Rub epilepsy in an infant with Turner syndrome.

We report a case of infantile refractory epilepsy associated with Turner syndrome (TS), showing very frequent, focal clonic seizures of the left upper extremity. Characteristically, in addition to spontaneous fits, her seizure was inducible by rubbing her left hand and forearm for a few seconds. Accordingly, she was diagnosed with a rare form of reflex epilepsy, "rub epilepsy". Neuroradiological investigation indicated the existence of cortical abnormalities, such as focal cortical dysplasia of the right parietal lobe. Patients with TS are reported to have neuroanatomical abnormalities, especially of the parietal lobe. Thus, our case may imply a causal relationship between potential cortical hyperexcitability of the parietal lobe and epilepsy in TS. This is the first reported infantile case of rub epilepsy, and more generally, reflex epilepsy associated with TS.

Evaluation of seizure foci and genes in the Lgi1(L385R/+) mutant rat.

Mutations in the leucine-rich, glioma inactivated 1 (LGI1) gene have been identified in patients with autosomal dominant lateral temporal lobe epilepsy (ADLTE). We previously reported that Lgi1 mutant rats, carrying a missense mutation (L385R) generated by gene-driven N-ethyl-N-nitrosourea (ENU) mutagenesis, showed generalized tonic-clonic seizures (GTCS) in response to acoustic stimuli. In the present study, we assessed clinically relevant features of Lgi1 heterozygous mutant rats (Lgi1(L385R/+)) as an animal model of ADLTE. First, to explore the focus of the audiogenic seizures, we performed electroencephalography (EEG) and brain Fos immunohistochemistry in Lgi1(L385R/+) and wild type rats. EEG showed unique seizure patterns (e.g., bilateral rhythmic spikes) in Lgi1(L385R/+) rats with GTCS. An elevated level of Fos expression indicated greater neural excitability to acoustic stimuli in Lgi1(L385R/+) rats, especially in the temporal lobe, thalamus and subthalamic nucleus. Finally, microarray analysis revealed a number of differentially expressed genes that may be involved in epilepsy. These results suggest that Lgi1(L385R/+) rats are useful as an animal model of human ADLTE.

[Selection for catatonic reaction in rats: a study of interstrain differences by magnetic resonance imaging].

Brain studies by magnetic resonance imaging, angiography, and spectroscopy have been performed with rat strains Wistar, GC (genetic and catatonia), and PM+ (pendulum movements). Both GC and PM+ rats show similar deviations from the ancestral Wistar population in having smaller areas of the right striatum (coronal slice). The anterior horns of lateral ventricles in GC rats are smaller than in the control strain. The maximum blood flow velocity in the common carotid arteries of PM+ rats is greater. The GC and PM+ strains differ in myo-inositol level in the hippocampus. The PM+ strain is characterized by a lower taurine level in the hippocampus, which may be one of the participants regulated the predisposition to audiogenic seizures.

Seizure-free after surgery in a patient with non-lesional startle epilepsy: a case report.

We present the case of a patient with startle epilepsy provoked by auditory, somatosensory and visual stimuli during video-electrocorticography (ECoG) recording. Ictal ECoG of all types of seizures triggered by the three kinds of stimuli showed that seizure onset originated from the left supplementary sensorimotor area (SSMA). The patient has been seizure-free after the cortex around the left SSMA only had been resected. Therefore, we speculate that left SSMA is the epileptogenic zone of startle epilepsy in this patient and perhaps the primary cortex to modulate the startle reflex in healthy persons.

Music and epilepsy: a critical review.

