Épilepsies généralisées idiopathiques chez le sujet âgé : le point de vue du gériatre

Introduction

Long-term follow-up studies indicate a low remission rate in idiopathic generalised epilepsies (IGE) (Martinez-Juarez et al., 2006), suggesting they may persist to an advanced age. However there are few estimates of IGE frequency in the elderly.

Methods

EEGs of 700 patients aged over 70 years, recorded between January 2006 and March 2007, were reviewed for anomalies consistent with IGE. We then examined the clinical history of patients with these anomalies.

Results

A persistent IGE was identified in four female patients (mean age: 79 years); in two cases it was a juvenile myoclonic epilepsy (JME) and in two an epilepsy with grand mal seizures. Seizures in three patients had begun in childhood or adolescence and in one at 40 years. Before hospitalization, few or no seizures were reported and IGE had not been diagnosed. IGE was revealed in each patient by a relatively severe event: an absence status (AS), subcontinuous myoclonic seizures or repeated convulsive generalised seizures (CGS). These events were not situation-related but in one patient the relapse of simple convulsive seizures, may have been related to the withdrawal of anti-epileptic drugs (AED) several months previously. EEG records showed generalised spikes or polyspikes and waves organised in a status epilepticus or in interictal rhythmic discharges. In one case they were evident only from a 24 hours recording. Clonazepam injection was used to suppress the AS episode and the subintrant myoclonia. After the AS, interictal generalised epileptic discharges persisted. Two of the four patients had familial history of epilepsy or febrile seizures but in no case was an epileptogenic lesion evident in brain CT scan or MRI. Clinical exams and biologic parameters were normal. All of the patients had worked and were married with children. Appropriate therapies were followed after the diagnosis of IGE. One patient with JME had been treated by Valproate which was discontinued by the general practitioner because of lethargy and replaced by Carbamazepine; seizures were aggravated under both Carbamazepine and then Lamotrigine and until the patient became seizure-free on Levetiracetam. The antiepiletic treatment was also modified in a second patient, while the two others responded well to Valproate.

Conclusions

IGE can exacerbate in the elderly, as different types of seizures including AS, subintrant myoclonia or repeated CGS. Our data suggest persistent IGE are quite frequent in an aged population and may be underestimated due to difficulties in diagnosis. Correctly diagnosed, adjustment of AED may offer substantial clinical improvements in IGE of the elderly.     

Menkes disease and infantile epilepsy

Objectives

Menkes disease, an X linked recessive neurodegenerative disorder, results from a mutation in the gene coding for the copper transporting ATPase (ATP7A). Epilepsy is a major clinical feature of this disorder. We describe the clinical presentation, evolution of epilepsy and explore the biological underpinnings of epileptogenesis in Menkes disease.

Methods

Longitudinal case study illustrating the natural history of epilepsy and results of subcutaneous cupric chloride supplementation in a patient with Menkes disease and literature review.

Results

The onset and evolution of epilepsy in Menkes disease is marked by different stages. Early presentations typically involve focal seizures, with progression to epileptic spasms and a chronic late stage of epilepsy characterized by tonic seizures, myoclonic jerks, and multifocal epileptiform activity on the EEG. Morphological correlates in the brain include evidence of atrophy of grey matter, ventriculomegaly, tortuous intracranial vasculature, and white matter signal changes consistent with loss of myelin and axons. The presence of significant lactic acidosis in brain and cerebrospinal fluid suggests widespread disturbance in oxidative metabolism. Molecular consequences of the pathogenic ATP7A gene mutation lead to impairment in copper transport, which in turn causes deficiencies of key copper containing enzymes (dopamine β hydroxylase and cytochrome c oxidase). Microarray studies suggest widespread effects in dysregulation of genes involved in cellular responses to oxidative stress, ribosomal translation, signal transduction, mitochondrial function, and immune responses. Impairment of copper mediated NMDA receptor function further enhances neuronal excitability, excitotoxic neuronal injury, setting up a cascade that creates conditions for epileptogenesis to follow.

Conclusion

Neurological manifestations are likely related to perturbations in copper dependent enzymatic pathways involved in neurotransmitter and energy metabolism. Early diagnosis and institution of copper supplementation has been shown to be beneficial particularly in patients with residual ATP7A activity.     

