Epilepsy and psychosis.

Psychotic disorders are eight times more frequent in epilepsy than in the general population. The various clinical syndromes are classified according to their chronology of onset in relation to epileptic seizures: ictal psychoses (during epileptic discharge), post-ictal psychoses (PIP, after a seizure), interictal psychoses (IIP, with no chronological link) and those related to complete seizure control. Antiepileptic drugs can cause psychotic disorders in all these situations. Post-ictal psychoses (PIP) are affective psychoses that occur after a lucid interval lasting 12 to 120hours following a cluster of seizures. They last an average of 10days, with an abrupt beginning and end. PIP are directly linked to epileptic seizures, and disappear when the epilepsy is controlled. Interictal psychoses are schizophrenias. The management of psychotic disorders in epilepsy is neuropsychiatric, and requires close collaboration between epileptologists and psychiatrists. Antipsychotics can be prescribed in persons with epilepsy. Even today, psychotic disorders in epilepsy are poorly understood, under-diagnosed and under-treated.

Prospective observational study of stroke in Cayenne, Tours and Besançon: The BECATOUR study.

BACKGROUND: Stroke is a major public health issue. Its epidemiology is still poorly known in French Guiana. METHOD: We conducted a prospective observational study including 100 consecutive patients hospitalized for stroke in Cayenne (in French Guiana), and Tours and Besançon (in metropolitan France). We compared their age, medical history, cardiovascular risk factors, pre-admission Rankin score, Glasgow and NIHSS scores, usual treatments, acute phase management, type of stroke, duration of hospitalization, mechanism of stroke according to TOAST classification, NIHSS and Rankin scores at discharge, discharge treatments, and mode of discharge. RESULTS: In French Guiana, the average age of patients was 7years lower (62 y), patients were more frequently affected by hypertension (75%) and diabetes (31%). Lacunar strokes were overrepresented (16.1%), and infarctions of cardioembolic origin were underrepresented (12%). NIHSS entry and Glasgow scores were similar between French Guiana and mainland France. Acute management was different: thrombolysis rate (9.3%) was 3 to 4 times lower, thrombectomy was not available. Fewer patients were transferred to rehabilitation centers and more patients were transferred to home hospitalization. DISCUSSION: In Tours and Besançon, patients eligible for thrombectomy were overrepresented. This bias explains the overrepresentation of more severe infarctions and probably the overrepresentation of strokes of cardioembolic origin. Infarctions of undetermined origin were more numerous in French Guiana because patients were often discharged from hospital with an incomplete cardiological workup. CONCLUSION: Despite some caveats, the profile of patients admitted for stroke in French Guiana is different from mainland France. The establishment of a stroke unit and an information campaign on the symptoms of stroke would allow better management.

[Interictal psychosis of epilepsy]. / Les psychoses épileptiques interictales.

