Characterizing Sunflower syndrome: a clinical series.

To characterize the clinical phenotype of Sunflower syndrome. Sunflower syndrome is a rare photosensitive epilepsy syndrome characterized by highly stereotyped seizures, photosensitivity, and heliotropism. We retrospectively reviewed the medical records of patients seen in the Massachusetts General Hospital for Children (MGHfC) pediatric epilepsy program with a history of Sunflower syndrome. Twenty-four patients were identified; 18 were female. At the time of initial MGHfC evaluation, patients' ages ranged from 6.4 to 25 years, with a median age of 11.5 years. All patients presented with hand-waving episodes (HWEs), although one patient no longer demonstrates this, but now has eye blinking episodes on exposure to light. Four have associated eye fluttering as a component of their most prevalent light-induced seizures. The average age at onset of HWEs was six years. Seventeen developed other symptoms prior to the onset of HWEs. The most prevalent symptom was an attraction to light and possible absence seizures. Light-induced seizures were generally refractory to broad-spectrum antiepileptic drugs (AEDs). Only three patients had a reduction of HWEs with the use of AEDs. Several non-pharmacological strategies reduced seizure frequency, however, efficacy varied. These non-pharmacological strategies included avoiding stimulus, focusing on other tasks, and occupying or restraining the hand that was involved in hand-waving. The use of tinted glasses reduced seizure frequency in 17 patients, however, no patient achieved seizure freedom. Twenty-two patients had available EEGs, 20 of which showed interictal epileptiform discharges. Additionally, many of the patients experienced a negative impact on their self-concept due to anxiety, depression, or negative interactions with peers. Sunflower syndrome is a generalized, pharmacoresistant epilepsy with childhood onset and remains poorly understood. To improve clinical care and scientific understanding, long-term prospective research exploring the natural history, etiology, and effective treatments for Sunflower syndrome should be conducted. [Published with video sequence].

Morphological and molecular correlates of altered hearing sensitivity in the genetically audiogenic seizure-prone hamster GASH/Sal.

Rodent models of audiogenic seizures, in which seizures are precipitated by an abnormal response of the brain to auditory stimuli, are crucial to investigate the neural bases underlying ictogenesis. Despite significant advances in understanding seizure generation in the inferior colliculus, namely the epileptogenic nucleus, little is known about the contribution of lower auditory stations to the seizure-prone network. Here, we examined the cochlea and cochlear nucleus of the genetic audiogenic seizure hamster from Salamanca (GASH/Sal), a model of reflex epilepsy that exhibits generalized tonic-clonic seizures in response to loud sound. GASH/Sal animals under seizure-free conditions were compared with matched control hamsters in a multi-technical approach that includes auditory brainstem responses (ABR) testing, histology, scanning electron microscopy analysis, immunohistochemistry, quantitative morphometry and gene expression analysis (RT-qPCR). The cochlear histopathology of the GASH/Sal showed preservation of the sensory hair cells, but a significant loss of spiral ganglion neurons and mild atrophy of the stria vascularis. At the electron microscopy level, the reticular lamina exhibited disarray of stereociliary tufts with blebs, loss or elongated stereocilia as well as non-parallel rows of outer hair cells due to protrusions of Deiters' cells. At the molecular level, the abnormal gene expression patterns of prestin, cadherin 23, protocadherin 15, vesicular glutamate transporters 1 (Vglut1) and -2 (Vglut2) indicated that the hair-cell mechanotransduction and cochlear amplification were markedly altered. These were manifestations of a cochlear neuropathy that correlated to ABR waveform I alterations and elevated auditory thresholds. In the cochlear nucleus, the distribution of VGLUT2-immunolabeled puncta was differently affected in each subdivision, showing significant increases in magnocellular regions of the ventral cochlear nucleus and drastic reductions in the granule cell domain. This modified inputs lead to disruption of Vglut1 and Vglut2 gene expression in the cochlear nucleus. In sum, our study provides insight into the morphological and molecular traits associated with audiogenic seizure susceptibility in the GASH/Sal, suggesting an upward spread of abnormal glutamatergic transmission throughout the primary acoustic pathway to the epileptogenic region.

