SCN1A is one of the most relevant epilepsy genes. In general, de novo severe mutations, such as truncating mutations, lead to a classic form of Dravet syndrome (DS), while missense mutations are ...associated with both DS and milder phenotypes within the GEFS+ spectrum, however, these phenotype‐genotype correlations are not entirely consistent.
Case report. We report an 18‐year‐old woman with a history of recurrent febrile generalized tonic‐clonic seizures (GTCS) starting at age four months and afebrile asymmetric GTCS and episodes of arrest, suggestive of focal impaired awareness seizures, starting at nine months. Her psychomotor development was normal. Sequencing of SCN1A revealed a heterozygous de novo truncating mutation (c.5734C>T, p.Arg1912X) in exon 26.
Conclusion. Truncating mutations in SCN1A may be associated with milder phenotypes within the GEFS+ spectrum. Accordingly, SCN1A gene testing should be performed as part of the assessment for sporadic patients with mild phenotypes that fit within the GEFS+ spectrum, since the finding of a mutation has diagnostic, therapeutic and genetic counselling implications.
Lafora disease is a fatal form of progressive myoclonic epilepsy caused by mutations in the
EPM2A
or
NHLRC1
/
EPM2B
genes that usually appears during adolescence. The
Epm2a
−/−
and
Epm2b
−/−
...knock-out mouse models of the disease develop behavioral and neurological alterations similar to those observed in patients. The aim of this work is to analyze whether early treatment with metformin (from conception to adulthood) ameliorates the formation of Lafora bodies and improves the behavioral and neurological outcomes observed with late treatment (during 2 months at 10 months of age). We also evaluated the benefits of metformin in patients with Lafora disease. To assess neurological improvements due to metformin administration in the two mouse models, we evaluated the effects on pentylenetetrazol sensitivity, posturing, motor coordination and activity, and memory. We also analyzed the effects on Lafora bodies, neurodegeneration, and astrogliosis. Furthermore, we conducted a follow-up study of an initial cohort of 18 patients with Lafora disease, 8 treated with metformin and 10 untreated. Our results indicate that early metformin was more effective than late metformin in Lafora disease mouse models improving neurological alterations of both models such as neuronal hyperexcitability, motor and memory alterations, neurodegeneration, and astrogliosis and decreasing the formation of Lafora bodies. Moreover, patients receiving metformin had a slower progression of the disease. Overall, early treatment improves the outcome seen with late metformin treatment in the two knock-out mouse models of Lafora disease. Metformin-treated patients exhibited an ameliorated course of the disease with slower deterioration of their daily living activities.
Objective
To assess the effectiveness and tolerability of eslicarbazepine acetate (ESL) monotherapy in routine clinical practice for the treatment of focal‐onset seizures.
Methods
Multicenter, ...retrospective, observational study conducted in patients older than 16 years treated with ESL as first‐line monotherapy or converted to ESL monotherapy from polytherapy or other monotherapy. Outcomes included 1‐year retention rate, seizure‐free rates after 6 and 12 months of monotherapy treatment, and safety/tolerability issues.
Results
A total of 256 patients were included (106 first‐line and 150 conversion to monotherapy; 56 patients aged >65 years). Overall, the 1‐year retention rate was 79% (72.7% in the ≥65 years subgroup) and seizure‐free rates at 6 and 12 months were 59.3% and 55.3% (72.2% and 67.3% in the ≥65 years subgroup), without significant differences when comparing first‐line vs conversion‐to‐ESL monotherapy groups (P = .979). However, the conversion group was heterogeneous and included 43 (29.1%) patients that were seizure free the year prior ESL introduction. A substantially higher proportion of patients remained seizure free for the entire follow‐up among those who initiated ESL due to tolerability problems compared with those treated due to inadequate seizure control (71.4% vs 37.3%). Overall, 62 of 256 (24.2%) patients reported AEs (39.3% in >65 years subgroup) and led to discontinuation in 20/256 (7.8%) patients (12.5% in >65 years subgroup). Commonly reported AEs were somnolence (6.6%), dizziness (6.3%), and headache (4.3%). Hyponatremia was recorded in five patients, the majority (4/5) of whom were older than 65 years.