Apport d’une démarche électroclinique dans le diagnostic de l’épilepsie chez une population de sujets âgés confus

Background

Delusion symptoms often occur in old people; epilepsy is one of the main reasons behind these acute episodes. Current guidelines and recommendations from the Academy of Medicine have proposed a double clinical and electroencephalographic approach. Recently, a working group of French experts has issued an electro-clinical scale. The aim of our study was to compare the usual approach with the new one based on the electro-clinical score.

Method

All EEG requests performed since December 2008 in Bretonneau Hospital for elderly people aged over 75 years for delusion syndromes were retained for this study.

Results

One hundred and fifteen old patients from a geriatric-hospital (age 83.5 ± 6.06 years) were included in this protocol. The classical diagnostic process yielded the diagnosis of epilepsy for 50 subjects. The electro-clinical scale confirmed the diagnosis of epilepsy in 30 patients and ruled it out in 29 patients.

Conclusion

This study underscores the importance of evidence-based medicine for the diagnosis of epilepsy in old people and points out the underuse of the new technical tool, EEG-monitoring, for the management of these patients.     

Juvenile Myoclonic Epilepsy: Factors of Error Involved in the Diagnosis and Treatment

Juvenile myoclonic epilepsy (JME), a common form of idiopathic generalized epilepsy, has a distinct clinical and electroencephalographic profile. Often JME is not recognized, with serious consequences on the sufferers. We examined factors contributing to the missed diagnosis even in an epilepsy clinic. Of 70 JME patients, 66 (91.4%) were not diagnosed on referral and 22 (33%) were not initially recognized in the epilepsy clinic. The correct diagnosis was established after a mean of 8.3 +/- 5.5 years from disease onset and an interval of 17.7 +/- 10.4 months from first evaluation in the epilepsy clinic. Myoclonic jerks, the hallmark of the disease, were not usually reported by patients. Similarly, relevant questioning may not be included in the history. Absence seizures antedating jerks by many years, myoclonic jerks reported as unilateral, generalized tonic-clonic seizures occurring during sleep and focal EEG abnormalities are other factors contributing to not recognizing JME. Our study reemphasizes the need to have not only a correct seizure diagnosis but also a correct epilepsy-disease diagnosis.     

Caractéristiques des enfants ayant une épilepsie suivis au CHU de Marrakech

Introduction

Epilepsy is one of the most frequent neurological diseases in the pediatric population. Many epidemiological studies have been published, but with rather discordant results, because of methodological differences. In our context, epilepsy constitutes a public health problem. National epidemiological data are scarce.

Objectives

To describe the characteristics of children with epilepsy, to analyze the risk factors and to assess the impact of the disease on schooling.

Methods

This was a retrospective study concerning 592 children attending the Mohammed VI university hospital center pediatric unit A outpatient clinic for epilepsy from August 2003 to December 2007.

Results

Epileptic syndromes were classified according to the criteria of the International League Against Epilepsy of 1989. Prevalence of epilepsy was 8.5%. Average age was 6 years 7 months. Age of seizure onset ranged from 2 months to 14 years. Male gender predominated. Antecedents were dominated by peri- and neonatal complications. Parental consanguinity and a family history of epilepsy were found in 19.2 and 11.6% of cases, respectively. Schooling was perturbed in more than one-third of the school-age children. Generalized seizures were most common (70.5%). Association with cerebral palsy was present in 18.6% of cases, with mental retardation in 4.7%. The epilepsy was idiopathic for 41% of the children, symptomatic for 39% and cryptogenic for 20%. Generalized epileptic syndromes were the most frequent, epilepsy absence (12%), Lennox-Gastaut syndrome (6%), West syndrome (5.5%) and myoclonic epilepsy (4%). The most common partial epileptic idiopathic syndrome was benign childhood epilepsy with centrotemporal spikes. Single-drug therapy was the rule for first intention treatment (96.8%). Sodium valproate was the antiepileptic drug most widely used (82%). Treatment led to resolution of the seizures in 76% of the children.

Conclusion

Preventive measures should be reinforced in our context with a considerable proportion of children presenting neonatal risk factors. Efforts should be made to improve schooling for children with epilepsy.     

