Cortico-striato-thalamo-cerebellar networks of structural covariance underlying different epilepsy syndromes associated with generalized tonic-clonic seizures.

Generalized tonic-clonic seizures (GTCS) are the severest and most remarkable clinical expressions of human epilepsy. Cortical, subcortical, and cerebellar structures, organized with different network patterns, underlying the pathophysiological substrates of genetic associated epilepsy with GTCS (GE-GTCS) and focal epilepsy associated with focal to bilateral tonic-clonic seizure (FE-FBTS). Structural covariance analysis can delineate the features of epilepsy network related with long-term effects from seizure. Morphometric MRI data of 111 patients with GE-GTCS, 111 patients with FE-FBTS and 111 healthy controls were studied. Cortico-striato-thalao-cerebellar networks of structural covariance within the gray matter were constructed using a Winner-take-all strategy with five cortical parcellations. Comparisons of structural covariance networks were conducted using permutation tests, and module effects of disease duration on networks were conducted using GLM model. Both patient groups showed increased connectivity of structural covariance relative to controls, mainly within the striatum and thalamus, and mostly correlated with the frontal, motor, and somatosensory cortices. Connectivity changes increased as a function of epilepsy durations. FE-FBTS showed more intensive and extensive gray matter changes with volumetric loss and connectivity increment than GE-GTCS. Our findings implicated cortico-striato-thalamo-cerebellar network changes at a large temporal scale in GTCS, with FE-FBTS showing more severe network disruption. The study contributed novel imaging evidence for understanding the different epilepsy syndromes associated with generalized seizures.

Impairments of cingulated cortex in the generalized tonic-clonic seizure epilepsy by combining morphological and functional connectivity magnetic resonance imaging.

Previous studies suggested that the patients with generalized tonic-clonic seizure had structural abnormalities in the thalamus, cingulated cortex and some other specific brain regions. Concurrently, the abnormality in thalamocortical network and basal ganglia network has been found in idiopathic generalized epilepsy. The cingulated cortex, a nexus of information processing and regulation in human brain, is implicated in the propagation of generalized spike in IGE and the previous studies have suggested that the structural features and functional connectivity of the cingulated cortex have been changed. The aim of this study was to demonstrate the alterations in the cingulated cortex in generalized tonic-clonic seizure by combining morphological and functional connectivity magnetic resonance imaging. 19 patients with generalized tonic-clonic seizure and 19 age-and gender-matched healthy controls were involved in the study. The three-dimensional high-resolution T1-weighted magnetic resonance imaging data were acquired for voxel-based morphometry analysis, two-sample t-test run on the T1-weighted structural images revealed clusters exhibiting significant decreases in grey-matter volume in the generalized tonic-clonic seizure group, located within the cingulated cortex, thalamus, frontal lobe, temporal lobe, and cerebellum. The decreased gray matter volume in the cingulated cortex indicating that the cingulated cortex has structural impairments in generalized tonic-clonic seizure patients. The bilateral cingulated cortex, as detected with decreased gray matter volume in patients with generalized tonic-clonic seizure through voxel-based morphometry analysis, was selected as seed regions for functional connectivity analysis. Compared with controls, we found decreased functional connectivity to left anterior cingulated cortex (ROI1) in the cuneus, frontal lobe and precentral gyrus. There was no significant result when seeding at the right anterior cingulum gyrus (ROI2). The results of the ROI3 (left middle cingulum) revealed the significantly decreased functional connectivity in the parietal lobe and frontal lobe. Seeding at the ROI4 (right middle cingulum), decreased functional connectivity showed in the occipital lobe, temporal lobe, frontal lobe. Seeding at the ROI5 (left posterior cingulum), decreased functional connectivity showed in the temporal lobe and frontal lobe. Seeding at the ROI6 (right posterior cingulum), decreased functional connectivity showed in the cuneus and frontal lobe. We did not find any increased functional connectivity of the posterior cingulated cortex (ROI3-ROI6) for the generalized tonic-clonic seizure patients in comparison to the controls (p<0.001). Our findings demonstrated that the abnormalities of the functional connectivity were likely to be related to the decreased gray matter volume in the cingulated cortex.

