Search

Background: The association between the pattern of cortical thickness (CT) and executive dysfunction (ED) in mild cognitive impairment (MCI) and subjective cognitive complaints (SCC) is still poorly understood. We aimed to investigate the association between CT and ED in a large French cohort (MEMENTO) of 2323 participants with MCI or SCC., Methods: All participants with available CT and executive function data (verbal fluency and Trail Making Test [TMT]) were selected (n=1924). Linear regressions were performed to determine relationships between executive performance and the brain parenchymal fraction (BPF) and CT using FreeSurfer., Results: The global executive function score was related to the BPF (sß: 0.091, P<0.001) and CT in the right supramarginal (sß: 0.060, P=0.041) and right isthmus cingulate (sß: 0.062, P=0.011) regions. Literal verbal fluency was related to the BPF (sß: 0.125, P<0.001) and CT in the left parsorbitalis region (sß: 0.045, P=0.045). Semantic verbal fluency was related to the BPF (sß: 0.101, P<0.001) and CT in the right supramarginal region (sß: 0.061, P=0.042). The time difference between the TMT parts B and A was related to the BPF (sß: 0.048, P=0.045) and CT in the right precuneus (sß: 0.073, P=0.019) and right isthmus cingulate region (sß: 0.054, P=0.032)., Conclusions: In a large clinically based cohort of participants presenting with either MCI or SCC (a potential early stage of Alzheimer's disease [AD]), ED was related to the BPF and CT in the left pars orbitalis, right precuneus, right supramarginal, and right isthmus cingulate regions. This pattern of lesions adds knowledge to the conventional anatomy of ED and could contribute to the early diagnosis of AD., (Copyright © 2024. Published by Elsevier Masson SAS.)

