ILAE clinical practice recommendations for the medical treatment of depression in adults with epilepsy.

The aim of this document is to provide evidence-based recommendations for the medical treatment of depression in adults with epilepsy. The working group consisted of members of an ad hoc Task Force of the International League Against Epilepsy (ILAE) Commission on Psychiatry, ILAE Executive and the International Bureau for Epilepsy (IBE) representatives. The development of these recommendations is based on a systematic review of studies on the treatment of depression in adults with epilepsy, and a formal adaptation process of existing guidelines and recommendations of treatment of depression outside epilepsy using the ADAPTE process. The systematic review identified 11 studies on drug treatments (788 participants, class of evidence III and IV); 13 studies on psychological treatments (998 participants, class of evidence II, III and IV); and 2 studies comparing sertraline with cognitive behavioral therapy (CBT; 155 participants, class of evidence I and IV). The ADAPTE process identified the World Federation of Societies of Biological Psychiatry guidelines for the biological treatment of unipolar depression as the starting point for the adaptation process. This document focuses on first-line drug treatment, inadequate response to first-line antidepressant treatment, and duration of such treatment and augmentation strategies within the broader context of electroconvulsive therapy, psychological, and other treatments. For mild depressive episodes, psychological interventions are first-line treatments, and where medication is used, selective serotonin reuptake inhibitors (SSRIs) are first-choice medications (Level B). SSRIs remain the first-choice medications (Level B) for moderate to severe depressive episodes; however, in patients who are partially or non-responding to first-line treatment, switching to venlafaxine appears legitimate (Level C). Antidepressant treatment should be maintained for at least 6 months following remission from a first depressive episode but it should be prolonged to 9 months in patients with a history of previous episodes and should continue even longer in severe depression or in cases of residual symptomatology until such symptoms have subsided.

Postictal psychosis, a cause of secondary affective psychosis: A clinical description study of 77 patients.

OBJECTIVE: Postictal psychosis (PIP) is a severe complication occurring at least in 2% of patients with epilepsy. Since the 19th century, psychiatrists have reported the specificity of PIP presentation, but descriptions did not clearly distinguish PIP from after-seizure delirium. This study aimed to provide a precise description of psychiatric signs occurring during PIP, and improve recognition of PIP. METHODS: We performed a review of clinical descriptions available in literature (48 patients), that we gathered with a retrospective multicentric case series of patients from three French epilepsy units (29 patients). For each patient, we collected retrospectively the psychiatric signs, and epilepsy features. RESULTS: We found a high prevalence of persecutory (67.5%) and religious (55.8%) delusions, with almost systematic hallucinations (83.1%) and frequent mood disturbances (76.6%), especially euphoria. Severe consequences were not negligible (other-directed assault in 20.8%, self-directed in 13.0%). The type of delusion was associated with mood symptoms (p = 0.017). Episode onset was mainly sudden/rapid (90.9%), its duration was mostly between one and 14 days (64.9%) and the response to antipsychotic medication was good. Disorder was recurrent in more than a half of the sample (57.1% of patients with at least 2 episodes). CONCLUSION: Considering our findings, PIP resembles more an affective psychosis, than a purely psychotic disorder. The presence of affective signs differentiates PIP from other psychotic comorbidities in epilepsy. Additionally, resemblance between PIP and psychotic manic episode might help to discuss links between epilepsy and bipolar disorder.

Post-traumatic factors are involved in the evolution of the number of seizures in patients with PNES.