Conclusions
Eslicarbazepine acetate was effective and well‐tolerated as first‐line or conversion to monotherapy in a clinical setting in adult and elderly patients with focal‐onset seizures.
Ictal asystole can appear in patients with focal epilepsy, even in early phases. We present our experience of 7 cases, remarking the electrocardiographic characteristics, the role of apnea, treatment ...and long-term evolution. Awareness of this entity and collaboration between neurologists and cardiologists are essential for a correct diagnosis and management.
•Electrical activity spreading through autonomic nervous system areas results in heart rhythm disturbances.•Ictal asystole is a cause of recurrent and unpredictable syncope.•The gold standard for diagnosis is an EEG-ECG, but high clinical suspicion is essential.•Seizure control is the basis of treatment, when it is impossible, pacing therapy should be considered.
Eyelid myoclonia (EM) with absences (EMA) is a generalized epilepsy syndrome with a prognosis and clinical characteristics that are still partially undefined. We investigated electroclinical ...endophenotypes and long-term seizure outcome in a large cohort of patients with EMA.
In this multicenter retrospective study, patients with EMA with ≥5 years of follow-up were included. We investigated prognostic patterns and sustained terminal remission (STR), along with their prognostic factors. Moreover, a 2-step cluster analysis was used to investigate the presence of distinct EMA endophenotypes.
We included 172 patients with a median age at onset of 7 years (interquartile range IQR 5-10 years) and a median follow-up duration of 14 years (IQR 8.25-23.75 years). Sixty-six patients (38.4%) displayed a nonremission pattern, whereas remission and relapse patterns were encountered in 56 (32.6%) and 50 (29.1%) participants. Early epilepsy onset, history of febrile seizures (FS), and EM status epilepticus significantly predicted a nonremission pattern according to multinomial logistic regression analysis. STR was achieved by 68 (39.5%) patients with a mean latency of 14.05 years (SD ±12.47 years). Early epilepsy onset, psychiatric comorbid conditions, and a history of FS and generalized tonic-clonic seizures were associated with a lower probability of achieving STR according to a Cox regression proportional hazards model. Antiseizure medication (ASM) withdrawal was attempted in 62 of 172 patients, and seizures recurred in 74.2%. Cluster analysis revealed 2 distinct clusters with 86 patients each. Cluster 2, which we defined as EMA-plus, was characterized by an earlier age at epilepsy onset, higher rate of intellectual disability, EM status epilepticus, generalized paroxysmal fast activity, self-induced seizures, FS, and poor ASM response, whereas cluster 1, the EMA-only cluster, was characterized by a higher rate of seizure remission and more favorable neuropsychiatric outcome.
Early epilepsy onset was the most relevant prognostic factor for poor treatment response. A long latency between epilepsy onset and ASM response was observed, suggesting the effect of age-related brain changes in EMA remission. Last, our cluster analysis showed a clear-cut distinction of patients with EMA into an EMA-plus insidious subphenotype and an EMA-only benign cluster that strongly differed in terms of remission rates and cognitive outcomes.
Highlights • We report clinical outcomes of lacosamide monotherapy in patients with focal epilepsy. • Long-term seizure freedom was achieved in more than two-thirds of the patients. • Tolerability ...was good and only few patients discontinued the drug due to side effects.
Abstract Eslicarbazepine acetate (ESL, Aptiom™) is a once-daily anticonvulsant, approved as adjunctive treatment of partial-onset seizures (POS). Historical-controlled trials investigating the use of ...ESL as monotherapy have demonstrated a favorable efficacy and tolerability profile in patients with POS. This prospective, non-interventional study recruited POS patients in 17 hospitals in Spain. After a 3-month baseline period, ESL therapy was initiated as 400 mg QD and up-titrated to an optimal maintenance dose based on clinical response and tolerance. The incidence of seizures was assessed via seizure calendars and the nature and severity of adverse events (AEs) were also recorded. A total of 117 patients (aged 9–87 years) enrolled in the study and were treated with ESL at either 400 mg/day (3.4% patients), 800 mg/day (61% patients), 1200 mg/day (27.1% patients) or 1600 mg/day (8.5% patients). At 3 months, 82.0% (n = 72) of patients achieved a ≥ 50% reduction in seizure frequency, compared to 79.7% (n = 67) of patients at 6 months and 83.0% (n = 49) at 12 months. Patients who suffered secondary generalized tonic-clonic (SGTC) seizures had seizure-free rates of 71% (n = 27), 69.6% (n = 29), and 72.7% (n = 16) at 3, 6, and 12 months, respectively. Overall, 18 patients (15.3%) reported AEs of instability and dizziness (n = 9), somnolence (n = 3), mild hyponatremia (n = 3), headache (n = 1), hypertriglyceridemia (n = 1), and allergic reaction (n = 1), which caused ESL discontinuation of ESL treatment. ESL is effective and well tolerated as monotherapy for patients with POS, which supports previous findings. Early use is supported by its frequent use as monotherapy in this study and lack of severe side effects.
