Familial mesial temporal lobe epilepsy (FMTLE)

Introduction Familial mesial temporal lobe epilepsy (FMTLE) is characterized by prominent psychic and autonomic seizures, often without hippocampal sclerosis (HS) or a previous history of febrile seizures (FS), and good prognosis. The genetics of this condition is largely unknown.We present the electroclinical and genetic findings of 15 MTLE Italian families. Patients and methods FMTLE was defined when two or more first-degree relatives had epilepsy suggesting a mesial temporal lobe origin. The occurrence of seizures with auditory auras was considered an exclusion criterion. Patients underwent video-EEG recordings, 1.5-Tesla MRI particularly focused on hippocampal analysis, and neuropsychological evaluation. Genetic study included genotyping and linkage analysis of candidate loci at 4q, 18q, 1q, and 12q as well as screening for LGI1/Epitempin mutations. Results Most of the families showed an autosomal dominant inheritance pattern with incomplete penetrance. Fifty-four (32 F) affected individuals were investigated. Twenty-one (38.8 %) individuals experienced early FS. Forty-eight individuals fulfilled the criteria for MTLE. Epigastric/visceral sensation (72.9 %) was the most common type of aura, followed by psychic symptoms (35.4 %), and déjà vu (31.2 %). HS occurred in 13.8% of individuals, three of whom belonged to the same family. Prognosis of epilepsy was generally good. Genetic study failed to show LGI1/Epitempin mutations or significative linkage to the investigated loci. Discussion FMTLE may be a more common than expected condition, clinically and genetically heterogeneous. Some of the reported families, grouped on the basis of a specific aura, may represent an interesting subgroup on whom to focus future linkage studies.     

Magnetic resonance imaging evidence of hippocampal sclerosis in asymptomatic,first-degree relatives of patients with familial mesial temporal lobe epilepsy

OBJECTIVE: To investigate the presence of hippocampal atrophy (HA) and other magnetic resonance imaging (MRI) signs of hippocampal sclerosis (HS) in asymptomatic relatives of patients with familial mesial temporal lobe epilepsy (FMTLE). METHODS: We invited first-degree, asymptomatic relatives of patients with FMTLE to participate in our MRI protocol. After obtaining informed consent, all participating individuals underwent an MRI examination. Hippocampal abnormality was determined by qualitative and volumetric analyses, using a standard protocol. RESULTS: We studied 52 asymptomatic individuals (27 men), with a mean age of 32 years (range, 7-71 years), from 11 families with FMTLE. Volumetric studies showed HA in 18 (34%) of 52 individuals: 11 had left HA and 7 had bilateral HA. In addition, careful visual analysis of T1- and T2-weighted images showed additional classic MRI signs of HS (such as abnormal T2 signal and/or abnormal internal structure) in 14 of these 18 individuals. There was no age difference between individuals with and without HA (t test, P =.80). CONCLUSIONS: Our findings indicate that MRI evidence of HS is not necessarily related to seizure severity and may occur in individuals who never had seizures. In addition, these observations strongly indicate that HS in FMTLE is not a consequence of recurrent seizures and is determined by a strong genetic predisposition. The determination of seizure severity in patients with FMTLE probably depends on the interaction of different factors, both genetic and environmental.     

Progress in searching for the febrile seizure susceptibility genes

Febrile seizures (FS) represent the most common form of childhood seizures. They affect 2–5% of infants in the Caucasian population and are even more common in the Japanese population, affecting 6–9% of infants. Some familial FS are associated with a wide variety of afebrile seizures. Generalized epilepsy with febrile seizures plus (GEFS+) is a familial epilepsy syndrome with a spectrum of phenotypes including FS, atypical FS (FS+) and afebrile seizures. A significant genetic component exists for susceptibility to FS and GEFS+: extensive genetic studies have shown that at least nine loci are responsible for FS. Furthermore, mutations in the voltage-gated sodium channel subunit genes (SCN1A, SCN2A and SCN1B) and the GABA_A receptor subunit genes (GABRG2 and GABRD) have been identified in GEFS+. However, the causative genes have not been identified in most patients with FS or GEFS+. Common forms of FS are genetically complex disorders believed to be influenced by variations in several susceptibility genes. Recently, several association studies on FS have been reported, but the results vary among different groups and no consistent or convincing FS susceptibility gene has emerged. Herein, we review the genetic data reported in FS, including the linkage analysis, association studies, and genetic abnormalities found in the FS-related disorders such as GEFS+ and severe myoclonic epilepsy in infancy.     