The effect of music on patients with epileptic seizures is complex and at present poorly understood. Clinical studies suggest that the processing of music within the human brain involves numerous cortical areas, extending beyond Heschl's gyrus and working within connected networks. These networks could be recruited during a seizure manifesting as musical phenomena. Similarly, if certain areas within the network are hyperexcitable, then there is a potential that particular sounds or certain music could act as epileptogenic triggers. This occurs in the case of musicogenic epilepsy, whereby seizures are triggered by music. Although it appears that this condition is rare, the exact prevalence is unknown, as often patients do not implicate music as an epileptogenic trigger and routine electroencephalography does not use sound in seizure provocation. Music therapy for refractory epilepsy remains controversial, and further research is needed to explore the potential anticonvulsant role of music. Dopaminergic system modulation and the ambivalent action of cognitive and sensory input in ictogenesis may provide possible theories for the dichotomous proconvulsant and anticonvulsant role of music in epilepsy. The effect of antiepileptic drugs and surgery on musicality should not be underestimated. Altered pitch perception in relation to carbamazepine is rare, but health care professionals should discuss this risk or consider alternative medication particularly if the patient is a professional musician or native-born Japanese. Studies observing the effect of epilepsy surgery on musicality suggest a risk with right temporal lobectomy, although the extent of this risk and correlation to size and area of resection need further delineation. This potential risk may bring into question whether tests on musical perception and memory should form part of the preoperative neuropsychological workup for patients embarking on surgery, particularly that of the right temporal lobe.

Unilateral opercular lesion and eating-induced seizures.

Eating-induced seizures are an uncommon presentation of reflex epilepsy, a condition characterized by seizures provoked by specific stimuli. Most reports have identified aetiology associated with malformations of cortical developmental, hypoxic brain injury, previous meningoencephalitis or static encephalopathy. We present a patient with eating-induced reflex seizures, which began several years after treatment for an opercular primitive neuroectodermal tumour (PNET), and who subsequently underwent in-depth clinical and video-EEG analysis for her seizures. This patient noted rapid improvement with decreased frequency of seizure activity after treatment with valproic acid. We discuss the aetiology of reflex epilepsy, the anatomical basis of eating-induced epilepsy, and review the current literature.

Electroclinical characterization of epileptic seizures in leucine-rich, glioma-inactivated 1-deficient mice.

Mutations of the LGI1 (leucine-rich, glioma-inactivated 1) gene underlie autosomal dominant lateral temporal lobe epilepsy, a focal idiopathic inherited epilepsy syndrome. The LGI1 gene encodes a protein secreted by neurons, one of the only non-ion channel genes implicated in idiopathic familial epilepsy. While mutations probably result in a loss of function, the role of LGI1 in the pathophysiology of epilepsy remains unclear. Here we generated a germline knockout mouse for LGI1 and examined spontaneous seizure characteristics, changes in threshold for induced seizures and hippocampal pathology. Frequent spontaneous seizures emerged in homozygous LGI1(-/-) mice during the second postnatal week. Properties of these spontaneous events were examined in a simultaneous video and intracranial electroencephalographic recording. Their mean duration was 120 +/- 12 s, and behavioural correlates consisted of an initial immobility, automatisms, sometimes followed by wild running and tonic and/or clonic movements. Electroencephalographic monitoring indicated that seizures originated earlier in the hippocampus than in the cortex. LGI1(-/-) mice did not survive beyond postnatal day 20, probably due to seizures and failure to feed. While no major developmental abnormalities were observed, after recurrent seizures we detected neuronal loss, mossy fibre sprouting, astrocyte reactivity and granule cell dispersion in the hippocampus of LGI1(-/-) mice. In contrast, heterozygous LGI1(+/-) littermates displayed no spontaneous behavioural epileptic seizures, but auditory stimuli induced seizures at a lower threshold, reflecting the human pathology of sound-triggered seizures in some patients. We conclude that LGI1(+/-) and LGI1(-/-) mice may provide useful models for lateral temporal lobe epilepsy, and more generally idiopathic focal epilepsy.

Surgical treatment for musicogenic epilepsy.