Delayed diagnosis of juvenile myoclonic epilepsy.

Fifteen cases of juvenile myoclonic epilepsy (JME) were identified from one hundred and eighty consecutive patients referred to a new epilepsy clinic at St Thomas' Hospital between April 1989 and December 1990, a prevalence of 8.3%. Of these, only one was referred with a putative diagnosis of JME. Diagnosis of the other patients on referral included "epilepsy", "grand mal", "temporal lobe epilepsy", "photoconvulsive epilepsy" and "alcohol-induced epilepsy". At least 11 of the 15 patients had been seen by a neurologist in the United Kingdom before referral. Definitive diagnosis was delayed by a mean of 14.5 years. In seven patients inappropriate anticonvulsants had been prescribed. Control of seizures was improved in most patients after diagnosis. Factors responsible for the delay in diagnosis include lack of familiarity with the syndrome, failure to elicit a history of myoclonic jerking and high prevalence of focal abnormalities on the EEG. Precipitation of fits by alcohol and sleep deprivation may not be recognised by the physician as part of the syndrome of JME. Diagnosis may also be delayed in patients whose absence and generalised tonic-clonic seizures pre-date myoclonic jerks.     

The Time of Day Sleepiness Scale to assess differential levels of sleepiness across the day

Objective

The study evaluated the Time of Day Sleepiness Scale (ToDSS) to determine subjective estimates of sleepiness in the morning, afternoon, and evening. Scores on the ToDSS were compared to the Epworth Sleepiness Scale (ESS). The ToDSS was evaluated on three cohorts of patients at a sleep medicine clinic.

Method

The items of the ToDSS are modified from the ESS to enable subjective assessment in the morning (before noon), afternoon (noon to 1800 h), and evening (after 1800 h). The scale takes about 5 min to complete. For each item, patients provide an estimate of their level of sleepiness in three separate columns, each indicating the time of day (morning, afternoon, and evening).

Results

Each ToDSS score evidenced a one factor structure. The ToDSS enabled the assessment of differential levels of sleepiness across the day among several cohorts, with scores increasing in the afternoon and evening. The ESS and each score of the ToDSS demonstrated high correlations. Lower subjective estimates of sleepiness were documented after treatment with continuous positive airway pressure.

Conclusions

The ToDSS was shown to have comparable psychometric features to the ESS and provided perceived sleepiness levels across the day in an efficient and cost-effective manner. It also enabled characterization of treatment response among a cohort of patients with obstructive sleep apnea.     

Hémorragie méningée focale et angiopathie amyloïde cérébrale : une association non fortuite

Introduction

Cerebral amyloid angiopathy is a degenerative angiopathy due to amyloid deposits in the walls of the meningeal and cortical vessels. It is considered as a major cause of cerebral hemorrhage to the elderly. It was recently demonstrated that the association of focal meningeal bleedings and cerebral hemorrhage is very suggestive of cerebral amyloid angiopathy. In contrast, the links between subarachnoid hemorrhage and amyloid angiopathy are less well-known.

Cases reports

We report nine cases of cerebral amyloid angiopathy. The clinical presentation was variable, but all had at least one inaugural meningeal bleeding. As cortico-meningeal biopsies were not performed the Boston criteria were used to establish the diagnosis.

Conclusion

Cerebral amyloid angiopathy is an underestimated cause of subarachnoid hemorrhage. Our observations show that this diagnosis should be evoked when focal meningeal bleeding occurs without head trauma or when focal subarachnoid hemorrhage is followed by a subcortical hematoma in an elderly subject.     

Juvenile myoclonic epilepsy: Clinical features and factors related to misdiagnosis

We identified 37 patients with juvenile myoclonic epilepsy (JME) out of 740 consecutive epilepsy patients. Only three were initially diagnosed with JME. Factors leading to misdiagnosis included warnings (auras) suggesting partial seizures before tonic—clonic seizures (GTCS), confusion between absence and complex partial seizures, failure of patients to spontaneously report or for physicians to obtain a history of myoclonic jerks, and failure to report myoclonic jerks to medical personnel despite specific questioning. Psychiatric disorders were common: depression occurred in nine and panic disorder in seven patients. Following diagnosis, 86% of patients were seizure-free on antiepileptic drugs. To improve diagnostic sensitivity, patients with epilepsy should be routinely questioned about the occurrence of myoclonic seizures, and JME should not be excluded because patients report nonspecific warnings before GTCS.     