Outcome of surgical treatment in familial mesial temporal lobe epilepsy

PURPOSE: To describe postoperative outcome in patients with familial mesial temporal lobe epilepsy (FMTLE). METHODS: We studied FMTLE patients who underwent surgical treatment for refractory seizures. FMTLE was defined when at least two individuals in a family had a clinical EEG diagnosis of MTLE. Preoperative investigation included magnetic resonance imaging (MRI), interictal/ictal EEGs, and neuropsychological evaluation. We used Engel's classification for postoperative outcome. RESULTS: To date, 20 FMTLE patients have been operated on, with 1.6 to 9.8 years of follow-up (mean, 5.5 years). Hippocampal atrophy (HA) and other signs of mesial temporal sclerosis (MTS) were present in 18 patients (15 unilateral). Seizures were recorded in 19 patients. Seventeen (85%) patients are in class I. Two patients had normal hippocampal volumes (HcV): one (5%) is in class II and the other (5%) in class IV (extratemporal seizures developed after surgery). One (5%) patient had bilateral HA and is in class III. Qualitative histopathology showed MTS with different degrees of severity. CONCLUSIONS: Refractory FMTLE patients have good surgical outcome when unilateral or clearly asymmetric HA is identified. Preoperative investigation should be the same as that in patients with sporadic refractory MTLE.     

THE SCN2A gene is not a likely candidate for familial mesial temporal lobe epilepsy

A transgenic mouse model carrying a mutation in the Scn2a gene showed chronic focal seizures associated with extensive cell loss and gliosis in the hippocampus, a similar phenotype found in familial mesial temporal lobe epilepsy (FMTLE). Our objective was to test whether the human homolog of the Scn2a gene is responsible for hippocampal abnormalities in FMTLE by linkage analysis. We conclusively ruled out the SCN2A gene as candidate in FMTLE.     

Mesial temporal lobe epilepsy: clinical and neuropathologic findings of familial and sporadic forms

Purpose: To evaluate the clinical and hippocampal histological features of patients with mesial temporal lobe epilepsy (MTLE) in both familial (FMTLE) and sporadic (SMTLE) forms.
Methods: Patients with FMTLE (n = 20) and SMTLE (n = 39) who underwent surgical treatment for refractory seizures were studied at the University of São Paulo School of Medicine at Ribeirão Preto. FMTLE was defined when at least two individuals in a family had clinical diagnosis of MTLE. Hippocampi from all patients were processed for Nissl/HE and Timm's stainings. Both groups were compared for clinical variables, hippocampal cell densities, and intensity of supragranular mossy fiber staining.
Results: There were no significant differences between FMTLE and SMTLE groups in the following: age at the surgery, age of first usual epileptic seizure, history of initial precipitating injury (IPI), age of IPI, latent period, ictal and interictal video-EEG patterns, presence of hippocampal atrophy and signal changes at MRI, and postoperative outcome. In addition, no differences were found in cell densities in hippocampal cornu ammonis subfields (CA1, CA2, CA3, CA4), fascia dentata, polymorphic region, subiculum, prosubiculum, and presubiculum. However, patients with SMTLE had greater intensity of mossy fiber Timm's staining in the fascia dentata-inner molecular layer (p< 0.05).
Discussion: Patients with intractable FMTLE present a clinical profile and most histological findings comparable to patients with SMTLE. Interestingly, mossy fiber sprouting was less pronounced in patients with FMTLE, suggesting that, when compared to SMTLE, patients with FMTLE respond differently to plastic changes plausibly induced by cell loss, neuronal deafferentation, or epileptic seizures.     