Interictal psychosis (IIP) refers to psychosis that occurs in clear consciousness in persons with epilepsy (PWE) with temporal onset not during or immediately following a seizure. The pooled prevalence estimate of psychosis in PWE is 5.6%. PWE and schizophrenia have very high mortality, and more than one in four persons with both disorders die between the age of 25 and 50years. IIP can manifest in brief or chronic forms. The chronic forms of IIP may closely resemble schizophrenia. However, some authors have described the typical presence of persecutory and religious delusions, sudden mood swings and the preservation of affect, as well as rarity of negative symptoms and catatonic states, but these differences remain controversial. Typically, IIP starts after many years of active temporal lobe epilepsy. Several epilepsy-related variables are considered pathogenically relevant in IIP including epilepsy type and seizure characteristics. Risk factors for developing IIP are family history of psychosis, learning disability, early age of onset of epilepsy, unilateral or bilateral hippocampal sclerosis, history of status epilepticus, history of febrile seizures, and poorly controlled temporal lobe epilepsy. In patients with epilepsy and psychosis, structural imaging studies have shown several relevant changes leading to conflicting findings. Altered neuronal plasticity and excitability have been described in epilepsy and psychotic disorders. Neuropathological data suggest that IIP are not the result of classic epileptic pathology of the temporal lobe. Forced normalization (FN) and alternating psychosis refer to patients with poorly controlled epilepsy (focal or generalized) who have had psychotic episodes associated with remission of their seizures and disappearance of epileptiform activity on their EEGs. FN mainly occurs in temporal lobe epilepsy when patients have frequent seizures that are abruptly terminated triggered by an antiepileptic drug, vagus nerve stimulation or epilepsy surgery. Treatment is based on withdrawal of the responsible drug, and by transient use of antipsychotics for acute symptomatic control on a case-by-case basis. FN is an entity whose pathophysiology remains uncertain. Antiepileptic drugs (AEDs) may sometimes induce psychotic symptoms and psychosis could be a direct effect of the AEDs. IIP has been reported more frequently following the initiation of zonisamide, topiramate, and levetiracetam when compared with other antiepileptic drugs. However, AEDs do not appear to be the only determinant of IIP. The management of IIP requires a multidisciplinary approach with early involvement of a liaison psychiatrist associated with a neurologist. IIP are underdiagnosed and mistreated. Existing recommendations are extrapolated from those established for the treatment of schizophrenia with some additional guidance from expert opinions. A two-step procedure, not necessarily consecutive, is suggested. The first step requires reevaluation of the antiepileptic treatment. The second step requires initiation of atypical neuroleptics. Antipsychotic drugs should be selected with consideration of the balance between pharmacological profiles, efficacy, and adverse effects. Regarding pharmacokinetic interactions, AEDs with inducing properties reduce the blood levels of all antipsychotics. It is important to consider implications of combining neuroleptics and AEDs with a similar spectrum of side effects. Regarding the duration of treatment, IIP episodes are more likely to be recurrent than in primary schizophrenia. In practice, atypical neuroleptics with few motor side effects such as risperidone can be used as first choice, given the low propensity for drug-drug interactions and the low seizure risk, with the added suggestion to start low and go slow. Clozapine could be prescribed in selected cases.

Psychogenic non-epileptic seizures (PNES).

Psychogenic non-epileptic seizures (PNES) are defined as change in behavior or consciousness resembling epileptic seizures but which have a psychological origin. PNES are categorized as a manifestation of dissociative or somatoform (conversion) disorders. Video-EEG recording of an event is the gold standard for diagnosis. PNES represent a symptom, not the underlying disease and the mechanism of dissociation is pivotal in the pathophysiology. Predisposing, precipitating and perpetuating factors should be carefully assessed on a case-by-case basis. The process of communicating the diagnosis using a multidisciplinary approach is an important and effective therapeutic step.

Impact of a direct-admission stroke pathway on delays of admission, care, and rates of intravenous thrombolysis.

INTRODUCTION: This study examined the impact of a "direct potential thrombolysis" pathway with direct admission to a neurological stroke unit (SU) on delays of admission, stroke care and proportion of patients with ischemic stroke (IS) treated with intravenous (IV) rtPA. METHODS: This prospective study included all patients admitted in the intensive SU for potential thrombolysis over a 2-month period. Data collected included the time of symptom onset, mode of transport, National Institutes of Health Stroke Scale (NIHSS) score on arrival, delays of care, delays of imaging and modalities, diagnosis and therapeutic data. RESULTS: During the 2-month study period, 81 patients (mean age of 65 years) were included in the study. The Emergency Medical Services (EMS) were involved in 86% of admissions, with a median delay of admission of 1h48 and access within 4.5h in 84% of cases. Every patient underwent immediate neurovascular assessment and imaging examination, which was a MRI in 80% of cases. Only 70% of patients had a final diagnosis of stroke. Intravenous rtPA therapy was administered to 26 patients (32%), and 58% of patients with IS. The median door-to-needle time delay was 63min. CONCLUSION: A direct 'potential thrombolysis' pathway, based on EMS and located in the SU, can result in earlier admission, reaching the recommended care delay, and a large proportion (58%) of IS patients receiving rtPA therapy. On the other hand, the proportion of patients with stroke mimics is high, thereby increasing the chances of intermittent periods of saturation of this specific pathway.