Clinical features, EEG findings and diagnostic pitfalls in juvenile myoclonic epilepsy: a series of 63 patients

Juvenile myoclonic epilepsy (JME) is a common idiopathic generalized epileptic syndrome distinctively characterized by myoclonic jerks often associated to generalized tonic-clonic seizures (GTCS) and typical absence seizures. In spite of typical clinical and EEG profiles, JME is widely underdiagnosed. In the present study we retrospectively revised clinical and EEG data of JME patients referring to our Epilepsy Service. A diagnosis of JME could be made in 63 patients, that is 5.7% of all the epileptic patients referring to our Service and 25.9% of those suffering from an idiopathic generalized epilepsy. General features as well as modality of onset and course of the syndrome of our JME subjects were in accordance with literature. Regarding EEG findings, asymmetries were detected in 38.1% of cases. At referral to our Service only 31.7% of JME patients were correctly diagnosed. Main factors responsible for misdiagnosis were failure in eliciting a history of myoclonic jerks and misinterpretation of myoclonic jerks as simple partial seizures. EEG asymmetries were misleading in 13 patients. In conclusion, a correct JME diagnosis is strictly dependent on the knowledge of the syndrome leading the interviewer to look for and correctly interpret myoclonic jerks whereas EEG is just an ancillary diagnostic tool.     

The topographical distribution of epileptic spikes in juvenile myoclonic epilepsy with and without photosensitivity

Objective

Up to 30% of people with juvenile myoclonic epilepsy (JME) have photoparoxysmal responses (PPR). Recent studies report on structural and pathophysiological differences between people with JME with (JME+PPR) and without PPR (JME?PPR). We investigated whether electrophysiological features outside photic stimulation differ between these subtypes.

Occurrence of only myoclonic jerks in juvenile myoclonic epilepsy

Objectives - The clinical data on individuals who were diagnosed to have juvenile myoclonic epilepsy (JME) on the basis of myoclonic jerks alone has been analysed. The points in favour and against individuals with only myoclonic jerks being classified as "affected" for research on JME are discussed.
Materials and methods - We studied 15 persons diagnosed with JME on the basis of only myoclonic jerks in a series of 161 patients with JME and their relatives. Detailed information on the seizure types in JME patients and their family members was collected. All affected individuals were examined by one person and had at least one conventional scalp EEG. CT/MRI of the brain was done as and when indicated.
Results - Nine of these were probands while 6 were the relatives of JME patients. The EEG was abnormal in 8 of 9 probands and 1 of 6 relatives with only myoclonic jerks. All the 9 probands and 2 relatives with only myoclonic jerks were treated with anti-epileptic drugs. Three of the 4 relatives had spontaneous remission of jerks after variable intervals. Four of 15 persons with only myoclonic jerks had a first degree relative with definite JME.
Conclusions - It appears that persons with myoclonic jerks alone may represent a benign subgroup of JME that may be genetically distinct from classic JME and the jerks may even spontaneously remit in a few cases. It is suggested that those persons with only myoclonic jerks and a first degree relationship with a definite diagnosis of JME can be classified as "affected" for inclusion into molecular studies, till molecular tools are available to settle the issue of phenotypic variations in hereditary neurological disorders like JME.     

Familial cortical myoclonic tremor with epilepsy (FCMTE): Clinical characteristics and exclusion of linkages to 8q and 2p in a large French family

Introduction

Familial cortical myoclonic tremor with epilepsy (FCMTE) is defined by an autosomal-dominant inheritance, adult onset of myoclonus of the extremities, infrequent epileptic seizures, a non-progressive course, polyspikes on electroencephalography (EEG), photosensitivity, giant somatosensory-evoked potentials (SEP), enhancement of C-reflex and a premyoclonus spike detected by jerk-locked EEG back-averaging. Two genes yet to be identified are mapped to 8q23.3-q24.1 and 2p11.1-q12.2.