Alterations in brainstem auditory processing, the acoustic startle response and sensorimotor gating of startle in Wistar audiogenic rats (WAR), an animal model of reflex epilepsies.

While acute audiogenic seizures in response to acoustic stimulus appear as an alteration in sensory-motor processing in the brainstem, the repetition of the stimulus leads to the spread of epileptic activity to limbic structures. Here, we investigated whether animals of the Wistar Audiogenic Rat (WAR) strain, genetically selected by inbreeding for seizure susceptibility, would have alterations in their auditory response, assessed by the auditory brainstem responses (ABR) and sensory-motor gating, measured as pre-pulse inhibition (PPI), which could be related to their audiogenic seizures susceptibility or severity. We did not find differences between the amplitudes and latencies of ABR waves in response to clicks for WARs when compared to Wistars. Auditory gain and symmetry between ears were also similar. However, hearing thresholds in response to some tones were lower and amplitudes of wave II were larger in WARs. WARs had smaller acoustic startle reflex amplitudes and the percentages of startle inhibited by an acoustic prepulse were higher for WARs than for Wistars. However, no correlation was found between these alterations and brainstem-dependent seizure severity or limbic seizure frequency during audiogenic kindling. Our data show that while WARs present moderate alterations in primary auditory processing, the sensory motor gating measured in startle/PPI tests appears to be more drastically altered. The observed changes might be correlated with audiogenic seizure susceptibility but not seizures severity.

Neurología del éxtasis y fenómenos aledaños: epilepsia extática, orgásmica y musicogénica. Síndrome de Stendhal. Fenómenos autoscópicos / Neurology of ecstatic religious and similar experiences: Ecstatic, orgasmic, and musicogenic seizures. Stendhal syndrome and autoscopic phenomena

Todas las vivencias del ser humano, incluidas las experiencias místicas y religiosas, tienen que ver en último término con la actividad funcional de su cerebro. El estudio, mediante técnicas de neuroimagen estructural (RM) y funcional (RMf, PET, SPECT) y técnicas neurofisiológicas con registros y estimulación mediante electrodos intracraneales, de casos de epilepsia extática nos ha proporcionado un mejor conocimiento de ciertos estados mentales, en los que hay síntomas con especiales connotaciones placenteras-afectivas y de clarividencia. Se postula que tales estados de éxtasis se producen por activación de la corteza insular anterior, conexionada con redes neuronales (por defecto, saliencia y neuronas en espejo), que intervienen en la introspección, cognición social, el procesado emocional y la memoria. De este modo, la neurociencia puede aportar una explicación científica, incluso de un modo retrospectivo, a algunos hechos y situaciones relacionados con personajes relevantes (Pablo de Tarso, Teresa de Cepeda y Ahumada, Dostoievski), que, en ámbitos extracientíficos, se consideran de origen paranormal o hasta sobrenatural. Con la epilepsia extática comparten síntomas y mecanismos fisiopatológicos la epilepsia orgásmica (excitación sexual que puede desembocar en orgasmos espontáneos en el transcurso de crisis comiciales), la epilepsia musicogénica (crisis comiciales desencadenadas por particulares emociones generadas al escuchar un determinado fragmento musical), así como en el síndrome de Stendhal (cuadros neuropsiquiátricos precipitados por una contemplación masiva de obras de arte) y algunos fenómenos autoscópicos (sobre todos las experiencias extracorporales, que ocasionalmente tienen lugar en situaciones de muerte inminente): en todos ellos existe sintomatología placentera-afectiva de alto impacto para los sujetos afectados

