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Two familial X-linked dominant syndromes of cortical maldevelopment have recently been described: double cortex/lissencephaly syndrome and bilateral periventricular nodular heterotopia. We report on 12 kindreds with familial perisylvian polymicrogyria (FPP) presenting at 10 centers, examine the clinical presentation in these familial cases, and propose a possible mode of inheritance. The clinical and radiological pattern was variable among the 42 patients, with clinical differences among the families and even within members of the same family. Pseudobulbar signs, cognitive deficits, epilepsy, and perisylvian abnormalities on imaging studies were not found in all patients. When present, they displayed a spectrum of severity. The only clear correlation in this study was between bilateral imaging findings and abnormal tongue movements and/or pronounced dysarthria. Most of the families provided evidence suggestive of, or compatible with, X-linked transmission. On the other hand, the pedigrees of 2 families ruled out X-linked inheritance. The most likely mode of inheritance for these 2 families was autosomal dominant with decreased penetrance; however, autosomal recessive inheritance with pseudodominance could not be ruled out in 1 family. We conclude that FPP appears to be genetically heterogeneous. However, most of the families probably represent a third previously undescribed X-linked syndrome of cortical maldevelopment. Ann Neurol 2000;48:39–48

Early identification of Marfan's syndrome is fundamental in the prevention of aortic dilatation, but the wide phenotypic expression of the disorder makes the clinical diagnosis very difficult. Dural ectasia has been classified as a major diagnostic criterion; however, its prevalence is not known. We aimed to identify the true prevalence of dural ectasia in Marfan's syndrome, and to investigate its relation to aortic pathology.

We report a patient affected by progressive supranuclear palsy who also presented with bilateral internuclear ophthalmoplegia. The computed tomographic (CT) scan showed the previously described radiological picture characteristic of the syndrome and two additional unusual findings. The significance of these findings is discussed and the importance of the CT scan in the diagnosis of progressive supranuclear palsy is emphasized.

We studied 16 patients with partial epilepsy and drop attacks. The drop attacks appeared 1 to 29 years after onset of epilepsy; 15 patients had these attacks weekly or daily, despite therapy. After the appearance of drop attacks, 6 patients had severe mental disorders, and social life was disrupted in 13. There was a high rate of adversive seizures, atypical absences, and diffuse spike-wave discharges in the EEG, electroclinical features that suggest a frontal origin of epilepsy. Drop attacks are ominous because they occur so frequently, resist therapy, are physically dangerous, and portend personality change.

• Thirty-one patients with severe drugresistant epilepsy entered the study. Vigabatrin (2 to 3 g/d, stratified according to weight) and placebo were administered orally, as add-on therapy in random order under double-blind conditions, each for three months using a crossover design. Thirty patients completed both periods. Of these, ten patients (33%) showed a decrease in seizure frequency of 50% or more. In the 15 patients presenting with complex partial seizures, "temporal" electroencephalographic abnormalities, and relatively low seizure frequency, there was a significant reduction in seizure frequency during vigabatrin treatment. No significant treatment effect was found for the remaining 15 patients, who presented with mixed seizure types, multifocal electroencephalographic abnormalities, and high seizure frequencies. Tolerability to vigabatrin was good; the most frequently reported unwanted effect was drowsiness. Plasma concentrations of phenytoin showed a significant reduction during the vigabatrin period. The results demonstrate the efficacy and good tolerability of vigabatrin therapy in patients with severe complex partial epilepsy.

‘Double cortex’ is a neuroblast migrational disorder characterized by a diffuse band of heterotopic grey matter between the lateral ventricles and cerebral cortex which may be normal or macrogyric. The authors report two girls with ‘double cortex’ syndrome presenting intractable partial epilepsy and severe mental retardation. EEG data are analysed in detail because such patients presented a particular interictal EEG background activity, not only with very stable features during the different stages of vigilance, but also uninfluenced by seizure frequency or duration. The authors raise the possibility that a further in vivo diagnostic parameter for this syndrome has been identified.

The diurnal variation in total and free plasma phenytoin (PHT) concentration at steady state was examined in eight epileptic patients receiving combination therapy with tid valproic acid (VPA) as sodium salt. Eight patients treated with PHT, but not with VPA, were studied for comparison purposes. In the absence of VPA coadministration, total and free PHT concentrations did not change significantly during the day and showed only minor intrapatient fluctuations (14 and 13, respectively). In patients receiving VPA, the mean total PHT did not change significantly, whereas the free PHT increased during the day (p < 0.05). The fluctuations in total and free PHT in these patients were 16 and 17 on average. In the presence of VPA, the free PHT fraction was higher than in controls (13.9 ± 2.3 versus 8.3 ± 1.9; p < 0.01) and fluctuated to a greater extent (29 versus 14 in controls; p < 0.01), mainly as a result of combined opposite swings in both total and free concentration. The diurnal changes in free PHT concentration and fraction correlated positively with the changes in plasma VPA. An inverse relationship between total PHT concentration and plasma VPA was found in some patients. These data demonstrate that the displacement interaction between PHT and VPA is subject to diurnal variation, probably as a result of the fluctuation in plasma VPA. The implications of these findings are discussed.