Hand postures in primary and secondary generalized tonic-clonic seizures.

OBJECTIVE: To evaluate and identify the frequency of hand postures during generalized convulsions in patients with genetic generalized epilepsy (GGE), localization-related epilepsy (LRE), and nonepileptic attacks (NEA). METHODS: We retrospectively analyzed 98 consecutive videos of generalized convulsions in 62 patients who were admitted for diagnostic video-EEG monitoring. Demographics were recorded, and hand postures were subdivided into fanning, fisting, index-finger pointing (IFP), clawing, and flaccid posturing. Hand postures were then compared between patients with GGE, LRE, and NEA for each stage of the convulsion and for the whole event. RESULTS: In patients with LRE, 96% had IFP, where fanning occurred in 91.3% of GGE (and only at onset), and the flaccid hand posture occurred in 56.0% of NEA. Fisting, fanning, and IFP postures all occurred significantly more frequently during epileptic seizures than during NEA (74.0% vs 32.0%, p = 0.0003; 60.3% vs 20.0%, p = 0.0005; 83.6% vs 12.0%, p < 0.0001). The claw hand posture was present only during NEA, and the flaccid posture occurred significantly more frequently during NEA than during epileptic seizures (56.0% vs 15.1%, p = 0.0001). CONCLUSIONS: Distinct ictal hand or finger posturing is present in patients with GGE, LRE, and NEA. The presence of any fisting, fanning, clawing, IFP, or flaccid hand posturing can help distinguish epileptic seizures from NEA. IFP suggests LRE while fanning with evolution suggests GGE. Overall, hand posturing during seizures provides unique information and aids in the differential diagnosis and classification of epilepsy.

Real-time magnetic resonance imaging-guided frameless stereotactic brain biopsy: technical note.

OBJECTIVE: The object of this study was to assess the feasibility, accuracy, and safety of real-time MRI-compatible frameless stereotactic brain biopsy. METHODS: Clinical, imaging, and histological data in consecutive patients who underwent stereotactic brain biopsy using a frameless real-time MRI system were analyzed. RESULTS: Five consecutive patients (4 males, 1 female) were included in this study. The mean age at biopsy was 45.8 years (range 29-60 years). Real-time MRI permitted concurrent display of the biopsy cannula trajectory and tip during placement at the target. The mean target depth of biopsied lesions was 71.3 mm (range 60.4-80.4 mm). Targeting accuracy analysis revealed a mean radial error of 1.3 ± 1.1 mm (mean ± standard deviation), mean depth error of 0.7 ± 0.3 mm, and a mean absolute tip error of 1.5 ± 1.1 mm. There was no correlation between target depth and absolute tip error (Pearson product-moment correlation coefficient, r = 0.22). All biopsy cannulae were placed at the target with a single penetration and resulted in a diagnostic specimen in all cases. Histopathological evaluation of biopsy samples revealed dysembryoplastic neuroepithelial tumor (1 case), breast carcinoma (1 case), and glioblastoma multiforme (3 cases). CONCLUSIONS: The ability to place a biopsy cannula under real-time imaging guidance permits on-the-fly alterations in the cannula trajectory and/or tip placement. Real-time imaging during MRI-guided brain biopsy provides precise safe targeting of brain lesions.

Disrupted glutamate-glutamine cycle in acute encephalopathy with biphasic seizures and late reduced diffusion.

INTRODUCTION: Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is the most common subtype of infectious pediatric encephalopathy in Japan. It is sometimes difficult to make an early diagnosis of AESD; excitotoxicity is postulated to be the pathogenesis based on elevated glutamine (Gln) and glutamate (Glu) complex (Glx = Glu + Gln) observed on MR spectroscopy. It is uncertain whether Gln or Glu contributes to the elevated Glx, or whether MR spectroscopy is useful for an early diagnosis. METHODS: Five Japanese patients with AESD (three boys and two girls, 1 year of age) were enrolled in this study. MR spectroscopy was acquired from the frontal white matter (repetition time (TR) of 5000 ms, echo time (TE) of 30 ms) with a 1.5- or 3.0-T scanner. MR spectroscopy was performed four times for two patients, three times for one patient, and two times for two patients. Quantification of Glu and Gln was performed using LCModel. RESULTS: Glu was elevated in three of four studies on days 1-4 and became normal or low afterward. Gln was normal in three studies on days 1-2, elevated in all seven studies on days 4-12, and became normal or low afterward. CONCLUSION: These findings suggest that MR spectroscopy may be useful for an early diagnosis. Acute Glu elevation changes to subacute Gln elevation, suggesting that a disrupted Glu-Gln cycle may play an important role.