All human experiences, including mystical and religious ones, are the result of brain functional activity. Thanks to the study of cases of ecstatic epilepsy with structural (MRI) and functional neuroimaging (fMRI, PET, SPECT) and neurophysiological technologies (recording and stimulation with intracranial electrodes), we now have a better knowledge of certain mental states which involve pleasant and affective symptoms and clarity of mind. These ecstatic experiences are thought to be caused by the activation of the anterior insular cortex and some neuronal networks (basically related to mirror neurons and salience) participating in introspection, social cognition, memory, and emotional processes. Thus, neuroscience could explain in a retrospective way some facts surrounding the situations of such relevant figures as Paul the Apostle, Teresa de Cepeda y Ahumada, and Dostoevsky, whose origin was previously considered paranormal or supernatural. Ecstatic epilepsy shares symptoms and mechanisms with orgasmic epilepsy (spontaneous orgasms in the course of epileptic seizures), musicogenic epilepsy (epileptic seizures triggered by listening to a certain musical piece), and also with Stendhal syndrome (neuropsychiatric disturbances caused when an individual is exposed to large amounts of art) and some autoscopic phenomena (out-of-body experiences that occasionally take place in imminent death situations). In all these events, there are pleasant and affective symptoms which have a great impact on patients

Affect-induced reflex seizures (AIRS): A case series based on a systematic literature review.

Seizures are commonly thought to occur in a spontaneous, unpredictable manner. However, it is well-established that a subset of patients with epilepsy can experience reflex seizures that are consistently elicited by a specific stimulus. While various forms of reflex epilepsy have been documented in the literature, acute affective states have not been commonly described as a potential reflex seizure trigger. We performed a systematic literature review to determine if acute emotional states can trigger reflex seizures. We included any case in which reflex seizures repeatedly occurred in response to a patient-specific stimulus that was reported as emotionally relevant by the authors. This yielded our case series of ten patients who have been described to have reflex seizures in response to emotional stimuli. We characterized features of these cases including the following: age, gender, developmental and psychiatric history, seizure semiology and duration, emotional triggers, other reflex triggers, relationship between reflex triggers and seizures, investigations, localization, final diagnosis, treatment, and outcome. Considerable variability was found between cases. A trend toward limbic seizure semiology with psychic aura originating in networks involved in emotional processing was noted, with temporal lobe epilepsy being the most common, although without clear laterality or gender predominance. In addition, the report of a significant life stressor occurring at epilepsy onset in three of ten patients as well as the initial suspicion that reflex epileptic seizures were psychogenic in three cases both emphasize the role of electroencephalography in assessment of such presentations to avoid missing a diagnosis of epilepsy. Findings from these ten cases suggest that a patient-specific affective stimulus may trigger reflex seizures in a subset of patients, and that this could be underrecognized or mislabeled as nonepileptic. We encourage future studies with larger numbers to further characterize this phenomenon. Insights gained may enhance our understanding of seizure localization and bear potential treatment implications.

Neurology of ecstatic religious and similar experiences: Ecstatic, orgasmic, and musicogenic seizures. Stendhal syndrome and autoscopic phenomena. / Neurología del éxtasis y fenómenos aledaños: epilepsia extática, orgásmica y musicogénica. Síndrome de Stendhal. Fenómenos autoscópicos.

All human experiences, including mystical and religious ones, are the result of brain functional activity. Thanks to the study of cases of ecstatic epilepsy with structural (MRI) and functional neuroimaging (fMRI, PET, SPECT) and neurophysiological technologies (recording and stimulation with intracranial electrodes), we now have a better knowledge of certain mental states which involve pleasant and affective symptoms and clarity of mind. These ecstatic experiences are thought to be caused by the activation of the anterior insular cortex and some neuronal networks (basically related to mirror neurons and salience) participating in introspection, social cognition, memory, and emotional processes. Thus, neuroscience could explain in a retrospective way some facts surrounding the situations of such relevant figures as Paul the Apostle, Teresa de Cepeda y Ahumada, and Dostoevsky, whose origin was previously considered paranormal or supernatural. Ecstatic epilepsy shares symptoms and mechanisms with orgasmic epilepsy (spontaneous orgasms in the course of epileptic seizures), musicogenic epilepsy (epileptic seizures triggered by listening to a certain musical piece), and also with Stendhal syndrome (neuropsychiatric disturbances caused when an individual is exposed to large amounts of art) and some autoscopic phenomena (out-of-body experiences that occasionally take place in imminent death situations). In all these events, there are pleasant and affective symptoms which have a great impact on patients.

The electroclinical features of idiopathic generalized epilepsy patients presenting with fixation-off sensitivity.

