Bilateral periventricular nodular heterotopia in France: frequency of mutations in FLNA, phenotypic heterogeneity and spectrum of mutations.

Bilateral periventricular nodular heterotopia (BPNH) is the most common form of periventricular heterotopia. Mutations in FLNA, encoding filamin A, are responsible for the X linked dominant form of BPNH (FLNA-BPNH). Recently, atypical phenotypes including BPNH with Ehlers-Danlos syndrome (BPNH-EDS) have been recognised. A total of 44 FLNA mutations have so far been reported in this phenotype. Most of these mutations lead to a truncated protein, but few missense mutations have also been described. Here, the results of a mutation screening conducted in a series of 32 BPNH patients with the identification of 12 novel point mutations in 15 patients are reported. Nine mutations were truncating, while three were missense. Three additional patients with BPNH-EDS and a mutation in FLNA are described. No phenotype-genotype correlations could be established, but these clinical data sustain the importance of cardiovascular monitoring in FLNA-BPNH patients.

[Basal ganglia deep-brain stimulation for treatment of drug-resistant epilepsy: review and current data]. / La stimulation cérébrale profonde des ganglions de la base comme traitement des épilepsies pharmacorésistantes: revue et données actuelles.

The surgical treatment of intractable epilepsies involving eloquent areas of the cortex is still challenging. Deep-brain stimulation could be an alternative to resective surgery because it can modulate the remote control systems of epilepsy, such as the thalamus and basal ganglia. The surgical experience acquired in the field of movement disorder surgery and the low morbidity of this technic could allow one to apply DBS to intractable epilepsies, such as generalized, motor and bitemporal epilepsies. Here we discuss the main experimental and clinical data reported so far in the literature and taken from our own experience.

[Epileptogenic and non-epileptogenic zones: blood flow studies of temporo-limbic seizures]. / Zones épileptogènes et non-épileptogènes: imagerie de perfusion des crises temporo-limbiques.

To assess the contribution of ictal SPECT to the definition of the epileptogenic zone (EZ) prior to surgery in focal drug-resistant epilepsies, we investigated the effect of the timing of injection and seizure semiology on patterns of perfusion and cerebral blood flow changes (CBF) beyond the EZ. In the rat model of amygdala-kindled seizures, we measured CBF changes with the quantitative [(14)C]-iodoantipyrine autoradiographic method during secondary generalized (SGS, n=26 fully-kindled rats) and focal seizures (FS, n=19 partially kindled rats), according to sequential timing of injection with respect to seizure onset. During SGS, the correct lateralization and rough localization of the focus within limbic structures was only possible at the early ictal and post-ictal times, in between we observed widespread rCBF increases. The switch from hyper to hypoperfusion occurred at the time of late ictal injection. The accurate localization of the EZ was obtained in the study of the more subtle FS (stage 0). At stage 1 of the kindling, there was already a remote widespread spreading of hyperperfusion. In patients surgically cured from a mesio-temporal lobe epilepsy (mean post-operative follow-up: 66 months), we retrospectively studied 26 pairs of ictal and interictal pre-operative SPECTs, classified in 3 groups according to the progression of ictal semiology. Using visual analysis of subtracted SPECTs (SISCOM) and group comparisons with a control group (using SPM), we observed more widespread combined hyper and hypoperfusion with the increasing complexity of seizures. In simple partial seizures, the SISCOM analysis allowed a correct localization of the focus in 4/8 patients, whereas the SPM analysis failed to detect significant changes, due to individual variation, spatial normalization and small magnitude of CBF changes. In complex partial seizures with automatisms, SISCOM and SPM analysis showed antero-mesial temporal hyperperfusion (overlapping the EZ), extending to the insula, basal ganglia, and thalamus in the group of patients having dystonic posturing (DP group) in addition to automatisms. Ictal hypoperfusion involved pre-frontal and parietal regions, the anterior and posterior cingulate gyri, to a greater extent in the DP group. In both human and animals studies, we observed a correlation between the extent of composite patterns of hyper/hypoperfusion and the severity of seizures, and the recruitment of remote sub-cortical structures. Hypoperfused areas belong to neural networks involved in perceptual decision making and motor planning, whose transient disruption could support purposeless actions, i.e. motor automatisms.

[What is needed for rTMS to become a treatment?]. / Que manque-t-il à la rTMS pour devenir une thérapie?