Análisis descriptivo y estadístico del tratamiento de estados epilépticos en un hospital de referencia / Descriptive statistical analysis of the treatment of status epilepticus in a referral hospital

Introducción. Los estados epilépticos se definen como crisis recurrentes sin recuperación de la conciencia entre ellas o una sola crisis de más de 30 minutos. Objetivos. Realizar un análisis descriptivo de los datos más relevantes de pacientes con estados epilépticos ingresados en la unidad de cuidados intensivos pediátricos (UCIP) y revisar los factores de riesgo asociados a estado epiléptico de mal pronóstico. Pacientes y métodos. Se estudiaron las variables principales de los pacientes ingresados en la UCIP con estado epiléptico de un hospital terciario en un período de seis años. Resultados. Se recogieron 68 pacientes (el 55,9%, varones) con una edad media de 3,7 años. La semiología más frecuente fue en forma de crisis tonicoclónicas generalizadas (50%). La duración media de los estados epilépticos fue de 51,44 minutos. Se utilizaron 3,21 fármacos antiepilépticos de media para yugular las crisis, y la media de fármacos utilizados previamente al ingreso en la UCIP fue de 2,37. El fármaco de primera línea más utilizado fue el diacepam (83,8%) rectal (75%), seguido del diacepam (52,9%) por vía intravenosa en segundo lugar, y la fenitoína fue el fármaco más utilizado como tercera línea. La causa más frecuente de estado epiléptico fue padecer epilepsia previa (33,9%), y el síndrome de Dravet fue la etiología epiléptica más frecuente. Conclusiones. El tratamiento de los estados epilépticos es complejo y exige un manejo multidisciplinar e individualizado. Es necesaria la elaboración y revisión de protocolos y guías clínicas para un adecuado manejo de estos pacientes (AU)

Introduction. Status epilepticus is defined as either recurring seizures without regaining consciousness between them or one single seizure lasting more than 30 minutes. Aims. To perform a descriptive analysis of the most relevant data on the patients with status epilepticus who were admitted to a paediatric intensive care unit (PICU) and to review the risk factors associated to status epilepticus with a poor prognosis. Patients and methods. A study was conducted of the main variables of the patients with status epilepticus hospitalised in the PICU of a tertiary hospital over a period of six years. Results. Data were collected on a total of 68 patients (55.9% males), the mean age being 3.7 years. The most frequent signs and symptoms were generalised tonic-clonic seizures (50%). The mean duration of the status epilepticus was 51.44 minutes. The mean number of antiepileptic drugs used to stem the seizures was 3.21 and the mean number of drugs used prior to admission to the PICU was 2.37. The most commonly used first choice drug was diazepam (83.8%) administered rectally (75%), followed by intravenous diazepam (52.9%) in second place and phenytoin was the most frequently used drug as the third choice. The most usual cause of status epilepticus was having previously suffered from epilepsy (33.9%), and Dravet’s syndrome was the most frequent epileptic causation. Conclusions. Treatment of status epilepticus is complex and requires multidisciplinary and personalised management. Protocols and clinical guidelines need to be drawn up and reviewed to achieve an adequate management of these patients (AU)

A novel missense mutation in the NSDHL gene identified in a Lithuanian family by targeted next-generation sequencing causes CK syndrome.

