Repetitive transcranial magnetic stimulation for patients with functional paralysis: a randomized controlled study.

BACKGROUND AND PURPOSE: Repetitive transcranial magnetic stimulation (rTMS) has been proposed to treat functional neurological disorders. Here, the aim was to assess the efficacy of rTMS to treat functional paralysis in a controlled randomized trial. METHODS: Patients received two sessions of active or sham 0.25 Hz rTMS (60 stimuli each), with a 1-day interval, applied over the motor cortex contralateral to the paralysis. The primary outcome was the number of patients with an increase in motor score between baseline and after the second rTMS session, rated by two investigators blinded to the treatment allocation. Secondary outcomes were changes in global and fine motor scores between groups after rTMS, and the occurrence of adverse events. RESULTS: Sixty-two patients (46 female; mean [SD] age, 35.2 [13.9] years) were enrolled and randomized. Thirteen out of 32 (41%) and 11/30 (37%) patients had increased motor strength after active or sham rTMS, respectively (p = 0.80). Changes in both global and fine motor scores after rTMS relative to baseline were also not significantly different between treatment groups (median difference in the global motor score 0.62 [0.83] and 0.37 [0.61], and in the fine motor scores 0.12 [0.18] and 0.08 [0.11], in active and sham rTMS groups, respectively; p = 0.14). Six serious adverse events, consisting of three cephalalgia in the active group and two cephalalgia and one asthenia in the sham group, were observed. CONCLUSIONS: Two sessions of sham or active low frequency rTMS were effective to improve functional paralysis, suggesting a placebo effect of this non-invasive brain stimulation technique.

Vagus nerve stimulation for drug-resistant epilepsy: a European long-term study up to 24 months in 347 children.

OBJECTIVE: To gain insight into the long-term impact of vagus nerve stimulation (with VNS Therapy) in children with drug-resistant epilepsy, we conducted the largest retrospective multicenter study to date over an extended follow-up period of up to 24 months. METHODS: The primary objective was to assess change in seizure frequency of the predominant seizure type (defined as the most disabling seizure) following VNS device implantation. Treating physicians collected data from patient records from baseline to 6, 12, and 24 months of follow-up. RESULTS: The analysis population included 347 children (aged 6 months to 17.9 years at the time of implant). At 6, 12, and 24 months after implantation, 32.5%, 37.6%, and 43.8%, respectively, of patients had ≥ 50% reduction in baseline seizure frequency of the predominant seizure type. The responder rate was higher in a subgroup of patients who had no change in antiepileptic drugs (AEDs) during the study. Favorable results were also evident for all secondary outcome measures including changes in seizure duration, ictal severity, postictal severity, quality of life, clinical global impression of improvement, and safety. Post hoc analyses demonstrated a statistically significant correlation between VNS total charge delivered per day and an increase in response rate. VNS Therapy is indicated as adjunctive therapy in children with focal, structural epilepsies, who for any reason are not good candidates for surgical treatment following the trial of two or more AEDs. Children with predominantly generalized seizures from genetic, structural epilepsies, like Dravet syndrome or Lennox-Gastaut syndrome, could also benefit from VNS Therapy. SIGNIFICANCE: The results demonstrate that adjunctive VNS Therapy in children with drug-resistant epilepsy reduces seizure frequency and is well tolerated over a 2-year follow-up period. No new safety issues were identified. A post hoc analysis revealed a dose-response correlation for VNS in patients with epilepsy.

Efficacy of the histamine 3 receptor (H3R) antagonist pitolisant (formerly known as tiprolisant; BF2.649) in epilepsy: dose-dependent effects in the human photosensitivity model.

