Total cerebral volume is reduced in patients with localization-related epilepsy and a history of complex febrile seizures

CONTEXT: Febrile seizures may lead to later epilepsy. They have been associated with hippocampal atrophy but their effect on total cerebral volume is unknown. OBJECTIVE: To compare total cerebral volume in patients with mesial temporal lobe epilepsy with and without a history of complex febrile seizures (CFS). DESIGN: Survey. SETTING: Epilepsy monitoring center. SUBJECTS: Forty patients with localization-related epilepsy and temporal lobe onset determined by video electroencephalogram and 20 controls. INTERVENTION: Magnetic resonance imaging measurement of cerebral volume. MAIN OUTCOME MEASURE: Total cerebral volume. RESULTS: Patients with a history of CFS had significantly reduced total cerebral volume compared with patients without CFS. In addition, male patients with CFS had significantly lower total cerebral volume than male normal controls. There was no significant difference between patients without CFS, or all patients, and controls. CONCLUSION: Complex febrile seizures may have a global effect on brain development.     

Degree of hippocampal atrophy is not related to a history of febrile seizures in patients with proved hippocampal sclerosis

OBJECTIVES: To examine the degree of hippocampal atrophy in patients with temporal lobe epilepsy and proved hippocampal sclerosis to determine whether or not patients with febrile seizures have more severe hippocampal atrophy. To determine whether or not there is a relation between age of seizure onset, duration of temporal lobe epilepsy, or seizure frequency, and severity of hippocampal atrophy. METHODS: Hippocampal volumes were measured from volumetrically acquired MR images in 77 consecutive surgical patients with temporal lobe epilepsy (37 febrile seizures (FS)+, 40 FS-) with proved hippocampal sclerosis, and compared with 98 controls. RESULTS: Ipsilateral and contralateral hippocampal volumes were not significantly different between the FS+ and FS- groups. There was no difference in the age of onset of habitual seizures, duration of epilepsy, or age at the time of surgery, between these groups. No clinically significant correlations were found between hippocampal volumes and age of onset of first non-febrile seizure, duration of temporal lobe epilepsy, or complex partial and secondarily generalised seizure frequency, in patients with and without febrile seizures. CONCLUSIONS: Although febrile seizures was associated with hippocampal sclerosis in 48% of patients in this surgical series, the degree of MRI determined hippocampal atrophy was not related to a history of such seizures. The results do not support the view that febrile seizures cause more severe hippocampal sclerosis and are consistent with the hypothesis that hippocampal sclerosis is a pre-existing abnormality.     

Fieberkrämpfe

Febrile seizures are the most common seizure type in man and may be classified as simple or complex. The overall recurrence rate is 30–35%. Predictors of recurrence include a family history of febrile seizures, age at onset of less than 18 months, and a relatively low body temperature at the time of the seizure. The risk of subsequent epilepsy is only slightly elevated in children with simple febrile seizures. Factors that increase epilepsy risk are complex febrile seizures, abnormal neurological development, and a family history of epilepsy. While older studies did not report increased mortality in children with frebrile seizures, a recent large population-based study found increased mortality during the first 2 years after a febrile seizure in children with complex febrile seizures, seizure onset in the first year of life as well as seizures triggered by a body temperature of less than 39°C. Semiology and prognosis of febrile seizures are heterogeneous. Simple febrile seizures have a good prognosis with diagnostic and therapeutic procedures being uniform at the international level. Children with complex febrile seizures have a poorer prognosis, concerning both risk of epilepsy and mortality within the first 2 years after the first febrile seizure. In these children, decisions concerning diagnostic work-up and medical management are based on the risk profile of the individual patient.     

Familial clustering of epilepsy and behavioral disorders: evidence for a shared genetic basis