To determine the electroclinical features of fixation-off sensitivity (FOS) in patients with idiopathic generalized epilepsy (IGE). We searched the EEG database using the terms "fixation-off sensitivity" and "idiopathic generalized epilepsy" over a four-year period from March 2014 to April 2018 in the Xijing Hospital, Xi'an, China. FOS was evaluated according to the technique proposed by Panayiotopoulos. Photic stimulation procedure and neuropsychological testing were performed during video-EEG monitoring. FOS was observed in eight patients with several different IGE syndromes, including four with eyelid myoclonia/Jeavons syndrome, two with juvenile myoclonic epilepsy, one with photosensitivity epilepsy, and one with epilepsy with generalized tonic-clonic seizures only. FOS was associated with seizures in five patients manifesting with eyelid myoclonic, myoclonic, and myoclonic-tonic-clonic seizures, and eyelid myoclonic status. FOS coexisted with photosensitivity in six patients as independent EEG features. Neuropsychological testing revealed transitory cognitive impairments associated with FOS. FOS is associated with several different IGE syndromes and may coexist with photosensitivity in the same patient as independent EEG features. FOS may be associated with both clinical seizures and cognitive impairments. Intermittent photic stimulation and registration of different eye conditions with and without fixation will aid the study of the dynamics of the visual system in epilepsy patients. [Published with video sequences on www.epilepticdisorders.com].

Successful treatment of reflex epilepsy with praxis induction by stimulus avoidance only.

PURPOSE: Reflex epilepsy is a type of epilepsy with seizures that are consistently triggered by a specific stimulus. Zipai is a Chinese ancient card game which has been popular in Southern China for hundreds of years. We sought to report and characterize clinical features of patients with reflex epilepsy evoked by playing Zipai. METHODS: We collected and analyzed clinical data of patients with Zipai-induced epilepsy. Patients were regarded as having Zipai-induced epilepsy if they suffered at least two seizure attack during the course of playing Zipai. Prolonged electroencephalography (EEG) and brain magnetic resonance imaging (MRI) were applied to all patients. All patients were advised to avoid watching and playing Zipai games in daily life, instead of using antiepileptic drugs. The seizure outcome was assessed during outpatient visits and by telephone contact. RESULTS: Five patients were included in this study. No spontaneous seizures occurred in all five patients. No patients had experienced myoclonic and coexistent absences with generalized tonic-clonic seizures (GTCS). All patients had normal MRI and prolonged EEG findings. All patients were advised to avoid the Zipai game, and became seizure-free without medication during the follow-up period (mean 5.4 years, range 3.5-7 years). CONCLUSION: Zipai-induced epilepsy may be an unreported subtype form of reflex epilepsy with praxis induction. Nonpharmacological conservative treatment plays a significant role in the treatment of reflex epilepsy.

A case of epilepsy induced by eating or by visual stimuli of food made of minced meat.

We report a 34-year-old woman with eating epilepsy induced not only by eating but also seeing foods made of minced meat. In her early 20s of age, she started having simple partial seizures (SPS) as flashback and epigastric discomfort induced by particular foods. When she was 33 years old, she developed SPS, followed by secondarily generalized tonic-clonic seizure (sGTCS) provoked by eating a hot dog, and 6 months later, only seeing the video of dumpling. We performed video electroencephalogram (EEG) monitoring while she was seeing the video of soup dumpling, which most likely caused sGTCS. Ictal EEG showed rhythmic theta activity in the left frontal to mid-temporal area, followed by generalized seizure pattern. In this patient, seizures were provoked not only by eating particular foods but also by seeing these. This suggests a form of epilepsy involving visual stimuli.

Wistar audiogenic rats display abnormal behavioral traits associated with artificial selection for seizure susceptibility.