A new class of drugs, the nonimidazole histamine 3 receptor (H3R) antagonists, has been developed in the past decade for treatment of various brain diseases. Pitolisant is such a drug. We studied the pharmacodynamic effect of pitolisant in patients with epilepsy in early Phase II, using the photosensitivity proof of concept model. A total of 14 adult patients (11 females and 3 males; 5 drug naïve) were studied for three days to evaluate the effect of a single oral dose of pitolisant on EEG photosensitivity ranges. All patients showed repeatedly a generalized photoparoxysmal response (PPR) prior to drug administration on placebo Day 1. A statistically significant suppressive effect (standardized photosensitive response [SPR] reduction as measured with paired t-tests) for 20-, 40-, or 60-mg doses of pitolisant was seen in 9/14 (64%) patients of whom 6/14 (43%) showed abolition of the response to intermittent photic stimulation (IPS). Patients on the highest dosage (60 mg) showed the strongest effect with an effect lasting up to 28 h. Thus, full-scale Phase II studies with this novel H3R antagonist, pitolisant, in patients with epilepsy are warranted.

Epilepsy in the Sanaga-Mbam valley, an onchocerciasis-endemic region in Cameroon: electroclinical and neuropsychological findings.

OBJECTIVE: Epilepsy is highly prevalent in onchocerciasis-endemic African regions. Various types of epilepsy have been described in such regions based essentially on clinical characteristics. METHODS: We conducted a clinical, neurophysiological and neuropsychological study of epilepsy in the onchocerciasis-endemic region of Ntui, Sanaga-Mbam area, Cameroon. RESULTS: One hundred and eighty-seven persons with presumed epilepsy were recruited in an epilepsy clinic in Ntui. Epilepsy was clinically confirmed in 144 (79%) subjects, 69 (46.0%) of them met the onchocerciasis-associated epilepsy (OAE) criteria, and 51 of 106 tested (48.1%) presented Ov16 antibodies. Electroencephalograms (EEG) were recorded in 91 participants, of which 36 (33%) were considered abnormal and 27 of 36 (75%) revealed bifrontotemporal spike and slow waves. Concerning the neuropsychological evaluation, 29% showed severe global cognitive impairment, 28% severe episodic memory impairment, and 66% severe frontal cognitive impairment. Half of the persons with epilepsy (PWE) suffered from a mental disorder. SIGNIFICANCE: In PWE in the Sanaga-Mbam area in Cameroon, we observed EEG patterns similar to those described among persons with OAE, including nodding syndrome in other onchocerciasis-endemic areas. Most PWE presented with severe cognitive impairment. We hypothesize that onchocerciasis may induce neurocognitive disorders and epilepsy via a mechanism that involves mainly the frontal and temporal regions of the brain.

Psychogenic paralysis and recovery after motor cortex transcranial magnetic stimulation.

Psychogenic paralysis presents a real treatment challenge. Despite psychotherapy, physiotherapy, antidepressants, acupuncture, or hypnosis, the outcome is not always satisfactory with persistent symptoms after long-term follow-up. We conducted a retrospective study to assess clinical features and to propose an alternative treatment based on repetitive transcranial magnetic stimulation (rTMS). Seventy patients (44 F/26 M, mean age: 24.7 +/- 16.6 years) experienced paraparesis (57%), monoparesis (37%), tetraparesis (3%), or hemiparesis (3%). A precipitating event was observed in 42 patients, primarily as a psychosocial event or a physical injury. An average of 30 stimuli over the motor cortex contralateral to the corresponding paralysis was delivered at low frequency with a circular coil. The rTMS was effective in 89% of cases, with a significantly better outcome for acute rather than chronic symptoms. In conclusion, motor cortex rTMS seem to be very effective in patients with psychogenic paralysis and could be considered a useful therapeutic option.

Treatment of primary headache in children: a multicenter hospital-based study in France.

The aim of this 6-month, prospective, multicenter study of 398 children and adolescents with primary headaches was to collect data on headache treatment in neuropediatric departments. Treatments were compared before and after consultation. Prior to consultation, the acute treatments that had been prescribed most frequently were paracetamol (82.2% of children) and non-steroidal anti-inflammatory drugs treatment (53.5%); 10.3% had received a prophylactic treatment. No differences in either acute or prophylactic treatment with respect to headache diagnosis were observed. After the neuropediatric consultation, paracetamol was replaced by a non-steroidal anti-inflammatory drug in about three-quarters of cases and by triptan in about one-quarter of cases. The number of children prescribed a prophylactic treatment nearly doubled, whereas there was a 5-fold and 23-fold increase in psychotherapy and relaxation training, respectively, between pre-referral and referral. We conclude that specific treatments were underused for primary headache.