Background and objectives
Many patients with epilepsy are treated with antiepileptic drug (AED) polytherapy. Several factors influence the choice of early add-on therapy, and deciding on the most ...appropriate drug can be difficult. This study aimed to assess the efficacy and tolerability of lacosamide as early add-on therapy in patients with partial-onset seizures.
Methods
REALLY (REtrospective study of lAcosamide as earLy add-on aLong one Year) was a multicenter, retrospective, 1-year, real-life study. Patients included were aged older than 16 years, had partial-onset seizures, and were treated with lacosamide as add-on therapy after one or two prior AEDs. Data were collected retrospectively from clinical records. The primary study objective was to assess the efficacy of lacosamide over 12 months (seizure-free and responder rates), and the secondary objective was to assess the tolerability of lacosamide at 3, 6, and 12 months adverse events (AEs) and discontinuation.
Results
One hundred and ninety-nine patients were enrolled in the study; 89 patients (44.7 %) had tried one AED and 110 patients (55.3 %) had tried two AEDs before lacosamide. At 12 months, the proportion of patients who were seizure free was 44.9 %, and 76 % of patients were responders. The seizure-free rate at 12 months for patients who had previously received one or two AEDs was 58 and 34.3 %, and the responder rate at 12 months was 83.0 and 70.4 %, respectively. The AE rate was 21.5 % at 3 months, 27.1 % at 6 months, and 31.2 % at 12 months, with 7.0 % of patients discontinuing treatment because of an AE. The most common AE reported was dizziness (11.6 %). Cryptogenic epilepsy, a higher number of prior AEDs, and the use of a sodium channel blocker at onset were associated with a worse outcome. The number of concomitant AEDs decreased over 1 year (
Z
= 5.89;
p
< 0.001). Twenty-two patients were converted to lacosamide monotherapy with at least one evaluation ≥6 months from the beginning of monotherapy conversion.
Conclusions
Lacosamide was effective and well tolerated as early add-on treatment in patients who had received one or two previous AEDs.
Episodes of loss of consciousness are common, even in young, healthy people, and can sometimes represent a diagnostic challenge. The main diagnoses to consider are syncope and epileptic seizures, ...both of which may have similar symptomatology such as dizziness, loss of consciousness, falls, or “convulsive” phenomena. We present the case of a young male patient with a background of two venous thrombosis episodes (superior vena cava thrombosis and cerebral venous thrombosis), attributed to protein C and S deficiency and complicated by high intracranial pressure. A lumboperitoneal shunt was performed and anticoagulant therapy was initiated. He did not experience any medical problems until several years later, when he suddenly began to develop frequent, repetitive, transient episodes of dizziness, followed by loss of consciousness. Simultaneous video-EEG and ECG performed during these events showed a typical pattern normally observed during syncope. Due to the absence of changes in heart rate or blood pressure, and taking into account his medical history, intracranial hypertension was considered as a possible cause of cerebral hypoperfusion. Cerebral arteriography demonstrated chronic thrombosis of all the cerebral sinuses, and the lumbar puncture an intracranial pressure of 47 mm Hg. The lumboperitoneal shunt was replaced and the patient has since not presented with any episodes. The use of simultaneous video-EEG and ECG is a reliable and efficient approach to differentiate between syncope and seizure and in this case, was the key to finding the cause of these episodes.
Published with video sequences
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