Accumulating evidence from different animal models has contributed to the understanding of the bidirectional comorbidity associations between the epileptic condition and behavioral abnormalities. A strain of animals inbred to enhance seizure predisposition to high-intensity sound stimulation, the Wistar audiogenic rat (WAR), underwent several behavioral tests: forced swim test (FST), open-field test (OFT), sucrose preference test (SPT), elevated plus maze (EPM), social preference (SP), marble burying test (MBT), inhibitory avoidance (IAT), and two-way active avoidance (TWAA). The choice of tests aimed to investigate the correlation between underlying circuits believed to be participating in both WAR's innate susceptibility to sound-triggered seizures and the neurobiological substrates associated with test performance. Comparing WAR with its Wistar counterpart (i.e., resistant to audiogenic seizures) showed that WARs present behavioral despair traits (e.g., increased FST immobility) but no evidence of anhedonic behavior (e.g., increased sucrose consumption in SPT) or social impairment (e.g., no difference regarding juvenile exploration in SP). In addition, tests suggested that WARs are unable to properly evaluate degrees of aversiveness (e.g., performance on OFT, EPM, MBT, IAT, and TWAA). The particularities of the WAR model opens new venues to further untangle the neurobiology underlying the co-morbidity of behavioral disorders and epilepsy. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic".

Reflex epileptic mechanisms in humans: Lessons about natural ictogenesis.

The definition of reflex epileptic seizures is that specific seizure types can be triggered by certain sensory or cognitive stimuli. Simple triggers are sensory (most often visual, more rarely tactile or proprioceptive; simple audiogenic triggers in humans are practically nonexistent) and act within seconds, whereas complex triggers like praxis, reading and talking, and music are mostly cognitive and work within minutes. The constant relation between a qualitatively, often even quantitatively, well-defined stimulus and a specific epileptic response provides unique possibilities to investigate seizure generation in natural human epilepsies. For several reflex epileptic mechanisms (REMs), this has been done. Reflex epileptic mechanisms have been reported less often in focal lesional epilepsies than in idiopathic "generalized" epilepsies (IGEs) which are primarily genetically determined. The key syndrome of IGE is juvenile myoclonic epilepsy (JME), where more than half of the patients present reflex epileptic traits (photosensitivity, eye closure sensitivity, praxis induction, and language-induced orofacial reflex myocloni). Findings with multimodal investigations of cerebral function concur to indicate that ictogenic mechanisms in IGEs largely (ab)use preexisting functional anatomic networks (CNS subsystems) normally serving highly complex physiological functions (e.g., deliberate complex actions and linguistic communication) which supports the concept of system epilepsy. Whereas REMs in IGEs, thus, are primarily function-related, in focal epilepsies, they are primarily localization-related. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic".

Behavioral, Ventilatory and Thermoregulatory Responses to Hypercapnia and Hypoxia in the Wistar Audiogenic Rat (WAR) Strain.

INTRODUCTION: We investigated the behavioral, respiratory, and thermoregulatory responses elicited by acute exposure to both hypercapnic and hypoxic environments in Wistar audiogenic rats (WARs). The WAR strain represents a genetic animal model of epilepsy. METHODS: Behavioral analyses were performed using neuroethological methods, and flowcharts were constructed to illustrate behavioral findings. The body plethysmography method was used to obtain pulmonary ventilation (VE) measurements, and body temperature (Tb) measurements were taken via temperature sensors implanted in the abdominal cavities of the animals. RESULTS: No significant difference was observed between the WAR and Wistar control group with respect to the thermoregulatory response elicited by exposure to both acute hypercapnia and acute hypoxia (p>0.05). However, we found that the VE of WARs was attenuated relative to that of Wistar control animals during exposure to both hypercapnic (WAR: 133 ± 11% vs. Wistar: 243 ± 23%, p<0.01) and hypoxic conditions (WAR: 138 ± 8% vs. Wistar: 177 ± 8%; p<0.01). In addition, we noted that this ventilatory attenuation was followed by alterations in the behavioral responses of these animals. CONCLUSIONS: Our results indicate that WARs, a genetic model of epilepsy, have important alterations in their ability to compensate for changes in levels of various arterial blood gasses. WARs present an attenuated ventilatory response to an increased PaCO2 or decreased PaO2, coupled to behavioral changes, which make them a suitable model to further study respiratory risks associated to epilepsy.

Multimodal effective connectivity analysis reveals seizure focus and propagation in musicogenic epilepsy.

