Slow Wave Discharges Research Articles

Restricted Cortical Activity Involving Parietal Lobe and Sublobar Region Leads to Generalized Spike-Wave Discharges of Juvenile Myoclonic Epilepsy: Evidence from an EEG Source Localization Study.

Previous studies have localized the origin of "generalized" spike-wave discharges of idiopathic generalized epilepsies to specific brain regions. Although there are studies in juvenile myoclonic epilepsy (JME) which have investigated the origin of spike-wave discharges, reports on the propagation of discharges are sparse. The current study investigated the propagation of spike-wave discharges in JME, which was investigated by statistically comparing the electroencephalography (EEG)-derived cortical source activity during (a) various phases of spike-wave discharge versus background (eyes closed) activity, and (b) various phases of the first spike wave versus the corresponding phase of subsequent spike waves. Fourteen patients with JME who had generalized spike/polyspike and slow wave discharges in interictal EEG were included in the study. A total of 179 spike waves (first discernible spike wave - 55; subsequent spike waves - 124) were selected for source localization. Source analysis was carried out using exact low-resolution electromagnetic tomography (eLORETA). Statistical analyses to estimate the probability distribution of differences in cortical activity between (a) eight phases of epileptic discharge versus background (eyes closed) activity and (b) phases of the first spike wave versus the corresponding phases of subsequent spike waves were performed by paired t-tests and corrected for multiple testing using LORETA-KEY software. Widespread activation of cortical voxels (more than 94%) was observed during all phases of epileptic discharge except the initial phase (pre-first spike) and terminal phase (post-peak of the subsequent wave). The parietal lobe, which was the most activated lobe during the pre-first spike, was found to be the least activated during the post-peak of first and subsequent waves. More than 93% of voxels in the sublobar region were consistently activated during all eight phases of discharge. The study findings suggest that the activity generated from the restricted brain network involving parietal lobe could be propagated through sublobar structures to cause widespread cortical activation during the subsequent phases of the spike-wave cycle.

A generalized seizure type: Myoclonic-to-tonic seizure

Background and purposeTo test the hypothesis that myoclonic seizures can evolve to tonic seizures, we documented the electroclinical features of this under-recognized seizure type. MethodsWe observed a distinct seizure pattern starting with myoclonus without returning to an interictal state, which subsequently evolved into generalized tonic seizures. The detailed symptomatic and electroencephalographic characteristics of this seizure were extracted, and the clinical manifestations, drug curative responses in patients with this seizure were reviewed and analyzed. ResultsThe onset of all seizures was characterized by a preceding period of myoclonus and bursts of generalized spike or poly-spike slow wave discharges with high amplitude. This was closely followed by the occurrence of tonic seizures, which were distinguished by bursts of generalized fast activity at 10 Hz or higher frequency. This under-recognized seizure type has been designated as myoclonic-to-tonic (MT) seizure. The number of patients identified with MT seizures in this study was 34. The prevalence rate of MT seizures was found to be higher in males. While MT seizures typically included a tonic component, it should be noted that some patients experiencing this seizure type never presented with isolated tonic seizures. Generalized Epilepsy not further defined (GE) accounted for approximately one-third of the diagnosed cases, followed by Lennox-Gastaut syndrome and Epilepsy with Myoclonic-Atonic seizures. In comparison to other types of epilepsy, GE with MT seizures demonstrated a more favorable prognosis. ConclusionsThe classification of myoclonic-to-tonic seizure represents a novel approach in comprehending the ictogenesis of generalized seizures and can provide valuable assistance to clinicians in epilepsy diagnosis.

