Prognostic factors in epilepsy with eyelid myoclonia (Jeavons syndrome).

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

Microendoscopic transventricular deep brain stimulation of the anterior nucleus of the thalamus as a safe treatment in intractable epilepsy: A feasibility study.

INTRODUCTION: Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is proposed in patients with severe intractable epilepsy. When used, the transventricular approach increases the risk of bleeding due the anatomy around the entry point in the thalamus. To avoid such a complication, we used a transventricular microendoscopic technique. METHODS: We performed a retrospective study of nine adult patients who were surgically treated for refractory epilepsy between 2010 and 2019 by DBS of the anterior thalamic nucleus. RESULTS: Endoscopy provides a direct visual control of the entry point of the lead in the thalamus through the ventricle by avoiding ependymal vessels. No hemorrhage was recorded and accuracy was systematically checked by intraoperative stereotactic MRI. We reported a responder rate improvement in 88.9% of patients at 1 year and in 87.5% at 2 years. We showed a significant decrease in global seizure count per month one year after DBS (68.1%; P=0.013) leading to an overall improvement in quality of life. No major adverse effect was recorded during the follow-up. ANT DBS showed a prominent significant effect with a decrease of the number of generalized seizures. CONCLUSION: We aimed at a better ANT/lead collimation using a vertical transventricular approach under microendoscopic monitoring. This technique permitted to demonstrate the safety and the accuracy of the procedure.

Will MRI replace the EEG for the diagnosis of nonconvulsive status epilepticus, especially focal?

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

Genetic/idiopathic generalized epilepsies: Not so good as that!

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

Divergence in physiological factors affecting swimming performance between anadromous and resident populations of brook charr Salvelinus fontinalis.

In this study, an anadromous strain (L) and a freshwater-resident (R) strain of brook charr Salvelinus fontinalis as well as their reciprocal hybrids, were reared in a common environment and submitted to swimming tests combined with salinity challenges. The critical swimming speeds (Ucrit ) of the different crosses were measured in both fresh (FW) and salt water (SW) and the variations in several physiological traits (osmotic, energetic and metabolic capacities) that are predicted to influence swimming performance were documented. Anadromous and resident fish reached the same Ucrit in both FW and SW, with Ucrit being 14% lower in SW compared with FW. The strains, however, seemed to use different underlying strategies: the anadromous strain relied on its streamlined body shape and higher osmoregulatory capacity, while the resident strain had greater citrate synthase (FW) and lactate dehydrogenase (FW, SW) capacity and either greater initial stores or more efficient use of liver (FW, SW) and muscle (FW) glycogen during exercise. Compared with R♀ L♂ hybrids, L♀ R♂ hybrids had a 20% lower swimming speed, which was associated with a 24% smaller cardio-somatic index and higher physiological costs. Thus swimming performance depends on cross direction (i.e. which parental line was used as dam or sire). The study thus suggests that divergent physiological factors between anadromous and resident S. fontinalis may result in similar swimming capacities that are adapted to their respective lifestyles.

Quantitative genetic analysis of the physiological stress response in three strains of brook charr Salvelinus fontinalis and their hybrids.

Three strains [domestic (D), Laval (L) and Rupert (R)] of brook charr Salvelinus fontinalis and their reciprocal hybrids were submitted to transport stress to measure stress resistance. Primary (cortisol) and secondary (glucose, osmolality and haematocrit) stress responses were measured for each cross. Significant heritabilities were observed for both levels of stress response, with mean ± S.E. heritability (h(2)) = 0.60 ± 0.20 for plasma cortisol and 0.61 ± 0.20 for plasma glucose. There were strain differences whereby the R strain was the least sensitive to stress at the primary and secondary levels. No heterosis was detected, and only one case of outbreeding depression was present. The outbreeding depression was observed in the D(♀) R(♂) hybrid, which had a 27% increase of plasma glucose compared to parental strains. The D(♀) R(♂) and R(♀) L(♂) hybrids had more pronounced variations (increase or decrease) in plasma osmolality than their respective parental strains, but these variations were difficult to relate definitively with the potential secondary stress response. These results indicate a strong potential for genetic improvement in the stress response to transport with the use of purebred crosses while hybridization has little value in this regard.

[Causes of status epilepticus]. / Recherche étiologique lors d'un état de mal épileptique.

Because of the wide range of etiologies which may provoke status epilepticus (SE), physical examination, laboratory tests and neuroimaging must be conducted according to a well-designed hierarchical system. While implementing intensive care management, clinicians must of course search for curable causes but also consider the possible interaction of multiple factors and hidden diseases favoring or triggering SE. Causes of SE in idiopathic or cryptogenic epilepsy and new-onset SE do not correlate but careful analysis of serum chemistry and neuroimaging abnormalities must nevertheless be conducted with the specific objective of establishing an etiological diagnosis.

[Satus epilepticus: epidemiology, definitions and classifications]. / Etats de mal épileptiques: épidémiologie, définitions et classifications.