Inflammation in rat pups subjected to short hyperthermic seizures enhances brain long-term excitability

Inflammatory processes in response to infection are involved in the pathophysiological mechanisms of febrile seizures (FS). Prolonged FS may promote the development of temporal lobe epilepsy. It has been shown in rats that prolonged hyperthermic seizures (HS) are followed by long-term modification of brain excitability. To examine whether short FS results in modification of brain excitability, we induced an inflammatory response in combination with short HS.

Methods

HS were induced in rat pups at either P11 or P16 using a heating lamp with a continuous monitoring of the core temperature. Rat pups were maintained at the temperature seizure threshold during 5 min. In order to induce an inflammatory response, lipopolysaccharide (LPS, Eschericha coli 055:B5) was injected i.p. at 5 μg/kg or 50 μg/kg, 2 h prior seizure induction. After 1 month, pentylenetetrazol threshold (PTZth) was used to assess the change of brain excitability. Histological studies were performed 24 h after the FS (Fluorojade-B) and after the PTZth (cresyl violet).

Results

The temperature thresholds to induce the seizures were not different among the groups. The PTZth was not significantly different between sham and FS only groups, and decreased dose-dependently when LPS was combined to FS. Histological studies suggested the absence of cell injury.

Conclusion

Lower PTZth obtained by using LPS in combination with HS in rat pups suggests a change in brain excitability. Our model with only 5 min of HS in combination with LPS suggests that an inflammatory response could, in part, explain long-term change in brain excitability following short FS.     

Seizures and epilepsy in Sotos syndrome: analysis of 19 Caucasian patients with long-term follow-up

Sotos syndrome (SS) is an overgrowth syndrome characterized by typical facial appearance, learning disability, and macrocephaly as cardinal diagnostic features. Febrile (FS) and afebrile seizures are reported in 9-50% of cases. There is no evidence that patients with SS and FS later develop epilepsy, and no studies have investigated the electroclinical features and the long-term outcome in epileptic SS patients. The authors report a series of 19 SS patients with FS and/or epilepsy during childhood and a long-term follow-up. More than half of FS evolved to epilepsy. Temporal lobe seizures were recorded in 40% of patients with SS. Seizures were easy to control with common antiepileptic drugs in almost all patients. A careful neurologic evaluation is useful for SS patients, since seizures are an important finding among people with this overgrowth syndrome.     

Consanguinity in patients with mesial temporal lobe epilepsy due to hippocampal sclerosis in a Saudi population

Objectives:To investigate if there is an association between consanguinity and hippocampal sclerosis (HS) in the Saudi population.Methods:A retrospective case-control study was conducted by assessing the prevalence of consanguinity in patients with pathologically proven HS, who underwent epilepsy surgery at King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia, between January 2004 and December 2015. We reviewed the medical records to extract data, which included; age, gender, duration of epilepsy, history of febrile seizure, family history of epilepsy in a first or second-degree relative, and pathology reports.Results:A total of 120 patients, out of which 40 patients (65% male) having mesial temporal lobe epilepsy due to HS, and 80 controls (56% male) with cryptogenic epilepsy, were identified. Twenty-two patients (53.5%) in the HS group had a history of consanguinity. In the control group, 30 patients (37.5%) had a history of consanguinity. The odds ratio was 2.04 (95% confidence interval = 0.94 - 4.4, p = 0.052). A family history of epilepsy was found in 28% of the patients with HS and 32.5% cryptogenic epilepsy. Only 8 patients (19.5%) with HS reported a history of febrile seizure.Conclusion:Our retrospective case-control study suggests that consanguinity might increase the likelihood of developing HS.