Repetitive trans-cranial magnetic stimulation (rTMS) can modulate cortical excitability. Consequently, it appears appealing for the treatment of some affections such as depression or hallucinations. There is already some proof that the concept is valid, but rTMS is slow in progressing in the therapeutic field as a true armamentum. Indeed its effects are of short duration and even inconstant from one patient to the next. These drawbacks depend on certain factors that we will discuss. Until now, there has been inadequate control of the stimulation site. It is possible that this site could vary on an individual basis. It seems logical to propose the use of functional imaging for such a purpose, but its use should be adapted to the symptom. Even after localizing the site, the coil has to be placed accurately. This could be facilitated by a neuronavigator. Stimulation protocols are currently defined by three parameters: the frequency modulating the cortical action either as a stimulation (>5 Hz) or an inhibition (<1 Hz), the intensity and the number of stimuli influencing, notably, the amplitude and duration of the effect. Unfortunately, the effect is inconstant in a given patient and paradoxical reactions have been observed in more than 15% of normal individuals. Improved reliability and amplification of the effect rely on the better control of other parameters: pattern of stimulation, pre and post-conditioning, state of the cortex during stimulation, associated medications, endogenous idiosyncratic factors and related pathology. We will review the current physiological literature to discuss the possible options that would constitute a rational basis for setting up more efficient protocols.

[Selective memory impairment for public events associated with accelerated forgetting in a patient with left temporal lobe epilepsy]. / Déficit sélectif de la mémoire des faits publics associé à un oubli accéléré chez un patient atteint d'épilepsie du lobe temporal gauche.

BACKGROUND: Memory for the past has been much less explored than anterograde memory in temporal lobe epilepsy. No data are available about the course after surgical treatment. Moreover, case-reports showing isolated memory deficit for publics events with preserved autobiographical memory are notorious for their paucity. METHODS: We report the case of a patient with a left hippocampal lesion associated with intractable temporal lobe epilepsy. Comprehensive neuropsychological assessments were carried out before and after temporal lobectomy, stressing particularly memory for the past by means of standardised and tailor-made tests. RESULTS: The patient exhibited preserved memory for autobiographical events and facts but impaired scores on several public event tests, in the context of preserved general abilities. Furthermore, we found an accelerated forgetting rate for verbal and non verbal material. CONCLUSION: Our findings suggest that the patient's impaired long-term consolidation might have contributed to the impaired performance on public event memory tests. We discuss the specific features of new events processing that may contribute to its increased vulnerability relative to autobiographical memory, in the event of accelerated forgetting.

Neuroprotective effects of chronic estradiol benzoate treatment on hippocampal cell loss induced by status epilepticus in the female rat.

Neuroprotective properties of estrogen are supported by extensive experimental evidence. In this study, the effects of estrogen were examined on the neurodegeneration secondary to status epilepticus induced by kainic acid in the rat. Chronic supplementation of ovariectomized rats with estradiol benzoate (20 microg/day) did not modify the expression of seizures monitored by electroencephalography, but significantly reduced cellular loss in the hippocampus. This neuroprotection was in particular observed in the dentate hilus and CA3 pyramidal layer when treatment with estradiol benzoate was started five days before status epilepticus induction. These findings suggest that estrogen can exert neuroprotective effects in a model of status epilepticus, in the absence of anti-epileptic properties.

[Neuroimaging evaluation of adult patients with uncontrolled localization-related epilepsy]. / L'imagerie morphologique des épilepsies partielles pharmaco-résistantes chez l'adulte.

A consensus is that, in patients with partial epilepsy, magnetic resonance imaging is necessary to identify the underlying epileptogenic lesion, to determine the likely site of seizure onset, and contribute to the selection of appropriate candidates for epilepsy surgery. Despite variable protocols and a continuously evolving technology, a cautious analysis of available literature provides some general guidelines for clinical practice.

[Medical and medico-social case management of drug-resistant partial epilepsy. Specific implementation of long-term antiepileptic treatment in the adult]. / Prise en charge médicale et médico-sociale des EPPR. Conduite spécifique du traitement antiépileptique au long cours chez l'adulte.

Medical treatment of refractory localisation-related epilepsies in adults should always be considered with regard to surgical possibilities. When long-term therapy with antiepileptic drugs is necessary, the treatment tries to achieve maximal efficacy with the lowest unavoidable toxicity. Until an evidence-based choice can be made, the management is currently based on empirical knowledge. In this article, the available literature on effectiveness and monitoring of long term antiepileptic therapy is reviewed.

