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.

Psychiatric comorbidity in temporal DNET and improvement after surgery.

BACKGROUND: "Alien tissue" may be responsible for a higher frequency of psychiatric disorders in patients with temporal lobe epilepsy (TLE). Also, ganglioglioma and dysembryoplastic neuroepithelial tumors (DNET) could represent a risk-factor for the development of post-surgical psychoses. Classically, severe psychiatric disorders contra-indicate epilepsy surgery. OBJECTIVES: Assessment of inter-ictal psychiatric disorders in 10 consecutive patients with temporal DNET, before and after epilepsy surgery with a minimum of a 2-year follow-up evaluation. METHODS: DNETs were confirmed on histological examination. Psychiatric disorders were classified according to the DSM-IV-TR. RESULTS: Five patients presented inter-ictal psychiatric disorders with, according to the DSM-IV-TR, undifferentiated schizophrenia (one case), "borderline" personality (two cases), intermittent explosive disorder with slight mental retardation (one case), and personality disorders not otherwise specified but with some traits of dependent personality and with mythomania (one case). The condition of these five patients dramatically improved after surgery. No psychiatric behavior or "de novo" psychosis was observed after surgery in any of the patients. CONCLUSION: The prevalence of inter-ictal psychiatric disorders appears to be high in epileptic patients with a temporal lobe DNET primarily in relation to personality and behavioral problems with some degree of impulsivity and verbal aggressiveness. The improvements after surgery suggest that this therapy could be performed in these patients and severe psychiatric disorders do not contra-indicate this procedure.

Activation of wicket spikes by REM sleep.

INTRODUCTION: Wicket spikes consist of monophasic arciform waveforms seen over the temporal regions, either bilaterally or independently over the two hemispheres. They should not be misinterpreted as epileptic abnormalities. They are usually found during light NREM sleep or drowsiness. In this study, we report an activation of wicket spikes by REM sleep. METHODS: Two patients underwent 48-hour video-EEG. Their sleep macrostructure was analyzed. The presence of wicket spikes was correlated to each specific sleep stage. RESULTS: In one case, wicket spikes appeared exclusively during REM sleep. In another patient, although wicket spikes were present throughout all sleep stages, their frequency was much higher during REM sleep (64% during REM sleep, 22% during light NREM sleep, 14% during drowsiness). DISCUSSION: This study highlights that wicket spikes may be present exclusively during REM sleep and that this stage of sleep can activate them. This para-physiological rhythm, when first described, was linked to drowsiness and light NREM sleep. The persistence of wicket spikes during REM sleep has been only recently described and an increase in their frequency during this sleep stage has never been previously observed.

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.

Wicket spikes misinterpreted as focal abnormalities in idiopathic generalized epilepsy with prescription of carbamazepine leading to paradoxical aggravation.

Wicket spikes (WS) are a normal variant EEG pattern that sometimes can be mistaken for epileptiform activity. We present a patient with WS and idiopathic generalized epilepsy who had been wrongly diagnosed with focal epilepsy, which leads to the prescription of carbamazepine with severe aggravation of generalized tonic-clonic seizures. She was referred for presurgical assessment of refractory focal epilepsy but long-term video-EEG showed sharp theta waves over the temporal regions during awakening, with a typical aspect of WS during drowsiness, nREM sleep stages I-II, and rapid eye movements (REM) sleep. There were a few generalized spike-waves during sleep but interictal changes were increased in frequency at awakening with bursts of fast-generalized spike-waves. Carbamazepine was progressively withdrawn and the patient was progressively switched to zonisamide. The patient no longer complained of generalized tonic-clonic seizures. At one year follow-up, this patient receives zonisamide with valproate. She has remained seizure-free.

[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.

[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.

[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.