Altered neurological and neurobehavioral phenotypes in a mouse model of the recurrent KCNB1-p.R306C voltage-sensor variant

Pathogenic variants in KCNB1 are associated with a neurodevelopmental disorder spectrum that includes global developmental delays, cognitive impairment, abnormal electroencephalogram (EEG) patterns, and epilepsy with variable age of onset and severity. Additionally, there are prominent behavioral disturbances, including hyperactivity, aggression, and features of autism spectrum disorder. The most frequently identified recurrent variant is KCNB1-p.R306C, a missense variant located within the S4 voltage-sensing transmembrane domain. Individuals with the R306C variant exhibit mild to severe developmental delays, behavioral disorders, and a diverse spectrum of seizures. Previous in vitro characterization of R306C described altered sensitivity and cooperativity of the voltage sensor and impaired capacity for repetitive firing of neurons. Existing Kcnb1 mouse models include dominant negative missense variants, as well as knockout and frameshifts alleles. While all models recapitulate key features of KCNB1 encephalopathy, mice with dominant negative alleles were more severely affected. In contrast to existing loss-of-function and dominant-negative variants, KCNB1-p.R306C does not affect channel expression, but rather affects voltage-sensing. Thus, modeling R306C in mice provides a novel opportunity to explore impacts of a voltage-sensing mutation in Kcnb1. Using CRISPR/Cas9 genome editing, we generated the Kcnb1R306C mouse model and characterized the molecular and phenotypic effects. Consistent with the in vitro studies, neurons from Kcnb1R306C mice showed altered excitability. Heterozygous and homozygous R306C mice exhibited hyperactivity, altered susceptibility to chemoconvulsant-induced seizures, and frequent, long runs of slow spike wave discharges on EEG, reminiscent of the slow spike and wave activity characteristic of Lennox Gastaut syndrome. This novel model of channel dysfunction in Kcnb1 provides an additional, valuable tool to study KCNB1 encephalopathies. Furthermore, this allelic series of Kcnb1 mouse models will provide a unique platform to evaluate targeted therapies.

Short Report: Clinical Features and Epilepsy Monitoring in an Adult With 22q11.2 Deletion Syndrome.

22q11.2 microdeletion is the most common microdeletion syndrome in humans with a prevalence of 13 per 100000 live births, and it is a multisystem condition with variable phenotypic presentations. We present a case of an adult patient with Dandy-Walker syndrome who presented to our epilepsy clinic with 2 years of new-onset seizures and cognitive decline and 1 year of psychotic symptoms. Patient had a non-revealing autoimmune and malignancy work-up. Continuous scalp vEEG study showed bursts of 1-2Hz generalized fronto-centrally predominant spike or polyspike and slow wave discharges. Several myoclonic jerks were time-locked with the generalized discharges indicative of cortical myoclonus. MRI brain revealed periventricular nodular heterotopia in addition to findings suggestive of Dandy-Walker syndrome. Array-based comparative genomic hybridization demonstrated a 22q11.2 microdeletion seen in 22q11.2 deletion syndrome. Our case illustrates the challenges of diagnosing genetic disorders in adults especially when the initial diagnosis is dependent on a number of factors, including the patient's age, the severity of the phenotypic features, and the awareness of the physician.

Neuronal ceroid lipofuscinosis: A case report

Neuronal ceroid lipofuscinoses (NCL) represent severe neurodegenerative conditions which is one of the lysosomal storage disorders. There are four main clinical forms of NCL among which late infantile variety is the second most common condition. Here, we discuss a case concerning a boy aged 5 years and 4 months who exhibited a continuous decline in cognitive and motor functions starting from the age of 4. As the disorder advanced, he experienced gradual deterioration of his eyesight, unsteady walking and myoclonic seizures. An electroencephalogram performed on the child demonstrated widespread instances of sharp and slow wave discharges alongside a slowed background activity. Magnetic resonance imaging revealed extensive cerebral and noticeable cerebellar degeneration. A skin biopsy extracted from the armpit area displayed distinctive eosinophilic inclusions within the cells and structures in the eccrine ducts which stained positively for periodic acid-Schiff. These findings indicated a possibility of neuronal ceroid lipofuscinoses. Bangabandhu Sheikh Mujib Medical University Journal 2023;16(3): 174-177

Changes in awake and sleep electroencephalography characteristics after 1-year treatment for childhood and juvenile absence epilepsy

PurposeTo compare electroencephalography (EEG) features of newly diagnosed drug-naive childhood absence epilepsy (CAE) and juvenile absence epilepsy (JAE) patients and analyze their response to anti-seizure medications (ASMs). MethodEEG characteristics between CAE and JAE patients and responders and non-responders to ASM at baseline and 12 months were compared, and the changes from baseline were analysed. ResultsA total of 62 patients (32 CAE and 30 JAE) were included. Discharges in baseline awake and sleep EEGs and interictal and polyspike discharges in baseline sleep EEGs were more frequent in JAE patients. Although the median discharge densities (discharge containing seconds per minute) were similar in baseline awake and sleep EEGs between the groups, the median was higher in the JAE group at 12 months and decreased significantly in both groups at 12 months compared to the baseline values. Responses to initial ASMs were 94% and 77% in the CAE and JAE groups, respectively. In initial sleep EEGs of non-responders with JAE, focal onset generalized spike and slow wave discharges (GSWDs) were more frequent, and the median ictal and interictal discharge densities were higher. ConclusionJAE patients had more frequent disorganized discharges at baseline in both awake and sleep EEGs and interictal and polyspike discharges in sleep EEGs than those of CAE patients. Improvement in EEG was more pronounced in CAE patients than in JAE patients. Focal-onset GSWDs and higher ictal and interictal discharge densities on baseline EEG were associated with a poor response to initial ASMs in JAE patients.

Novel guanidinoacetate methyltransferase (GAMT) mutation associated with cerebral creatine deficiency syndrome in a Syrian child: a case report.

A 2.5-year-old boy presented to the paediatric neurology clinic with evidence of neurodevelopmental delays and intellectual disabilities. Recurrent eye blinking, generalized non-motor (absence) seizures, hyperactivity, and poor eye contact were revealed in the neurological examination. Some athetoid and dystonic movements were noticed. His electroencephalography (EEG) was very disturbed because of generalized spike-wave and slow-wave discharges. Based on these findings antiepileptic drugs were administered. His seizures slightly improved, but then relapsed with myoclonic and drop attacks. After 6 years of unbeneficial treatment, a genetic test was required. Whole-exome sequencing was conducted and identified a novel homozygous GAMT variant (NM_138924.2:c.391+5G>C). Treatment with oral creatine supplementation, ornithine, and sodium benzoate was administered. After 1.7 years of follow-up, the child was almost seizure-free with a remarkable reduction of epileptic activity on EEG. He demonstrated good-but not complete-behavioural and motor improvement due to delayed diagnosis and treatment. GAMT deficiency should be considered in differential diagnoses in children with neurodevelopmental regression along with drug-refractory epilepsy. A special concern is needed in Syria for such genetic disorders; regarding the high prevalence of consanguinity. Whole-exome sequencing and genetic analysis can be used to diagnose this disorder. We reported a novel GAMT variant to extend its mutation spectrum and provide an additional molecular marker for the definitive diagnosis of GAMT deficiency patients and prenatal diagnosis in the affected families.

NUS1 Exon 2 Deletion: A Crossover Between Epilepsy and Movement Disorders (P12-1.009)

<h3>Objective:</h3> We present two cases of patients presenting with epilepsy and a concomitant movement disorder found to have a heterozygous pathogenic variant in NUS1 with a deletion in exon 2. <h3>Background:</h3> The NUS1 gene is associated with autosomal dominant developmental and epileptic encephalopathy. Movement disorders such as tremor, ataxia, and myoclonus have been reported, though this clinical phenotype is not well defined. <h3>Design/Methods:</h3> Case Series <h3>Results:</h3> <h3>Case 1:</h3> A 54-year-old man with a history of schizophrenia and moderate intellectual disability presented to Movement Disorders Clinic with debilitating ataxia and multifocal myoclonus involving limbs and facial muscles and to Epilepsy Clinic for generalized epilepsy. Seizure semiology was generalized tonic-clonic. The patient’s father reportedly had tremor and seizures; however, patient was under guardianship of a caregiver with limited familial information. MRI brain was unremarkable. EEG captured myoclonic jerks without a cortical correlate. Seizures were well controlled on Keppra and Depakote. <h3>Case 2:</h3> A 25-year-old woman presented to Epilepsy Clinic for Lennox Gastaut Syndrome and to Movement Disorders Clinic for an action tremor with action-induced myoclonus. Epilepsy started at age 2 and was refractory shortly after onset with concurrent global developmental delay. Seizure semiologies included atonic, clonic, absence, and generalized tonic-clonic. Her epilepsy was well controlled on Epidiolex, lamotrigine, and clobazam. MRI brain was unremarkable. Interictal EEG showed background slowing, paroxysmal beta frequency activities, and generalized slow spike and wave discharges. Depakote was previously weaned with no improvement in tremor or myoclonus. A genetic panel (INVITAE™) revealed a heterozygous pathogenic variant in NUS1 with a deletion in exon 2 in both cases. <h3>Conclusions:</h3> Despite epilepsy being well controlled, our cases had an ongoing debilitating movement disorders. In patients with epilepsy who present with subcortical myoclonus, ataxia, or tremor, a genetic panel should be considered as well as referral to Movement Disorders for interdisciplinary management. <b>Disclosure:</b> Dr. Terpak has nothing to disclose. Dr. Schuck has nothing to disclose. Dr. Culpepper has nothing to disclose. Dr. Shneyder has nothing to disclose. Dr. Krishnaiengar has nothing to disclose. Dr. Zarroli has nothing to disclose.

Clinical features of epileptic seizures in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes

Background and purposeThis study aimed to characterize the clinical features of epilepsy in mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) and analyze the clinical determinants for drug-resistant epilepsy in MELAS. MethodsA single-center, retrospective study was conducted to investigate the clinical features of epilepsy in patients with MELAS. Collected variables included seizure semiology, electroencephalography (EEG), muscle biopsy, genetic testing, neuroimaging findings, resting serum lactic value and modified Rankin scale (mRS) of patients with MELAS. We also investigated the differences between the adult-onset group and the child-onset group and analyzed the risk factors for drug-resistant epilepsy in MELAS. ResultsWe studied 97 patients (56 males: 41 females) with confirmed MELAS. Epileptic seizure occurred in 100.0% of patients and the initial symptom of 69.1% patients was epileptic seizure. The average age of disease onset was 21.0 years, ranging from 2 to 60 years. The seizure types of these patients with MELAS were variable, with generalized onset (51.5%) to be the most common type. The EEG changes in the patients with MELAS were mainly slow wave (90.9%) and epileptiform discharge (68.2%). The child-onset group with earlier seizure onset presented significantly higher resting serum lactic value (p = 0.0048) and lower incidence of stroke-like lesion in the brain (p = 0.003), especially in the temporal lobe (p < 0.001), compared with the adult-onset group. Importantly, drug-resistant epilepsy in MELAS was demonstrated to be closely related to the earlier age of seizure onset (p = 0.013), as well as the higher mRS score (p < 0.001) and higher resting serum lactic value (p = 0.009). ConclusionEarly identification of MELAS should be considered among individuals with recurrent epilepsy through clinical screening. Age of seizure onset and resting serum lactic value may predict the development of drug-resistant epilepsy in MELAS. Close observation and appropriate anti-epileptic treatment are indispensable for individuals with MELAS to improve the prognosis. Further studies with larger sample size are required to further evaluate the risk factors of drug-resistant epilepsy in MELAS and provide guidance on treatment of MELAS.

Paroxysmal slow-wave discharges in a model of absence seizure are coupled to gamma oscillations in the thalamocortical and limbic systems

ObjectiveUsing the gamma-butyrolactone (GBL) model of absence seizures in Long-Evans rats, this study investigated if gamma (30–160 Hz) activity were cross-frequency modulated by the 2–6 Hz slow-wave discharges induced by GBL in the limbic system. We hypothesized that inactivation of the nucleus reuniens (RE), which projects to frontal cortex (FC) and hippocampus, would affect the cross-frequency coupling of gamma (γ) in different brain regions. MethodsLocal field potentials were recorded by electrodes implanted in the FC, ventrolateral thalamus (TH), basolateral amygdala (BLA), nucleus accumbens (NAC), and dorsal hippocampus (CA1) of behaving rats. At each electrode, the coupling between the γ amplitude envelope to the phase of the 2–6 Hz slow-waves (SW) was measured by modulation index (MI) or cross-frequency coherence (CFC) of γ amplitude with SW. In separate experiments, the RE was infused with saline or GABAA receptor agonist, muscimol, before the injection of GBL. ResultsFollowing GBL injection, an increase in MI and CFC of SW to γ1 (30–58 Hz), γ2 (62–100 Hz) and γ3 (100–160 Hz) bands was observed at the FC, hippocampus and BLA, with significant increase in SW-γ1 and SW-γ3 coupling at TH, and increase in peak SW-γ1 CFC at NAC. Strong SW-γ modulation was also found during baseline immobility high-voltage spindles. Muscimol inactivation of RE, as compared to saline infusion, significantly decreased SW-γ1 CFC in the FC, and peak frequency of the SW-γ1 CFC in the thalamus, but did not significantly alter SW-γ CFCs in the hippocampus, BLA or NAC. SignificanceThe paroxysmal 2–6 Hz SW discharges, a hallmark of absence seizure, significantly modulate γ activity in the hippocampus, BLA and NAC, suggesting a modulation of limbic functions. RE inactivation disrupted the SW modulation of FC and TH, partly supporting our hypothesis that RE participates in the modulation of SW discharges.

Modulation of colonic function in irritable bowel syndrome rats by electroacupuncture at ST25 and the neurobiological links between ST25 and the colon.

Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disease characterized by abdominal pain and defecation disorders. Acupuncture therapy positively affects IBS, with ST25 being the main point. However, ST25 has mostly been used in conjunction with other acupoints. This study aimed to observe the therapeutic effect of electroacupuncture at ST25 alone in IBS and the neurobiological mechanism of ST25 associated with the colon. First, we observed the effect of electroacupuncture at ST25 on the visceral pain threshold and slow-wave discharge of the colon in IBS model rats. Second, we explored the neurobiological mechanism of ST25 associated with the colon using a neural tracer technique. The results showed that (1) electroacupuncture at ST25 alone can alleviate visceral hypersensitivity and restore normal slow-wave frequency and rhythm of the colon in IBS rats; (2) there is a close neuroanatomical connection between ST25 and the colon, i.e., in the dorsal root ganglion (DRG), ST25 is similar in innervation to the colon, mainly in the T8-L1 segment, while the presence of double-labeled positive neurons is present in a part of the DRG; retrogradely labeled motor neurons associated with ST25 were observed in the anterior horn of the spinal cord, and retrogradely labeled sympathetic postganglionic neurons associated with ST25 were observed in the sympathetic nerve chain. These findings suggested that the DRGs and the dorsal horn of the spinal cord are important targets for electroacupuncture at ST25 to reduce visceral hypersensitivity in IBS rats. The sympathetic ganglia may be an important site for ST25 to regulate intestinal motility. The neurobiological mechanism of ST25 action in IBS rats should be further investigated in the future by combining related techniques, such as pseudorabies virus, optogenetics, calcium imaging, and electrophysiology.

0830 A Pediatric Case of Myoclonic Seizures Precipitating Central Sleep Apnea And Sequences of Periodic Breathing During Sleep

Abstract Introduction Myoclonic seizures are known to be influenced by the sleep-wake cycle. Although myoclonic seizures have been shown to alter sleep architecture, little is known about their influence on sleep-disordered breathing. Report of Cases: A 7-year-old male with a history of generalized epilepsy of unknown etiology with absence as well as myoclonic seizures, poor impulse control, and fine motor delay was referred for restless sleep and frequent nocturnal awakenings. A routine electroencephalography (EEG) performed 33 months prior to presentation, at an outside institution, reportedly showed 3.0 Hz generalized frontally dominant spike and wave discharges lasting less than two seconds. Video EEG (vEEG) revealed diffuse bilateral poly-spike and slow wave discharges, predominantly during sleep, and myoclonic seizures with abrupt whole-body jerks. Polysomnography, at this time, was characterized by mild central sleep apnea (AHI: 3.7; OAHI: 0.0; CAI: 2.8; REM AHI: 14.4). His lamotrigine dosing was increased to from 1.8 mg/kg/day to 3.6 mg/kg/day, at presentation, with seizure control for three months but he developed a recurrence of myoclonic seizures in the setting of sleep deprivation. A repeat vEEG was similar to previous findings and his lamotrigine was increased further and clobazam was added. Due to worsening behaviors, clobazam was discontinued and a weaning plan for lamotrigine was formulated. Repeat polysomnography demonstrated worsening central sleep apnea (AHI: 18.3, OAHI: 2.3), without hypoventilation, characterized by sequences of periodic breathing that occurred in conjunction with myoclonic seizures. The majority of seizure-induced periodic breathing episodes were observed during a one-hour period of NREM sleep near the end of the study. Stereotyped epileptiform activity occurred in conjunction with a resumption of hyperventilatory respirations following apneic events. The increased respiratory drive, however, did not appear to be clinically epileptic in nature as the epileptiform activity either preceded or trailed the respirations. A variable REM and then NREM predominance of central events on successive polysomnograms further suggests that his central events are not intrinsic but that they are precipitated by epileptiform activity. Zonisamide, an anticonvulsant with carbonic anhydrase inhibitory properties was initiated and is being titrated to therapeutic goal. Conclusion This case illustrates an unusual presentation of myoclonic seizure-induced periodic breathing during sleep. Support (If Any) Cincinnati Children’s Research Foundation.

Mechanism analysis for excitatory interneurons dominating poly-spike wave and optimization of electrical stimulation.

In addition to inhibitory interneurons, there exist excitatory interneurons (EINs) in the cortex, which mainly have excitatory projections to pyramidal neurons. In this study, we improve a thalamocortical model by introducing EIN, investigate the dominant role of EIN in generating spike and slow wave discharges (SWDs), and consider a non-rectangular pulse to control absence seizures. First, we display here that the improved model can reproduce typical SWDs of absence seizures. Moreover, we focus on the function of EIN by means of bifurcation analysis and find that EIN can induce transition behaviors under Hopf-type and fold limit cycle bifurcations. Specifically, the system has three stable solutions composing a tri-stable region. In this region, there are three attraction basins, which hints that external stimulation can drive the system trajectory from one basin to another, thereby eliminating abnormal oscillations. Furthermore, we compare the increasing ramp with rectangular pulse and optimize stimulation waveforms from the perspective of electrical charges input. The controlling role of the single increasing ramp to absence seizures is remarkable and the optimal stimulus parameters have been found theoretically. This work provides a computational model containing EIN and a theoretical basis for future physiological experiments and clinical research studies.

HP17: Electroencephalography patterns on two case studies of absence status epilepticus in adults

Two cases of Absence Status Epilepticus (ASE), in two patients of different ages, within two different clinical contexts, and with two different Electroencephalogram (EEG) patterns. I describe here, two female patients, 30 years old (case report one) and 76 years old (case report two) that were diagnosed with ASE after prolonged EEG (260 hours and 20.5 hours, respectively) had been performed. In these cases, the clinical manifestation of ASE was different, with the cardinal symptom being memory loss in case report one and confusion in case report two. Furthermore, the EEG pattern of each patient was different as well. In case report one there were very frequent runs of high amplitude, at times sharpened, slow activity over frontal or fronto-temporal regions and bursts of 1-2Hz generalised spike/polyspike and slow wave. Conversely, in case report two there were continuous 2-3Hz generalised spike and slow wave discharges for approximately 30 hour. EEG is the gold standard technique for the diagnosis of ASE, however, it can still present variable electrographic patterns that sometimes may cast doubt on whether it constitutes a definite ASE in particular it can be difficult to ascertain whether the pattern seen is ictal or interictal, especially when clinical signs are subtle. These two cases illustrate the difficulties in diagnosis and the range of presentations of ASE.

Close patient observation and electroencephalography play an important role in the diagnosis of rare diseases. Presentation of a case of Creutzfeldt-Jakob disease

Creutzfeldt–Jakob disease is a rare, progressive spongiform encephalopathy caused by infectious proteins called prions. It is characterised by rapidly progressive dementia accompanied by cerebellar, visual, extrapyramidal, and pyramidal symptoms, as well as myoclonus and mutism in later stage of the disease. The most common type is sporadic Creutzfeldt– Jakob disease, accounting for 85% of all cases. Treatment of the disease is symptomatic. An important role in making the diagnosis is attributed to the observation of the patient and electroencephalography, showing characteristic cyclical discharges. We present the case of a patient whose first symptoms were psychiatric in nature, and who was diagnosed with Creutzfeldt–Jakob disease based on careful observation, presence of myoclonus, and repeated electroencephalography examinations in which typical 1–2 seconds of sharp and slow wave discharges appeared. By presenting this case of severe progressive encephalopathy, we would like to highlight the fact that even in the age of modern diagnostic methods, electroencephalography, which has been in use for many years, may be crucial in the diagnostic process. We would also like to point out that the initial symptoms of Creutzfeldt–Jakob disease may suggest a psychiatric disorder.

Expanding the Treatment Landscape for Lennox-Gastaut Syndrome: Current and Future Strategies.

Lennox-Gastaut syndrome (LGS), a childhood-onset severe developmental and epileptic encephalopathy (DEE), is an entity that encompasses a heterogenous group of aetiologies, with no single genetic cause. It is characterised by multiple seizure types, an abnormal EEG with generalised slow spike and wave discharges and cognitive impairment, associated with high morbidity and profound effects on the quality of life of patients and their families. Drug-refractory seizures are a hallmark and treatment is further complicated by its multiple morbidities, which evolve over the patient’s lifetime. This review provides a comprehensive overview of the current and future options for the treatment of seizures associated with LGS. Six treatments are specifically indicated as adjunct therapies for the treatment of seizures associated with LGS in the US: lamotrigine, clobazam, rufinamide, topiramate, felbamate and most recently cannabidiol. These therapies have demonstrated reductions in drop seizures in 15%–68% of patients across trials, with responder rates (≥ 50% reduction in drop seizures) of 37%–78%. Valproate is still the preferred first-line treatment, generally in combination with lamotrigine or clobazam. Other treatments frequently used off-label include the broad spectrum anti-epileptic drugs (AED) levetiracetam, zonisamide and perampanel, while recent evidence from observational studies has indicated that a newer AED, the levetiracetam analogue brivaracetam, may be effective and well tolerated in LGS patients. Other treatments in clinical development include fenfluramine in late phase III, perampanel, soticlestat–OV953/TAK-953, carisbamate and ganaxolone. Non-pharmacologic interventions include the ketogenic diet, vagus nerve stimulation and surgical interventions; these are also expanding, with the potential for less invasive techniques for corpus callosotomy that have promise for reducing complications. However, despite these advancements, patients continue to experience a significant burden. Because LGS is not a single entity, tailoring of treatment is needed as opposed to a ‘one size fits all’ approach. Further research is needed into the underlying aetiologies and pathophysiology of LGS, together with advancements in treatments that encompass the spectrum of seizures associated with this complex syndrome.

Absence-to-bilateral-tonic-clonic seizure: A generalized seizure type.

ObjectiveTo test the hypothesis that absence seizures can evolve to generalized tonic-clonic seizures, we documented electroclinical features of this novel seizure type.MethodsIn 4 large video-EEG databases, we identified recordings of seizures starting with impaired awareness that, without returning to baseline interictal state, evolved to generalized tonic-clonic seizures. We extracted the detailed semiologic and electrographic characteristics of these seizures, and we documented the clinical background, diagnoses, and therapeutic responses in these patients.ResultsWe identified 12 seizures from 12 patients. All seizures started with a period of impaired awareness and bursts of generalized spike or polyspike and slow-wave discharges, the hallmark of absence seizures. Without returning to baseline, the nonmotor (absence) phase was followed by tonic-clonic convulsions. We called this novel generalized seizure type absence-to-bilateral-tonic-clonic seizure. Most patients had idiopathic generalized epilepsies, although with a high incidence of unusual features and poor therapeutic response.ConclusionsAbsence-to-bilateral-tonic-clonic seizures are a novel generalized seizure type. Clinicians should be aware of this seizure for correctly diagnosing patients. This novel seizure type may further elucidate generalized ictogenesis.

Recurrent epileptic seizures following cardiac catheterization with iodixanol: a case report

BackgroundContrast-induced encephalopathy (CIE) is a rare complication of cardiac catheterization; clinical manifestations include cortical blindness, seizures and focal neurological deficits. In general, recurrent epileptic seizures following cardiac catheterization with iodixanol occur more rarely than do other complications.Case presentationHere, we report a case of a 76-year-old male patient who experienced unstable angina for nearly 10 months and was admitted to our hospital. Repeat cardiac catheterization was performed using iodixanol. At approximately 20 h after the first cardiac catheterization, his upper limbs began to exhibit slight trembling; the patient was conscious and could not control these movements. A total of 6 episodes occurred before the second cardiac catheterization was performed, with each episode lasting approximately 2 s. These symptoms were not treated. At approximately 2 h after the second cardiac catheterization, the symptoms became more severe, and the frequency of the episodes increased significantly; the symptoms had fully subsided at 6 h after the second operation. An electroencephalogram (EEG) demonstrated diffuse slowing with epileptiform abnormalities. Paroxysmal spike-wave and slow wave discharges were observed in the bilateral areas, and the abnormalities were marked in the frontal areas. These observations led us to conclude that the patient was experiencing epileptic seizures. During 6 months of monthly clinical follow-up visits after discharge, no abnormalities of the nervous system were found by cardiologists or neurologists, and the patient’s EEG was normal. No antiepileptic drugs were administered throughout this process.ConclusionsCIE, especially recurrent epileptic seizures, is a rare but often reversible complication of cardiac catheterization with iodixanol. Its symptoms can be mild and therefore are easily ignored by physicians. Early CIE detection may be achieved by EEG. Repeated exposure to contrast agents carries the risk of recurrent epileptic seizures.

Risk factors for drug-resistant epilepsy: A systematic review and meta-analysis.

Drug resistant epilepsy (DRE) is very common among children and adults and studies had found some related risk factors for DRE, while the results were not consistent. The aim of this study was to identify risk factors for drug-resistant epilepsy. Three electronic databases (Medline, Embase and Cochrane library) were searched to identify studies with a cohort design reporting on epidemiologic evidence regarding risk factors for DRE. The pooled prevalence of DRE in newly diagnosed epilepsy patients was 25% (95% CI 17-32%). Abnormal electroencephalography (EEG) (both slow wave and epileptiform discharges) (RR 2.80; 95% CI 1.95-4.0), status epilepticus (SE) (RR 11.60; 95% CI 7.39-18.22), symptomatic etiology (RR 3.36; 95% CI 2.53-4.46), multiple seizure types (RR 3.66; 95% CI 2.37-5.64) and febrile seizures (RR 3.43; 95% CI 1.95-6.02) were identified as strong risk factors for DRE. In addition, firm conclusions cannot be drawn for poor short-term outcomes of therapy, neurodevelopment delay and high initial seizure frequency for the heterogeneity of study results. The predictive effect of focus onset seizure was not stable after removing one study and switching the effect model. Age of onset was not risk factors for DRE. The current meta-analysis identified potential risk factors for DRE. The results may contribute to better prevention strategies and treatments for DRE.

Encefalitis por virus influenza B en un paciente adulto. Reporte de caso

Neurological manifestations associated with influenza virus infection include encephalitis, encephalopathy, acute necrotizing encephalitis, transverse myelitis, acute disseminated encephalomyelitis, mild encephalitis with reversible splenial syndrome (MERS), and Guillaín Barré syndrome. We report a 16-year-old female who was admitted at our emergency department with seizures, confusion, nystagmus and motor clumsiness five days after an upper a respiratory tract infection. Influenza type B virus infection was confirmed by chain polymerase reaction analysis. The initial electroencephalogram demonstrated a pattern of global slowness without epileptic discharges. One week later, it showed a progression to slow-wave focal bilateral discharges at both temporal and occipital lobes. The patient had a favorable evolution and was discharged 19 days after admission with phenytoin to prevent seizures.