The NSDHL gene encodes 3ß-hydroxysteroid dehydrogenase involved in one of the later steps of the cholesterol biosynthetic pathway. Mutations in this gene can cause CHILD syndrome (OMIM 308050) and CK syndrome (OMIM 300831). CHILD syndrome is an X-linked dominant, male lethal disorder caused by mutations in the NSDHL gene that result in the loss of the function of the NSDHL protein. CK syndrome is an allelic X-linked recessive disorder. So far, 13 patients with CK syndrome from two families have been reported on. We present a new five-generation family with affected males manifesting clinical features of CK syndrome. Next generation sequencing was targeted to a custom panel of 542 genes with known or putative implication on intellectual disability. Missense mutation p.Gly152Asp was identified in the NSDHL gene in the DNA sample of the affected male. Mutation carrier status was confirmed for all the obligate carriers in the family. The clinical features of the affected males in the family manifested as weak fetal movements, severe intellectual disability, seizures, spasticity, atrophy of optic discs, microcephaly, plagiocephaly, skeletal abnormalities, and minor facial anomalies, including a high nasal bridge, strabismus, and micrognathia. A highly significant preferential transmission of the mutation was observed in this and previous families segregating CK syndrome. Our report expands the clinical spectrum of this syndrome to include weak fetal movements, spasticity, and plagiocephaly, and transmission ratio distortion. The various findings in these patients increase our understanding of the diversity of the clinical presentation of cholesterol biosynthesis disorders.

Selective medial temporal volume reduction in the hippocampus of patients with idiopathic generalized tonic-clonic seizures.

BACKGROUND: Different subtypes of idiopathic generalized epilepsy may indicate different mechanisms and outcomes, suggesting that it is necessary to use a 'pure sample' of a single subtype. METHODS: A volumetric study, in conjunction with cognition assessments, was performed in a pure sample of patients with idiopathic generalized tonic-clonic seizures (IGE-GTCS; 15 males and 15 females) matched with normal control subjects (15 males and 17 females). The volumetric measurements were focused on the hippocampus and its surrounding structures, including the amygdala, the parahippocampal gyrus, the entorhinal cortex and the perirhinal cortex. The Wechsler Adult Intelligence Scale-Revised in China was administered to assess cognitive status. RESULTS: A volume reduction was found only in the hippocampus, with a more severe effect on the left side than the right side. The total number and frequency of seizures had significant negative correlations with multiple cognitive measures. Furthermore, the hippocampal volume reduction was significantly correlated with some aspects of cognitive impairment. CONCLUSION: These findings suggest that compared with the other medial temporal structures, the hippocampus may be more vulnerable to the neuropathology of IGE-GTCS. The observation that cognitive deterioration was correlated with an increased frequency and total number of seizures highlights the critical importance of preventing seizures from recurrence.

Microstructural brain abnormalities of children of idiopathic generalized epilepsy with generalized tonic-clonic seizure: a voxel-based diffusional kurtosis imaging study.

PURPOSE: To investigate the diffusion abnormalities in the brain of children with idiopathic generalized epilepsy (IGE) with generalized tonic-clonic seizure (GTCS) by using diffusion kurtosis imaging (DKI). MATERIALS AND METHODS: Twenty-one IGE children with GTCS and 16 controls were recruited. DKI was performed and maps of radial diffusivity (λ⊥ ), axial diffusivity (λ// ), mean diffusivity (MD), fractional anisotropy (FA), radial kurtosis (K⊥ ), axial kurtosis (K// ) and mean kurtosis (MK) were calculated. Voxel-based analyses were employed to compare diffusion metrics in epilepsy versus the controls. RESULTS: In the case group, MD was found significantly higher in the right temporal lobe, the right occipital lobe, hippocampus, and some subcortical regions, while FA increased in bilateral supplementary motor area and the left superior frontal lobe (false discovery rate corrected P < 0.05). Analysis of λ⊥ and λ// showed that the increased MD was mainly due to the elevated λ// . Significantly decreased MK was also detected in bilateral temporo-occipital regions, the right hippocampus, the left insula, the left post-central area, and some subcortical regions (false discovery rate corrected P < 0.05). In most regions the changed MK were due to the decreased K// . CONCLUSION: The kurtosis parameters (K⊥ , K// , and MK) reflect different microstructural information in the IGE children with GTCS, and this support the value of DKI in studying children GTCS.