OBJECTIVE: The purpose of this prospective study was to identify predictive factors of the evolution of the number of seizures. METHODS: We included 85 individuals with a diagnosis of Psychogenic Nonepileptic Seizure (PNES) who completed at least two clinical interviews spaced by 6 months during a 24-month follow-up. Participants underwent a structured interview with an experimented clinician in PNES to complete standardized evaluation and validated scales. We collected sociodemographic and clinical data on PNES (number of seizures, duration of the disease), anxiety, depression, history of traumas, alexithymia, dissociation, and post-traumatic stress disorder (PTSD). We used a multivariate linear regression analysis to predict the characteristics independently associated with the evolution of the number of seizures in percentage. RESULTS: Dissociation score was significantly associated with a negative evolution of the number of seizures (p < 0.002). Conversely, the diagnosis of PTSD at inclusion was correlated to a positive evolution of the number of seizures (p < 0.029). CONCLUSION: Dissociation was related to a more pejorative evolution of the number of seizures while PTSD diagnosis was associated with a decreased number of seizures. It is therefore essential to improve detection and treatment of post-traumatic dissociation. Further studies are required to understand the impact of PTSD on the evolution of the number of seizures.

Differentiating PNES from epileptic seizures using conversational analysis on French patients: A prospective blinded study.

Psychogenic nonepileptic seizures (PNES) resemble epileptic seizures (ES) but are not caused by the occurrence of excessive cortical neuronal discharge. Previous studies in German-, English-, and Italian-speaking patients showed that patients used a different communicative style to talk about their seizures. They demonstrated that the diagnosis between PNES and ES could be predicted using qualitative assessment and a diagnostic scoring aid (DSA). The objective of our study was to evaluate the contribution of linguistic analysis in the differential diagnosis between ES and PNES in a French patient population. During an extended video-electroencephalogram (video-EEG) monitoring, 13 patients presented PNES and 19 patients with ES. Two neurologists blindly and independently analyzed the interview of each patient. Rater 1 predicted the correct diagnosis in 27 of 32 patients (84%) and Rater 2 in 28 of 32 patients (88%). Interrater reliability of qualitative analysis was satisfactory (k = 0.68, interrater agreement = 84.4%). Using a simplified DSA, Rater 1 and Rater 2 would have correctly diagnosed 88% (28/32 patients) and 91 % (29/32) of the cases, respectively. Our blinded prospective study confirms the diagnostic value of conversational analysis, performed by neurologists, to differentiate PNES from ES in French-speaking patients.

Epileptic psychoses are underrecognized by French neurologists and psychiatrists.

This study evaluates the knowledge about psychotic disorders associated with epilepsy among medical practitioners in France. A self-report questionnaire was sent, and responses of 486 participants were collected. Results showed the rate of correct responses being higher among neurologists compared to psychiatrists, respectively 70.6% and 58.3% (p < 10-11). The highest rate of correct responses was found for the participants trained in epileptology (71%), and a regression analysis confirmed that epilepsy-training was the most influential variable. However, we found that knowledge about epileptic psychosis was imprecise among all participants: current classification was not known to most participants (77%), there were false beliefs concerning postictal confusion and psychosis (41%), and both prevalence and duration of postictal psychosis were not well-known. There is the first survey to highlight such gaps of knowledge, and hopefully lead to measures to remedy this, especially specialists such as psychiatrists, neurologists, and epileptologists who may be called upon to treat such patients.

Do children with Dravet syndrome continue to benefit from stiripentol for long through adulthood?

