CT perfusion measurement of postictal hypoperfusion: localization of the seizure onset zone and patterns of spread.

PURPOSE: Seizures are often followed by a period of transient neurological dysfunction and postictal alterations in cerebral blood flow may underlie these symptoms. Recent animal studies have shown reduced local cerebral blood flow at the seizure onset zone (SOZ) lasting approximately 1 h following seizures. Using arterial spin labelling (ASL) MRI, we observed postictal hypoperfusion at the SOZ in 75% of patients. The clinical implementation of ASL as a tool to identify the SOZ is hampered by the limited availability of MRI on short notice. Computed tomography perfusion (CTP) also measures blood flow and may circumvent the logistical limitations of MRI. Thus, we aimed to measure the extent of postictal hypoperfusion using CTP. METHODS: Fourteen adult patients with refractory focal epilepsy admitted for presurgical evaluation were prospectively recruited and underwent CTP scanning within 80 min of a habitual seizure. Patients also underwent a baseline scan after they were seizure-free for > 24 h. The acquired scans were qualitatively assessed by two reviewers by visual inspection and quantitatively assessed through a subtraction pipeline to identify areas of significant postictal hypoperfusion. RESULTS: Postictal blood flow reductions of > 15 ml/100 g-1/min-1 were seen in 12/13 patients using the quantitative method of analysis. In 10/12 patients, the location of the hypoperfusion was partially or fully concordant with the presumed SOZ. In all patients, additional areas of scattered hypoperfusion were seen in areas corresponding to seizure spread. CONCLUSION: CTP can reliably measure postictal hypoperfusion which is maximal at the presumed SOZ.

The effect of immunomodulatory treatment on multiple sclerosis fatigue.

OBJECTIVE: To assess the effects of glatiramer acetate and beta interferon on fatigue in multiple sclerosis. METHODS: Fatigue was measured at baseline and six months using the fatigue impact scale (FIS). Groups (glatiramer acetate and beta interferon) were evaluated for the proportion improved, using Fisher's exact test. Logistic regression analysis assessed the relation between treatment group and improvement and controlled for confounding variables. RESULTS: Six month paired FIS assessments were available for 218 patients (76% female). Ages ranged between 19 and 61 years, with 86% having relapsing-remitting disease. Glatiramer acetate was used by 61% and beta interferon by 39%. At baseline, total FIS and subscale scores were comparable in the two groups. More patients improved on glatiramer acetate than on beta interferon on total FIS (24.8% v 12.9%, p = 0.033; adjusted odds ratio = 2.36, 95% confidence interval 1.03 to 5.42), and on physical (28.6% v 14.1%, p = 0.013) and cognitive subscales (21.1% v 10.6%, p = 0.045). Logistic regression analysis confirmed the association between glatiramer acetate use and improved fatigue, after accounting for baseline group differences. CONCLUSIONS: The odds of reduced multiple sclerosis fatigue were around twice as great with glatiramer acetate treatment as with beta interferon. Confirmation of this result is required.

Electroencephalographic findings during presyncope and syncope induced by tilt table testing.

OBJECTIVE: To determine electroencephalographic (EEG) changes occurring during syncope induced by headup tilt table testing. DESIGN: Prospective observational study. SETTING: Calgary General Hospital Syncope Clinic, Calgary, Alberta. PATIENTS: Eighteen patients with a history of recurrent syncope who developed syncope while undergoing diagnostic isoproterenol tilt table testing. INTERVENTIONS: Continuous EEGs were recorded in 18 sequentially consenting patients while they underwent diagnostic headup tilt table testing. MAIN RESULTS: Patients developed presyncope after 2.6 +/- 2.4 mins and syncope after 3.7 +/- 2.5 minutes. Systolic blood pressure dropped from 117 +/- 17 mmHg to 65 +/- 9 mmHg, and heart rate dropped from 124 +/- 26 beats/min to 65 +/- 27 beats/min. Fourteen patients developed presyncope, while five developed syncope without appreciable presyncope. Abnormal EEGs were recorded in 13 of 14 patients during presyncope and in 18 of 18 patients during syncope. No patients developed EEG abnormalities before the onset of presyncope, and the proportion of patients with EEG abnormalities gradually increased throughout presyncope. During presyncope, theta and delta wave slowing, and background suppression were noted in eight of 14, nine of 14 and one of 14 patients, respectively. During syncope, theta and delta wave slowing, and background suppression were noted in nine of 18, 11 of 18 and six of 18 patients, respectively (not significant versus presyncope). There were strikingly abrupt changes in the EEG rhythm within 15 s of the transition to syncope in 14 of 18 patients. Six patients developed new theta wave slowing, 11 developed new delta wave slowing, and seven developed background suppression. No epileptiform activity was recorded. CONCLUSIONS: Both presyncope and syncope induced by tilt testing are associated with EEG abnormalities, and no single EEG pattern is pathognomonic of either. The transition from presyncope to syncope is marked by abrupt EEG changes.