Consanguineous marriage, in clinical genetics, is defined as a union between couples related as second cousins or closer.1 Saudi Arabian culture has a higher consanguinity rate than other Arab, Asian, and Western communities. Consanguinity is not known to increase the risk of idiopathic or cryptogenic epilepsy, based on recent studies from Saudi Arabia and UAE.2,3 However, there is a strong evidence that the marriage of first cousins is one of the main reasons for the increased prevalence of autosomal recessive diseases.4The association between consanguinity and epilepsy due to hippocampal sclerosis (HS), the most common pathology found in patients with intractable focal epilepsy, has not been adequately studied.5 A familial type of mesial temporal lobe epilepsy (FMTLE) has been described with homogeneous and heterogeneous clinical manifestations.6-8 Moreover, magnetic resonance imaging (MRI) of the brain of asymptomatic first-degree relatives of patients with confirmed FMTLE showed evidence of HS, which supports the genetic predisposition to FMTLE.9 Although, FMTLE is widely recognized as an autosomal dominant disease with incomplete penetrance, autosomal recessive or X-linked forms have also been reported. Still, they have not been confirmed by extensive studies.10In this study, we aimed to investigate the association between consanguinity and HS in a Saudi population. This study may help expand our knowledge of the underlying mechanisms of HS and may shed some light on a possible genetic substrate that contributes to the development of HS in this population.     

DEPDC5 mutations are not a frequent cause of familial temporal lobe epilepsy

Mutations in the DEPDC5 (DEP domain–containing protein 5) gene are a major cause of familial focal epilepsy with variable foci (FFEVF) and are predicted to account for 12–37% of families with inherited focal epilepsies. To assess the clinical impact of DEPDC5 mutations in familial temporal lobe epilepsy, we screened a collection of Italian families with either autosomal dominant lateral temporal epilepsy (ADLTE) or familial mesial temporal lobe epilepsy (FMTLE). The probands of 28 families classified as ADLTE and 17 families as FMTLE were screened for DEPDC5 mutations by whole exome or targeted massive parallel sequencing. Putative mutations were validated by Sanger sequencing. We identified a DEPDC5 nonsense mutation (c.918C>G; p.Tyr306*) in a family with two affected members, clinically classified as FMTLE. The proband had temporal lobe seizures with prominent psychic symptoms (déjà vu, derealization, and forced thoughts); her mother had temporal lobe seizures, mainly featuring visceral epigastric auras and anxiety. In total, we found a single DEPDC5 mutation in one of (2.2%) 45 families with genetic temporal lobe epilepsy, a proportion much lower than that reported in other inherited focal epilepsies.     

Structural abnormalities are similar in familial and nonfamilial mesial temporal lobe epilepsy

BACKGROUND/OBJECTIVE: Diffuse temporal lobe abnormalities can be observed on MRI of patients with mesial temporal lobe epilepsy (MTLE). Our objective was to perform qualitative and quantitative analyses of temporal lobe structures in patients with familial MTLE (FMTLE) and nonfamilial MTLE. METHODS: Two groups of patients were ascertained: 67 FMTLE patients (14 with refractory seizures) and 30 patients with nonfamilial refractory MTLE. We performed qualitative analyses of MRI (with multiplanar reconstruction) and volumes of hippocampi and anterior temporal lobes in all patients, and in a normal control group of 23 individuals. We used the Chi-square test and ANOVA for statistical analyses. RESULTS: We identified anterior temporal lobe abnormalities by visual analysis in only 4% of FMTLE patients and atrophy of the anterior temporal lobe by volumetric analysis in 19%. In the group of nonfamilial MTLE patients we found anterior temporal lobe abnormalities by visual analysis in 17% of patients and anterior temporal lobe atrophy in 13%. Hippocampal atrophy was present in 90% of FMTLE and in 83% of nonfamilial MTLE. No signs of cortical dysplasia were observed. CONCLUSION: Anterior temporal lobe atrophy and other abnormalities outside the mesial portion of temporal lobes were infrequent in both familial and nonfamilial MTLE patients. Despite the genetic basis, hippocampal atrophy in FMTLE is not associated with other abnormalities outside the mesial temporal regions.     

Does a SCN1A gene mutation confer earlier age of onset of febrile seizures in GEFS+?

SCN1A is the most clinically relevant epilepsy gene and is associated with generalized epilepsy and febrile seizure plus (GEFS+) and Dravet syndrome. We postulated that earlier onset of febrile seizures in the febrile seizure (FS) and febrile seizure plus (FS+) phenotypes may occur in the presence of a SCN1A mutation. This was because of the age-related onset of Dravet syndrome, which typically begins in the first year of life. We found that patients with FS and FS+ with SCN1A mutations had earlier median onset of febrile seizures compared to the population median. Patients with GABRG2 mutations had a similar early onset in contrast to patients with SCN1B mutations where onset was later. This study is the first to demonstrate that a specific genetic abnormality directly influences the FS and FS+ phenotype in terms of age of onset.     

Are MRI‐detected brain abnormalities associated with febrile seizure type?

OBJECTIVE: Whether magnetic resonance imaging (MRI) is informative in febrile seizures (FS) is unknown. We undertook a study to determine the frequency of MRI-detected brain abnormalities and to evaluate their association with FS type and with specific features of complex FS. METHODS: A prospective cohort study, from 1999 to 2004, included children with first FS from one Pediatric Emergency Department. MRI of the brain was performed within 1 week of the seizure. FS type was categorized by experts blind to the prior clinical history and MRI results. MRI examinations were read blind to the child's clinical history and FS type, and interviewers were blind to MRI results. RESULTS: In 159 children with a first FS, imaging abnormalities occurred in 12.6% (N = 20). Eight of the 54 with complex FS had imaging abnormalities compared to 12 of the 105 with simple FS (n.s.). Compared to children with simple FS, children with both focal and prolonged FS (N = 14) were more likely to have imaging abnormality (OR = 4.3, 95% CI = 1.2-15.0), even after adjustment for abnormal neurological examination. Imaging abnormalities included those known to be associated with seizures (e.g., focal cortical dysplasia) and those not typically associated with seizures (e.g., subcortical focal hyperintensities > or = 5 mm). DISCUSSION: Our data suggest that brain abnormalities may lower seizure threshold in febrile children, predisposing to the development of FS. Clinical management was unaffected and therefore these data do not alter the recommendation that MRI is unnecessary in children with FS, without some other neurological indication.     

A deletion in SCN1B is associated with febrile seizures and early-onset absence epilepsy

Generalized epilepsy with febrile seizures plus (GEFS+) is a clinically and genetically heterogeneous syndrome with childhood onset, characterized by febrile seizures (FS) and a variety of afebrile epileptic seizure types. The authors performed a mutational analysis of SCN1B on 74 unrelated probands with GEFS+, FS, or FS plus (FS+). In a family with FS+ and early-onset absence epilepsy, a mutation was identified that predicts a deletion of five amino acids in the extracellular immunoglobulin-like domain of SCN1B and potential loss of function. SCN1B mutations are associated with GEFS+ and may have a role in the elicitation of absence seizures.     

A novel SCN1A mutation in a cytoplasmic loop in intractable juvenile myoclonic epilepsy without febrile seizures

Generalised (genetic) epilepsy with febrile seizures plus (GEFS+) is a familial epilepsy syndrome with various phenotypes. The majority of individuals with GEFS+ have generalised seizure types, in addition to febrile seizures (FS) or febrile seizures plus (FS+), defined as either continued FS after 6 years of age or afebrile seizures following FS. A 27‐year‐old man with no history of FS/FS+ experienced intractable generalised convulsive seizures. The patient's father had a history of similar seizures during puberty and the patient's siblings had only FS. No individual in the family had both generalised seizures and FS/FS+, although GEFS+ might be considered to be present in the family. Analysis of SCN1A, a sodium channel gene, revealed a novel mutation (c.3250A>T [S1084C]) in the cytoplasmic loop 2 of SCN1A in both the patient and his father. Most previously reported SCN1A mutations in GEFS+ patients are located in the conserved homologous domains of SCN1A, whereas mutations in the cytoplasmic loops are very rare. SCN1A gene analysis is not commonly performed in subjects with generalised seizures without FS. SCN1A mutation may be a clinically‐useful genetic marker in order to distinguish GEFS+ patients from those with classic idiopathic generalised epilepsy, even if they present an atypical clinical picture.     