Epilepsy surgery program in Tunisia, the Charles Nicolle Hospital experience.

BACKGROUND: Epilepsy surgery is the best treatment in case of intractable epilepsy. However, it is underused in developing countries, creating an enormous treatment gap. On 2006, an epilepsy surgery program was set up in the Neurological Department of Charles Nicolle Hospital, Tunis, Tunisia. AIM: To describe its establishment and to emphasize on its originality that is an exchange and surgery decision taken by two Neurological teams via the internet. METHODS: Patients underwent a phase 1 presurgical evaluation at the Neurological Department of Charles Nicolle Hospital of Tunis. It included a detailed clinical history, a neurological evaluation, brain MRI, a continuous video EEG scalp monitoring and a neuropsychological evaluation. RESULTS: According to the different electro clinical and radiological findings, the surgery indication was taken between the Neurological department of Charles Nicolle Hospital of Tunis and the Neurophysiological Department of Charles Nicolle Hospital in Rouen through the EUMEDCONNECT network project. ATL was performed and the four patients are actually seizure free. CONCLUSION: Epilepsy surgery is actually a possible treatment option in Tunisia and should be indicated in patients with intractable partial seizures.

Clinical and electroencephalographic abnormalities during the full duration of a sporadic hemiplegic migraine attack.

Electroencephalographic (EEG) abnormalities have been reported during migraine attacks but their spatial and temporal distributions are not well known. We report the temporospatial dynamics of EEG during the full duration of a migraine attack with aura in a 19-year-old woman. She experienced episodes of hemiplegic migraine since the age of 2.5 years, with right hemibody paralysis preceded by visual symptoms. She reported severe pain of the right hemibody just before hemiplegia that was enventually suggestive of possible epileptic seizure, justifying diagnostic video-EEG monitoring. Sporadic hemiplegic migraine was diagnosed in the absence of family history. EEG was normal at the beginning of visual aura. After 15minutes, posterior slow waves appeared over the migrainous hemisphere, spreading progressively towards anterior regions: first the central region (5minutes after onset of contralateral hemiplegia), then the frontal region and over both hemispheres. A new de novo mutation was identified in the SCN1A gene.

Impaired functional differentiation for categories of objects in the ventral visual stream: A case of developmental visual impairment.

We report the case of a 14-year-old girl suffering from severe developmental visual impairment along with delayed language and cognitive development, and featuring a clear-cut dissociation between spared dorsal and impaired ventral visual pathways. Visual recognition of objects, including faces and printed words, was affected. In contrast, movement perception and visually guided motor control were preserved. Structural MRI was normal on inspection, but Voxel Based Morphometry (VBM) revealed reduced grey matter density in the mesial occipital and ventral occipito-temporal cortex. Functional MRI during the perception of line drawings uncovered impaired differentiation which is normally observed at even younger ages: no local category preferences could be identified within the occipito-temporal cortex for faces, houses, words or tools. In contrast, movement-related activations appeared to be normal. Finally, those abnormalities evolved on the background of chronic bilateral occipital epileptic activity, including continuous spike-wave discharges during sleep, which may be considered as the primary cause of non-specific intellectual disability and visual impairment.

Delayed intracranial hematoma following stereoelectroencephalography for intractable epilepsy: case report.