Increased cerebral oxygenation precedes generalized tonic clonic seizures.

Based on previous fMRI and SPECT studies, it has been suggested seizures may be preceded by increased cerebral blood flow. Recently, we demonstrated transcutaneous regional cerebral oxygen saturation (rSO2) sensors are feasible for use in patients undergoing video EEG monitoring. We reanalyzed our data to determine if seizures were consistently marked by increased cerebral oxygenation. Patients with histories of generalized tonic clonic seizures (GTCS) were recruited into our study. All subjects were evaluated with continuous 30-channel scalp EEG and 2 rSO2 sensors placed on each side of the forehead. We calculated the mean rSO2 value for the 1h epochs in the non-ictal (2h prior to seizure onset) and pre-ictal (1h prior to onset) periods. Seven primary/secondarily GTCS from 5 patients were captured. The mean rSO2 value in the non-ictal period was 75.6 ± 5.7%. This increased to 76.0 ± 6% in the pre-ictal period (p=0.032). Four of the 7GTCS (57.1%) were marked by ≥ 3 sequential rSO2 values in the pre-ictal period that were ≥ 3 SDs greater than the mean non-ictal rSO2 value. Three GTCS (42.9%) were marked by sustained cerebral hyperemia for ≥ 15 consecutive readings. Our results suggest increased cerebral blood flow could be non-invasively used to predict seizure occurrence.

Seizures after heart transplantation--two cases of non-immunosuppressant drug interactions in young patients.

BACKGROUND: Neurological complications occur in 30-80% of patients following heart transplantation, and seizures account for 2-20% of these sequelae. The main risk factors are toxicity due to immunosuppression, infections, and brain lesions. We present 2 cases of grand mal type attacks that occurred on the 7th and 15th postoperative days. The origin of the attacks was an unusual interaction between 2 non-immunosuppressive drugs (metoclopramide and theophylline). CASE REPORT: We present 2 cases of seizure episodes during the early postoperative period in young heart transplant recipients (a 26-year-old female and a 33-year-old man). Grand mal type attacks occurred on the 7th and 15th postoperative day, respectively. Both patients were treated with standard triple immunosuppressive therapy including tacrolimus, mycophenolate mofetil, and steroids. Therapy with metoclopramide was started because the patients reported gastrointestinal disturbances. Theophylline was administered due to postoperative bradycardia. Serum theophylline levels were 33 and 34 mcg/ml, respectively. There were no neurological deficits noticed thereafter. The magnetic resonance imaging (MRI) was negative for stroke and central nervous system infection in both cases. CONCLUSIONS: We conclude that theophylline overdose combined with metoclopramide may provoke new-onset seizures, especially in young patients following heart transplantation.

Generalized epilepsy in a patient with mosaic Turner syndrome: a case report.

INTRODUCTION: Reports on cases of epilepsy in Turner syndrome are rare and most of them have cortical developmental malformations. We report the case of a Taiwanese patient with mosaic Turner syndrome with generalized tonic-clonic epilepsy and asymmetrical lateral ventricles but no apparent cortical anomaly. CASE PRESENTATION: A 49-year-old Taiwanese woman without family history presented with infrequent generalized tonic-clonic epilepsy since she was 11 years old. On examination, her short stature, webbed neck, swelling of hands and feet, retrognathic face, and mild intellectual disability were noted. She had spontaneous menarche and regular menses. Brain magnetic resonance imaging showed asymmetrical lateral ventricles and diffuse subcortical white matter T2-weighted hyperintensities. Chromosome studies disclosed low aneuploid (10%) 45,X/46,XX/47,XXX mosaic Turner syndrome. CONCLUSIONS: There is increasing evidence that epilepsy can be an uncommon presentation of Turner syndrome. Mosaic Turner syndrome with 47, XXX probably increases the risk of epilepsy but more research is needed to reach a conclusion. This case also strengthens our knowledge that Turner syndrome can be one of the pathologic bases of asymmetrical lateral ventricles. When a patient has idiopathic/cryptogenic epilepsy or asymmetrical lateral ventricles on brain images, the presence of a mild Turner phenotype warrants further chromosome studies.