Evidence of memory impairment in asymptomatic individuals with hippocampal atrophy

Our objective was to investigate if MRI-determined hippocampal atrophy (HA) is associated with memory deficits independent of seizure frequency. We studied three groups of individuals: (1) 10 asymptomatic first-degree relatives of patients with familial mesial temporal lobe epilepsy (FMTLE), all of them with HA; (2) 14 patients with benign FMTLE, 9 with HA, and 5 with normal hippocampal volumes; and (3) 16 patients with refractory FMTLE, all but one with HA. HA was associated with lower scores on general memory (P=0.015), verbal memory (P=0.020), and delayed recall (P=0.028), even in those with no or few seizures in life. General linear model analyses showed that the interaction between seizure outcome and HA was associated with worse verbal memory (P=0.029), visual memory (P=0.022), and delayed recall (P=0.039) as compared with each of these factors independently. Our findings suggest that seizures and HA are independently associated with memory impairment.     

The role of titration schedule of topiramate for the development of depression in patients with epilepsy

Purpose:   To determine whether a fast titration schedule of topiramate (TPM) has different effects on the occurrence of depression, in relation to other risk factors for TPM-induced depression, including history of depression (HxDEP), febrile seizures (FS), and hippocampal sclerosis (HS).
Methods:   Using data from a large case registry of patients prescribed TPM, two models were constructed: Model 1 examined the independent effect of rapid TPM titration after separate adjustment for FS, HxDEP, and HS. Model 2 examined effect of the cooccurrence of rapid titration on the development of depression with each of these risk factors.
Results:   A total of 423 patients were included (51.8% females), mean age (SD) 35.5 (11.8) years, mean duration of epilepsy of 22.2 (11.5) years. Forty-four patients (10.4%) developed depression during TPM therapy. A rapid TPM titration was associated with 5-fold increased risk of depression that increased to 12.7-fold in the presence of both FS and rapid TPM titration, 23.3-fold in the presence of both HxDEP and rapid TPM titration, and 7.6-fold in the presence of both HS and rapid TPM titration schedule.
Conclusions:   Our study suggests that a rapid titration schedule is associated with an increased risk of developing depression during TPM therapy. HxDEP and FS are major contraindications to the use of a rapid titration, with a 23.3-fold and 12.7 fold increased risk, respectively.     

Distinct increased metabotropic glutamate receptor type 5 (mGluR5) in temporal lobe epilepsy with and without hippocampal sclerosis

Metabotropic glutamate receptor type 5 (mGluR5) upregulation in temporal lobe epilepsy (TLE) and the correlation of its expression with features of hippocampal sclerosis (HS) remains unclear. Here we characterized mGluR5 immunoreactivity in hippocampus, entorhinal cortex (EC), and subiculum of TLE specimens with confirmed HS, with neocortical TLE (non‐HS) and necropsy controls. We correlated mGluR5 immunoreactivity with neuronal density, mossy fiber sprouting, astrogliosis (GFAP), and dendritic alterations (MAP2). TLE specimens showed increased mGluR5 expression, which was most pronounced in the EC, subiculum, CA2, and dentate gyrus outer molecular layer. Increased mGluR5 expression was seen in hippocampal head and body segments and was independent of neuronal density, astrogliosis, or dendritic alterations. Positive correlation between mGluR5 expression with mossy fiber sprouting and with MAP2 in CA3 and CA1 was found only in HS specimens. Negative correlation between mGluR5 expression with seizure frequency and epilepsy duration was found only in non‐HS cases. Specimens from HS patients without previous history of febrile seizure (FS) showed higher mGluR5 and MAP2 expression in CA2. Our study suggests that mGluR5 upregulation is part of a repertoire of post‐synaptic adaptations that might control overexcitation and excessive glutamate release rather than a dysfunction that leads to seizure facilitation. That would explain why non‐HS cases, on which seizures are likely to originate outside the hippocampal formation, also exhibit upregulated mGluR5. On the other hand, lower mGluR5 expression was related to increased seizure frequency. In addition to its role in hyperexcitability, mGluR5 upregulation could play a role in counterbalance mechanisms along the hyperexcitable circuitry uniquely altered in sclerotic hippocampal formation. Inefficient post‐synaptic compensatory morphological (dendritic branching) and glutamatergic (mGluR5 expression) mechanisms in CA2 subfield could potentially underlie the association of FS with HS and TLE. © 2013 The Authors. Hippocampus Published by Wiley Periodicals, Inc.     