Intracranial bleeding following stereoelectroencephalography (sEEG) is rare and commonly occurs early after electrode implantation. The authors report the case of a delayed intracranial hematoma following sEEG. This 10-year-old boy was referred to the authors' department to undergo an sEEG study for intractable epilepsy, with the hypothesis of a single localized epileptic zone in the left precentral region. To perform the exploration, 14 depth electrodes were implanted under stereotactic conditions. The results of a postoperative CT scan performed routinely at the end of the surgical procedure were normal. Eight days later, following an epileptic seizure, the child's condition worsened. The neurological examination revealed a left hemiparesis, agitation, and coma due to a right subdural hematoma with intraparenchymal bleeding. Despite a surgical evacuation followed by a decompressive craniectomy, the curative treatments were stopped 1 week later due to severe diffuse ischemic lesions found on MRI studies. This is the first observation of a delayed hematoma following an sEEG procedure. The mechanism underlying this complication remains unclear, but the rupture of a growing pseudoaneurysm caused by the electrode's implantation or the tearing of a neighboring vessel by an electrode were suspected. In consequence, physicians must remain vigilant during the entire sEEG recording period and probably also several days after electrode removal.

Epilepsy surgery program in Tunisia: an example of a Tunisian French collaboration.

OBJECTIVE: To describe the first Tunisian epilepsy surgery program establishment and to emphasize on its originality that is an exchange and surgery decision taken by two Mediterranean neurophysiological teams, via the Internet. METHODS: Patients with mesial temporal lobe epilepsy (MTLE) and refractory to antiepileptic drugs were included. A noninvasive protocol evaluation including a detailed history, neurological evaluation, brain imaging, scalp video-EEG monitoring and neuropsychological evaluation were performed. The different findings were discussed between the Neurophysiological Department of Charles Nicolle Hospital of Tunis and Rouen through the EUMEDCONNECT Internet network project. If cases of concordance of clinical, neuropsychological, neuroimaging data and video-EEG recordings, surgery was indicated. RESULTS: 15 patients (7 women and 8 men) with mean age of 30 years were included. 10 patients had right hippocampal sclerosis (HS) and 5 had left HS. MRI findings were concordant with the ictal EEG in 12 patients. One patient had bitemporal ictal EEG abnormalities and right HS on MRI. One patient had contralateral ictal clinical and EEG patterns to the side of HS. One patient had temporal 'plus' epilepsy. Surgery was performed in 10 cases. After surgery, all patients are seizure free, with no operative mortality or major surgery complications. CONCLUSION: Our model of twin affiliations between advanced epilepsy surgery programs in a developed country and starting programs in a developing country, using Internet technology, can be a model for collaboration in other countries.

Classification conundrums in paroxysmal dyskinesias: a new subtype or variations on classic themes?

Paroxysmal movement disorders are a group of heterogeneous entities that have been categorized based on their most salient features. The four classic categories of paroxysmal dyskinesias are kinesigenic, nonkinesigenic, hypnogenic, and exercise-induced. The phenotypic variability of these disorders, coupled with new insights into their possible etiologies, has made the task of classification increasingly problematic. We describe 4 cases that do not fit easily into the current classification scheme, compare them with four others recently described in the literature, and raise the question as to whether they constitute a new subtype.

Mechanism of intrachromosomal triplications 15q11-q13: a new clinical report.

We describe here a patient with intrachromosomal triplication 15q11-q13, a rare chromosomal event associated with severe mental retardation and intractable epilepsy. Cytogenetic studies including FISH on interphasic nuclei showed that the middle segment of the triplication was inverted in orientation. Molecular analyses demonstrated that the rearrangement was of maternal origin. Based on these cytogenetic and molecular data and those of the nine cases reported in the literature, we discuss the mechanistic origins of these triplications. We present several arguments for the mechanism involving two U-type exchanges occurring simultaneously at the pachytene stage of meiosis.

Severe myoclonus-dystonia syndrome associated with a novel epsilon-sarcoglycan gene truncating mutation.

Myoclonus-dystonia syndrome (MDS) is an autosomal dominant disorder characterized by myoclonic and dystonic muscle contractions, associated with psychiatric manifestations. MDS is usually considered as a benign disease. In most of the families, MDS is linked to chromosome 7q21 and mutations within epsilon-sarcoglycan (SGCE) gene have been recently described. We report a MDS family with a severe and heterogeneous phenotype, including myoclonus with important functional impact and several psychiatric features, characterized by obsessive-compulsive disorder, depression, and anxiety. This phenotype was shown to be associated with a novel truncating mutation located within exon 4 of SGCE.