OBJECTIVE: To evaluate continuing stiripentol treatment in adulthood in Dravet syndrome (DS). METHOD: Longitudinal data were collected from the last visit prior to age 15 years (V15 y ) to the last visit in adulthood (Vadult ) in the 40 DS patients (32 typical, eight atypical) of a French historical cohort (Paris) of subjects who continued stiripentol from childhood or adolescence to adulthood. RESULTS: At Vadult (18-40 years, median = 23 years), all the patients were still receiving stiripentol (exposure = 3-24 years, median = 18 years), associated with clobazam (40/40), valproate (39/40), and topiramate (21/40). Between V15 y and Vadult , stiripentol was interrupted in five patients (two for adverse events) but reintroduced following seizure aggravation. Loss of appetite affected 15 of 40 patients but resolved after reducing the dose of stiripentol or valproate; no other new stiripentol-related adverse events were reported. Mean stiripentol dose was progressively decreased from 39 to 25 mg/kg/d (P = 0.0002), whereas clobazam (0.27 mg/kg/d) and valproate (14 mg/kg/d) remained stable. At Vadult , 37 of 40 patients still had generalized tonic-clonic seizures, but none still had status epilepticus (vs three at V15 y ) and only one had myoclonia. During adulthood, generalized tonic-clonic seizure frequency and duration continued to decrease (P = 0.02, P = 0.008) and 10 patients experienced seizure-free periods ≥ 1 years (up to 5 years). All patients already had intellectual disability at V15 y , but retardation was more severe at Vadult (P = 0.03). Furthermore, neurological/gait condition had declined (two patients became bedridden) and behavior had worsened (P < 0.0002). Nevertheless, the 33 patients on stiripentol from infancy/childhood (<15 years) tended to have better seizure outcome in midadulthood than the seven treated from adolescence (>15 years) and the DS patients treated from adult age or stiripentol-naive subjects reported in the literature. SIGNIFICANCE: The efficacy and safety of the stiripentol/valproate/clobazam combination started at pediatric age are maintained at very long term during adulthood. Such prolonged stiripentol therapy tends to positively impact the late prognosis of epilepsy, especially when initiated before adolescence.

Pharmacotherapy in patients with epilepsy and psychosis.

The recognition and treatment of psychosis in persons with epilepsy (PWE) is recommended with the apparent dilemma between treating psychosis and opening the possibility of exacerbating seizures. The pooled prevalence estimate of psychosis in PWE is 5.6%. It has been proposed that a 'two hit' model, requiring both aberrant limbic activity and impaired frontal control, may account for the wide range of clinical phenotypes. The role of antiepileptic drugs in psychosis in PWE remains unclear. Alternating psychosis, the clinical phenomenon of a reciprocal relationship between psychosis and seizures, is unlikely to be an exclusively antiepileptic drug-specific phenomenon but rather, linked to the neurobiological mechanisms underlying seizure control. Reevaluation of antiepileptic treatment, including the agent/s being used and degree of epileptic seizure control is recommended. The authors found very few controlled studies to inform evidence-based treatment of psychosis in PWE. However, antipsychotics and benzodiazepines are recommended as the symptomatic clinical treatments of choice for postictal and brief interictal psychoses. The general principle of early symptomatic treatment of psychotic symptoms applies in epilepsy-related psychoses, as for primary psychotic disorders. In the authors' experience, low doses of antipsychotic medications do not significantly increase clinical risk of seizures in PWE being concurrently treated with an efficacious antiepileptic regimen.

Are the clinical classifications for psychogenic nonepileptic seizures reliable?

BACKGROUND: Psychogenic nonepileptic seizures (PNESs) are episodes that resemble epileptic seizures but are of psychological origin. A few studies have attempted to describe different types of PNES as a combination of clinical signs but their validation and robustness have not yet been reached. The aim of this study was to assess the inter-rater reliability (IRR) of five existing clinical PNES classifications. METHODS: A total of 107 PNESs from 54 patients were retrospectively analyzed independently by two trained epileptologists, who were blinded to each other's findings. The recorded events were grouped according to the five chosen classifications systems. The IRR was measured using a kappa (κ) coefficient for each PNES classification. We also report category-specific κ values. RESULTS: Our study demonstrated a mild to moderate IRR (κ from 0.44-0.68) for classifying PNES using the 5 proposed classification schemes. Within these classifications, the most reproducible classes are the subjective ones followed by the dialeptic group. Classes based on motor signs are the least reproducible. CONCLUSION: The IRR for current clinical classifications of PNES was only moderate. The difficulty to analyze motor signs could explain this poor reliability. It is necessary to ensure the reliability of clinical classifications of PNES in order for them to be a relevant tool in clinical practice or to explore correlations in clinical research. Future research would benefit from increased precision of diagnostic criteria specific to each class.