Purpose: To examine whether family history of unprovoked seizures is associated with behavioral disorders in epilepsy probands, thereby supporting the hypothesis of shared underlying genetic susceptibility to these disorders. Methods: We conducted an analysis of the 308 probands with childhood onset epilepsy from the Connecticut Study of Epilepsy with information on first‐degree family history of unprovoked seizures and of febrile seizures whose parents completed the Child Behavior Checklist (CBCL) at the 9‐year follow‐up. Clinical cutoffs for CBCL problem and Diagnostic and Statistical Manual of Mental Disorders (DSM)–Oriented scales were examined. The association between first‐degree family history of unprovoked seizure and behavioral disorders was assessed separately in uncomplicated and complicated epilepsy and separately for first‐degree family history of febrile seizures. A subanalysis, accounting for the tendency for behavioral disorders to run in families, was adjusted for siblings with the same disorder as the proband. Prevalence ratios were used to describe the associations. Key Findings: In probands with uncomplicated epilepsy, first‐degree family history of unprovoked seizure was significantly associated with clinical cutoffs for Total Problems and Internalizing Disorders. Among Internalizing Disorders, clinical cutoffs for Withdrawn/Depressed, and DSM‐Oriented scales for Affective Disorder and Anxiety Disorder were significantly associated with family history of unprovoked seizures. Clinical cutoffs for Aggressive Behavior and Delinquent Behavior, and DSM‐Oriented scales for Conduct Disorder and Oppositional Defiant Disorder were significantly associated with family history of unprovoked seizure. Adjustment for siblings with the same disorder revealed significant associations for the relationship between first‐degree family history of unprovoked seizure and Total Problems and Aggressive Behavior in probands with uncomplicated epilepsy; marginally significant results were seen for Internalizing Disorder, Withdrawn/Depressed, and Anxiety Disorder. There was no association between family history of unprovoked seizure and behavioral problems in probands with complicated epilepsy. First‐degree family history of febrile seizure was not associated with behavioral problems in probands with uncomplicated or in those with complicated epilepsy. Significance: Increased occurrence of behavioral disorders in probands with uncomplicated epilepsy and first degree family history of unprovoked seizure suggests familial clustering of these disorders. This supports the idea that behavioral disorders may be another manifestation of the underlying pathophysiology involved in epilepsy or closely related to it.     

Febrile seizures and mesial temporal sclerosis

PURPOSE OF REVIEW: The sequence of febrile seizures followed by intractable temporal lobe epilepsy is rarely seen from a population perspective. However, several studies have shown a significant relationship between a history of prolonged febrile seizures in early childhood and mesial temporal sclerosis. The interpretation of these observations remains quite controversial. One possibility is that the early febrile seizure damages the hippocampus and is therefore a cause of mesial temporal sclerosis. Another possibility is that the child has a prolonged febrile seizure because the hippocampus was previously damaged by a prenatal or perinatal insult or by genetic predisposition. RECENT FINDINGS: Imaging studies have shown that prolonged and focal febrile seizures can produce acute hippocampal injury that evolves to hippocampal atrophy, and that complex febrile seizures can originate in the temporal lobes in some children. Several lines of evidence now indicate that genetic predisposition is an important causal factor of febrile seizures and mesial temporal sclerosis. From recent clinical and molecular genetic studies, it appears that the relationship between febrile seizures and later epilepsy is frequently genetic, and there are several syndrome-specific genes for febrile seizures. SUMMARY: Mesial temporal sclerosis probably has different causes. A number of retrospective studies showed that complex febrile seizures are a causative factor for the later development of mesial temporal sclerosis and temporal lobe epilepsy. However, contradictory results have come from several prospective and retrospective studies. The association between febrile seizures and temporal lobe epilepsy probably results from complex interactions between several genetic and environmental factors.     

Benign mesial temporal lobe epilepsy

Benign mesial temporal lobe epilepsy (bMTLE), which is defined as at least 24 months of seizure freedom with or without antiepileptic medication, has probably been under-recognized because of a literature bias toward refractory epilepsy cases. Seizure onset in bMTLE tends to be in adolescence or adulthood, and patients frequently have a family history of febrile seizures and epilepsy. Long-term seizure freedom is observed with or without antiepileptic medication. On brain MRI, nearly 40% of patients with long-standing bMTLE show evidence of hippocampal sclerosis, a feature usually associated with refractory temporal lobe epilepsy. Prospective studies are needed to determine the features that allow prediction of a benign course, and to clarify the significance of hippocampal MRI changes.     

Idiopathic familial temporal lobe epilepsy with febrile convulsions.

Efforts to duplicate the genetic and molecular breakthroughs of autosomal dominant frontal lobe epilepsy have lead to increased interest in familial temporal lobe epilepsy. In this report we describe three kindreds. The epilepsy syndrome described manifests after the teenage years and was generally mild and treatment responsive. The predominant seizure types were simple and complex partial seizures, typical of mesial temporal onset. Some family members had febrile convulsions only and others had epilepsy without preceding febrile convulsions. Three patients had both febrile convulsions and temporal lobe epilepsy. High-resolution quantitative and qualitative MRI was normal. The syndrome in these three kindreds is distinct from temporal lobe epilepsy due to mesial temporal sclerosis and febrile convulsions and is probably a form of idiopathic localization related epilepsy. Its relation to other familial temporal lobe epilepsy phenotypes is discussed.     

Abnormal phonologic processing in familial lateral temporal lobe epilepsy due to a new LGI1 mutation

PURPOSE: Autosomal dominant lateral temporal lobe epilepsy (ADLTLE) is a rare familial epilepsy with onset in adolescence or early adulthood, associated with mutations of LGI1 in most families. We describe the clinical, neuropsychological, and molecular genetic study of a new ADLTLE Italian family. METHODS: A four-generation family from Sardinia was studied. Clinical, neuropsychological, and genetic analysis were performed in eight living affected family members. RESULTS: Nine family members had seizures over four generations; four of them had auditory auras and aphasia followed by secondarily generalized tonic-clonic seizures (SGTCs). One individual in addition had visual symptoms, and one family member had only vertigo followed by SGTCs. The side of seizure onset could not be determined in these five patients with focal seizures. The proband had febrile and afebrile tonic-clonic seizures. Two family members had only febrile seizures. Inheritance was autosomal dominant with 59% penetrance. Genetic molecular analysis showed a new LGI1 missense mutation causing a Leu154Pro substitution in six affected and one unaffected individuals. Dichotic listening performance was abnormal in four affected individuals compared with controls. Fluency and lexical abilities also were pathological in three patients. These findings showed that in patients, the left temporal lobe was less specialized in the auditory processing function than in controls. CONCLUSIONS: In this ADLTLE family, both seizure semiology and neuropsychological findings point to a lateral temporal lobe dysfunction. The newly identified LGI1 mutation might underlie both the seizure disorder and the neuropsychological deficits.     

The significance of ear plugging in localization-related epilepsy

PURPOSE: The localizing value of ear plugging in the treatment of auditory onset partial seizures, to our knowledge, has not been previously described. We propose that ear plugging is a clinical response to a sensory seizure manifested as an auditory hallucination and a tool for identifying the seizure focus in the auditory cortex on the superior temporal gyrus. METHODS: We report on three children who had prior epilepsy surgery for recurrent symptomatic localization-related epilepsy and who, subsequent to their surgery, displayed stereotyped unilateral or bilateral ear plugging at the onset of partial seizures. We studied scalp video electroencephalography (VEEG), magnetoencephalography (MEG), and magnetic resonance imaging (MRI) in all three. Additionally, we used electrocorticography (ECoG) in two patients, intracranial VEEG monitoring in one patient, and functional MRI language mapping in two patients. RESULTS: All three patients plugged their ears with their hands during auditory auras that localized to the superior temporal gyrus and were followed by partial seizures that spread to a wider field, as shown on scalp and intracranial VEEG. All three patients had MEG interictal discharges in the superior temporal gyrus. One patient who was nonverbal and unable to describe an auditory phenomenon plugged the ear contralateral to where temporal lobe-onset seizures and MEG interictal discharges occurred. CONCLUSIONS; Ear-plugging seizures indicate an auditory aura and may also lateralize seizure onset to the contralateral temporal lobe auditory cortex. Stereotyped behaviors accompanied by epileptic seizures in children who have poor communication skills are important in the seizure semiology of localization-related epilepsy.     

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.     

Clinical characteristics of 92 patients with temporal lobe focal cortical dysplasia identified by pathological examination

Focal cortical dysplasia (FCD) is frequently associated with focal epilepsy, and a broad spectrum of histopathology is included in the diagnosis of FCD. In 2011, an International League Against Epilepsy (ILAE) task force proposed an international consensus for a classification system to better characterise specific clinicopathological FCD entities. The clinical characteristics of patients with FCD should be confirmed according to the new ILAE classification. We retrospectively analysed 92 patients who had undergone surgical treatment for temporal lobe epilepsy and received a pathological diagnosis of FCD. The pathological sections were re-examined and diagnosed according to the 2011 ILAE classification. The clinical data from patients with different FCD subtypes were evaluated, including a detailed history regarding spontaneous abortions, trauma, ischaemic injury, encephalitis, and febrile seizures at an early age. The age of epilepsy onset, duration of epilepsy, age at surgery, seizure frequency, history of febrile seizures, and seizure type, particularly whether the seizures were secondarily generalised tonic-clonic seizures, were recorded. Clinical differences were found in the patients with temporal lobe FCD. The associated FCD subtypes have unique clinical characteristics, including a later age of epilepsy onset and a shorter duration of epilepsy, especially in FCD Type IIIc; and a high susceptibility to febrile seizures was observed in FCD Type IIIa.     

Classification of epilepsy syndromes and role of genetic factors

In this report the types of epilepsy syndromes seen in children in a tertiary referral center in Beirut, Lebanon were studied and the importance of consanguinity and family history in the occurrence of these syndromes was investigated. Records of 230 pediatric patients evaluated during a 1-year period with the diagnosis of single seizure, febrile seizure, or epilepsy were reviewed. Each patient was classified according to the International League Against Epilepsy classification. The occurrence of consanguinity, of family history of febrile seizures or epilepsy, and of other variables was noted. Thirty-six percent of patients were diagnosed with localization-related epilepsy, 21.7% with generalized epilepsy, 11.7% with undetermined generalized or focal, and 24.3% with special syndromes. Twelve percent of patients were diagnosed with idiopathic, 15.1% with symptomatic, and 30.3% with cryptogenic epilepsies. Consanguinity was more common in patients with symptomatic and cryptogenic epilepsies than in patients with idiopathic epilepsies or with incidental seizures (P < 0.05). Family history of epilepsy was more common in patients with symptomatic, cryptogenic, and idiopathic epilepsies than in patients with incidental seizures (P < 0.05). Family history of febrile seizures but not consanguinity was more common in patients with febrile seizures (P < 0.05). We conclude that genetic factors are important not only in idiopathic epilepsies and febrile seizures but also in cryptogenic and symptomatic epilepsies.     

Design and phenomenology of the FEBSTAT study

Purpose: Febrile status epilepticus (FSE) has been associated with hippocampal injury and subsequent hippocampal sclerosis (HS) and temporal lobe epilepsy. The FEBSTAT study was designed to prospectively examine the association between prolonged febrile seizures and development of HS and associated temporal lobe epilepsy, one of the most controversial issues in epilepsy. We report on the baseline phenomenology of the final cohorts as well as detailed aims and methodology. Methods: The “Consequences of Prolonged Febrile Seizures in Childhood” (FEBSTAT) study is a prospective, multicenter study. Enrolled are children, aged 1 month to 6 years of age, presenting with a febrile seizure lasting 30 min or longer based on ambulance, emergency department, and hospital records, and parental interview. At baseline, procedures included a magnetic resonance imaging (MRI) study and electroencephalography (EEG) recording done within 72 h of FSE, and a detailed history and neurologic examination. Baseline development and behavior are assessed at 1 month. The baseline assessment is repeated, with age‐appropriate developmental testing at 1 and 5 years after enrollment as well as at the development of epilepsy and 1 year after that. Telephone calls every 3 months document additional seizures. Two other groups of children are included: a “control” group consisting of children with a first febrile seizure ascertained at Columbia University and with almost identical baseline and 1‐year follow‐up examinations and a pilot cohort of FSE from Duke University. Key Findings: The FEBSTAT cohort consists of 199 children with a median age at baseline of 16.0 months (interquartile range [IQR] 12.0–24.0) and a median duration of FSE of 70.0 min (IQR 47.0–110.0). Seizures were continuous in 57.3% and behaviorally intermittent (without recovery in between) in 31.2%; most were partial (2.0%) or secondary generalized (65.8%), and almost all (98.0%) culminated in a generalized tonic–clonic seizure. Of the 199 children, 86.4% had normal development and 20% had prior febrile seizures. In one third of cases, FSE was unrecognized in the emergency department. The Duke existing cohort consists of 23 children with a median age of FSE onset of 18.0 months (IQR 14.0–28.0) and median duration of FSE of 90.0 min (IQR 50.0–170.0). The Columbia control cohort consists of 159 children with a first febrile seizure who received almost the same workup as the FEBSTAT cohort at baseline and at 1 year. They were followed by telephone every 4 months for a median of 42 months. Among the control cohort, 64.2% had a first simple FS, 26.4% had a first complex FS that was not FSE, and 9.4% had FSE. Among the 15 with FSE, the median age at onset was 14.0 months (IQR 12.0–20.0) and the median duration of FSE was 43.0 min (IQR 35.0–75.0). Significance: The FEBSTAT study presents an opportunity to prospectively study the relationship between FSE and acute hippocampal damage, the development of mesial temporal sclerosis, epilepsy (particularly temporal lobe epilepsy), and impaired hippocampal function in a large cohort. It is hoped that this study may illuminate a major mystery in clinical epilepsy today, and permit the development of interventions designed to prevent the sequelae of FSE.     

Seizures with Fever After Unprovoked Seizures: An Analysis in Children Followed from the Time of a First Febrile Seizure

Summary: Purpose: To determine how the onset of unprovoked seizures influences recurrence of seizures with fever in children followed from the time of a first febrile seizure.
Methods: In a prospective cohort of children (n = 428) identified at the time of a first febrile seizure, predictors of a second seizure with fever were identified. The occurrence of a first unprovoked seizure was treated as a time-dependent covariate in a Cox regression model rather than as a censoring point as it traditionally has been in the past.
Results: One hundred forty-three (33.4%) children had further seizures. Seven had further seizures with fever only after onset of unprovoked seizures. After adjustment was made for the four previously described predictors of recurrent febrile seizures (age at onset, family history, height of fever, and duration of fever), the onset of unprovoked seizures was associated with a rate ratio of 3.47 (p = 0.0015), indicating a large increase in the risk of further seizures with fever after onset of unprovoked seizures.
Conclusions: Young children who develop unprovoked seizures after a febrile seizure are at substantial risk for further seizures with fever. This may represent part of the spectrum of benign febrile seizures or it may represent the so-called "epilepsy triggered by fever" spectrum. It affects only a small proportion of children with febrile seizures; however, in some children, it may be useful information to consider when making treatment decisions.     

Cerebellar atrophy in temporal lobe epilepsy

PURPOSE: The goal of this work was to determine the presence and degree of cerebellar atrophy in chronic temporal lobe epilepsy, its clinical seizure correlates, and its association with general cortical atrophy. METHODS: Study participants were 78 persons with temporal lobe epilepsy and 63 age- and gender-matched healthy controls. All subjects underwent high-resolution MRI with manual tracing of the cerebellum. Clinical seizure features and history were obtained by structured interview and review of medical records. RESULTS: The epilepsy group exhibited significant abnormality in cerebellar volume, with mean reductions ranging from 4 to 6.6% depending on adjustments. Significantly more individual subjects with epilepsy exhibited cerebellar atrophy compared with controls across all operational definitions or thresholds of abnormality including z < or = -2.0 (13% TLE, 3.4% controls) and z < or = 1.5 (22% TLE, 3.4% controls). Clinical seizure features reflecting both neurodevelopmental (history of initial precipitating injuries) and severity of course (longer duration, increased number of lifetime generalized tonic-clonic seizures) factors were associated with cerebellar atrophy. Atrophy of the cerebellum could be observed independent of more general (cerebral) atrophic processes. CONCLUSIONS: The presence of cerebellar atrophy is a reflection of the extratemporal abnormalities that can be observed in localization-related temporal lobe epilepsy, which may be due, at least in part, to factors associated with epilepsy chronicity.     

A retrospective analysis of patients with febrile seizures followed by epilepsy.

This study was performed to investigate some clinical parameters of febrile seizures (FSs) in patients with epilepsy, testing any possible correlation between those parameters and the type of subsequent epilepsy. One hundred and nine patients with epilepsy having a history of FSs were evaluated for age at onset of FSs, interval between first FS and first afebrile seizure, recurrence rate, type of FSs, incidence of febrile status, family history for epilepsy and for FSs and the neurological status of the patient. The epilepsy that developed subsequently, were classified as generalised versus partial and also according to their syndromic subgroups. In temporal lobe epilepsy with mesial temporal sclerosis (TLE-MTS), statistical analyses revealed a younger age at onset of FSs, and a high incidence of episodes of febrile status and of complex FSs. Clinical characteristics of FSs followed by partial epilepsies were younger age at onset, presence of focal features and of febrile status, longer interval between the first FS and the first afebrile seizure, and a high incidence of FSs in the family history. In generalised epilepsies, however, a shorter interval between the first FS and the first afebrile seizure, a high incidence of single FS and of a family history of epilepsy were predominating characteristics. Results suggest that certain features of FSs may be predictive of a particular type of subsequent epilepsy.     