We report a patient with medically intractable musicogenic epilepsy (ME) who was treated with surgery. Using the non-invasive methods of ictal and interictal electroencephalography (EEG), MRI, interictal single photon emission computed tomography and clinical manifestations, we first localized the musicogenic seizures (MS). The ictal onset zone was then further localized using intracranial EEG to the middle part of the left superior temporal gyrus. Surgical resection of the epileptogenic zone was then performed. The patient had two seizures within 2 weeks post-operatively, but has then had no seizures during the following year (Engel class II). The results suggest that patients who have medically intractable ME combined with unilateral ictal onset zones should be considered for the surgical treatment of epilepsy.

Investigating neuromagnetic brain responses against chromatic flickering stimuli by wavelet entropies.

BACKGROUND: Photosensitive epilepsy is a type of reflexive epilepsy triggered by various visual stimuli including colourful ones. Despite the ubiquitous presence of colorful displays, brain responses against different colour combinations are not properly studied. METHODOLOGY/PRINCIPAL FINDINGS: Here, we studied the photosensitivity of the human brain against three types of chromatic flickering stimuli by recording neuromagnetic brain responses (magnetoencephalogram, MEG) from nine adult controls, an unmedicated patient, a medicated patient, and two controls age-matched with patients. Dynamical complexities of MEG signals were investigated by a family of wavelet entropies. Wavelet entropy is a newly proposed measure to characterize large scale brain responses, which quantifies the degree of order/disorder associated with a multi-frequency signal response. In particular, we found that as compared to the unmedicated patient, controls showed significantly larger wavelet entropy values. We also found that Renyi entropy is the most powerful feature for the participant classification. Finally, we also demonstrated the effect of combinational chromatic sensitivity on the underlying order/disorder in MEG signals. CONCLUSIONS/SIGNIFICANCE: Our results suggest that when perturbed by potentially epileptic-triggering stimulus, healthy human brain manages to maintain a non-deterministic, possibly nonlinear state, with high degree of disorder, but an epileptic brain represents a highly ordered state which making it prone to hyper-excitation. Further, certain colour combination was found to be more threatening than other combinations.

A clinical and magnetoencephalography study of MRI-negative startle epilepsy.

OBJECTIVE: The goal of this study was to investigate clinical findings, ictal semiology, and results of video/electroencephalography (video/EEG), and magnetoencephalography (MEG) in patients with startle epilepsy and normal brain MRI. METHODS: Four patients (mean age 12.5 years) with startle epilepsy were investigated with MRI, video/EEG, and MEG. RESULTS: Epilepsy diagnosis was established in childhood, and all had spontaneous and reflex seizures. Reflex seizures were triggered by sudden, unexpected sounds and tactile stimuli. The neurological examinations and MRIs were normal. MEG recordings showed focal epileptiform activity. An ictal MEG was obtained in one patient. Source modeling yielded dipole sources in right central frontal region. CONCLUSION: The present study demonstrates that the origin of epileptiform activity in startle epilepsy can be localized in brain areas associated with supplementary motor seizures, even in patients with normal brain MRI. MEG adds complementary information to the localization of epileptiform activity and can be useful in planning invasive studies in cases evaluated for epilepsy surgery.

Hot water epilepsy with cerebral lesion: a report of five cases with cranial MRI findings.

Hot water epilepsy (HWE) is included in the reflex epilepsies. Although, in general, not common, HWE is concentrated in certain regions of the world. Different bathing habits and genetic factors may be responsible for the high incidence of HWE in these regions. However, the exact pathogenesis of HWE is not known. The facts that complex partial seizures are the most common clinical presentation and EEG recordings show an epileptic focus in the temporal lobe suggested the presence of a structural lesion in the temporal lobe. To our knowledge, however, there were no demonstrable structural changes on MRI and CT scans except in a few case reports. Here, we describe an additional five cases of HWE having an intracranial pathology, for example, hippocampal sclerosis, dysplasia, and a huge cystic lesion. We believe that investigations with new detailed neuroimaging techniques, in addition to experimental and clinical studies, might help us to understand the mechanism of this reflex epilepsy.

c-Fos immunohistochemical mapping of the audiogenic seizure network and tonotopic neuronal hyperexcitability in the inferior colliculus of the Frings mouse.