Purpose: To describe the prognostic factors of drug resistance in 40 patients with epilepsy with eyelid myoclonia or Jeavons syndrome., Method: Retrospective analysis from two French tertiary centers., Results: Forty patients were enrolled (31 females and 9 males; mean age at epilepsy onset: 6.2±3.4 years [range: 1-15 years]). Half of the patients (20/40) achieved at least a one-year remission from all seizure types. In the responders, seizure freedom was achieved after a mean 13.85±13.43 years from the onset of epilepsy (range: 1-44). The presence of intellectual disability and an earlier onset of the disease (≤5 years) were the most powerful predictors of poor seizure control (P=0.003 and P=0.005, respectively). When considering the age of onset, patients with early-onset seizures (≤5 years) presented more frequently with intellectual disabilities, psychiatric comorbidities, absences, and a major risk of refractoriness (70% versus 30%, P=0.01) than patients with onset after 5 years. At the last follow-up, 15 patients (37.5%) were taking a single drug, 16 (40%) were taking two, and seven (17.5%) were taking more than two. The most frequent drugs were valproate (23/40, 57.7%), followed by levetiracetam (16/40, 40%), and lamotrigine (14/40, 35%)., Conclusion: Patients with Jeavons syndrome present a high rate of pharmaco-resistance with the need for long-term treatment. Early onset of epilepsy and the presence of intellectual disability appeared to be the most relevant predictors of poor seizure control, suggesting the use of genetic tests to individualize specific etiologies and perhaps adapt the therapeutic strategy., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Sleep-wake disorders (SWD) are acknowledged risk factors for both ischemic stroke and poor cardiovascular and functional outcome after stroke. SWD are frequent following stroke, with sleep apnea (SA) being the most frequent SWD affecting more than half of stroke survivors. While sleep disturbances and SWD are frequently reported in the acute phase, they may persist in the chronic phase after an ischemic stroke. Despite the frequency and risk associated with SWD following stroke, screening for SWD remains rare in the clinical setting, due to challenges in the assessment of post-stroke SWD, uncertainty regarding the optimal timing for their diagnosis, and a lack of clear treatment guidelines (i.e., when to treat and the optimal treatment strategy). However, little evidence support the feasibility of SWD treatment even in the acute phase of stroke and its favorable effect on long-term cardiovascular and functional outcomes. Thus, sleep health recommendations and SWD treatment should be systematically embedded in secondary stroke prevention strategy. We therefore propose that the management of SWD associated with stroke should rely on a multidisciplinary approach, with an integrated diagnostic, treatment, and follow-up strategy. The challenges in the field are to improve post-stroke SWD diagnosis, prognosis and treatment, through a better appraisal of their pathophysiology and temporal evolution., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Magnetic resonance imaging (MRI) can now be used to diagnose or to provide confirmation of focal nonconvulsive status epilepticus (NCSE). Approximately half of patients with status epilepticus (SE) have signal changes. MRI can also aid in the differential diagnosis with generalized NCSE when there is a clinical or EEG doubt, e.g. with metabolic/toxic encephalopathies or Creutzfeldt-Jakob disease. With the development of stroke centers, MRI is available 24h/24 in most hospitals. MRI has a higher spatial resolution than electroencephalography (EEG). MRI with hyperintense lesions on FLAIR and DWI provides information related to brain activity over a longer period of time than a standard EEG where only controversial patterns like lateralized periodic discharges (LPDs) may be recorded. MRI may help identify the ictal nature of LPDs. The interpretation of EEG tracings is not easy, with numerous pitfalls and artifacts. Continuous video-EEGs require a specialized neurophysiology unit. The learning curve for MRI is better than for EEG. It is now easy to transfer MRI to a platform with expertise. MRI is more accessible than single photon emission computed tomography (SPECT) or positron emission tomography (PET). For the future, it is more interesting to develop a strategy with MRI than SPECT or PET for the diagnosis of NCSE. With the development of artificial intelligence, MRI has the potential to transform the diagnosis of SE. Additional MRI criteria beyond the classical clinical/EEG criteria of NCSE (rhythmic versus periodic, spatiotemporal evolution of the pattern…) should now be systematically added. However, it is more complicated to move patients to MRI than to perform an EEG in the intensive care unit, and at this time, we do not know how long the signal changes persist after the end of the SE. Studies with MRI at fixed intervals and after SE cessation are necessary., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Genetic or idiopathic generalized epilepsies (IGEs) account for 15-20% of all epilepsies. These syndromes have always been considered as good prognosis forms of epilepsy over time; however, for some patients, there is a need to maintain antiseizure drugs (ASD) for a long-time. Drug resistance is not uncommon (7-15%). Lifestyle remains essential and is an integral part of the treatment. Comorbidities such as obstructive sleep apnea syndrome must be considered and treated. A highly underestimated condition is the risk of sudden unexpected death in epilepsy (SUDEP). Very few data are available about the prevalence of SUDEP in IGE, but patients with generalized tonic-clonic seizures (GTCS) are exposed to this risk. IGEs are also characterized by a specific pharmalogical sensisitivity but may be aggravated by ASDs. Historically, the treatment of IGEs has relied mostly on valproate but this drug should be avoided in women of childbearing potential. Women with IGE not treated with valproate are more likely to have unsatisfactory seizure control. Female gender appears now as a new risk factor for drug-resistance. Finally, aside from the typical forms, there are epilepsies that fulfill most of the criteria of IGE, but that have an unusual history with GTCS, absences, falls, and drug resistance. Patients do not have psychomotor regression, brain magnetic resonance imaging is normal. EEG shows generalized fast rhythms during NREM sleep. These patients with refractory generalized epilepsy with sleep-related fast activities do not belong to a well-established syndromic category. These cases are considered "intermediary" between IGE and epileptic encephalopathies., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Spinal muscular atrophy (SMA) refers to a group of disorders affecting lower motor neurons. The age of onset of these disorders is variable, ranging from the neonatal period to adulthood. Over the last few years, there has been enormous progress in the description of new genes and phenotypes that throw new light on the molecular pathways involved in motor neuron degeneration. Advances in our understanding of the pathophysiology of the most frequent forms, SMA linked to SMN1 gene mutations and Kennedy disease, has led to the development of therapeutic strategies currently being tested in clinical trials. This report provides a general overview of the clinical features and pathophysiological mechanisms in adult-onset genetic SMA disorders in which the causative gene has been identified (SMN1-related SMA, Kennedy disease, CHCHD10, TRPV4, DYNC1H1 and BICD2). Sporadic lower motor neuron disease, also known as progressive muscular atrophy (PMA), is also discussed. The finding of TDP-43 aggregates in immunohistochemical studies of PMA strongly supports the idea that it is a phenotypic variant of amyotrophic lateral sclerosis (ALS)., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Central hypersomnias principally involves type 1 narcolepsy (NT1), type 2 narcolepsy (NT2) and idiopathic hypersomnia (IH). Despite great progress made in understanding the physiopathology of NT1 with low cerebrospinal fluid hypocretin-1 levels, current treatment remains symptomatic. The same applies to NT2 and IH, for which the physiopathology is still largely unknown. Controlling excessive daytime sleepiness (EDS), cataplexy, hypnagogic hallucinations, sleep paralysis and disturbed night-time sleep are key therapeutic targets in NT1. For IH and NT2, reducing EDS is the main objective. Based on European and American directives for the treatment of narcolepsy, we propose French recommendations for managing central hypersomnias as well as strategies in the case of drug-resistance. Stimulating treatments target EDS, and Modafinil is the first-line treatment. Other stimulants such as methylphenidate, pitolisant, and exceptionally dextro-amphetamine can be prescribed. Selective serotonin and noradrenaline reuptake inhibitor antidepressants are effective for the management of cataplexy in NT1. Sodium oxybate is an effective treatment for several symptoms, including EDS, cataplexy and disturbed night-time sleep. Treatment of central hypersomnia must also take into consideration frequent cardiovascular, metabolic and psychiatric comorbidities, particularly in NT1. New therapies are currently under study with the development of new stimulants and anti-cataplectics. The next few years will see innovative emerging therapies, based on a physiopathological approach, aiming to restore hypocretinergic transmission or to interrupt the autoimmune processes causing the loss of hypocretin neurons., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

