Telephone-induced seizures: a new type of reflex epilepsy

PURPOSE: To report a new form of reflex epilepsy in which the seizures are repeatedly and exclusively triggered by answering the telephone. METHODS: Three patients with a history of telephone-induced seizures were studied in detail by means of clinical, EEG, and neuroradiologic investigations. Intensive video-EEG monitoring to record the reflex seizures also was performed in all cases. RESULTS: The patients (two men, one woman, aged 21 to 30 years) had the onset during early adulthood of complex partial and secondarily generalized seizures exclusively triggered by answering the telephone. The seizures were stereotyped, with subjective auditory or vertiginous auras and inability to speak or understand the spoken voices. In one patient, a telephone-induced seizure arising from the dominant temporal lobe was recorded by means of video-EEG technique. In the interictal EEGs, temporal abnormalities were detected in all cases. The patients had a normal neurologic examination and normal magnetic resonance imaging or computed tomography scans. CONCLUSIONS: We suggest that telephone epilepsy is a previously unrecognized form of reflex epilepsy induced by a complex auditory stimulus involving the lateral temporal areas.     

C-reactive protein and seizures in focal epilepsy: a video-electroencephalographic study

Purpose: C‐reactive protein (CRP) has been studied extensively in many noninflammatory neurologic conditions, but there has been little study of CRP in the context of seizures or epilepsy. The purpose of this study was to examine CRP concentrations in patients with refractory focal epilepsy who were undergoing video‐electroencephalography (EEG) monitoring compared with healthy controls, and CRP change during 24 h after a seizure. Methods: CRP levels were measured in serum at the onset of video‐EEG recording (CRP‐0h) and at 3, 6, 12, and 24 h after index seizure (the first verified localized‐onset seizure) in 31 patients during inpatient video‐EEG monitoring by using high sensitivity measurement of CRP concentration. The patients were categorized into two groups: temporal lobe epilepsy (TLE; n = 15) and extratemporal lobe epilepsy (XLE; n = 16). Eighty healthy volunteers served as controls. Key Findings: CRP‐0h concentration was significantly higher in patients with refractory focal epilepsy than in controls (3.5 vs. 0.7 mg/ml, p < 0.001). All five patients with elevated CRP‐0h (>mean + 2 standard deviations in controls) had TLE (vs. none in XLE; p = 0.018). Index seizure type was associated with CRP increase from baseline to maximum level after index seizure (p = 0.005). The most important predictor of increase in CRP level was secondarily generalized tonic–clonic seizure (SGTCS; p = 0.030). Significance: The higher baseline levels in patients with epilepsy compared with healthy controls demonstrates that CRP concentrations are also affected in refractory epilepsy. Our data suggest that SGTCS stimulates CRP production. These results emphasize the association between inflammation and refractory epilepsy.     

Perioral reflex myoclonias: a controlled study in patients with JME and focal epilepsies

PURPOSE: Perioral reflex myoclonias (PORM) are obvious, frequent, but often unobserved focal seizures in different epileptic syndromes and the leading seizure type in reading epilepsy. PORMs remain often undiagnosed because the patients are not aware that these are epileptic seizures and fail to report them. Their semiology is not fundamentally different in various epileptic syndromes. METHODS: We studied the frequency of PORM in patients with juvenile myoclonic epilepsy (JME) compared with patients with focal epilepsies. Twenty-five patients with JME were investigated with a standardized neuropsychological test program and compared with 25 matched patients with focal epilepsies. Statistical significance was calculated by using Fisher's exact test. RESULTS: We found significant differences between the groups regarding both frequency of PORM and activation of epileptic discharges. These observations seem to indicate that PORM, like praxis-induced seizures, are typical traits in JME. CONCLUSIONS: PORM are more frequent in JME compared with focal epilepsies. The distinction between focal and generalized epileptic ictogenesis may be less clear than is traditionally believed.     

Early‐onset epileptic encephalopathy with migrating focal seizures associated with a FARS2 homozygous nonsense variant

Epilepsy of infancy with migrating focal seizures (EIMFS) is now a well‐recognized early‐onset syndrome included in the ILAE classification of the epilepsies. KCNT1 gain‐of‐function variants are identified in about half of patients. In the remaining cases, the underlying genetic component is far more heterogeneous with sporadic mutations occasionally reported in SCN1A, SCN2A, SLC12A5, TBC1D24, PLCB1, SLC25A22, and KCNQ2. Here, we report, for the first time, a homozygous deleterious variant in the FARS2 gene, identified using a 115‐gene panel for monogenic epilepsies, in a patient with EIMFS. This boy was the second child born to healthy consanguineous parents. The first seizures occurred at six weeks of age. The patient rapidly developed severe epilepsy with focal discharges on EEG, migrating from one brain region to another, highly suggestive of EIMFS. At five months of age, he had daily multifocal clonic seizures and erratic myoclonic fits, which were not consistently related to spikes or spike‐and‐wave discharges. Neurological status was severely abnormal from onset and the patient died at 10 months of age from respiratory distress. Using the gene panel, a homozygous missense variant of FARS2 was identified, at Chr6 (GRCh37):g.5404829C>T, c.667C>T (NM_001318872.1), inherited from both parents, leading to an arginine‐to‐cysteine substitution, p.(Arg223Cys). FARS2 is a member of the mitochondrial aminoacyl tRNA transferase (ARS) enzymes. ARS variants are increasingly recognized causes of early‐onset epileptic and neurodevelopmental encephalopathies, however, the associated epileptic phenotype is not completely described. This case shows that FARS2‐related seizures can mimic EIMFS in the early stage of the disease. Furthermore, in the setting of migrating focal seizures of infancy, FARS2 should be considered as a further candidate gene, and increased lactate level and occurrence of refractory myoclonic seizures are possible key features to suspect FARS deficiency.     

Electroclinical features of a family with simple febrile seizures and temporal lobe epilepsy associated with SCN1A loss-of-function mutation

PURPOSE: To report in detail the electroclinical features of a large family in which we recently identified a missense mutation (M145T) of a well-conserved amino acid in the first transmembrane segment of domain I of the human SCN1A. We showed that the mutation is associated with a loss of SCN1A function. METHODS: The family originates from southern Italy and contains 35 members spread over four generations. Of the 14 affected individuals, the 13 still living members (7 males, mean age 36.6 +/- 20.4) underwent a complete electroclinical evaluation. RESULTS: All 13 affected family members had febrile seizures (FS) up to the age of 6 years. Age at onset of FS ranged from 5 to 45 months with a mean age of 12.8 +/- 12.9 months. One of the 13 was affected by post-traumatic epilepsy. Three of the 13 later developed temporal lobe epilepsy (TLE) with both simple focal seizures, and also very rare focal complex or nocturnal secondary generalized tonic-clonic seizures. In two of the three patients who later developed TLE, the MRI studies revealed mesial temporal sclerosis. CONCLUSIONS: Our findings illustrate that SCN1A mutations can cause simple FS associated with TLE, which differ from the characteristic clinical spectrum of GEFS+. It is open to conjecture if this unusual phenotype might at least in part be related to the fact that M145T is the first missense mutation found in DIS1 of SCN1A.     

Focal seizures with affective symptoms are a major feature of PCDH19 gene–related epilepsy

Purpose: Mutations of the protocadherin19 gene (PCDH19) cause a female‐related epilepsy of variable severity, with or without mental retardation and autistic features. Despite the increasing number of patients and mutations reported, the epilepsy phenotype associated with PCDH19 mutations is still unclear. We analyzed seizure semiology through ictal video–electroencephalography (EEG) recordings in a large series of patients. Methods: We studied 35 patients with PCDH19 gene–related epilepsy and analyzed clinical history and ictal video‐EEG recordings obtained in 34 of them. Key Findings: Clusters of focal febrile and afebrile seizures had occurred in 34 patients, at a mean age of 10 months. The predominant and more consistent ictal sign was fearful screaming, occurring in 24 patients (70.5%); it was present since epilepsy onset in 12 and appeared later on, during the course in the remaining 12 patients. In infancy, fearful screaming mainly appeared within the context of seizures with prominent hypomotor semiology, whereas during follow‐up it was associated with prominent early motor manifestations. In 16 patients, seizures were video‐EEG recorded both at onset and during follow‐up: in five patients (31%) seizure semiology remained identical, in 7 (44%) semiology varied and in four patients it was unclear whether ictal semiology changed with age. Three patients (9%) had both focal and generalized seizures, the latter consisting of absences and myoclonus. Ictal EEG during focal seizures showed a prominent involvement of the frontotemporal regions (22 patients). About 45% of patients had an alternating EEG pattern, with the ictal discharge migrating from one hemisphere to the contralateral during the same ictal event. Status epilepticus occurred in 30% of patients. Cognitive impairment occurred in 70%, ranging from mild (42%) to moderate (54%) and severe (4%); autistic features occurred in 28.5%. Direct sequencing detected 33 different heterozygous candidate mutations, 8 of which were novel. Mutations were missense substitutions (48.5%), premature termination (10 frameshift, 4 nonsense, and 2 splice‐site mutations; 48.5%), and one in‐frame deletion. Thirty candidate mutations (91%) were de novo. No specific genotype–phenotype correlation could be established, as missense and truncating mutations were associated with phenotypes of comparable severity. Significance: Most patients with PCDH19 mutations exhibit a distinctive electroclinical pattern of focal seizures with affective symptoms, suggesting an epileptogenic dysfunction involving the frontotemporal limbic system. Awareness of this distinctive phenotype will likely enhance recognition of this disorder.     

Defecation reflex seizures: a case report with long‐term VEEG monitoring,neuroimaging and comprehensive epilepsy evaluation

Reflex seizures are consistently elicited by a specific afferent sensory stimulus or an activity undertaken by the patient. Among many known stimuli, defecation has rarely been reported. We describe the case of a child with reflex seizures triggered by defecation, considering the diagnostic challenge, epilepsy evaluation with video‐EEG monitoring, as well as impact on neuropsychology, behaviour and quality of life. The child was a 10‐year‐old boy with seizure onset at age four with epilepsy diagnosis established one and a half years later. Seizures were focal with impaired awareness triggered by defecation. Video‐EEG and structural and functional neuroimaging were performed and all pointed to the left temporal region. The patient became seizure‐free with carbamazepine and valproic acid. Neuropsychological and quality of life assessments suggested global impairment, both before and after seizure control. This is the third case of epilepsy induced by defecation reported in the literature. The rarity of this entity may be a diagnostic challenge and postpone specific treatment. Reporting of cases of defecation reflex epilepsy may provide a better understanding of its physiopathology and optimize effective treatment, avoiding cognitive, behavioural and poor social consequences. [Published with video sequence]     

Self‐induction seizures in sunflower epilepsy: a video‐EEG report

Seizures triggered by visual stimuli are the most common type of reflex seizure. Self‐induced seizures produced by stimulation of natural light are rare and self‐induction is a mode of seizure precipitation employed by either intellectually disabled or healthy photosensitive individuals. Absences and myoclonic jerks are the most common seizure types in self‐induction. We report on a girl with normal intelligence who self‐induced seizures by waving her outspread fingers in front of a bright light. This situation is called sunflower epilepsy. [Published with video sequences]     

Drug‐resistant epilepsy after treatment for childhood acute lymphocytic leukaemia: from focal epilepsy to Lennox‐Gastaut syndrome

Drug‐resistant epilepsy, not associated with acute brain complications or central nervous system leukaemic involvement, can develop in patients treated for acute lymphocytic leukaemia during childhood. It has been postulated that this rare complication may be due to CNS oncological treatment neurotoxicity, related to intrathecal drugs, such as methotrexate, and brain radiotherapy. We report four patients who developed drug‐resistant epilepsy sometime after receiving treatment for acute lymphocytic leukaemia. All patients were female and received intrathecal methotrexate. One received additional intrathecal cytarabine, and two concomitant brain radiotherapy. Two developed Lennox‐Gastaut type syndrome, one multifocal epilepsy, and one focal epilepsy related to a radiotherapy‐induced cavernous angioma. The development of drug‐resistant epilepsy after treatment for acute lymphocytic leukaemia is a rare complication that may vary, from focal epilepsy to an epileptic encephalopathy. This may appear even years after the treatment has finished and is most likely associated with treatment‐related neurotoxicity.     

Time to onset of sustained ≥50% responder status in patients with focal (partial‐onset) seizures in three phase III studies of adjunctive brivaracetam treatment

Time to onset of sustained ≥50% responder status (SRS) was assessed for the pooled patient population receiving brivaracetam (BRV) 50, 100, or 200 mg/day or placebo in three randomized phase III studies (NCT00464269, NCT00490035, and NCT01261325). Patients were aged ≥16 years with well‐characterized focal (partial‐onset) seizures (FS) uncontrolled by 1–2 concomitant antiepileptic drugs. After an 8‐week baseline period, patients received study drug without up‐titration for a 12‐week (84‐day) treatment period. A patient was a sustained ≥50% responder on a particular day if they completed the entire treatment period through day 84 and was a ≥50% responder (based on percent reduction in FS frequency from baseline) both on that day and every successive day until day 84 (end of treatment period). In the pooled efficacy population (N = 1,160), 15.5%, 18.1%, and 19.4% of patients taking BRV 50, 100, or 200 mg/day, respectively, achieved SRS on day 1 versus 6.7% for placebo (p < 0.001). Statistically significant SRS was also achieved for most of the BRV‐treated groups in the three separate studies. This suggests that BRV has an early, sustained onset of action in a subset of responders. The incidence of adverse events during the first week was similar to that in the overall treatment period.     

RFT1‐congenital disorder of glycosylation (CDG) syndrome: a cause of early‐onset severe epilepsy

RFT1‐congenital disorder of glycosylation (CDG) syndrome, a recessive N‐glycosylation disorder caused by mutation in the RFT1 gene, is a very rare subtype of CDG syndrome associated with deafness, developmental delay, and non‐specific epilepsy. The aim of this report is to describe the electroclinical presentation of epilepsy associated with this condition. [Published with video sequences online]