[Postictal psychoses: Clinical and neurobiological findings]. / Clinique et neurobiologie des psychoses post-ictales.

Psychosis in epilepsy can be categorized in relation to seizures in two main categories: interictal psychosis and postictal psychosis. Postictal psychosis (PIP) is a specific syndrome in relation to seizure activity: a clear temporal relation exists between the psychotic state of sudden onset and a precipitating bout of complex partial or generalized seizures. However, this very specific syndrome is not included as such within the DSM-5, and PIP belongs to the category "Psychotic disorder due to another medical condition". Diagnostic criteria are: (1) episode of psychosis within 1 week after a seizure(s); (2) psychosis lasts more than 15hours and less than 2 months; (3) delusions, hallucinations in clear consciousness, bizarre, or disorganized behavior, formal thought disorder, or affective changes; and (4) no evidence AED toxicity, non-convulsive status epilepticus, recent head trauma, alcohol, or drug intoxication or withdrawal, prior chronic psychotic disorder. The presence of a lucid interval between the last seizure and start of changes rules out a simple postictal delirium. The outcome is characterized by a remission of the psychotic symptoms over several days (mean: 1 week), with or without any treatment. Prepsychotic EEG abnormalities persist during the psychosis. Risk factors for PIP include: long standing localization-related epilepsy, extratemporal onset, bilateral epileptiform activity, secondary generalization, slowing of the EEG background activity and personal or family history of psychiatric disorders. Brain MRI frequently shows structural abnormalities. Several functional neuroimaging studies have shown hyperperfusion in various cerebral regions during PIP, suggesting an excessive activation of particular structures of the brain rather than a postictal depression of cerebral activity. Implanted electrode studies have shown that the EEG correlate of psychotic symptoms differs from the ictal EEG correlate of epileptic seizures. The value of antipsychotic treatment in PIP requires further studies. Despite their role in symptomatic relief, there is no clear effect of neuroleptics on duration or prognosis of PIP. Different combinations of pharmaceutical interventions can be tried on a case by case basis: (1) oral administration of benzodiazepine; (2) combined oral administration of benzodiazepine and atypical neuroleptics; (3) intramuscular administration of dopamine-blockers for rapid tranquilization of violent or agitated patients. The notion that neuroleptic drugs lower the seizure threshold has no clinical significance: there is no evidence that antipsychotic drugs increase seizure frequency in epileptic patients treated with antiepileptic drugs.

[Geriatric particularities of Parkinson's disease: Clinical and therapeutic aspects]. / Particularités gériatriques de la maladie de Parkinson: aspects cliniques et thérapeutiques.

Parkinson's disease (PD) is a frequent and complex progressive neurological disorder that increases in incidence with age. Although historically PD has been characterized by the presence of progressive dopaminergic neuronal loss of the substantia nigra, the disease process also involves neurotransmitters other that dopamine and regions of the nervous system outside the basal ganglia. Its clinical presentation in elderly subjects differs from that in younger subjects, with more rapid progression, less frequent tremor, more pronounced axial signs, more frequent non-motor signs linked to concomitant degeneration of non-dopaminergic systems, and more frequent associated lesions. Despite the high prevalence of PD in elderly subjects, few therapeutic trials have been conducted in geriatric patients. Nevertheless, to improve functional disability while ensuring drug tolerance, the principles of optimized and multidisciplinary clinical management have to be known. The aim of this review is to provide an update on clinical and therapeutic features of PD specifically observed in elderly subjects.

[American Academy of Neurology, Washington, 18-25 April 2015]. / American Academy of Neurology, Washington, 18-25 avril 2015.