The Frings mouse is a model of audiogenic seizure (AGS) susceptibility. The genetic locus responsible for the AGS phenotype in the Frings mouse has been named monogenic audiogenic seizure-susceptible (MASS1). MASS1 is unique in that it is one of only two identified seizure loci that are not associated with an ion channel mutation. Furthermore, Frings mice display a robust AGS phenotype demonstrating very high and prolonged susceptibility to sound-induced tonic extension seizures. The purpose of this investigation was to use c-Fos immunohistochemistry to map the brain structures involved in the Frings AGS and to examine neuronal hyperexcitability in the inferior colliculus, the brain structure that is recognized as the site of AGS initiation. AGS mapping revealed that intense seizure-induced neuronal activation was mostly limited to structures involved in a brainstem seizure network, including the external and dorsal nuclei of the inferior colliculus, as observed in other AGS rodents. Acoustically induced c-Fos expression in the central nucleus of the inferior colliculus to sub-AGS threshold tone stimulations displayed a greater level of neuronal activation in AGS-susceptible Frings, DBA/2J and noise-primed C57BL/6J mice compared to AGS-resistant C57BL/6J and CF1 mice. The AGS-susceptible mice also displayed c-Fos immunoreactivity that was more focused within the tonotopic response domain of the inferior colliculus compared to AGS-resistant mice. Furthermore, Frings mice displayed significantly greater tonotopic hyper-responsiveness compared to other AGS-susceptible mice.

Hot water epilepsy and focal malformation of the parietal cortex development.

Hot water epilepsy (HWE) refers to a specific type of reflex epilepsy precipitated by the stimulus of bathing in hot water. HWE is considered to be a geographically specific epileptic syndrome since it mainly occurs in the Indian community. Spontaneous seizures may also occur later in life. The seizure pattern includes complex partial attacks. Although the pathogenesis of HWE is still unknown, temporal lobe has been thought to take part in the epileptogenesis. This paper reports on a 4-year-old girl who, at the age of 6 months, experienced complex partial seizures triggered by bathing in hot water. Non-provoked seizures intercritical EEG showed isolated spikes and spike-and-waves in the left parietal region. Brain MRI detected a left parietal focal cortical dysplasia. This is the second patient with HWE in whom a cortical malformation has been observed. The observation present here and data reported in the literature seem to indicate that the sensory cortex might also be involved in triggering seizures precipitated by a bath in hot water. Moreover, the authors believe that MRI examination should be considered for this group of patients.

A mitochondrial encephalo-myo-neuropathy with a nucleotide position 3271 (T-C) point mutation in the mitochondrial DNA.

We report three members of a family, who exhibited a phenotype similar to 'myoclonus epilepsy with ragged-red fibers' but had a genotype usually associated with 'mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes'. The patients, a 48-year-old female, and her two sons, aged 21 and 19 respectively, presented with photo-reactive syncopal episodes, disturbances of gait and writing, dysarthria and finger tremor since the 3rd and 2nd decade of life, respectively, that were accompanied also by numbness and weakness of the extremities. Subsequently, cerebellar ataxia and myoclonus were also noted. Electromyography revealed both myogenic and neurogenic muscular changes, and nerve conduction studies demonstrated a sensory-motor neuropathy. Biopsy showed ragged-red fibers with strongly stained SDH-positive vessels in skeletal muscles, and a marked loss of myelinated fibers of the sural nerves. Mitochondrial (mt) DNA analyses of peripheral blood, muscles and nerves revealed that all members had a heteroplasmic np3271 (T-C) point mutation in the mitochondrial tRNA-Leu gene (UUR). This family is unique, in that all patients presented with a myoclonus epilepsy with ragged-red fibers-like phenotype and had a distinctive peripheral neuropathy, while the detected mtDNA 327l (T-C) mutation has been reported to date only in rare cases of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes