Giovanni Ambrosetto

Familial perisylvian polymicrogyria: a new familial syndrome of cortical maldevelopment

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

Multilobar polymicrogyria, intractable drop attack seizures, and sleep-related electrical status epilepticus.

Background and Objective: 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. Methods: The nine patients had follow-up periods lasting 4 to 19 years. All underwent brain MRI, serial sleep EEG recordings, and cognitive testing during and after ESES. Results: ESES and drop attack seizures appeared between the ages of 2 and 5 years(mean, 4 years) and ceased between the ages of 5 and 12 years (mean, 8 years). At the last visit patients were 8 to 23 years of age (mean, 14.5 years) and were either seizure free or had very infrequent focal motor seizures during sleep. Three patients were free from antiepileptic drugs. In no patient was definite cognitive deterioration apparent after ESES in comparison with earlier evaluations. Conclusions: Age-related secondary bilateral synchrony underlying ESES may be facilitated in multilobar polymicrogyria. The good seizure outcome contrasts with that usually found in the presence of cortical malformations. For children with polymicrogyria and drop attack seizures, surgical treatment of the epilepsy should be considered cautiously, and sleep EEG recordings should be performed systematically.

Diurnal Fluctuations in Free and Total Steady‐State Plasma Levels of Carbamazepine and Correlation with Intermittent Side Effects

Summary: The relationship between diurnal fluctuations in free (unbound) and total plasma carbamazepine levels and the appearance of intermittent side effects was investigated in nine epileptic patients receiving chronic therapy with carbamazepine, alone or in combination with phenobarbital. On a three‐times‐daily or four‐times‐daily dosing schedule, both total and free carbamazepine levels fluctuated considerably (on an average, 41 and 45%, respectively, around the mean). Side effects (particularly diplopia and nystagmus) were observed in five patients and showed an intermittent pattern in four. Side effects were never found at total carbamazepine levels<34 μmol/L but invariably appeared at levels >38 μmol/L. At levels between 34 and 38 (μmol/L adverse effects were inconsistently observed. The correlation between plasma carbamazepine levels and manifestations of toxicity was slightly stronger when free rather than total levels were considered. Side effects were always apparent at free levels >7.2 μmol/L. These data underline the limitations of relying on a single drug level determination during the monitoring of carbamazepine therapy and emphasize the necessity of carefully adjusting the dosing schedule, to minimize the appearance of intermittent adverse effects.

Antiepileptic Drug Treatment of Benign Childhood Epilepsy with Rolandic Spikes: Is It Necessary?

Summary: Ten untreated and 20 treated patients with benign childhood epilepsy with rolandic (centrotemporal) spikes (BERS) were studied retrospectively after recovery. Seizure frequency, seizure recurrence, and duration of active epilepsy were similar in both groups. No differences were found in social adjustment. Antiepileptic treatment may be unnecessary in most cases of BERS.

Orthostatic tremor: essential and symptomatic cases

We studied clinically and electrophysiologically 8 patients affected by ortho‐static tremor (OT), which is an unusual movement disorder consisting of shaking movements of the legs and trunk in the standing position. We failed to find any cause in 6 of the 8 cases. In 2 patients OT was clearly secondary to neurologic disease: hydrocephalus due to non‐tumoral acqueduct stenosis and chronic relapsing polyradiculoneuropathy. The findings obtained suggest a relationship between OT and essential tremor (ET).

Unilateral opercular macrogyria and benign childhood epilepsy with centrotemporal (rolandic) spikes : report of a case

Summary: An 18‐year‐old mentally normal epileptic boy had frequent left brachiofacial or unilateral motor seizures which started at age 4 years and ceased 10 years later. Seizures were exclusively sleep‐related. No relapse followed antiepileptic drug (AED) discontinuation. Left arm slight paresis and left hand astereognosia occurred at age 10 years. Awake EEGs showed persistent right rolandic discharges increased by sleep. Somatosensory evoked potentials (SEPs) were giant with left median nerve stimulation. Computed tomography (CT) and magnetic resonance imaging (MRI) disclosed right opercular macrogyria. We suggest that the structural brain lesion was causally related to his “idiopathic” partial epilepsy. Similar case reports and pathologic studies will elucidate the morphologic substrate of the underlying functional disorder in idiopathic partial epilepsies.

Occipital lobe seizures related to clinically asymptomatic celiac disease in adulthood.

Summary: We report the electroclinical ictal findings of four epileptic patients with clinically asymptomatic celiac disease (CD). Celiac disease diagnosis was suspected by past history and/or computed tomography (CT) findings in all patients and confirmed by laboratory tests and jejunal biopsy. All patients had paroxysmal visual manifestations and ictal EEG discharges arising from the occipital lobe. Epilepsy evolution was favorable in two patients and severe in 2, regardless of CT evidence of occipital corticosubcortical calcifications in 2 patients. Occipital lobe seizures may be characteristic of the epilepsy related to CD, and epileptic patients with these seizures of unknown etiology should be carefully investigated for malabsorption. If past history and/or laboratory tests suggest gastrointestinal (GI) dysfunction they should also undergo small intestinal biopsy even if they do not have GI tract symptoms.

Sturge-Weber syndrome without port-wine facial nevus: report of 2 cases studied by CT

2 cases of Sturge-Weber syndrome without facial nevus are reported. The patients presented different forms of epilepsy. The diagnosis was made by computed tomography (CT) which showed typical intracranial calcifications in both occipital regions. The problems concerning the atypical and incomplete forms of the syndrome are briefly discussed. The importance of CT as a diagnostic procedure for this disease is emphasized.

Treatable Partial Epilepsy and Unilateral Opercular Neuronal Migration Disorder

Summary: Five patients with treatable partial epilepsy and unilateral opercular neuronal migration disorder (NMD) are reported. Outcome was considered favorable when seizure control was prompt and complete with appropriate antiepileptic drug (AED) therapy, and when there was no relapse after AED discontinuation. Minor cortical sensorimotor defects were noted in 4 patients. All had normal mental status. No epileptic discharges were observed in the EEG of 4 patients, but rolandic spikes were observed in 1. The electroclinical and evolutive features suggested partial idiopathic epilepsy in 2 patients. Cases with focal neuronal migration disorders and favorable epilepsy outcome are probably more common than has been reported previously. The extent and location of the underlying microscopic lesions associated with the radiologically detectable cortical dysplasia may influence clinical outcome.

Drop attacks: An ominous change in the evolution of partial epilepsy

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.