CEREBROVASCULAR DISEASES: The benefit of the thrombectomy using stents retrievers in the acute stroke phase is now demonstrated when there is a proximal occlusion of an intracranial artery, whatever its mechanism. The place of the anticoagulants in the management of cervical artery dissections remains uncertain, while the benefit of the blood pressure control in the secondary prevention of deep and lobar intracerebral hemorrhages is critical. The development of cardiac MRI, prolonged cardiac monitoring and transcranial doppler seems to improve the diagnosis of cardio-embolic sources of stroke. EPILEPSY: A specialized urgent-access single seizure clinic represents a model which reduces wait-times and improves patient access after a first fit. Co-locating a psychiatrist within outpatient epilepsy center leads to a reduction in psychiatric symptoms and people with psychogenic non-epileptic seizures. When neurologists around the world assess identical case scenarios for the diagnosis of epilepsy, concordance is between moderate and poor, showing that epilepsy diagnosis remains difficult. More than one third of elderly with new-onset epilepsy of unknown etiology exhibit temporal lobe atrophy on brain imaging. MOVEMENT DISORDERS: There is no major progress in the therapeutic approach of Parkinson's disease but the discovery of new genetic markers such as glucocerebrosidase mutations may greatly change our knowledge of the disease process and may induce new therapeutic strategies in the future. The natural history of the disease is also better understood from the prodromal phase to the post-mortem analysis of the brain and the classification of the processes based on abnormal protein deposits. DEMENTIA: The respective value of biomarkers (amyloid imaging versus CSF biomarkers) for in vivo diagnosis of Alzheimer's disease (AD) has been detailed. Therapeutic expectations mainly rely on anti-Aß immunization trials performed in preclinical (and no longer prodromal) stages of AD, with the aim of slowing the evolution of neuronal loss. Besides a lot of communications on dementia genetics or physiopathogeny, fascinating and promising results were presented on deep brain stimulation for depression resistant to medical treatment. PERIPHERAL NEUROPATHY: Ibudilast, administered with riluzole, is safe and tolerable in patients with amyotrophic lateral sclerosis (ALS), improves ALS function and delays progression. Patients with painful small fiber neuropathy have a high rate of mutations in the SCN9A gene, coding for Nav1.7 voltage-gated sodium-channels. Peripheral nerve lymphoma (NL) is a multifocal painful neuropathy that causes endoneurial inflammatory demyelination: primary NL is less severe than secondary NL, which occurs after remission, suggesting that nerve may be considered a "safe lymphoma haven". MULTIPLE SCLEROSIS (MS): Biotin in progressive forms of MS and daclizumab in relapsing-remitting forms appear to be promising treatments. In case of failure of current first-line and/or second-line therapeutics, alemtuzumab may be an interesting alternative treatment. Teriflunomide, dimethyl fumarate and fingolimod are oral treatments with confirmed efficacy and acceptable safety. Besides vitamin D insufficiency and smoking, which are confirmed risk factors for the disease, testosterone insufficiency (in males) and obesity are emerging risk factors, which could also be corrected.

[Adult patients treated for focal epilepsy with antiepileptic drugs (AEDs) in combination in France: description according to the 2009 ILAE definition of AED resistance (ESPERA study)]. / Patients adultes traités par une association d'antiépileptiques pour une épilepsie focale en France: description et mode de prise en charge selon les nouveaux critères de définition de la pharmacorésistance (étude ESPERA).