In the new international classification of sleep disorders (ICSD-3), narcolepsy is differentiated into two distinct pathologies: type 1 narcolepsy (NT1) and type 2 narcolepsy (NT2). NT1 is characterised by periods of an irrepressible need to sleep, cataplexy (a sudden loss of muscle tone triggered by emotion) and in some cases the presence of symptoms such as hypnagogic hallucinations, sleep paralysis and disturbed night-time sleep. Its physiopathology is based on the loss of hypocretin neurons in the hypothalamus, seemingly connected to an auto-immune process. By definition, cataplexy is absent and the hypocretin levels in the CSF are normal in NT2. Confirming the diagnosis requires polysomnography and multiple sleep latency tests. The choice of further investigations is based on the presence or absence of typical cataplexy. Further investigations include HLA typing, lumbar puncture to measure the hypocretin level in the CSF, or even brain imagery in the case of narcolepsy suspected to be secondary to an underlying pathology. In this consensus we propose recommendations for the work-up to be carried out during diagnosis and follow-up for patients suffering from narcolepsy., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Idiopathic hypersomnia is a rare, central hypersomnia, recently identified and to date of unknown physiopathology. It is characterised by a more or less permanent, excessive daytime sleepiness, associated with long and unrefreshing naps. Night-time sleep is of good quality, excessive in quantity, associated with sleep inertia in the subtype previously described as "with long sleep time". Diagnosis of idiopathic hypersomnia is complex due to the absence of a quantifiable biomarker, the heterogeneous symptoms, which overlap with the clinical picture of type 2 narcolepsy, and its variable evolution over time. Detailed evaluation enables other frequent causes of somnolence, such as depression or sleep deprivation, to be eliminated. Polysomnography and multiple sleep latency tests (MSLT) are essential to rule out other sleep pathologies and to objectify excessive daytime sleepiness. Sometimes the MSLT do not show excessive sleepiness, hence a continued sleep recording of at least 24hours is necessary to show prolonged sleep (>11h/24h). In this article, we propose recommendations for the work-up to be carried out during diagnosis and follow-up for patients suffering from idiopathic hypersomnia., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Sleepiness is one of the most frequently reported complaints in adults and children during specialised sleep consultations. It is responsible for an alteration that can be severe in quality of life, a lowering of academic or professional performance, and domestic or work accidents. Hypersomnolence is the first cause of road accidents on the highway, responsible for a third of fatal accidents. Furthermore its presence is associated with an increased risk of morbi-mortality related to cardiovascular and neurodegenerative pathologies. Hence, its represents a real public health issue. Recent revisions in international classifications have clarified confusing terminology, and the complaint of hypersomnia has now been replaced by the terms hypersomnolence or excessive sleepiness. It is clinically defined as an excessive quantity of sleep over 24hours, and/or by an alteration in the quality of arousal defined as incapacity to maintain a satisfactory level of vigilance during the day or in the morning on awakening (defined as sleep inertia). The evaluation of sleepiness requires a rigorous clinical approach, completed by subjective and objective measurements. The Epworth Sleep Scale, Multiple Sleep Latency Tests and the Maintenance of Wakefulness Test are the most studied and used in clinical practice. However, to date, no gold standard measurement of excessive sleepiness exists, and there are no quantifiable biological markers. It is therefore important to optimise our evaluation tools, improve our pathophysiological understanding of sleepiness, and define genetic and environmental risk factors., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Post-lumbar puncture headache (PLPH) is a well-known syndrome resulting from spinal fluid leakage and delayed closure of a dural defect. The main symptom of PLPH is headache in upright posture relieved by lying down. Outcome is usually benign and complications are uncommon. The functional impact can however be important, leading to delayed discharge, sick leave and, if information delivery is ineffective, iterative consultations. Preventive measures have been published, but the prevalence of PLPH remains high (15 to 40% after diagnostic lumbar puncture). Needle size and type are probably the most important factors for reducing the risk of PLPH. Recovery can be rapid, within a few days. If PLPH persists after four days, an epidural blood patch should be discussed. The objective of this review is to summarize the literature on PLPH, and share the experience of our emergency headache center with an atraumatic 25-gauge needle (pencan, 0.5×90mm or 0.5×103mm, Braun, Germany)., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Introduction: Cerebrotendinous xanthomatosis, a metabolic leukodystrophy with an autosomal recessive inheritance, is secondary to deficiency of sterol 27-hydroxylase, an enzyme involved in cholesterol catabolism. Classical symptoms include clinical or infraclinical xanthomas affecting the skin and tendons, early cataracts, neurological signs and diarrhea. Brain imaging reveals involvement of the dentate nuclei and periventricular white matter hyperintensities. The diagnosis is based on an increased cholestanol level in serum, confirmed by the presence of a mutation in the CYP27A1 gene. Treatment is based on chenodeoxycholic acid., Method: We report a retrospective multicentric study of 15 cases of cerebrotendinous xanthomatosis diagnosed in French adults. Clinical, molecular and MRI findings were recorded in all patients., Results: The average age at diagnosis was 39years (range 27-65). Disease onset occurred in childhood in 73% of patients and in adulthood in 27%. All patients with a pediatric onset were diagnosed during adulthood (age range 28-65years). Clinical symptoms variably associated cerebellar syndrome, pyramidal syndrome, cognitive decline, epilepsy, neuropathy (sought in 10 of our patients, present in forms in 8), psychiatric disorders, cataract and xanthomas. One patient had an atypical presentation: monoparesis associated with xanthomas. Brain MRI was abnormal in all: findings consisted in T2-weighted hyperintensity of the dentate nuclei (47%), periventricular leuoencephalopathy (73%) which preferentially involved the posterior cerebral part (60%), leucoencephalopathy with a vascular pattern (7%), hyperintensity of the cortico-spinal tracts (53%), globi pallidi, corpus callosum and cerebral atrophy (33%). Serum cholestanol was elevated in 93% of patients. The most frequent mutation was 1183C>T (n=5/15). Under treatment with chenodeoxycholic acid, eight patients improved initially, followed by stabilization in five of them, and worsening in the others. Four patients died., Conclusion: Patients with the xanthoma-neurological disorder association should be tested for cerebrotendinous xanthomatosis. The disease often begins in childhood with a diagnostic delay but also in adulthood. Involvement of the dentate nuclei is specific but not sensitive and the supratentorial leucoencephalopathy is not specific but with an antero-posterior gradient. A vascular distribution and involvement of the corpus callosum are possible. Serum cholestanol assay is very reliable: an elevated level provides the diagnosis, which must nevertheless be confirmed by molecular biology., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Introduction: Cavitary white matter changes are mainly described in leukodystrophies and especially in vanishing white matter disease. Large cavitary lesions are not typical for multiple sclerosis (MS)., Methods: We studied MS patients with large cavitary brain lesions. Patient characteristics, disease onset/duration/subtype, expanded disability status scale (EDSS), mini mental state (MMS), vanishing white matter disease genetic analysis, and MRI characteristics of the cavitary lesions were analyzed., Results: Twenty patients were analyzed (6 men and 14 women). Mean age at disease onset was 37.6 (range 17-58). Mean disease duration was 10 years (range 2-20). Five patients had initial relapsing-remitting MS and nine patients had primary-progressive MS. Mean EDSS was 5.5 (range 2-8). Mean MMS was 20/30. Vanishing white matter disease genetic analysis was performed and negative in seven patients. Inferior corpus callosum lesions were seen in all patients with available sagittal FLAIR sequences. Cavitary lesions were strictly supratentorial, and located inside the diffuse leukoencephalopathy, with often a posterior predominance., Conclusion: MS patients with large cavitary lesions seem to represent a MS subgroup, predominantly women, with relatively late disease onset, predominantly primary-progressive type, relatively high EDSS scores, and severe cognitive dysfunction., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Introduction: White matter lesions seen on MR scan reflect small vessel disease of the brain; increasing age and high blood pressure are the main risk factors. In young patients without vascular risk factors, screening for CADASIL mutation has to be done. Our aim was to describe clinical as well as radiological features of a series of patients without NOTCH3 mutation with severe vascular leukoencephalopathy not explained by the presence of vascular risk factors., Material and Methods: Inclusion criteria were grade 3 leukoencephalopathy according to the Fazekas scale, age<70years at onset, and negative screening for NOTCH3 gene. Patients with severe vascular risk factors or atherosclerosis were excluded. Clinical and MRI findings were analysed., Results: Eight patients (four men) were included, five did not have any vascular risk factor. Mean age at onset was 59.5years. Initial symptoms were progressive in six cases of eight cases. They consisted of astasia-abasia and progressively worsened; of note one patient died 4years after disease onset. Cerebral MRI disclosed marked atrophy in five patients out of eight, temporal lobe (two out of eight) and external capsule (five out of eight) involvement was moderate. Four patients did not have any other atherosclerosis lesion. Seven out of eight had no retinal microangiopathy. High blood pressure was identified in two patients., Conclusion: The identification of vascular leukoencephalopathy in young patients without any vascular risk factors should lead the clinician to perform a complete work-up to search for treatable conditions including high blood pressure. Patients with vascular leukoencephalopathy usually present with astasia-abasia. In this context, cerebral MRI, cannot perfectly discriminate between patients with CADASIL from those with acquired small-vessel disease of the brain so that sequencing of NOTCH3 gene exons 2-24 is recommended., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Introduction: Cerebellar ataxia and stiff person-syndrome are the main neurological syndromes associated with antibodies to glutamic acid decarboxylase (GAD)., Case Report: A 59-year-old patient, with history of polymyalgia rheumatica and active smoking, was admitted for subacute cerebellar ataxia and memory dysfunction explained by limbic encephalitis on brain MRI. He also presented with orthostatic hypotension and erectile dysfunction revealing autonomic dysfunction. CSF was inflammatory and antibodies to GAD were positive. Onconeuronal antibodies including GABA(B) receptor antibodies were negative. Patient's condition quickly improved after intravenous immunoglobulins. A few months later, a small cell lung carcinoma was diagnosed and precociously treated., Conclusion: This case report underlines the importance of appropriate studies to confirm a primitive neoplasia, when confronted with limbic encephalitis and cerebellar ataxia, even if anti-GAD antibodies rarely define paraneoplastic syndromes., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Introduction: Neuralgic amyotrophy is considered to be a form of mononeuropathy multiplex which generally involves the nerves of the upper limbs., Observations: We describe four cases of neuralgic amyotrophy revealed by dyspnea due to phrenic nerve involvement, with asymptomatic motor deficit in the upper part of the brachial plexus., Conclusion: Phrenic nerve involvement revealed by dyspnea is rare. Associated with neurologic signs, the diagnosis is evocative. In case of an isolated attack, the key to diagnosis is the electromyographic exam., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Introduction: Demyelinating disease affecting both the central and the peripheral nervous systems has rarely been reported., Case Report: A 30-year-old man, presented with ataxia and diffuse areflexia due to polyneuropathy fullfilling demyelination criteria. His medical history was notable for central nervous system demyelination compatible with multiple sclerosis. He improved transiently with intravenous immunoglobulin and then stabilized with methotrexate., Conclusion: This case report distinguishes a new kind of inflammatory disease affecting both central and peripheral nervous system. It seems to be different from multiple sclerosis and chronic immune demyelinating polyneuropathy, because of high hyperproteinorachia and absence of oligoclonal bands in the cerebrospinal fluid., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Introduction: Neurological complications of infectious mononucleosis are rare. Various disorders have been described: meningitis, encephalitis, peripheral neuropathy. Isolated cranial nerve palsy has rarely been reported., Observation: A 16-year-old man was admitted for isolated and unilateral hypoglossal nerve palsy, four weeks after infectious mononucleosis. Cerebral MRI, cerebrospinal fluid study and electromyography were normal. IgM anti-VCA were positive. Two months later, without treatment, the tongue had almost fully recovered., Conclusion: To the best of our knowledge, only seven cases of isolated palsy of the hypoglossal nerve complicating infectious mononucleosis have been previously reported., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Introduction: Candida infection limited to the central nervous system is extremely rare, and may be confused with tuberculosis on the grounds of the clinical and cerebrospinal fluid findings., Case Report: A 23-year-old immunocompetent drug addict presented with alternating sciatica over a period of several months, followed by multiple cranial nerve involvement in the setting of marked weight loss. The histopathologic examination of a leptomeningeal neurosurgical biopsy was required to establish the diagnosis of neuromeningeal infection with Candida albicans., Conclusion: This case report underlines diagnostic difficulties of candidal meningitis and reviews current therapeutic recommendations., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

Introduction: Recurrent Guillain-Barré syndrome is a very rare entity. Few cases have been reported., Case Report: We report two patients who have developed a recurrent Guillain-Barré syndrome where one or even two episodes occurred after the same type of surgery, a hip prosthesis replacement., Discussion: Occurrence of Guillain-Barré syndrome after surgery has mainly been reported in relation to epidural anesthesia and less frequently general anesthesia. Although underlying pathogenic mechanisms remain unknown, a molecular mimicry phenomenon has been proposed.

Introduction: We describe a case of insulinoma presenting as a refractory frontal lobe epilepsy in a 44-year-old man with a history of severe head trauma., Case Report: Despite escalating treatment, his seizure frequency worsened during the previous year. He also developed psychomotor slowing and sweating occurring early in the morning. He gained weight. Insulinoma was diagnosed based on the presence of episodes of hypoglycemia, abnormal insulin/blood glucose ratio and a tumor in the pancreas (echo-ultrasound). After partial pancreatectomy, the patient became seizure free and anti-epileptic drugs were progressively stopped, with a follow-up of five years., Conclusion: Insulinoma should be considered in patients with no reason for having drug-resistant epilepsy, especially when seizures occur early in the morning or when episodes of neuropsychiatric symptoms with sweating are present.

Electroencephalography is a useful tool in the diagnosis and management of status epilepticus (SE) and it can also give prognostic information. It can help to confirm that an episode of SE has ended. It can identify the patients who have unsuspected subclinical seizures. There is a wide range of presentations of SE. Nearly all types of seizures have the potential of occurring in a repeated or continuous form. The polymorphic EEG patterns in SE reflect this wide variety. But controversial patterns also exist in the form of periodic epileptiform discharges. While some authors considered these patterns to be interictal or postictal, others postulate that these patterns are ictal. In these cases, clinical features are very important in order to conclude. Generalized convulsive SE is a medical emergency and the EEG is not necessary to make a diagnosis. Convulsive generalized SE requires immediate treatment and in this case, EEG is used in guiding treatment especially in refractory SE that may evolve into subtle SE. In non-convulsive SE, diagnosis is not obvious on the basis of clinical signs and symptoms alone and the diagnosis must be confirmed by urgent EEG. EEG can also be used to distinguish SE from psychogenic seizures, movement disorders and in patients who have causes of persistent loss of consciousness (metabolic encephalopathy, postanoxic encephalopathy). This article proposes a protocol for the use of the EEG in SE, guidelines and simple vocabulary for a good interpretation and comprehension of the EEG.

Narcolepsy is a rare, disabling sleep disorder, with a prevalence of 20 to 30 per 100,000. Its onset, from childhood to the fifties, peaks in the second decade. The main features are excessive daytime sleepiness and cataplexy or sudden loss of muscle tone triggered by emotional situations. Other less consistent symptoms include hypnagogic hallucinations, sleep paralysis, sleep maintenance insomnia, REM sleep behavior disorders, attention deficit and weight gain at disease onset. Narcolepsy with cataplexy remains a clinical diagnosis but nighttime and daytime polysomnography (multiple sleep latency tests) are useful to document a mean sleep latency below 8 min and at least two sleep-onset REM periods. HLA typing shows an association with HLA DQB1*0602 in more than 92% of cases but was not included in the new diagnostic criteria. In contrast, a low hypocretin levels (values below 110 pg/ml) in the cerebrospinal fluid (CSF) was highly specific for narcolepsy with cataplexy. The deficiency of the hypocretin system is well-established in animal models of narcolepsy (murine and canine narcolepsy) but also in human narcoleptics with a 90% reduction of CSF hypocretin levels in relation with an early loss of hypocretin neurons. The cause of human narcolepsy remains unknown, however an autoimmune process is most probable. The treatment of narcolepsy includes stimulants against sleepiness (modafinil, methylphenidate), anticataplectic drugs (antidepressants) and sodium oxybate. The current therapeutic target is oriented towards hypocretine agonists, histamine (an arousal system) H3 antagonists and immunosuppressants.

Background: Carbamazepine is associated with clinically relevant drug interactions especially with macrolide antibiotics such as troleandomycin and erythromycin. These drugs inhibit the metabolism of carbamazepine. Clarithromycin, a macrolide antibiotic similar to erythromycin, is widely used to treat respiratory tract infections and is used for the treatment of atypical mycobacterial infections and Helicobacter pylori-associated peptic ulcer disease., Methods: To report an interaction between carbamazepine and clarithromycin, we present a study that includes three regular attenders at the epilepsy department of Montpellier and seven cases reported by the French national drug safety center., Results: In patients receiving carbamazepine alone or in combination with other drugs, administration of clarithromycin led to a transitory overdosage (ataxia, dizziness, diplopia, nausea, vomiting, drowsiness). Blood level was available in 8 patients with a concentration of carbamazepine ranging from 13.3 to 28.5 mg/l., Conclusion: Carbamazepine is extensively metabolized by cytochrome P450 enzymes, especially CYP34A. As clarithromycin is also metabolized by CYP3A4, this drug has the propensity to inhibit the metabolism of carbamazepine. Clarithromycin should be thus avoided in patients taking carbamazepine.

The genetic inquiry in the diagnostic process of amyotrophic lateral sclerosis (ALS) need to be precise and systematic. Several hereditary neurologic disorders may initially mimic ALS, such as dominant spino-cerebellar ataxia or spastic paraplegia. Other hereditary motor neuron disorders are clinically more difficult to distinct from ALS such as Kennedy's disease, adult-onset spinal muscular atrophies or juvenile ALS. When a final diagnostic of ALS is established, the genetic inquiry aims at identifying a familial ALS (FALS) case. Almost 10 to 20 percent of ALS cases are familial. It is now admitted that 10 to 20 percent of those cases are due to SOD1 gene mutations. Such mutations may have a dominant or recessive inheritance. They are mainly found in multigenerational families. In 80 percent of the FALS cases, only two ALS cases are found in the pedigree. One cannot know whether this represent dominant cases with low penetrance, recessive inheritance or a multigenic, hereditary complex, disorder. More other, not all the SOD1 mutations have been demonstrated as causal. These elements are strong enough to suggest to precisely study, in the presence of a given SOD1 mutation, both the clinical phenotype, the data from the literature and, as often as possible, the segregation of the mutation into the family, before ascertaining that the mutation is responsible for a hereditary case of ALS. In every case, the genetic inquiry together with its conclusions should be done with caution, taking into account both the patient's need of a clear information and his anxiety regarding his descent.

Amyotrophic lateral sclerosis is a devastating disorder for which the psychological consequences of both the diagnosis announcement and the evolution of paralysis not only concern the patient but also his family. The role of the psychologist is to develop an individualized follow up considering the patient in his globality. The first consultation is, ideally, initiated after a medical consultation explaining the importance of the psychological area in ALS patient care. The psychological follow up will consist in an empathic listening of history and problems. Information will also be given to the patient by the psychologist who's role should not be only passive. When talking about "globality" of the psychological intervention for a given patient, his family takes a determinant place. The psychologist should be able to establish a contact with the family members concerned by the daily support to the patient. The psychological processes through which a patient will evolve should be explained to the family. Depression frequently affects family members, and a specific follow up in those cases has to be undertaken as soon as possible. Such a depressive reaction may also take place after death and a psychological follow up do not end after the death of a patient. The role of a psychologist in ALS care ideally takes places in the context of a multidisciplinary team such as a motoneuron clinic now largely available in our country. The burden of care is frequently heavy both for the family and the team of professional carers into and outside the hospital. The psychologist has a role of mediation between those persons, facilitating verbal exchanges, paying attention to specific difficulties and maintaining a fruitful exchange between the carers, the patient and his family. More prospectively, the psychologist also has a pedagogic role for the carers explaining psychological processes and giving clues for a constructive relationship between the patient and his family and also between this patient and his carers.

Introduction: Leflunomide is a new drug for the treatment of rheumatoid arthritis. Its mechanism of action is based on lymphocyte inhibition. We report the cases of two patients treated with leflunomide who developed severe sensory-motor axonal polyneuropathy., Observation: Two women (61- and 70-year-old) presented with a sensory-motor axonal polyneuropathy beginning 5 months after onset of leflunomide treatment. Etiologic investigations were negative. The symptoms rapidly improved after withdrawing leflunomide., Discussion: The analysis of drug watch data found twelve patients with leflunomide-related neuropathy. Ten of them were more than 60 years old. The mean delay for onset of neuropathy was 9 months. The neuropathy improved after treatment withdrawal in seven patients., Conclusion: We consider these data strongly suggest that leflunomide is a cause of axonal sensory-motor neuropathy. The prevalence of such adverse events is still unknown.

Since the early sixties, many concepts concerning neurogenesis have been progressively ruled out. Proof of the persistence of a physiological neurogenesis in adult mammals, including humans, raised the concept of a unique precursor cell giving birth to neurons and glial cells. According to this concept, a real continuum between neuroepithelial cells, radial glia and astrocytes exists from the embryonic period to adult age and generates both neurons and glial cells. Different factors, either secreted in situ or transported by blood, can influence this physiological neurogenesis process. The targets and role of newborn neurons are not clearly understood. In pathological conditions (ischemia, epilepsy, lesions), the physiological neurogenesis process is enhanced; however the significance of this neurogenesis excess (beneficial or deleterious) is not completely known. Advances in understanding the regulation of neurogenesis in these different conditions represent hopes of new therapeutic procedures, not only by improving the control of differentiation and survival of transplanted stem cells, but also by the possibility of modifying the processes of "endogenous neurogenesis".

Introduction: Bupropion hydrochloride (Zyban) is prescribed for smoking cessation. It is contraindicated in patients with seizure disorders. We report three patients with generalized tonic-clonic seizure that occurred a few days after the intake of this drug., Observations: The first two patients had no personal or family seizure history. They had generalized tonic-clonic seizure after taking bupropion (300 mg per day) for a few days. Acute symptomatic seizures were diagnosed in both cases. The third patient suffered from myoclonic jerks during adolescence, had a history of seizure after high dose codeine treatment and a family seizure history. She had generalized tonic-clonic seizure after taking bupropion 300 mg per day. EEG showed paroxystic generalized activity and photosensitivity, consistent with the diagnosis of juvenile myoclonic epilepsy., Discussion: Bupropion can lower seizure threshold. The incidence of seizure at 300 mg per day is 1/1000 patients treated., Conclusion: Many commonly prescribed drugs can trigger epileptic seizure, bupropion is one of them. When prescribing this drug, this adverse effect must be acknowledged and health practitioners should be aware of this risk.

Management of refractory epilepsy requires a comprehensive approach with cooperation between primary care physicians, neurologists or neuropaediatricians and specialist epilepsy centres. A regional or interregional network organisation may provide improved access to care provision including inpatient facilities for emergencies, early referral to an epilepsy specialist centre. Such organisation should be appropriate to quality standards for neurophysiology and neuroimaging assessment, epilepsy surgery programme and psychological and social counselling services.

The most important criteria of severity of intractable focal epilepsies are the high frequency of seizure and the type of seizure, in particular seizures with fall. However, the presence of a brain lesion and its localization, handicap, number of antiepileptic drugs, poor social integration, history of status epilepticus, mortality, traumas, cognitive impairments, depressive symptoms and alteration of quality-of-life are also criteria of gravity. In this article, we propose a review of these various elements limiting our discussion to adults.

In this article, we describe the social and economic aspects of adult epileptic patients in France. The different measures to facilitate their reintegration and employment are presented. The missions of the COTOREP (Technical Commission for Professional Orientation and Reclassification) include the identification of a disability rate, the recognition of status as a disabled worker, and orientation to an individually adapted job, e.g. in a specialized center. The COTOREP provides information and training. For patients with major disabilities, the commission can decide on admission in a specialized institution. The COTOREP but also the French national Social Security propose allocations and financial assistance for patients with low income or who have a work inaptitude. In this text, we also describe the general French laws for the protection of adult patients which include measures not specific for epileptic patients.

Spinal muscular atrophies are heterogeneous group. The diagnostic process should be careful to uncover the main differential diagnoses and to identify familial cases. Clinical phenotype is highly variable. In familial ALS cases with SOD1 mutation, the clinical scene may mimic spinal muscular atrophy. A careful questionning and a complete electroneuromyographic exam are warranted to allow the neurologist to choose among more invasive investigations for differential and positive diagnosis such as MRI, nerve or muscle biopsy, genetic analysis.

About 20 p. cent of cases of amyotrophic lateral sclerosis are familial (FALS). Fifteen percent of FALS cases are associated with an abnormality in the superoxide dismutase 1 (SOD1) gene. To date, more than 100 different genetic abnormalities have been reported, all except two are autosomal dominant. The clinical characteristics of patients presenting with FALS associated with an SOD1 abnormality is homogeneous when there is no doubt about the hereditary aspect of the genetic abnormality: mean age at onset 42 years, limb onset, slow evolution. Except when present in the setting of a clearly inherited disease (FALS) (several patients through several generations), the causality of a given SOD1 mutation often remains an open question. Consequently, search for SOD1 mutation is not warranted when atypical features such as young age at onset or slow progression are present. Conversely, a complete family study is justified to determine the precise role of a given SOD1 mutation because of the large number of potential SOD1 mutations, the variability of the transmission mode, and the non-exceptional absence of proven causality for ALS. Specific cases where a frequent SOD1 mutation with a recognized causal effect is recognized (no more than 15 out of more than 90 mutations) would be an exception.

Narcolepsy is a rare disabling sleep disorder whose main features are excessive daytime sleepiness and cataplexy. Human narcolepsy is most frequently a sporadic disorder with both genetic and environmental factors playing a role in its pathophysiology. Implication of the hypocretin system is well-established: as mutations in both canine and murine narcolepsies and as a consistent reduction in hypocretin neuron in human narcolepsy. The cause of human narcolepsy remains unknown. However degenerative, autoimmune and/or genetic processes are the most probable causes of the hypocretin neurons loss. Acting on a specific genetic background, an autoimmune process with hypocretin neuron degeneration, in response to environmental factors, is the most probable hypothesis for most cases of human narcolepsy with cataplexy. Although narcolepsy presents one of the tightest association with a specific HLA antigen (DQB1*0602), there is strong evidence that non-HLA genes also confer susceptibility. Monoaminergic, immune (TNF alpha) and hypocretinergic systems seem to be involved and may interfere with the phenotype. Treatment has not evolved significantly over the last few years. However, new drugs, such as hypocretin agonists, are currently being developed.

There are three slow wave sleep (SWS) parasomnias: confusional arousal, sleepwalking and night terrors grouped together in arousal disorders because impaired arousal from sleep has been postulated as a cause of these disorders. The onset of these disorders at the beginning of the night in slow wave sleep (SWS) is a typical feature. Night sleep is characterised by a great sleep fragmentation specially in SWS, and by a very strong SWS intensity reflected by both an increase of slow wave activity (SWA) before the parasomnia and a slower decay of wave activity (SWA) during the night. An abnormal deep sleep associated with a high SWS fragmentation is responsible for the occurrence of arousal disorders parasomnias.

Since the discovery of an almost 100 p. cent association of human narcolepsy with the HLA gene DQB1*0602, research has been focused on autoimmune mechanisms. Epidemiological data (age of onset, triggering factors, association with multiple sclerosis) would lend support to this hypothesis. However it has remained largely impossible to demonstrate immune abnormalities in blood or CSF by means of usual techniques. The canine form of the disease was supposed to be also immunologically mediated, since a linkage with a human immunoglobulin-related gene had been demonstrated. This was eventually demonstrated to be a pseudo-linkage, the real cause being a mutation in the closely related hypocretin receptor gene. This recently discovered neuropeptide is clearly involved in some aspects of sleep regulation. Soon thereafter, hypocretin deficiency was found in human narcoleptics, due to a severe neuronal loss in the hypothalamus; gliosis having been evidenced, it may be considered as the evidence of a prior inflammatory reaction, possibly due to an immune attack.

In narcolepsy, homeostatic process is preserved while sleep/wake circadian process is impaired. Other circadian components (body temperature, endocrine secretions, subjective sleepiness) are preserved. This circadian system weakness permits the occurrence of a very strong ultradian component, modulating sleep/wake rhythm. So, a 4 hour ultradian rhythmicity of Slow Wave Activity, and a 2 hour NREM/REM cycle longer than in normal subjects, has been evidenced in narcoleptic patients. These circadian and ultradian alterations can explain a major part of the narcoleptic symptoms.

Amyotropic lateral sclerosis is a severe degenerative disease of the nervous system. Progressive death of central and peripheral motor neurons leads to rapidly extensive paralysis of the four limbs, the bulbar region and the respiratory system. Sleep respiratory disorders is a useful sign to follow in these patients. Apnea is generally central rather than obstructive. Hypoventilation, particularly during REM sleep has been reported and causes nocturnal desaturation. These patients also appear to have a disrupted sleep pattern with a longer phase I and a shorter total duration of sleep. These nocturnal respiratory disorders observed in amyotropic lateral sclerosis are similar to those observed in muscle diseases. Management must however be undertaken very early in these patients because outcome can be rapidly fatal after the development of significant desaturation. Nasal ventilation can improve not only quality of life but also life expectancy for these patients.

In 1976 Bedrich Roth coined the term "idiopathic hypersomnia" and described two forms of the disease, one monosymptomatic, manifested only by excessive daytime sleepiness, and one polysymptomatic, characterized by excessive daytime sleepiness, nocturnal sleep of abnormally long duration and signs of "sleep drunkenness" on awakening. In comparison with that of narcolepsy, the pathophysiology of idiopathic hypersomnia remains poorly known. There are two main reasons for that: the absence of clinical and polysomnographic criteria pathognomonic or at least characteristic of the condition, as the cataplexies and the sleep onset REM periods of narcolepsy, and also the absence of a natural animal model comparable with the canine model of narcolepsy. The first investigations have stressed the frequent familial pattern of idiopathic hypersomnia. Later on biochemical assays have been performed in the CSF with results in favour of a dysfunction of noradrenergic systems. In the light of the two process model of sleep regulation in which sleep propensity is determined by a homeostatic process S and a circadian process C and of the later three-process model of regulation in which sleepiness/alertness are simulated by the combined action of a homeostatic process, a circadian process and sleep inertia, we suggest that idiopathic hypersomnia is not a pathological entity in itself, but rather the consequence of chronic sleep deprivation in very long sleepers.

Narcolepsy is known to be a complex disorder; both genetic and environmental factors play a role in its pathophysiology. Although narcolepsy presents one of the tightest association with a specific HLA antigen (DQB1*0602), there is strong evidence that non-HLA genes also confer susceptibility, both monoaminergic and hypocretinergic systems seem to be involved and may interfere with the phenotype. Implication of the hypocretin system is well-established in both canine and murine narcolepsy (caused by mutation) and a consistent reduction in hypocretin neuron seems to be the cause of human narcolepsy. An autoimmune process is probable.