The annual incidence of status epilepticus based on the definitions of the International League Against Epilepsy (1993) ranges from 10.3 to 41 per 100,000 inhabitant. Half of the cases of status epilepticus concern epileptic patients. In all studies, incidence is higher in epileptic patients, young children and the elderly. It is estimated that 13% of patients with status epilepticus will experience recurrence during the two first years. The three leading etiologies are low-dose antiepileptic drugs, non-acute brain lesions and acute stroke. Seizures are generalized in 9 to 33% of patients and focal in 25 to 75%. Secondary generalized seizures can be observed in 19 to 66% of patients. Mortality ranges from 7.6 to 39% and varies as a function of inclusion of postanoxic encephalopathies and difference in initial care. The definition retained and the classification adopted for status epilepticus also affect mortality estimates. Status epilepticus is defined as the existence of a prolonged seizure or a series of seizures during which the patient does not recover, or incompletely recovers, consciousness. The duration parameter used to distinguish status epilepticus from a seizure remains controversial. At the present time, there is general agreement in the literature distinguishing two definitions based on different durations according to the clinical type of status epilepticus and its potential severity: (i) a status epilepticus is defined by a seizure lasting more than 30 minutes or recurrent seizures without recovery of consciousness over a period of 30 minutes; (ii) considering its severity, tonic-clonic status epilepticus has a specific definition leading to earlier therapeutic management. This operational definition is continuous, generalized, convulsive seizure lasting more than five minutes or two or more seizures during which the patient does not return to baseline consciousness. Several types of background can be used to establish a classification for status epilepticus: clinical manifestations, prognostic and therapeutic course, epidemiological data, pathophysiological mechanisms... At the present time, the classifications most commonly used in France for status epilepticus are derived from the syndromic epileptic classification, the seizure classification or the classification proposed by the French consensus workshop on status epilepticus. For routine clinical practice, an operational classification can be used to adopt therapeutic strategies adapted to probable prognosis: short-term life-threatening, mid-term life-threatening, not life-threatening.

[Pathophysiologic basis of status epilepticus]. / Bases physiopathologiques des états de mal épileptiques.

The mechanisms that induce epileptic activity and make it durable, leading to status epilepticus (SE), are poorly known. They probably result from an imbalance between the activating systems of neuronal depolarisation (excitatory amino acids release with postsynaptic N-methyl-d-aspartate [NMDA] receptor activation, spreading depolarisation following abnormal progression) and the inhibiting systems (GABAergic synapses). Status epilepticus leads to many direct and indirect cerebral disorders, as well as systemic disorders, with intertwined mechanisms and consequences. These disorders are more frequent in case of convulsive SE with generalized tonic-clonic seizures. Direct neuronal damage (selective neuronal loss and epileptogenesis) results mostly from excitotoxicity, which arises from enhanced and extended neuronal activation. Indirect neuronal damage results from the inability of the circulatory system to supply sufficient oxygen and glucose contribution compared to the high metabolism level of the highly depolarized and synchronized neurons. This energetic deficit is usually patent after 30 minutes of SE, when systemic compensation mechanisms (cardiac output increase) are exhausted. Understanding these pathophysiologic aspects is essential for effective treatment of SE.

[Electroencephalography in status epilepticus: Glossary, protocol and interpretation]. / Electroencéphalographie dans les états de mal épileptiques : glossaire, protocole et interprétation.

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

[Juvenile myoclonic epilepsy in a patient with history of infantile hemiplegia]. / Epilepsie myoclonique juvénile chez une patiente atteinte d'hémiplégie infantile.

INTRODUCTION: The 1989 International Classification of Epilepsies and Related Syndromes considers normal cognitive, neurologic and anatomic findings to be prerequisites for the diagnosis of idiopathic forms of epilepsy. CASE REPORT: We report the case of a woman with juvenile myoclonic epilepsy (JME) and a history of infantile hemiplegia. When she was a teenager, she had two generalized tonic-clonic seizures, later followed by a few seizures with loss of consciousness misinterpreted as complex partial seizures. Physical examination revealed right hemiparesis. A CT scan documented a left rolandic infarction and a wrong diagnosis of focal epilepsy was made. At 20 years, a nap video-EEG was performed. A burst of generalized spike-waves was recorded on awakening. Photic stimulation and watching a Japanese cartoon on television disclosed a marked photoparoxysmal response associated with myoclonic jerks. Myoclonic jerks were in fact known by the patients but unreported. She had jerks on roads with trees due to shade/sunlight alternance. A diagnosis of JME was made. CONCLUSION: This observation illustrates that patients' situation with a presumed genetic predisposition for JME are at equal risk for brain lesions as others subjects. Misdiagnosis of focal epilepsy may have dramatic consequences in patient with JME, as some patients will be aggravated by inadequate antiepileptic drugs.

[Insulinoma presenting as pseudo-drug-resistant focal epilepsy]. / Un insulinome se présentant comme une épilepsie focale pharmacorésistante.

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

Slow alpha variant during REM sleep.