Randomized, double-blind, placebo-controlled crossover trial of modafinil in the treatment of excessive daytime sleepiness in narcolepsy.

Seventy-five patients meeting international diagnostic criteria for narcolepsy enrolled in a 6-week, three-period, randomized, crossover, placebo-controlled trial. Patients received placebo, modafinil 200 mg, or modafinil 400 mg in divided doses (morning and noon). Evaluations occurred at baseline and at the end of each 2-week period. Compared with placebo, modafinil 200 and 400 mg significantly increased the mean sleep latency on the Maintenance of Wakefulness Test by 40% and 54%, with no significant difference between the two doses. Modafinil, 200 and 400 mg, also reduced the combined number of daytime sleep episodes and periods of severe sleepiness noted in sleep logs. The likelihood of falling asleep as measured by the Epworth Sleepiness Scale was equally reduced by both modafinil dose levels. There were no effects on nocturnal sleep initiation, maintenance, or architecture, nor were there any effects on sleep apnea or periodic leg movements. Neither dose interfered with the patients' ability to nap voluntarily during the day nor with their quantity or quality of nocturnal sleep. Modafinil produced no changes in blood pressure or heart rate in either normotensive or hypertensive patients. The only significant adverse effects were seen at the 400-mg dose, which was associated with more nausea and more nervousness than either placebo or the 200-mg dose. As little as a 200-mg daily dose of modafinil is therefore an effective and well-tolerated treatment of excessive daytime somnolence in narcoleptic persons.

Unusual form of seizures induced by eye closure.

Seizures induced by eye closure are a rare but well-recognized form of reflex epilepsy. Two types have been reported: those induced by movement of the eyelids and those caused by lack of visual input. The EEG pattern is typically that of spike and wave discharges, either isolated to the occipital regions or greatest there. We report the case of a 19-year-old woman with a previously undescribed form of seizures induced by eye closure in whom both the physical act of eye closure and total lack of visual input were required for induction of a seizure. Both the EEG pattern of paroxysmal high-amplitude generalized beta activity and poor response to medication were different from what has been previously noted in patients with seizures induced by eye closure. We believe that a third form of seizures induced by eye closure exists and that its prognosis may be significantly worse than that of previously reported forms.

Recurrent cerebral infarction during anticoagulation therapy in patients with mitral valve prolapse.

Mitral valve prolapse has been associated with an increased risk of transient or lasting ischemic events. Recurrence is uncommon after initiation of antiplatelet or anticoagulant therapy. In this communication we report two patients, both female, who had mitral valve prolapse as the major risk factor for cerebrovascular disease and who developed cerebral infarction despite anticoagulation. The cerebral infarctions were bilateral and extensive in one patient and led to the patient's death. In the second case, three infarctions resulted in moderate disability.

Familial paroxysmal hypnogenic dystonia.

We studied a family with dystonic spasms that occurred with non-REM sleep. This familial disorder may be related to the sporadic cases reported previously.

The use of resonance Raman spectroscopy to monitor catalytically important bonds during enzymic catalysis. Application to the hydrolysis of methyl thionohippurate by papain.

Resonance Raman spectra were obtained of the dithioacyl-enzyme intermediate produced during the papain-catalayzed hydrolysis of methyl thionohippurate. Intense resonance Raman features were observed in (formula; see text) and (formula; see text) stretching regions from the intermediate's (formula; see text) chromophore. These results demonstrate that by using a single atom replacement, i.e. sulfur for oxygen, the catalytically crucial bonds in the ester moiety can be monitored during enzymolysis via the resonance Raman spectrum. The method can be extended to other enzymes whose catalytic mechanisms involve the formation of a thiol-acyl intermediate.