The incidence of lateral gaze nystagmus and its correlation with free and total plasma concentrations of carbamazepine CBZ and carbamazepine10,11epoxide CBZE were examined in 97 epileptic patients receiving chronic treatment with CBZ alone n 54 or in combination with phenobarbital PB n 43. All patients had plasma CBZ concentrations within the clinically optimal range <50 molL, Nystagmus was seen in 26 of patients receiving monotherapy and in 33 receiving combination therapy, Within each group. however, nystagmus was much more frequent among patients with higher CBZ concentrations. For patients receiving PB in combination the CBZ levels above which nystagmus was particularly frequent appeared to be lower than in the monotherapy patients—a finding that could not be attributed to differences in plasma PB concentrations. The correlation of CBZE levels or the sum of CBZ CBZE with the occurrence of nystagmus was no better than that observed with CBZ levels alone. Free drug levels did not appear to be superior to total levels in discriminating between patients with or without nystagmus. These results indicate that the occurrence of nystagmus is concentrationdependent within the therapeutic plasma CBZ concentration range and suggest that the threshold at which this neurological sign appears is reduced in the presence of PB, possibly as a result of a pharmacodynamic interaction.

The diurnal fluctuations in free and total plasma levels of carbamazepine (CBZ) and carbamazepine-10, 11-epoxide (CBZ-E) and their relationship with intermittent side effects were examined in 10 epileptic patients stabilized on chronic CBZ therapy alone or in combination with phenobarbital (PB). With a t.i.d. or q.i.d. dosing schedule, total plasma levels of CBZ and CBZ-E fluctuated to a similar extent (average 34 and 29, respectively). The diurnal changes in free levels of both compounds mirrored closely those of the total levels. Free fraction values ranged from 13 to 26 for CBZ and from 24 to 66 for CBZ-E. Owing to the lower protein binding of the metabolite, CBZ-E/CBZ ratios were higher in plasma water (0.49) than in whole plasma (0.22). A good correlation was found between both total and free CBZ levels and dose-related side effects (diplopia, nystagmus). On the other hand, no apparent relationship was found between side effects and either total or free plasma CBZ-E. The correlation with the presence of neurological signs of toxicity for the sum of CBZ ± CBZ-E levels was no better than that observed for CBZ levels alone. These data do not support the hypothesis that CBZ-E contributes significantly to the development of dose-related side effects in CBZ-treated patients.

Computed tomographic (CT) findings of three patients affected by progressive supranuclear palsy (PSP) are reported. The radiological picture consisted of atrophy of the midbrain and quadrigeminal plate, with prominent interpeduncular, crural, ambient, and quadrigeminal plate cisterns, and dilatation of the aqueduct and third ventricle. These features were not related to the duration of the illness and degree of neurological deficits. In the authors' opinion CT is useful in the differential diagnosis of PSP and other extrapyramidal disorders. Index Terms: Brain, diseases—Brain, atrophy—Computed tomography.

Patients with cortical malformations often have intractable seizures and are candidates for epilepsy surgery. Within an unselected series of patients with various forms of cortical malformation, nine patients with multilobar polymicrogyria had electrical status epilepticus during sleep (ESES) accompanied by infrequent focal motor seizures. Eight patients also had intractable atonic drop attack seizures. Because ESES usually is accompanied by a good long-term seizure prognosis, the objective of this study was to examine ESES outcome among patients with a structural lesion that is usually highly epileptogenic and has a low seizure remission trend.

In the period of time from Oct., 1956, to June, 1958, in the Department of Neurology of the University of Bari, 4 cases of posttraumatic chronic subdural hematomas were observed in which the clinical symptoms and the characteristic arteriographic picture regressed completely without surgical intervention.1 Their treatment consisted of bed rest and an ample diet fortified with a variety of vitamins, antihemorrhagic and vasoprotective drugs, corticosteroids, and intravenous injections of hypertonic glucose solutions.Since that time, several other unpublished cases have been observed which responded as well to this supportive therapy. Some of these patients are still under observation and warrant a longer follow-up. Three of them, however, may be considered symptom-free and will be herein reported. REPORT OF THREE CASES Case 1.—A 57-year-old man was admitted to the Department of Neurology on Oct. 9, 1958, with a history of headaches, more marked in the left frontal region, of