Methods

The present study involved five generations of a French family presenting with FCMTE, including 76 family members. Clinical analyses were performed in 39 living subjects and electrophysiological studies in five patients. Altogether, 27 relatives (21 living and six deceased) had the clinical characteristics of FCMTE, 17 of whom were analyzed. Linkage analyses were performed with microsatellites encompassing the two known loci (8q 23.3-q24.1 and 2p11.1-q12.2).

Results

Mean age at onset in the 17 living patients was 28.8 years (range 24-41). All had myoclonus/cortical tremor, and 11/17 had generalized tonic-clonic seizures. Other clinical symptoms were photosensitivity (16 cases), partial seizures (five cases), sensitivity to starvation/exercise (six cases) and vibration (four cases), ophthalmic migraine (six cases) and gait disorders (10 cases). Electrophysiological studies confirmed the FCMTE diagnosis in the five studied patients. Of the remaining relatives, 14 were considered healthy (asymptomatic subjects aged more than 40 years) and eight were of unknown status (asymptomatic aged lesser than 40 years). The pattern of inheritance was consistent with autosomal-dominant inheritance, although the two loci responsible for FCMTE were excluded.

Conclusion

This large family highlights some unusual clinical characteristics and suggests the presence of a third gene. Genetic research is ongoing to identify the mutated gene.     

Left mesiotemporal lesions and anterograde memory impairement: a case of neurosyphilis

Introduction

Neurosyphilis has become uncommun in the developed countries.

Observation

We report a case of neurosyphilis with limbic presentation, left mesiotemporal lesions on MRI and severe anterograde amnesia.

Discussion

Pathogeneses of MRI findings are unknown. We suggest the implication of arteritis wich affects small vessels, parenchymatous and excitotoxic lesions. The absence of mesiotemporal lesion in immunodeficient patients, the limbic systematization of pathology underlines the involvement of probably auto-immune process. Neurosyphilis should always be considered in the differential diagnosis of limbic encephalitis in order to initiate treatment and to prevent cognitives sequelaes. At last, partial status epilepticus should be diagnosed and excitotoxicity lesions prevents with antiepileptic treatment.     

Progressive paraparesis with sensorineural deafness and leukoencephalopathy revealing neurobrucellosis

Introduction

Brucellosis is a rare disease with variable neurological and imaging manifestations.

Case report

A 54-year-old woman presented with progressive paraparesis and sensorineural hearing loss over 18 months. The presence of diffuse white matter changes on brain magnetic resonance imaging (MRI) and cerebrospinal fluid findings led to the diagnosis of neurobrucellosis. Spinal MRI did not show any lesion that could explain the paraparesis that was finally attributed to the leukoencephalopathic lesions. The patient improved clinically after three months of antibiotic treatment but no significant changes were noticed on brain imaging.

Discussion and conclusion

Neurobrucellosis is a treatable disease which should be discussed when a patient presents with the triade progressive paraparesis, sensorineural hearing loss and leukoencephalopathy on MRI. Outcome can be favorable if adapted treatment is given early.     

Rotatory seizures in juvenile myoclonic epilepsy

Rotatory seizures have been reported in association with focal intracranial lesions. This type of seizure was also described in patients with primary generalized epilepsies. To our knowledge, there is only one previous publication denoted an association between juvenile myoclonic epilepsy (JME) and rotatory seizures. We present two female patients with JME and rotatory seizures together. The onset of myoclonic jerks and generalized tonic clonic (GTC) seizures was in their midteens. Their interictal EEGs showed bilateral symmetric spike and polyspike wave discharges. The rotatory seizures of the patients started at age of 26 and 33 years, respectively. In one of the patients, turning to the left was followed by three or four complete turns, after then, she had GTC seizures. The other patient has turned to the right with only one or two turns and sometimes continued with GTC seizures. Neuroradiologic investigations including brain CT, MRI, and SPECT were performed. Response to valproate therapy of rotatory seizures was good. We believe that rotatory seizures are rarely seen in JME patients, and this causes false diagnosis which lead unsuitable drug choice.     