Dynamic causal modeling (DCM) is a method to non-invasively assess effective connectivity between brain regions. 'Musicogenic epilepsy' is a rare reflex epilepsy syndrome in which seizures can be elicited by musical stimuli and thus represents a unique possibility to investigate complex human brain networks and test connectivity analysis tools. We investigated effective connectivity in a case of musicogenic epilepsy using DCM for fMRI, high-density (hd-) EEG and MEG and validated results with intracranial EEG recordings. A patient with musicogenic seizures was examined using hd-EEG/fMRI and simultaneous '256-channel hd-EEG'/'whole head MEG' to characterize the epileptogenic focus and propagation effects using source analysis techniques and DCM. Results were validated with invasive EEG recordings. We recorded one seizure with hd-EEG/fMRI and four auras with hd-EEG/MEG. During the seizures, increases of activity could be observed in the right mesial temporal region as well as bilateral mesial frontal regions. Effective connectivity analysis of fMRI and hd-EEG/MEG indicated that right mesial temporal neuronal activity drives changes in the frontal areas consistently in all three modalities, which was confirmed by the results of invasive EEG recordings. Seizures thus seem to originate in the right mesial temporal lobe and propagate to mesial frontal regions. Using DCM for fMRI, hd-EEG and MEG we were able to correctly localize focus and propagation of epileptic activity and thereby characterize the underlying epileptic network in a patient with musicogenic epilepsy. The concordance between all three functional modalities validated by invasive monitoring is noteworthy, both for epileptic activity spread as well as for effective connectivity analysis in general.

Loudness perception affected by early age hearing loss.

Tinnitus and hyperacusis, commonly seen in adults, are also reported in children. Although clinical studies found children with tinnitus and hyperacusis often suffered from recurrent otitis media, there is no direct study on how temporary hearing loss in the early age affects the sound loudness perception. In this study, sound loudness changes in rats affected by perforation of the tympanic membranes (TM) have been studied using an operant conditioning based behavioral task. We detected significant increases of sound loudness and susceptibility to audiogenic seizures (AGS) in rats with bilateral TM damage at postnatal 16 days. As increase to sound sensitivity is commonly seen in hyperacusis and tinnitus patients, these results suggest that early age hearing loss is a high risk factor to induce tinnitus and hyperacusis in children. In the TM damaged rats, we also detected a reduced expression of GABA receptor δ and α6 subunits in the inferior colliculus (IC) compared to the controls. Treatment of vigabatrin (60 mg/kg/day, 7-14 days), an anti-seizure drug that inhibits the catabolism of GABA, not only blocked AGS, but also significantly attenuated the loudness response. Administration of vigabatrin following the early age TM damage could even prevent rats from developing AGS. These results suggest that TM damage at an early age may cause a permanent reduction of GABA tonic inhibition which is critical towards the maintenance of normal loudness processing of the IC. Increasing GABA concentration during the critical period may alleviate the impairment in the brain induced by early age hearing loss.

Metoprine induced behavioral modifications and brain regional histamine increase in WAG/Rij and Wistar rats.

The effects of metoprine, an inhibitor of histamine N-methyltransferase, on open field activity and brain regional histamine (HA) content were examined in rats with mixed, absence and audiogenic, epilepsy (WAG/Rij-AGS), rats with audiogenic epilepsy (Wistar-AGS) and in non-epileptic control rats (Wistar-nAGS). HA content was increased by metoprine (20mg/kg, i.p.) in the cortex, striatum, thalamus, hypothalamus and hippocampus of the rats from all three tested groups. However, WAG/Rij rats showed a lower rate of metoprine-induced HA accumulation in the striatum and thalamus than Wistar rats. For the open field test, the main effect of metoprine (20mg/kg, i.p.) was a general increase of locomotor activity although distinctive features, such as hyperlocomotion and exaggerated sniffing, were characteristic for the epileptic rats (WAG/Rij-AGS and Wistar-AGS, respectively). Individual rats from all the groups showed stereotyped behavior of shuttle type and head bobbing. Electroencephalographic data obtained in WAG/Rij-AGS rats confirmed that metoprine-induced behavioral activation was accompanied by suppression of spike-wave discharges, the main hallmark of absence seizures. Taken together, these results show that inhibition of the histamine catabolism may induce motor activation of particular patterns in epileptic rats and provoke stereotyped behavior.