Epilepsy duration, febrile seizures, and cerebral glucose metabolism

PURPOSE: Studies using magnetic resonance imaging have shown that reduced hippocampal volume is associated with a history of febrile seizures, the duration of epilepsy, and the number of generalized tonic-clonic seizures. It is uncertain whether these factors have the same influence on functional as on structural measures of the integrity of the epileptogenic zone. METHODS: We used positron emission tomography (PET) with fluorine 18 2-deoxyglucose to study 91 patients with temporal lobe seizure foci localized by ictal video-EEG. PET was performed in the awake interictal resting state with ears plugged and eyes patched. We recorded surface EEG during injection (5 mCi) and the 30-min uptake period. We used a standard template to analyze PET scans. RESULTS: A significant negative relation was found between the duration of epilepsy and hippocampal glucose metabolism ipsilateral to the epileptic focus. Patients with a history of either any febrile seizures, or complex, or prolonged febrile seizures, did not have greater hypometabolism ipsilateral to the epileptic focus than did patients without a febrile seizure history. We found no effect of generalized tonic-clonic seizure history. CONCLUSIONS: Longer epilepsy duration is associated with greater hypometabolism, suggesting that epilepsy is a progressive disease.     

Limitations in the Medical Treatment of Cryptogenic or Symptomatic Localization-Related Epilepsies of Childhood Onset

Summary: We retrospectively examined 169 patients who had cryptogenic or symptomatic localization-related epilepsies (LRE) and were followed-up for more than 5 years. The probability of seizure control was 0.13 during the first year of treatment, 0.25 during the first 5 years, and 0.09 during the second and third 5 years. No patients who continued to have intractable seizures for 15 years became free of seizures. The onset of LRE at the age of 3 years or less, seizure cluster, mesial temporal sclerosis (MTS), and temporal lobe epilepsy (TLE) were significantly associated with a poor seizure control. If an antiepileptic drug (AED) failed to control seizures, probability of seizure control by the next drug was low, in particular in patients in whom more than 4 AEDs have already been tried, and seizure control could not be expected after a trial of 6 AEDs. A tentative indication of epilepsy surgery for LRE of childhood onset may be 5 years of poor seizure control and/or failure of four AEDs.     

Hippocampal and amygdaloid damage in partial epilepsy: a cross-sectional MRI study of 241 patients

Patients with drug-refractory temporal lobe epilepsy (TLE) often have hippocampal and amygdaloid damage. The present study investigated the factors associated with the occurrence and severity of damage in patients with partial epilepsy. Magnetic resonance imaging was used to measure the volumes of the hippocampus and the amygdala in 241 patients with different durations of epilepsy. We also investigated the association of damage with the location of seizure focus and clinical factors (age at onset of seizures, lifetime seizure number and medical history of complex febrile convulsions, intracranial infection or status epilepticus) with regression analysis. We found that high lifetime seizure number (P<0.05), history of complex febrile convulsions (P<0.01), and age < or = 5 years at the time of the first seizure (P<0.01) were significant risk factors for reduced hippocampal volume in TLE patients. The severity of amygdaloid damage did not differ between TLE patients with different durations of epilepsy or seizure frequency, but complex febrile convulsions (P<0.05) and intracranial infection (P<0.05) were associated with amygdaloid damage. In patients with extratemporal or unclassified partial epilepsy, the hippocampal and amygdaloid volumes did not differ when patients with different durations of epilepsy were compared with controls. The present findings indicate that a high seizure number, the occurrence of complex febrile convulsions, and an early onset of seizures contribute to hippocampal volume reduction in patients with TLE. The data provided have important implications with regard to early and effective management and seizure control in vulnerable patients.     

Fieberkrampf und Magnetresonanztomographie

It is rare that a febrile seizure results immediately in a pharmacoresistant focal epilepsy. Population-based studies, however, report an association between complicated febrile seizures (i.e., those with focal features, a prolonged course, or an occurrence as status epilepticus) in childhood and temporal lobe epilepsy with mesial temporal sclerosis in early adolescence. There is controversy whether a seemingly harmless event like a febrile seizure can lead to treatment refractory epilepsy after a silent period often of many years. Three main hypotheses are formulated: 1. “Innocent bystander” hypothesis: a normal hippocampus is damaged by the complicated febrile seizure and the damage develops to become mesial temporal sclerosis; 2. “Two hit” hypothesis: subtle pre-existing structural changes in the hippocampus and temporal lobe predispose for hippocampal damage by febrile status epilepticus which develops to mesial temporal sclerosis; 3. “Been there, done that” hypothese: mesial temporal sclerosis exist prior to febrile seizures and develops further afterwards. Neuroimaging studies demonstrate postictal hippocampal damage after complicated febrile seizures. Subtle hippocampal malformations, in the sense of malformations, seem to increase the susceptibility to damage following febrile seizures. A prominent MRI feature after febrile seizures might be hippocampal edema. Patients with hippocampal edema after febrile seizures might be a target group for the pharmacological prevention of the further development towards mesial temporal sclerosis.