The mortality and morbidity of febrile seizures

Approaches to the treatment and investigation of febrile seizures have changed since the main reference studies on outcomes were conducted in the 1960s and 1970s. We have, therefore, conducted a systematic review of literature from the past 15 years to see whether outcomes have also changed. We found that simple febrile seizures do not carry a risk of death, but there is a very small risk of death after complex febrile seizures (CFSs), particularly febrile status epilepticus. There is no evidence that SUDEP (sudden unexpected death in epilepsy) occurs in association with febrile seizures. The risk of later epilepsy after a febrile seizure lies between 2.0% and 7.5%, and the risk of developing epilepsy after CFSs is estimated at around 10-20%. There is no evidence of any risk of hippocampal or mesial temporal sclerosis (HS/MTS) in association with simple febrile seizures. Serial imaging has shown that HS/MTS develops in 0-25% of patients over time after prolonged febrile seizures; the range in prevalence reflects selection bias in different studies. The overall risk of HS/MTS associated with CFSs is around 3%. Approximately 40% of patients with medically refractory temporal lobe epilepsy and HS/MTS on neuroimaging have a history of febrile seizures.     

Current management of febrile seizures in Japan: An overview

Febrile seizures (FS) require both acute and chronic management. Acute management includes the treatment and differential diagnosis of FS and depend on the presence of seizures and a patient’s level of consciousness upon arrival at hospital: a patient may be discharged after physical examination if there are no seizures and no alteration of consciousness; close observation and laboratory examinations may be indicated in cases when there are no seizures but the patient exhibits altered consciousness; and intravenous diazepam (DZP) is indicated if seizures persist. Central nervous system infections should be ruled out: if the patient has signs of meningeal irritation or increased intracranial pressure, disturbed consciousness for >1 h, atypical seizures (partial seizures, seizures for >15 min, or recurrent seizures within 24 h), cerebrospinal fluid examinations and/or computed tomography/magnetic resonance imaging are warranted. Chronic management includes the prevention of recurrent FS, counseling parents, and vaccination. Japanese guideline for the prevention of recurrent FS defines two types of warning factors (WF) for selecting patients who should be monitored carefully: factors related to the onset of epilepsy (EP factors) and recurrence of FS (FS factors). The EP factors consist of neurological or developmental abnormalities prior to the onset of FS, atypical seizures, and history of epilepsy in parents or siblings. The FS factors include the onset of FS before 1 year of age and a history of FS in one or both parents. The guideline recommends no medication for children with two or fewer past episodes of FS without WF; prophylactic DZP for children with prolonged FS exceeding 15 min, or two or more episodes of FS with two or more WF; and daily administration of phenobarbital or valproate for children in whom FS occur under 38 °C or who have prolonged FS despite prophylactic DZP. To reduce parents’ anxiety, the natural history of FS should be explained. A child can be given all current vaccinations 2–3 months after the last episode of FS by his/her family doctor with information provided to the parents as to how to cope with fever and convulsions.