Les dyskinésies paroxystiques kinésigéniques : une « canalopathie » ? Étude de 19 cas

Introduction

Paroxysmal kinesigenic dyskinesia (PKD) is characterized by brief episodes of dystonia and choreoathetosis triggered by sudden voluntary movements. Disease onset is seen in the first or second decade. The attacks typically last less than one minute. Three autosomal dominant PKD loci are identified: EKD1, EKD2 and EKD3. EKD1 has an overlap with the locus of the “Infantile Convulsion and Choreoathetosis (ICCA) syndrome”. The favorable natural history, the episodic nature of the symptoms and their sensitivity to anticonvulsant therapy suggest channelopathy as a mechanism of PKD.

Patients and methods

We reviewed the clinical features, the family history, the treatment response, the evolution and the technical investigations in 19 affected individuals.

Results

All cases were idiopathic. Ten patients had a positive familial history. Three patients suffered from ICCA syndrome. Some atypical features were seen, such as the association of kinesigenic and nonkinesigenic attacks and the presence of migraine, ataxia, seizures and myoclonus. Acetazolamide responsiveness was seen in two patients.

Conclusion

The coexistence of PKD and nonkinesigenic dyskinesia in several patients confirms the earlier described presence of intermediary forms, nonrepresented in the current classification of paroxysmal dyskinesias. Our study results suggest channel dysfunction and basal ganglia involvement in the pathophysiology of PKD.     

Polynévrite, crise convulsive, syndrome cérébelleux, complication d’un traitement par métronidazole. Apport de l’IRM

Introduction

Neurological complications of metronidazole are rare, predominantly peripheral neuropathies, especially in patients on a long-term high-dose regimen. Cerebellar syndrome or seizures are less frequently reported. The concomitant occurrence of the three complications is exceptional.

Case report

We report herein a case with these three complications as side effects of metronidazole. For the cerebellar syndrome, the T2-weighted brain MRI showed a rounded and well-delimited zone of high signal intensity in the cerebellar dentate nuclei, extending up to the protuberance and the subthalamic nucleus, bilaterally and symmetrically.

Conclusion

Neurological complications are possible when a treatment with metronidazole is prescribed for a long duration or at high dose. In our patient, the clinical abnormalities and MRI signs regressed a few months after treatment withdrawal.     

Atypical childhood absence epilepsy with preceding or simultaneous generalized tonic clonic seizures

Objective

Although the current diagnostic criteria for childhood absence epilepsy (CAE) do not specifically exclude children with generalized tonic clonic seizures (GTCSs) occurring before or early in the course of the active absence seizures, some workers have suggested that they should be interpreted as doing so. The aim of this study was to compare the clinical features between children with typical CAE and those with atypical CAE with preceding or simultaneous episodes of GTCS (atypical CAE-GTCS).

Methods

A total of 11 patients with atypical CAE-GTCS and 30 with typical CAE were identified by using the current CAE criteria. Their clinical data, including age, sex, family history of epilepsy, personal history of febrile convulsions, onset ages of absences and GTCS, treatment, and outcome were statistically analyzed.

Results

The two groups had the same mean onset age of absences (6 years), and their seizure outcome was comparably favorable in terms of both absences and GTCS. There was no significant difference in other clinical data except for the onset age of GTCS between the groups.

Conclusion

These findings show the similarity in the main clinical features between the groups, suggesting that some patients with atypical CAE-GTCS may have a variant form of CAE with early onset of GTCS.     

Diplégie faciale au cours d’une neuropathie démyélinisante inflammatoire aiguë secondaire à une varicelle

Introduction

Primo-infection by varicella-zoster virus (VZV) may be associated with several neurologic complications. Bilateral facial palsy is a rather uncommon manifestation.

Case report

We report the case of a 38-year-old woman who developed bilateral facial diplegia and paresthesia affecting all four limbs with subacute onset several days after varicella virus primoinfection. Ancillary tests showed hyperproteinorachia and signs of demyelinating polyneuropathy in nerve conduction tests. The diagnosis of Guillain-Barré syndrome was retained and a treatment with intravenous immunoglobulines was started, leading to progressive improvement.

Conclusion

Immunotherapy is a possible therapeutic approach in the context of neurologic postinfectious complications after VZV infection where an underlying mechanism is probable.