Bertrand de Toffol

International consensus clinical practice statements for the treatment of neuropsychiatric conditions associated with epilepsy

In order to address the major impact on quality of life and epilepsy management caused by associated neuropsychiatric conditions, an international consensus group of epileptologists met with the aim of developing clear evidence‐based and practice‐based statements to provide guidance on the management of these conditions. Using a Delphi process, this group prioritized a list of key management areas. These included: depression, anxiety, psychotic disorders, nonepileptic seizures, cognitive dysfunction, antiepileptic drug (AED)–related neurobehavioral disorders, suicidality, disorders in children and adolescents, disorders in children with intellectual disability, and epilepsy surgery. Clinical practice statements were developed for each area and consensus reached among members of the group. The assessment and management of these conditions needs to combine knowledge of psychiatric disorders, knowledge of the impact of epilepsy and its treatment on psychopathology, and an ability to deliver care within epilepsy services. The aim of these statements is to provide guidance on quality care for people with epilepsy that have a range of neuropsychiatric disorders.

Abnormal SMN1 gene copy number is a susceptibility factor for amyotrophic lateral sclerosis

The etiology of amyotrophic lateral sclerosis remains unknown in the majority of cases. Homozygous SMN1 (survival motor neuron) gene deletion causes spinal muscular atrophy, and SMN2 gene deletions are possible risk factors in lower motor neuron disease. We studied SMN1 and SMN2 genes copy numbers in 167 amyotrophic lateral sclerosis patients and in 167 matched controls. We noted that 16% of amyotrophic lateral sclerosis patients had an abnormal copy number of the SMN1 gene (1 or 3 copies), compared with 4% of controls. An abnormal SMN1 gene locus may be a susceptibility factor for amyotrophic lateral sclerosis.

Malnutrition at the time of diagnosis is associated with a shorter disease duration in ALS

BACKGROUND Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. During the course of the illness, malnutrition can occur and may shorten survival. The aim of our study was to determine whether clinical nutritional parameters that are used in daily practice are associated with prognosis and whether they can help guide therapeutic decisions. METHODS We retrospectively reviewed a cohort of ALS patients in our institution between January 2002 and January 2006. Clinical and demographic outcomes were compiled. To evaluate predictors of survival, we analyzed several clinical nutritional parameters available in daily practice (body mass index, weight loss exceeding 10% of premorbid weight at the time of diagnosis and during the course of the disease and the use of technical supports such as percutaneous endoscopic gastrostomy (PEG) and non-invasive ventilation). RESULTS Sixty-three patients were retrospectively studied. Thirteen patients had weight loss exceeding 10% of premorbid weight at the time of diagnosis and thirty patients had weight loss meeting this criterion at final examination. Weight loss exceeding 10% at the time of diagnosis was associated with a shorter duration of disease (17±6months versus 35±26months; p=0.002). A linear correlation was found between mean disease duration and time between onset and diagnosis (p<0.0001). The subgroup of patients with a PEG had a longer survival time than the other subgroup of patients (p=0.02). CONCLUSIONS In ALS patients, early and marked weight loss significantly predicts a worse prognosis. The percentage of premorbid weight loss is a suitable and useful measure that can be used in daily practice to identify patients with a poor prognosis.

Outcome at adulthood of the continuous spike-waves during slow sleep and Landau-Kleffner syndromes

Summary:  Purpose: The aim of this study was to determine the clinical, social, and/or professional and cognitive outcomes in adulthood of the continuous spike–waves during slow sleep (CSWS) and Landau–Kleffner syndromes, which are two rare epileptic syndromes occurring in children.

Emergent EEG in clinical practice.

