a study in which both the EEG and the devices using data reduction be used continuously and concurrently.

Epidural spinal cord compression from metastatic cancer: clinical features and management.

We retrospectively analyzed thirty-three patients (21 males, 12 females) with malignancy induced spinal cord compression (SCC). The mean age of the patients was 42.8 years and almost half (51%) of them presented with SCC. Mean duration of symptoms was 4.5 months and the mean interval between the original diagnosis of cancer and the development of SCC was 14.6 months. Back pain was the most frequent (97%) symptom with an equal number of patients having subjective or objective evidence of lower limb weakness. Majority (73%) of the patients were non-ambulatory at the time of diagnosis. Spinal level involvement was mostly thoracic (62%) followed by lumber (38%). Breast cancer was the commonest underlying malignancy (21%). Lung (12%), prostrate (12%), multiple myeloma (9%), and carcinoma with unknown primary (12%) were also frequently encountered. There was an overall response rate of 22% to the therapeutic interventions: mostly observed in the ambulatory patients. Only 7% of the non-ambulatory patients regained ability to walk. None of the responders had bladder or bowel dysfunction. Twenty-two percent of the responders are still ambulatory with a mean follow-up of six months.

Spinal cord dysfunction complicating meningococcal meningitis.

A 29 year old male developed paraplegia during the acute phase of meningococcal meningitis. Possible mechanisms for this unusual complication are discussed and the literature regarding spinal cord complications of pyogenic meningitis is reviewed.

Cocaine-induced seizures.

We retrospectively studied 474 patients seen at Hennepin County Medical Center because of medical complications related to acute cocaine intoxication. Of the 474, 403 had no history of seizures. Seizures within 90 minutes of cocaine use was the primary diagnosis in 32 (7.9%) of the 403. The majority of seizures were single, generalized, induced by intravenous or "crack" cocaine, and not associated with any lasting neurologic deficits. Most that were focal, multiple, or induced by nasal cocaine were associated with an acute intracerebral complication or concurrent use of other drugs. Of 71 patients with a history of non-cocaine-related seizures, 12 (16.9%) presented with cocaine-induced seizures; most of these were multiple, of the same type as those in their history, and induced by even nasal cocaine. In the 44 cocaine-induced seizure patients, a pattern of habitual cocaine abuse was associated with diffuse brain atrophy on CT and diffuse slowing on EEG.

Factors influencing serum levels of carbamazepine and carbamazepine-10,11-epoxide in children.

Carbamazepine-10,11-epoxide (CBZ-E), the principal metabolite of carbamazepine (CBZ), is reported to have antiepileptic and toxic effects similar to CBZ. Steady-state CBZ and CBZ-E levels (high performance liquid chromatography, HPLC assay) were reviewed in 225 outpatient children and young adults taking CBZ with or without other antiepileptic drugs (AEDs). In patients on CBZ alone, mean serum concentration of CBZ was 7.9 +/- 1.9 micrograms/ml and of CBZ-E was 1.5 +/- 0.6 micrograms/ml. The CBZ-E/CBZ ratio was 19.6 +/- 2.4%. Serum CBZ increased with increasing age and with CBZ dose. CBZ-E increased with increasing CBZ dose but was unaffected by age. The CBZ-E/CBZ ratio progressively declined with age. Co-medication with barbiturates or valproic acid significantly increased CBZ-E. Phenytoin showed a similar trend while ethosuximide caused the least change. Patients on CBZ and two or more other AEDs had highest CBZ-E levels and CBZ-E/CBZ ratio. CBZ and CBZ-E levels are variably affected by age, CBZ dose, and co-medication with other AEDs. When other AEDs are administered, careful monitoring is especially indicated in order to avoid toxicity.

Voiced calls evoked by hypothalamic stimulation in the cat.

Voiced vocalizations evoked by hypothalamic stimulation were studied in a series of six awake adult cats. Electrical stimulation was found to evoke vocalizations at numerous sites within the hypothalamus, ranging from A + 8 to A + 16. Regions showing the largest number of responsive sites were the preoptic region, the ventromedial area, the perifornical region, the lateral and the dorso-medial hypothalamus. The form of the evoked calls was generally similar to the spontaneous calls of the same animal. Call latency, duration, and intensity were not significantly affected by changes in stimulus intensity or duration but all three of these call parameters were significantly affected by changes in stimulus frequency. In general, call latency was longest at sites in the rostral hypothalamus and shortest at sites in the caudal hypothalamus. This study is the first to investigate systematically voiced call producing areas in the hypothalamus of awake cats and to document similarities between these calls and spontaneously produced voiced calls.

Focal medial temporal lobe spike-wave complexes evoked by a memory task.

Several factors are known to modulate the occurrence of interictal spike-wave complexes (SWC). During performance of a recent memory task by a patient with uncontrolled complex partial seizures and implanted electrodes, visually presented stimuli consistently evoked focal medial temporal lobe interictal SWC with an average latency of 228 +/- 29 ms. The SWC were more often lateralized to the left medial temporal lobe. No consistent change in interictal spike rate was observed during performance of several other cognitive tasks during which visual or auditory stimuli were presented. This suggests that performance of specific cognitive tasks--in this case, recognition memory of words--can trigger interictal SWC.

Interictal spike-wave complexes in the human medial temporal lobe: typical topography and comparisons with cognitive potentials.

Ten of 16 patients with complex partial epilepsy displayed an interictal spike-slow wave sequence with characteristic morphology and depth voltage topography. This 'typical slow wave' (TSW) lasted 300-600 msec, was usually largest and negative in the anterior hippocampus, and positive in the amygdala. Simultaneous recordings from ipsilateral cingulate, supplementary motor, orbitofrontal, and lateral temporal cortices, as well as from the contralateral medial temporal lobe (MTL), revealed only small, apparently volume-conducted, wave forms. Simultaneously recorded multiunit activity within the focal MTL was profoundly inhibited during the TSW. The TSW propagated to the scalp, producing a large widespread positivity. A large endogenous potential with similar latency range and task correlates as the scalp-P3 was recorded from the MTL to infrequent tones in a simple discrimination task. This 'depth-P3' had very similar polarity and relative amplitude across MTL sites, as was observed for the TSW at the same electrode contacts. However, at more superficial intracranial sites, the TSW was relatively smaller than the P3. Similarly, from MTL to surface, the P3 was found to decrement about half as much as the TSW decrements. This evidence suggests that the surface P3 is generated, but in part only, by the MTL.