[Post-radiotherapy multifocal meningioma]. / Méningiome multifocal post-radiothérapique.

We report one case of radio-induced meningiomas revealed by an intracranial hypertension in an 46 year-old woman. A history of cephalic irradiation during infancy for a vascular nevus, not spontaneously reported by the patient, had been discovered because of the association with a radio-induced cataract. Meningiomas are a rare, severe and late complication of cephalic radiotherapy. The history of irradiation is not always spontaneously reported by the patient.

[Spontaneous regression of an acute spinal subdural hematoma. MR imaging]. / Régression spontanée d'un hématome sous-dural aigu rachidien. Données de l'IRM.

We report a case of acute spinal subdural hematoma which developed then regressed spontaneously. MR imaging contributed essential information for diagnosis and follow-up after conservative treatment. We made a short review of the literature and discuss the causes, pathogenesis, clinical presentation and usual treatment of acute spinal subdural hematoma. The differential diagnosis with the more frequent and extradural hematoma requiring immediate surgical evacuation is fundamental.

Thalamic nuclei activity in idiopathic generalized epilepsy: an EEG-fMRI study.

OBJECTIVE: Idiopathic generalized epilepsies (IGE) are characterized by specific EEG changes including 3- to 5-Hz generalized spike-and-wave discharges. The thalamus and its cortical interactions are considered essential in the production and propagation of spike-and-wave discharges. In animal studies, corticoreticular and limbic system property changes have been observed in absence seizures and during spike-and-wave discharges and suggest the involvement of different types of thalamic nuclei. With the development of deep brain stimulation in epilepsy, the role of the thalamic nuclei needs to be clarified in human IGE. METHODS: Ten patients with IGE were recorded using 3T EEG-fMRI during spike-and-wave discharges. Hemodynamic response functions were calculated for 4 regions of interest corresponding to the anterior thalamic and centromedian and parafascicular (CM-Pf) nuclei of each thalamus. The time to peak of the hemodynamic response function was compared within thalamic structures (left compared to right) and between structures (anterior thalamic compared to CM-Pf nucleus). RESULTS: CM-Pf and anterior nucleus are both activated during GSWDs. However, the positive time to peak in the CM-Pf (4.4 +/- 2.5 s) occurred significantly earlier than in the anterior nucleus (7.6 +/- 3.2 s). CONCLUSIONS: We demonstrated in humans the involvement of the centromedian and parafascicular part of the corticoreticular system and of the anterior nucleus part of the limbic system during generalized spike-and-wave discharges. The different time courses suggest that the posterior intralaminar nuclei may be involved in epileptic discharge initiation or early propagation, while the anterior nucleus may only play a role in its maintenance. These results may help to understand the clinical effect of deep brain stimulation within thalamic nuclei in intractable idiopathic generalized epilepsy patients.

SPM analysis of ictal-interictal SPECT in mesial temporal lobe epilepsy: relationships between ictal semiology and perfusion changes.

A combination of temporo-limbic hyperperfusion and extratemporal hypoperfusion was observed during complex partial seizures (CPS) in temporal lobe epilepsy (TLE). To investigate the clinical correlate of perfusion changes in TLE, we analyzed focal seizures of increasing severity using voxel-based analysis of ictal SPECT. We selected 26 pre-operative pairs of ictal-interictal SPECTs from adult mesial TLE patients, seizure-free after surgery. Ictal SPECTs were classified in three groups: motionless seizures (group ML, n=8), seizures with motor automatisms (MA) without dystonic posturing (DP) (group MA, n=8), and seizures with DP with or without MA (DP, n=10). Patients of group ML had simple partial seizures (SPS), while others had CPS. Groups of ictal-interictal SPECT were compared to a control group using statistical parametric mapping (SPM). In ML group, SPM analysis failed to show significant changes. Hyperperfusion involved the anteromesial temporal region in MA group, and also the insula, posterior putamen and thalamus in DP group. Hypoperfusion was restricted to the posterior cingulate and prefrontal regions in MA group, and involved more widespread associative anterior and posterior regions in DP group. Temporal lobe seizures with DP show the most complex pattern of combined hyper-hypoperfusion, possibly related both to a larger spread and the recruitment of more powerful inhibitory processes.