Early age conductive hearing loss causes audiogenic seizure and hyperacusis behavior.

Recent clinical reports found a high incidence of recurrent otitis media in children suffering hyperacusis, a marked intolerance to an otherwise ordinary environmental sound. However, it is unclear whether the conductive hearing loss caused by otitis media in early age will affect sound tolerance later in life. Thus, we have tested the effects of tympanic membrane (TM) damage at an early age on sound perception development in rats. Two weeks after the TM perforation, more than 80% of the rats showed audiogenic seizure (AGS) when exposed to loud sound (120 dB SPL white noise, < 1 min). The susceptibility of AGS lasted at least sixteen weeks after the TM damage, even the hearing loss recovered. The TM damaged rats also showed significantly enhanced acoustic startle responses compared to the rats without TM damage. These results suggest that early age conductive hearing loss may cause an impaired sound tolerance during development. In addition, the AGS can be suppressed by the treatment of vigabatrin, acute injections (250 mg/kg) or oral intakes (60 mg/kg/day for 7 days), an antiepileptic drug that inhibits the catabolism of GABA. c-Fos staining showed a strong staining in the inferior colliculus (IC) in the TM damaged rats, not in the control rats, after exposed to loud sound, indicating a hyper-excitability in the IC during AGS. These results indicate that early age conductive hearing loss can impair sound tolerance by reducing GABA inhibition in the IC, which may be related to hyperacusis seen in children with otitis media.

Reading epilepsy as the initial symptom of idiopathic hypoparathyroidism.

Reading epilepsy is a rare form of reflex epilepsy that occurs exclusively during reading. In this report, we describe a patient in whom seizure was the initial symptom of idiopathic hypoparathyroidism. A 31-year-old man experienced seizures three times in different bookshops while browsing. Chvostek's sign was observed. Serum calcium and parathyroid hormone levels were decreased. Brain computed tomography revealed symmetrical calcification at the dentate nuclei of the cerebellum and the basal ganglia. The interictal electroencephalography was normal. There was no photoparoxysmal response. After amelioration of serum calcium level with oral administration of vitamin D, seizure attacks ceased without antiepileptic drugs. This case is, to our knowledge, the first report of reading epilepsy associated with hypocalcemia due to idiopathic hypoparathyroidism. The psychological stress of reading at bookshops without buying might have triggered seizures under CNS hyperexcitability due to hypocalcemia.

Genetic reduction of group 1 metabotropic glutamate receptors alters select behaviors in a mouse model for fragile X syndrome.

INTRODUCTION: Genetic heterogeneity likely contributes to variability in the symptoms among individuals with fragile X syndrome (FXS). Studies in the Fmr1 knockout (KO) mouse model for FXS suggest that excessive signaling through group I metabotropic glutamate receptors (Gp1 mGluRs), comprised of subtypes mGluR1 and mGluR5, may play a role. Hence, Gp1 mGluRs may act as modifiers of FXS. Currently no studies have addressed whether manipulation of mGluR1 activity may alter Fmr1 KO behavioral responses, and only a few have reported the effects of mGluR5 manipulation. Therefore, the goals for this study were to extend our understanding of the effects of modulating Gp1 mGluR activity on Fmr1 KO behavioral responses. METHODS: The present study determined if genetically reducing mGluR1 or mGluR5 by 50% affects an extensive array of behaviors in the Fmr1 KO. RESULTS: Reduction of mGluR1 moderately decreased Fmr1 KO activity. Reduction of mGluR5 caused an analgesic response in the Fmr1 KO and decreased active social behavior. Modulation of either mGluR1 or mGluR5 did not significantly alter audiogenic seizures, anxiety- and perseverative-related responses, sensorimotor gating, memory, or motor responses. CONCLUSIONS: Genetic reduction of mGluR1 or mGluR5 modified a few select Fmr1 KO behaviors, although these modifications appeared to be subtle in nature and/or limited to select behaviors. This may indicate that 50% reduction of either mGluR1 or mGluR5 is insufficient to produce behavioral changes, and therefore, these receptors may not be dominant modifiers of a number of Fmr1 KO behavioral phenotypes.