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Dravet syndrome is currently considered as an developmental and epileptic encephalopathy and, recently, mandatory, alert, and exclusionary criteria have been proposed. Here, we describe three patients with Dravet syndrome with the typical early presentation including febrile and afebrile alternating hemiclonic seizures due to loss-of-function SCN1A variants. Subsequently, they developed episodes of febrile focal status epilepticus (SE) associated with hemiparesis and cerebral hemiatrophy with posterior focal seizures, as a consequence of Dravet syndrome. This sequence of events has been previously published in patients with Dravet syndrome and does not contradict the recent classification by the International League Against Epilepsy (ILAE). The ILAE guidance identifies "Focal neurological findings" as alert criteria and "MRI showing a causal focal lesion" as exclusionary criteria for making an initial diagnosis of Dravet syndrome at presentation. Our three patients would correspond to a severe phenotype, similar to the well-known presentation of generalized atrophy following prolonged status epilepticus. Common genetic findings in cases of diffuse and unilateral brain involvement may help explain these clinical presentations. Further genotype-phenotype studies may provide additional insights into this electroclinical behavior., (© 2023 International League Against Epilepsy.)

Although the classic phenotype of episodic ataxia type 1 (EA1) caused by variants in KCNA1 includes episodic ataxia and myokymia, further genotype-phenotype correlations are difficult to establish due to highly heterogeneous clinical presentations associated with KCNA1 pathogenic variants. De novo variants in the paralogous Pro-Val-Pro motif (PVP) of KCNA2, an essential region for channel gating, have been reported to be associated with severe epilepsy phenotypes, including developmental and epileptic encephalopathies (DEE). Here, we describe the first patient with a DEE who developed an encephalopathy related to status epilepticus during sleep (ESES) and cerebellar signs, harbouring a variant in the Kv-specific PVP motif of the KCNA1 gene. Interestingly, he showed a remarkable long-term electroclinical response to IM ACTH therapy. This report extends the range of phenotypes associated with KCNA1 variants to include that of ESES, and suggests that ACTH therapy is likely to have a positive effect in patients with these variants.

We report a child who developed myoclonic status epilepticus (MSE) at four months of age, associated with rhythmic high-amplitude delta and superimposed (poly) spikes (RHADS), harbouring a GABRB2 (β2 subunit of the GABA A receptor) variant. The patient was treated under a presumptive diagnosis of neonatal-onset Alpers syndrome (AS) and underwent targeted sequence analysis for POLG1 (polymerase gamma 1) and subsequent whole-exome sequence analysis (WES). The patient is currently a 10-year, eight-month-old boy, suffering from daily MSE associated with RHADS and severe global developmental delay from early infancy. Although POLG1 mutation was negative, WES revealed a de novo missense variant of GABRB2 (NM_021911.2: c.784G>T, p.[Val262Phe]). Based on a review of case series with GABRB2 variants, we found that five of the 18 cases shared the clinical and EEG characteristics associated with our patient. In summary, this de novo GABRB2 variant was associated with an AS phenotype, characterized by treatment-resistant MSE and RHADS, and may represent an alternative aetiology for neonatal-onset AS without POLG1 mutation [Published with video sequence].

Status epilepticus (SE) is a medical emergency with increased risk of morbidity and mortality in all age groups. Recent research has identified a variety of new genes implicated in disorders with severe epilepsies as a prominent feature. Autoimmune mechanisms have also been recently recognised as a cause of epilepsies with SE as a characteristic symptom. Knowledge about the aetiology potentially underlying SE may help to guide diagnostics and eventually influence treatment decisions. This review recapitulates, in brief, the risk of SE in specific clinical settings, provides an overview of paediatric epilepsy syndromes more commonly, or by definition, associated with SE, and summarizes some recent research data on genetic defects and disease mechanisms implicated in the pathogenesis of epilepsies frequently accompanied by SE.

Neurofibromatosis type 2 (NF2) is a dominantly inherited syndrome caused by mutations of the tumour-suppressor NF2, which encodes the merlin protein. Mutations are associated with a predisposition to development of benign tumours in the central nervous system. Even though cerebral cortical lesions are frequently associated with seizures, epilepsy is rarely described in NF2. Here, we describe an adult case of NF2 in which the onset of symptoms was characterised by status epilepticus. In this patient, we identified the novel c.428_430delCTTdel mutation in NF2, involving the amino-terminal FERM domain, which is fundamental for the correct tumour suppressor function of the protein. Bioinformatic analyses revealed an important structural perturbation of the FERM domain, with a predicted impairment of the anti-tumour activity.

Epilepsy is the most common and serious neurological symptom in ring chromosome 14 syndrome, also characterised by mild dysmorphisms, acquired microcephaly, cognitive impairment, hypotonia and ocular abnormalities. Typically, early-onset, polymorphous and drug-resistant seizures are reported. Status epilepticus has not been previously reported. We describe a nine-year-old Caucasian boy with ring 14 syndrome who presented a severe early-onset and drug-resistant focal epilepsy with secondary generalised seizures and repetitive episodes of convulsive and non-convulsive status epilepticus. The electro-clinical evaluation of prolonged seizures and their long-term consequences is important for the practical management of these patients and for a better comprehension of the syndrome.