"Le grand mal intellectuel" by Jules Falret (1861), the first complete description of postictal psychosis.

This paper presents the first complete description of postictal psychosis, made by the French psychiatrist Jules Falret. This description, written in 1861, was the first to fulfill modern diagnostic criteria. We will examine why this syndrome, well defined in the 19th century, was forgotten for over a century.

Adjunctive perampanel in refractory epilepsy: Experience at tertiary epilepsy care center in Tours.

PURPOSE: The purpose of this study was to evaluate the effectiveness and safety of PER as add-on treatment in patients with severe refractory epilepsy with a particular focus on patients with learning disability and/or psychiatric comorbidity. METHOD: We pooled retrospective data from adult patients with refractory epilepsy prescribed perampanel from a tertiary center in France between 1st May 2014 and 3rd June 2015. Data collection was done on February 2016. RESULTS: One hundred and one patients were included (mean age: 41.2years, 37.6% with learning disability and 49.5% with psychiatric comorbidity). Mean retention was 8.1months (range: 14days to 17months). On final evaluation, a >50% reduction in seizure frequency was reached in 41.6% of patients, and 7 patients (6.9%) became seizure-free. Sixty-three patients (62.4%) experienced adverse effects. The most common adverse effects were irritability, asthenia, aggression, and sedation. Efficacy, retention of treatment, and safety were equally similar in patients with learning disability or psychiatric comorbidity as for those without. The only significant difference was in percentage of seizure-free patients: 11.1% in the group without learning disability compared with 0% in the group with (p=0.043). CONCLUSION: Adjunctive PER can achieve clinically meaningful improvement, or even seizure freedom, in more than one-third of patients suffering from severe refractory epilepsies. It seems similarly safe and effective in the subgroup of these patients with learning disability or with psychiatric comorbidity. However, the rate of psychiatric side effects is high,; of note, we asked both patient and caregivers at each visit especially focusing on psychiatric side effects. Patients, caregivers, and families should be informed of potential psychiatric/behavioral risks associated with taking perampanel especially during the initial titration period.

A cross-sectional survey on French psychiatrists' knowledge and perceptions of psychogenic nonepileptic seizures.

OBJECTIVE: The principal aim of the study was two-fold: to determine French psychiatrists' level of general knowledge of psychogenic nonepileptic seizures (PNES) and to evaluate their perceptions of this condition in a standardized way. The secondary aim was to describe the relationship between level of education and knowledge of PNES and level of experience of case management and perceptions of PNES. METHODS: In this study, psychiatrists were invited by email to answer an online survey. The questionnaire asked about their general knowledge of PNES, and perceptions of PNES were scored using the Brief Illness Perception Questionnaire (Brief IPQ). RESULTS: We received 1242 replies, and data from 963 respondents were included. The survey revealed that three-quarters of psychiatrists working in France (75%) had never received any training on PNES, and 42% had never managed patients suffering from PNES. In general, participants considered PNES to be a chronic disease with significant impact on patients' quality of life. Although psychiatrists were aware of the importance of psychological trauma in the etiology of PNES, they showed only moderate understanding of this pathology. Terminology and classification of these disorders were poorly known, and the relation between PNES and histrionic personality was massively overvalued. Prior training on PNES was associated with a better level of knowledge and different perceptions of trained psychiatrists compared with that of psychiatrists with no prior training. CONCLUSIONS: The condition of PNES remains relatively unknown to French psychiatrists, and some of their perceptions were inaccurate. Specific training seems essential for a better understanding of PNES.

Sinking skin flap syndrome (or Syndrome of the trephined): A review.

BACKGROUND: Bone defects of the skull are observed in various pathological conditions, including head trauma and conditions requiring surgery of the skull. Independent of the consequences of the original aetiology that necessitated the craniectomy, the bone defect alone may be the cause of the symptoms, called 'trephined syndrome' or 'sinking skin flap syndrome'. Despite the early recognition of neurological symptoms directly linked to craniectomy, the description of this syndrome has often relied on a small series or single clinical case reports. OBJECTIVES: To list the previously reported symptoms of SSFS. DATA SOURCES: We selected the references for this review by searching PubMed, focusing on articles published prior to June 2013 and using references from relevant articles. STUDY ELIGIBILITY CRITERIA: We used the following search terms: 'trephined syndrome', 'syndrome of the trephined', 'Sinking skin flap', and 'sinking skin flap syndrome'. There were no language restrictions. The final reference list was generated on the basis of its relevance to the topics covered in this review. CONCLUSIONS: Clinicians need to be aware of sinking skin flap syndrome and to look for abnormal neurological developments in patients with craniectomy in order to avoid unnecessary testing and to prevent its occurrence. Accordingly, cranioplasty can be undertaken as soon as necessary.

The effect of age and educational level on the cognitive processes used to comprehend the meaning of pictograms.

BACKGROUND AND AIMS: Pictograms, designed to be a universal communication system, are often created from several concrete and easily recognizable drawings. Does understanding depend on a logical approach? Or is it the ability to inhibit the concrete sense of each picture that allows access to a higher level of comprehension? (ability to abstract). These executive functions are sensitive to the effects of aging and educational level. The aim of our study was to evaluate the nature of the cognitive processes underlying the meaning of pictograms and to test the effect of aging and educational level. METHODS: We enrolled 19 older adults (60-69 years old) and 63 young adults (20-29 years old). Of these 63 young adults, 43 had a high educational level (Young-High participants), and 20 had a lower educational level (Young-Low participants). Each participant was asked the meaning of 20 pictograms and underwent an assessment of abstraction and logical abilities with WAIS-III test. RESULTS: Older adults had lower pictogram assessment scores and abstraction and logical abilities when compared with young adults. In both groups, abstraction and logical abilities were correlated with the interpretation of pictograms but only abstraction ability remains strongly correlated with pictogram comprehension in the older group after adjustment of sex, age and educational level. Consequently, the poorer performances of older adults to determine the meaning of pictograms could be explained by the decline of abstraction ability in elderly. CONCLUSIONS: Pictograms are not the universal communication system as we formerly thought. Age and educational level may influence the performance in determining the meaning of pictograms.

Diagnostic and therapeutic value of echocardiography during the acute phase of ischemic stroke.

BACKGROUND: Echocardiography is routinely used to identify potential cardiac sources of embolism (CSE) in the acute phase of ischemic stroke (IS). We know that transoesophageal echography (TEE) is superior to detect CSE than transthoracic echography (TTE). However, the indications of each technique remain controversial. We aimed to evaluate the diagnostic yield (DY) and the therapeutic impact (TI) of echocardiography (both techniques combined) in IS and to analyze impact of clinical factors on these values. METHODS: We included consecutive IS patients over a period of 22 months. All patients underwent TTE, and selected patients (young or with a high suspicion of cardioembolic origin) then underwent TEE. DY (detection of CSE) and TI (introduction of oral anticoagulant, closure of patent foramen ovale and targeted cardiologic consultation) were systematically evaluated. RESULTS: We analyzed 300 patients (mean age 61 years). All patients underwent TTE and 127 patients underwent TTE and TEE. Echocardiography overall detected CSE in 22% of patients with a TI in 11% of all cases. The TI was higher in patients less than or equal to 55 years of age. In contrast to other studies, the DY and TI of echocardiography were not associated with vascular risk factors. CONCLUSIONS: Echocardiography, as currently practiced in our stroke unit, allows detection of CSE in one patient in five, and leads to change in therapy in half of these cases. Our results suggest that TTE should be used for all patients admitted for IS, and to limit the use of TEE to younger patients.

A Rare Case of Hyperglycemia, Ketoacidosis, and Central Facial Paralysis in a Newly-Diagnosed Diabetic Woman.

BACKGROUND Diabetes mellitus is a chronic disease that occurs when the pancreas does not produce enough insulin or when the body is unable to effectively use the insulin it produces. Uncontrolled diabetes mellitus is usually associated with neurological manifestations, such as hemichorea, focal epileptic seizures, peripheral neuropathy, and peripheral facial paralysis. This report describes a 59-year-old woman presenting with hyperglycemia and ketoacidosis due to newly diagnosed diabetes mellitus, as well as a temporary episode of central facial paralysis, which regressed within a few days after medical treatment and metabolic correction. CASE REPORT A 59-year-old patient with hypertension and a family history of diabetes mellitus presented with polyuro-polydipsic syndrome and signs of metabolic ketoacidosis, with an elevated anion gap, compatible with newly discovered type 1 diabetes mellitus. Six hours after admission, we noted the abrupt onset of left central facial paralysis, with no brain damage shown on magnetic resonance imaging. Initially, the diagnosis was transient ischemic attack. After a second, normal cerebral magnetic resonance image on the fourth day, and clinical improvement on the fifth day after metabolic correction by insulin therapy and rehydration, the diagnosis of a regressive central facial paralysis was retained. CONCLUSIONS Central facial paralysis in diabetic ketoacidosis is a rare neuroendocrine entity. The pathophysiological mechanisms that can explain the occurrence of central facial paralysis are not yet described and require further investigation. This report highlights the importance of diagnosis, early management of hyperglycemia and diabetic ketoacidosis, and reversibility of central facial paralysis after treatment.

Basic treatment principles for psychotic disorders in patients with epilepsy.

In patients with epilepsy, coexisting psychoses, either interictal (IIP) or postictal (PIP), are associated with serious disturbance in psychosocial function and well-being, and often require the care of a specialist. Unfortunately, evidence-based treatment systems for psychosis in patients with epilepsy have not yet been established. This article aims to propose concise and practical treatment procedures for IIP and PIP based on currently available data and international consensus statements, and primarily targeting nonpsychiatrist epileptologists who are often the first to be involved in the management of these complex patients. Accurate and early diagnosis of IIP and PIP and their staging in terms of acuity and severity form the essential first step in management. It is important to suspect the presence of psychosis whenever patients manifest unusual behavior. Knowledge of psychopathology and both individual and epilepsy-related vulnerabilities relevant to IIP and PIP facilitate early diagnosis. Treatment for IIP involves (1) obtaining consent to psychiatric treatment from the patient, whenever possible, (2) optimization of antiepileptic drugs, and (3) initiation of antipsychotic pharmacotherapy in line with symptom severity and severity of behavioral and functional disturbance. Basic psychosocial interventions will help reinforce adherence to treatment and should be made available. Due consideration must be given to patients' ability to provide informed consent to treatment in the short term, with the issue being revisited regularly over time. Given the often prolonged and recurrent nature of IIP, treatment frequently needs to be long-term. Treatment of PIP consists of two aspects, that is, acute protective measures and preventive procedures in repetitive episodes. Protective measures prioritize the management of risk in the early stages, and may involve sedation with or without the use of antipsychotic drugs, and the judicious application of local mental health legislation if appropriate. As for preventative procedures, optimizing seizure control by adjusting antiepileptic drugs or by surgical treatment is necessary.

Encephalopathy induced by levetiracetam in an elderly woman.

Levetiracetam is frequently used in the elderly considering its favorable pharmacological profile, efficacy, and good tolerance. We reported an encephalopathy with levetiracetam in an elderly subject who had no renal failure, no concomitant valproate medication, and no other additional co-morbidities. Levetiracetam should be discontinued when this condition is suspected.