REM sleep resembles wakefulness or drowsiness. The pattern can be low-voltage, or else alpha-like. Alpha frequencies are present only during the tonic phases of REM sleep and, compared to wakefulness tracings, alpha activities are slightly slower by 1-2 Hz and are more monomorphic. The slow alpha-variant rhythm or subharmonic alpha pattern consists of rhythmic notched theta waves. It shares the same topography and reactivity with the alpha rhythm. We report its presence during the tonic phases of REM sleep without any modification in its morphology in the first case. In the second case, its morphology was similar to awakening but with slower amplitude. No alpha frequencies were found in REM sleep but only its slow alpha variant. This study provides evidence that REM sleep is a stage of sleep that contains rhythms similar to those seen during wakefulness and drowsiness.

Phantom spike-and-wave bursts during REM-sleep.

Phantom spike-and-wave bursts or 6Hz spike-and-wave bursts consist of brief bursts of spikes of very low amplitude with a repetition range of 5 to 7Hz. This pattern usually occurs bilaterally and synchronously during relaxed wakefulness, drowsiness or light sleep. Bursts disappear during deeper levels of sleep. We present the case of a patient in whom this pattern reappeared in REM-sleep. This observation confirms that the stage of REM-sleep is close to wakefulness or drowsiness and may contain EEG patterns that are seen in these stages.

[Visual auras in idiopathic generalized epilepsy]. / Auras visuelles dans les épilepsies généralisées idiopathiques.

Visual auras are reported to be uncommon or rare in patients with idiopathic generalized epilepsy. We describe three patients who experienced visual auras just before generalized tonic-clonic seizures. This study indicates that in idiopathic generalized epilepsy, visual auras manifest as flashes, lighting or the impression of seeing the sun. Unlike auras in occipital lobe epilepsy, they are very brief.

[Healthcare networks in the Languedoc-Roussillon region]. / Les réseaux de soins: situation en Languedoc-Roussillon.

Epilepsies Languedoc-Roussillon, a healthcare network in epileptology, was created in 1994 with all practitioners interested in epileptology in this region of southern France. This network is autonomous, receives no subsidies and works within the existing healthcare system. It proposes best practices for epilepsy management from diagnosis to epilepsy surgery and continuing education. This network provides patients with rapid accessibility to management of their epilepsy. In this paper, the history of this network in southern France, its organization, actions and goals are discussed.

[Medicoeconomic assessment of epilepsy surgery in adults with medically intractable partial epilepsy. Three-year outcomes from a multicenter French cohort]. / Evaluation médicoéconomique de la chirurgie des épilepsies partielles pharmacorésistantes de l'adulte. Résultats à trois ans d'une étude prospective multicentrique française.

PURPOSE: To compare resective surgery and medical therapy in a cost-effectiveness analysis in a multicenter cohort of adult patients with partial intractable epilepsy. POPULATION AND METHODS: Adult patients with partial, medically intractable, potentially operable epilepsy were eligible and followed every year over five years. Effectiveness was defined as one year without seizure. The long-term costs and effectiveness were extrapolated over the patients' lifetime with a Markov model. Productivity (indirect costs) and quality of life (QOLIE-31, SEALS) were also assessed. Changes before and after surgery were compared between the two groups. RESULTS: Two hundred and eighty-nine patients were included (119 with surgery, 161 medically treated, six not eligible, three lost to follow-up). One year after surgery, 81% of the patients were seizure-free; at two and three years, this rate was 78%. In the medical group, these rates were 10, 18, and 15%, respectively. The cost of the explorations was euro 8464; including surgery, it was euro 19,700. In the medical group, the average annual direct costs were between 3500 and euro 6000. At two years after surgery, the annual direct cost decreased to euro 2768, at three years, it was euro 1233, predominately antiepileptic drug costs. Surgery became cost-effective between seven and eight years. In the surgical group, all the quality-of-life scores improved at one year after surgery and were stable during the second and third years. CONCLUSION: Surgical therapy was cost-effective at the middle term even though indirect costs were not considered.

[Carbamazepine and clarithromycin: a clinically relevant drug interaction]. / Carbamazépine et clarithromycine: une interaction médicamenteuse cliniquement significative.

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

[Reintroduction of treatment with lamotrigine in combination with valproate after an initial allergic skin reaction]. / Réintroduction de la lamotrigine en association au valproate après une réaction cutanée allergique initiale.

INTRODUCTION: Lamotrigine (LTG) is effective for a variety of seizure types especially against absence seizures in cotherapy with valproate (VPA). Skin rash is the most frequent side effect leading to LTG discontinuation. OBSERVATIONS: We report two patients with refractory absence epilepsy and a previous history of allergic reaction to LTG in which LTG was rechallenged. LTG was effective in both cases without incident. DISCUSSION: High initial dose and rapid dose escalation is associated with increased rash rate. LTG is contraindicated in patients who have demonstrated hypersensitivity to the drug. However, because the initial dose and the dose titration play a crucial role, LTG was reintroduced with a very low initial dose and very slow titration schedule without recurrence of skin rash. CONCLUSION: Patients who have experienced a previous mild skin allergy may be reconsidered for a rechallenge with LTG if the expected therapeutic response to the drug is high. Patients must be warned about the risks.