OBJECTIVE Emergency situations require a rapid and precise diagnostic approach. However, the exact role and value of the electroencephalogram (EEG) in emergent conditions have yet to be clearly defined. Our objective was to determine why clinicians order an emergency EEG, to assess to what extent it helps establish a correct diagnosis and to evaluate the result it has on subsequent patient management. METHODS We studied all successive emergency EEGs ordered during a 3-month period in our institution. We analyzed the reasons why each EEG was ordered and interviewed the prescribing clinicians in order to determine the impact the result of the EEG had on the diagnosis and subsequent therapeutic management. RESULTS We prospectively studied a total of 111 consecutive recordings. The main reasons for ordering an emergent EEG were: suspected cerebral death (21%), non-convulsive status epilepticus (19.7%), subtle status epilepticus (14%) and follow-up of convulsive status epilepticus (11.2%). In 77.5% of the cases the clinicians considered that the EEG contributed to making the diagnosis and that it helped confirm a clinically-suspected diagnosis in 36% of the cases. When subtle status epilepticus (SSE) or non-convulsive status epilepticus (NCSE) was suspected, the diagnosis was confirmed in 45% and 43.3% of the cases, respectively. In 22.2% of the requests involving follow-up of convulsive status epilepticus after initial treatment, the EEG demonstrated persistent status epilepticus. It resulted in a change in patient treatment in 37.8% of all the cases. When the EEG helped establish the diagnosis, patient treatment was subsequently modified in 46.6% of the cases. CONCLUSIONS This prospective study confirms the value of an emergent EEG in certain specific clinical contexts: the management of convulsive status epilepticus following initial treatment or to rule out subtle status epilepticus. An emergent EEG can also be ordered if one suspects the existence of non-convulsive status epilepticus when a patient presents with mental confusion or altered wakefulness after first looking for the specific signs suggesting this diagnostic hypothesis. SIGNIFICANCE After 50 years of development and use in daily practice, the EEG remains a dependable, inexpensive and useful diagnostic tool in a number of clearly-defined emergency situations.

ALS and mercury intoxication: A relationship?

We report the case of an 81-year-old woman in whom clinical signs and features of electromyographic activity patterns were consistent with amyotrophic lateral sclerosis (ALS). Increased blood level and massive urinary excretion of mercury proved mercury intoxication. Despite a chelation treatment with Meso 2-3 dimercaptosuccininc acid (DMSA), she died after 17 months. The pathophysiology of sporadic ALS remains unclear. However, the role of environmental factors has been suggested. Among some environmental factors, exposure to heavy metals has been considered and ALS cases consecutive to occupational intoxication and accidental injection of mercury have been reported. Although no autopsy was performed, we discuss the role of mercury intoxication in the occurrence of ALS in our case, considering the results of experimental studies on the toxicity of mercury for motor neuron.

NEUROPSYCHOLOGIC AND ADAPTIVE FUNCTIONING IN ADOLESCENTS AND YOUNG ADULTS SHUNTED FOR CONGENITAL HYDROCEPHALUS

The major aim of this study was to assess whether the syndrome of nonverbal learning disabilities described in hydrocephalic children is observed in adulthood. Eleven adults shunted for congenital hydrocephalus related to spina bifida and eight adults shunted for hydrocephalus related to aqueductal stenosis were administered an extensive neuropsychologic battery to investigate discrepancies between verbal and visuospatial cognition, verbal and visuospatial long-term memory, and psycho-social adaptive abilities. The results showed no discrepancies between Wechsler Performance IQ or Verbal IQ in either hydrocephalic group. Nevertheless, the subjects with spina bifida appeared more cognitively impaired than the subjects with aqueductal stenosis, who performed normally on the Wechsler Adult Intelligence Scale-Revised. Memory assessment using Signorets Memory Battery revealed no discrepancy between verbal and visuospatial memory in the hydrocephalic group. Nevertheless, the subjects with spina bifida had poorer verbal and visuospatial memory performance than the subjects with aqueductal stenosis. There were no differences on the Vineland Adaptive Behavioral Scale between subjects with spina bifida and those with aqueductal stenosis in autonomy, socialization, and daily living skills. These results suggest that shunted congenital hydrocephalus is not characterized by nonverbal learning disabilities syndrome in adolescence or in adulthood. (J Child NeuroL 1999;14:144-150).

Migraine and Angina Pectoris by Coronary Artery Spasm

A migrainous patient who experienced chest pain attributed to engine pectoris by coronary artery spasm during a migraine attack is reported. Previous reports have already mentioned the association of these two conditions and suggested that it might be the manifestation of a generalized vasospastic disorder. This new report offers an opportunity to review and discuss the available data on such an association.

Brain biopsy is required in steroid-resistant patients with chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS).

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a treatable brainstem encephalitis recently described by Pittock et al. [1]. We report a case with clinical, radiological, and pathological signs of CLIPPERS but with final diagnosis of type B primary central nervous system lymphoma (PCNSL). In March 2010, a 33-year-old man with unremarkable personal history was first seen in the internal medicine unit for isolated vomiting with weight loss of 5 kg. The clinical and paraclinical examinations were unremarkable. In June, he was admitted to our unit for subacute gait ataxia, dysphagia, and binocular diplopia. Clinical examination revealed bilateral sixth nerve palsy and gait ataxia with pyramidal signs. Brain magnetic resonance imaging (MRI) showed hyperintense lesions on T2-weighted and fluidattenuated inversion recovery (FLAIR) sequences within the pons, medulla, and upper cervical cord, with enhancement after gadolinium administration. Cerebrospinal fluid (CSF) analysis showed elevated levels of proteins (1.10 g/l) with normal electrophoretic pattern and without abnormal cell count (2/mm). Extensive laboratory investigations were normal. Whole-body fluorodeoxyglucose positron emission tomography (FDG-PET), and labial salivary gland biopsies were negative, including aquaporin-4 water channel and onconeural antibodies. Biopsy of pons revealed perivascular lymphocyte infiltrates without any findings of sarcoidosis, lymphoma, glioma, or lymphomatoid granulomatosis (Fig. 1d). CLIPPERS syndrome was suspected, and the patient was treated for five consecutive days with 1,000 mg intravenous methylprednisolone followed by oral prednisone 60 mg (1 mg/kg/day) every day, with dramatic recovery except for persistence of moderate gait ataxia. In August 2010, a second brain MRI showed a reduction in the number and size of brainstem lesions. Localized proton magnetic resonance spectroscopy (MRS) examination showed a slight decrease of N-acetyl-aspartate/creatine (NAA/Cr) ratio (1:52) and an increase in choline/creatine (Cho/Cr) ratio (1:58) in the brain and medulla (Fig. 1a). The dose of steroids was reduced by 10 mg/week until 30 mg/ day was reached. In September 2010, he complained of numbness in all four limbs with worsening gait ataxia. A third brain MRI showed enlargement of the pontine lesions with necrosis. The MRS showed a slightly elevated Cho/ NAA ratio, as well as strong resonance of lipids and lactates (Fig. 1b). The patient was then treated with 1,000 mg intravenous methylprednisolone for 5 days; this was followed by double-filtration plasmapheresis. Because no further clinical improvement was observed, monthly intravenous cyclophosphamide was added. In October, the fourth brain MRI revealed radiological progression of brainstem lesions with the appearance of gadoliniumenhanced lesions localized close to the left lateral ventricle. N. Limousin (&) J. Praline O. Motica B. De Toffol Department of Neurology, CHRU, 2, Boulevard Tonnellé, 37044 Tours cedex, France e-mail: nadege.limousin@univ-tours.fr

Epilepsy and Language Development: The Continuous Spike-Waves during Slow Sleep Syndrome

Summary:  Background: Continuous spike‐waves during slow sleep syndrome (CSWSS) is a rare epileptic syndrome occurring in children, which is characterized by the association of epilepsy, neuropsychological disorders, and abnormal paroxysmal electroencephalographic (EEG) discharges activated by sleep. Language can be affected but, to date, language disorders and their long‐term outcome have been documented only rarely.