AIMS: To describe the adult population treated with antiepileptic drugs (AEDs) in combination for focal epilepsy according to the definition of AED resistance proposed by the International League Against Epilepsy (ILAE) in 2009 and to evaluate its implementation in current practice. METHODS: ESPERA was a multicenter, observational, cross-sectional study with a clinical data collection covering the past 12 months conducted by neurologists. Classifications according to AED responsiveness established by investigators for each enrolled patient were revised by two experts. RESULTS: Seventy-one neurologists enrolled 405 patients. Their mean age was 42.7 years (sex-ratioM/F 0.98). According to the investigators, 60% of epilepsies were drug-resistant, 37% drug-responsive and 3% had an undefined drug-responsiveness. After revision of experts, 71% of epilepsies were classified as drug resistant, 22% as responsive and 7% as undefined. Among the participating neurologists, 76% have made at least one error in classifying their patients according to the 2009 ILAE definition of AED resistance. Because of epilepsy, 24% of patients (age≤65) were inactive and 42% could not drive (respectively 29 and 49% of patients with AED resistant epilepsy). Half of patients had at least one other chronic condition. Number of prescribed drugs in combination and health care resource utilisation were significantly higher in patients with drug-resistant epilepsies than in patients with drug responsive epilepsies. CONCLUSION: ESPERA study shows that the use of new definition of drug-resistance in everyday practice seems difficult without any additional training and that the social and professional disability is frequent in adults with focal epilepsies treated with polytherapy.

Predictive value of motor evoked potentials in clinically isolated syndrome.

OBJECTIVES: To assess the predictive role of several measures obtained by transcranial magnetic stimulation (TMS) in patients with clinically isolated syndrome (CIS) for the risk of conversion to multiple sclerosis (MS) during the first 2 years. MATERIALS AND METHODS: We investigated 34 patients with CIS. After 2 years of follow-up and classification into two groups according to MS diagnosis, initial TMS measures were compared to determine their predictive values for conversion to MS. RESULTS: Sixteen patients developed MS. We observed a significant difference between the two groups for contralateral silent period and no significant difference for the central motor conduction time, amplitude ratio, motor threshold, ipsilateral silent period, and the transcallosal conduction time. CONCLUSIONS: Contralateral silent period (SP) seems to be a valuable parameter to early distinguish patients who will develop MS or not. This result about SP during CIS has never been described until now. An increased contralateral silent period would predict a conversion to MS with a positive predictive value of 75%, but this result needs to be confirmed in larger groups.

[Postictal psychosis]. / Les psychoses postictales.

In epilepsy patients, psychotic states are related to a group of psychotic disorders with a specific phenomenology in which potential pathophysiological mechanisms are believed to be closely related to the epileptic disorder itself. Postictal psychosis is a very specific syndrome in relation to seizure activity: a clear temporal relationship exists between the psychotic state of sudden onset and a precipitating bout of complex partial or generalized seizures, with a characteristic lucid interval which lasts from two to 120h. The psychotic state may be related to the withdrawal of anticonvulsants, often in connection with video-EEG monitoring. The phenomenology of the psychotic state is often pleomorphic, with abnormal mood, paranoid delusions and hallucinations, with some clouding of consciousness or no evidence of impaired consciousness. The outcome is characterized by a remission of the psychotic symptoms over several days (mean: 1 week), with or without neuroleptic treatment. The majority of the patients suffer from complex partial seizures with frequent psychic auras that secondarily become generalized. In the majority of cases, prepsychotic EEG abnormalities persist during the psychosis. Frequent bitemporal foci are recorded on the EEG and MRI abnormalities (including mesial temporal sclerosis) are seen in more than half of the cases. The results of clinical, morphologic and metabolic available studies will be briefly discussed.

[Vitamin B12 deficiency and neurological disorders: a case report and literature review]. / Carence en vitamine B12, ataxie cérébelleuse et troubles cognitifs.

INTRODUCTION: Vitamin B12 deficiency is often associated with neurological disorders of which combined sclerosis of the spinal cord is a common manifestation. CASE REPORT: We report the case of a woman who presented cerebellar ataxia and cognitive deficits associated with leukoencephalopathy on the brain MRI. These symptoms were associated with vitamin B12 deficiency due to Biermer's disease. Vitamin B12 supplementation led to symptom improvement. Later her treatment was discontinued and the patient's clinical status worsened to a bedridden status. CONCLUSION: Ataxia cerebellar dementia and leukoencephalopathy can result from vitamin B12 deficiency. To limit the risks of sequelae, vitamin B12 supplementation should be started at an early stage.

Epilepsy and dementia in the elderly.

Epilepsy is a frequent condition in the elderly; however, it remains a relatively understudied condition in older adults with dementia. The diagnosis of a seizure is particularly difficult and is most often based on questions to the caregiver. Epilepsy in dementia has significant consequences on the prognosis of the underlying dementia: it can result in a worsening of cognitive performance, particularly in language, as well as a reduction in autonomy, a greater risk of injury and a higher mortality rate. In this review, management strategies are recommended for the clinician. The presence of pre-existing Alzheimer's disease does not exempt the clinician from ruling out other symptomatic causes of seizures. Anti-epileptic drugs (AED) should be started only after the diagnosis has been clearly established, when the risk of recurrence is high, and with monotherapy whenever possible. Although few data are available, the more recent AED offer significant advantages over the older medications in this context.

[Knowledge, attitudes and practise of the general practitioners with the epileptic patients: qualitative research with 11 semi-structured interviews]. / Connaissances, attitudes et pratiques du médecin généraliste d'Eure-et-Loir face au patient épileptique : étude qualitative à partir de 11 entretiens semi-dirigés.

Studies on how general practitioners follow epileptic patients are few and far between. This is surprising, since for these patients, the general practitioner is the first person to be consulted in the context of the current standardised treatment pathway. Our goal was to describe and analyze general practitioners' knowledge, attitudes and habits concerning medical, psychological and social care of epileptic patients. We applied a qualitative method using semi-structured interviews with 11 general practitioners in the Eure-et-Loir, an administrative district in France. The interviews were recorded, with full transcripts being written and analyzed by themes. The results revealed great variability in care practices and in the perception general practitioners have of epilepsy. They report not knowing enough about the illness. They perceive clearly the anxiety of patients and their families, but exert little medical, psychiatric or social impact on patients. Treatment of the disease is at the core of the general practitioner's relationship with the patient. If attitudes towards epilepsy are to be changed, relevant knowledge and correct practices remain to be implemented. Demand for training is currently centred on treatment but it would be helpful to introduce inter-disciplinary training on standardisation of practices and more detailed correspondence with neurologists.

[Progressive anarthria: an individual entity]. / Anarthrie progressive: une entité propre.

INTRODUCTION: First described 15 years ago, primary progressive anarthria is a focal cortical atrophy defined as a rare progressive impairment of speech associated with orofacial apraxia and leading to mutism with a frontal lobe syndrome. The aim of this study was to analyze clinical and neuropsychological data and results of complementary tests in a series of patients presented with primary progressive anarthria. MATERIAL AND METHODS: We, retrospectively, studied five patients with primary progressive anarthria. We particularly analyzed the following parameters: age at onset, age at the diagnostic, disease time from onset to first consultation, the initial orientation, the neuropsychological and clinical data at the first visit, electromyography, brain MRI, and single photon emission computed tomography (SPECT) findings. Clinical and neuropsychological data were used to monitor disease course. RESULTS: The mean age at onset of symptoms was 75.2+/-5.8 years. Patients were primarily referred to a specialist in memory disease (n=3) or a specialist in motor neuron disease (n=2). The time from onset to first consultation was 11.2+/-3 months. Anarthria was associated with dysexecutive syndrome and sometimes, with impaired comprehension. Electromyography was always normal. Cranial MRI showed temporal or left frontal atrophy (n=3). Spect revealed decreased cerebral blood flow predominating in the left frontal or temporal region (n=4). CONCLUSION: Long delay for specialist consultation and inadequate initial orientation retard disease diagnosis, leading to severe incapacity. Complementary studies are required to confirm diagnostic and to rule out lateral amyotrophic sclerosis. During the early stages, involvement of the premotor cortex may be considered due to the speech apraxia. Secondary motor orofacial disturbances suggest an extension to the motor cortex. Primary progressive anarthria is a distinct individual entity within the spectrum of focal cortical atrophies.