Seizure response and alerting behaviour may spontaneously develop in dogs living with children or adults with epilepsy. Some dogs can also be reliably trained to respond and anticipate seizures. We describe the case of a dog, not previously trained for assistance work, showing complex seizure response behaviour. This is the first release of a home video recording of a dog reacting to its owner's seizure.

Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a familial partial epilepsy syndrome characterized by seizures suggesting a frontal lobe origin occurring predominantly during sleep. Up to a third of patients may have refractory seizures, with repeated episodes of status epilepticus, intellectual disability of variable degree and psychiatric disturbances. We report a patient with ADNFLE, refractory seizures and repeated episodes of life-threatening convulsive status epilepticus who underwent prolonged video-EEG monitoring and was implanted with a vagal nerve stimulator. At 3.5 years of follow-up, a decrease of more than 80% in seizure frequency was achieved, episodes of status were completely controlled and he displayed improved mood and alertness. Vagal nerve stimulation may be considered as therapy for patients with refractory epilepsies of genetic cause, as well as repeated status epilepticus.

Purpose: The only consistent symptom of ring chromosome 20 syndrome (r(20)) is severe, refractory epilepsy often associated with a characteristic, although not pathognomonic, EEG pattern. Patients suffer from severe seizures with accompanying cognitive decline and frequent episodes of non-convulsive status epilepticus (SE). Other features of this rare disorder, such as dysmorphic changes, mental retardation and behavioral disturbances are variable. Because of the variability of the clinical presentation, some patients with r(20) undergo invasive investigations before being diagnosed., Case Study: We present the case of a young boy with no dysmorphic traits, who was only diagnosed with r (20) syndrome at the age of 13. His first seizure occurred at the age of four. Later seizures were of various types including non-convulsive SE, with deterioration of the background EEG and severe cognitive decline. Despite multiple trials of anti-epileptic medications, his seizures remained highly refractory, and he died as the result of an uncontrollable, prolonged SE, shortly after the diagnosis was made., Discussion: Non-convulsive SE is common in patients with r(20) syndrome and may be caused by a dysfunction in dopaminergic neurotransmission. However, until now, no case of lethal status epilepticus has been reported. This case report suggests that patients with unexplained refractory seizures and episodes of non-convulsive SE should undergo genetic testing early in their disease, even in the absence of any morphologic features or dysmorphic traits suggestive of a chromosomal disease.

As a generalized form of nonconvulsive status epilepticus (NCSE), absence status epilepticus is the most common form. It manifests as prolonged, confusional states of varying severity, and continuous or repetitive generalized discharges of spikes, multiple spikes, and slow waves on EEG. Jeavons syndrome (JS) is a new type of epilepsy syndrome. Hitherto, only four sets of monozygotic twin with JS have been reported. Absence status epilepticus occurring in monozygotic twins with JS have not been reported. Here we report on monozygotic male twins of Chinese origin with JS. Both of them presented with status epilepticus with eyelid myoclonia and absences.

Mossy fiber sprouting and other forms of synaptic reorganization may form the basis for a recurrent excitatory network in epileptic foci. Four major classes of axon guidance molecules--the ephrins, netrins, slits, and semaphorins--provide targeting information to outgrowing axons along predetermined pathways during development. These molecules may also play a role in synaptic reorganization in the adult brain and thereby promote epileptogenesis. We studied semaphorin gene expression, as assessed by in situ hybridization, using riboprobes generated from rat cDNA in an adult model of synaptic reorganization, kainic acid (KA)-induced status epilepticus (SE). Within the first week after KA-induced SE, semaphorin 3C, a class III semaphorin, mRNA content is decreased in the CA1 area of the hippocampus and is increased in the upper layers of cerebral cortex. Another class III semaphorin, semaphorin 3F, is also decreased in CA1 and CA3 of hippocampus within the first week after KA-SE. These changes in gene expression are principally confined to neurons. By contrast, there was little change in the semaphorin 4C mRNA content of CA1 neurons at this time. No changes in expression of semaphorin 3A and 4C genes were detected 28 days after KA-induced SE. Regulation of semaphorin gene expression after KA-induced SE suggests that neurons may regulate the expression of axonal guidance molecules and thereby contribute to synaptic reorganization after injury of the mature brain. The anatomic locale of the altered semaphorin gene expression may serve as a marker for specific networks undergoing synaptic reorganization in the epileptic brain.

We report the clinical history and the video-EEG recordings of three young adults with r(20), who exhibited repeated episodes of non-convulsive status epilepticus, often triggered by emotional events. This recognizable clinical entity associates a slight mental deficiency, behavioural disorder and epilepsy, often resistant to treatment and with a particular clinical presentation. We demonstrate with video EEG recording, atypical absence status triggered by emotional behaviour with ictal EEG characterized by bifrontal slow waves, often rhythmic, or sharp waves. Our report highlights the characteristic features of non-convulsive status in this electro-clinical syndrome.