Generalized tonic-clonic seizures: aberrant interhemispheric functional and anatomical connectivity.

PURPOSE: To characterize interhemispheric functional and anatomic connectivity in patients with idiopathic generalized epilepsy and generalized tonic-clonic seizures (GTCS). MATERIALS AND METHODS: This retrospective study was approved by the local institutional review board and was HIPAA compliant. All participants provided written informed consent. Resting-state functional and structural magnetic resonance images were acquired in 52 patients with GTCS and 65 healthy control subjects. The functional connectivity between bilateral homotopic voxels was calculated. Homotopic regions showing abnormal functional connectivity in patients were adopted as regions of interest for an analysis of diffusion-tensor imaging tractography. The fractional anisotropy and fiber length were compared between groups. Two-sample t test and nonparametric correlation analysis were used. RESULTS: Compared with control subjects, patients showed increased interhemispheric functional connectivity between the bilateral cuneus (P = .0008, corrected) and anterior cingulate cortex (P = .0003, corrected) and decreased functional connectivity between the bilateral olfactory cortex (P = .00005, corrected), inferior frontal gyrus (P = .00005, corrected), supramarginal gyrus (P = .0002, corrected), and temporal pole (P = .0003, corrected). Furthermore, the fiber length of the commissural fiber bundles connecting the bilateral anterior cingulate cortex (t = -2.30; P = .03, uncorrected) and the bilateral cuneus was shorter in patients than in control subjects (t = -3.19; P = .002, uncorrected). CONCLUSION: Our findings show that the bilateral anterior cingulate cortex may be critical to the pathophysiology of patients with GTCS and suggest that the corresponding commissural fiber bundle in the genu of the corpus callosum is a potential target for future surgical treatment in patients with intractable GTCS.

The protective effects of endothelin-A receptor antagonist BQ-123 in pentylenetetrazole-induced seizure in rats.

Endothelin-1 has been shown to increase neuronal activity and glutaminergic synaptic transmission by endothelin-A receptors (ETAR) in the nucleus tractus solitarius neurons that play an important role in epileptic seizures. Therefore, BQ-123 as an ETAR antagonist might attenuate neuronal excitability and glutaminergic synaptic transmission. The main purpose of the present study is to investigate the protective effect of acute BQ-123 treatment against pentylenetetrazole (PTZ)-induced tonic-clonic seizures. Wistar albino rats were divided into three groups: control, PTZ, and PTZ + BQ-123 groups. BQ-123 (3 mg/kg, intravenously) was administered for 15 min before injecting with PTZ (50 mg/kg, intraperitoneally). We determined a delay resulting from BQ-123 in "duration of the seizure onset." "Number of rats with major seizure" also decreased according to scoring with video camera in PTZ + BQ-123 group. In BQ-123-treated group, there were eight rats without a major seizure, but only one rat had a delayed major seizure. The brain tissue glutathione peroxidase activity was significantly decreased in the PTZ and PTZ + BQ-123 groups. According to the results of the control group, there was a significant increase in the protein carbonyl levels of the PTZ group and a significant increase in the nitric oxide levels of the PTZ + BQ-123 group. Histological examination showed an increase in the number of neuronal hyperchromatic nucleus especially in hippocampal gyrus dentatus region of BQ-123-treated group. We concluded that BQ-123 impeded the formation and spread of seizure to a great degree. The beneficial effects of BQ-123 were comparatively supported with biochemical parameters and histological examinations.

Alternative tacrolimus and sirolimus regimen associated with rapid resolution of posterior reversible encephalopathy syndrome after lung transplantation.

BACKGROUND: Neurotoxicity is a significant complication of calcineurin inhibitor use, and posterior reversible encephalopathy syndrome has been reported. Limited data exist on the use of alternative immunosuppression regimens in the management of posterior reversible encephalopathy syndrome in transplant recipients. METHODS: We present the immunosuppression management strategy of a girl who underwent bilateral lung transplantation for cystic fibrosis 6 months earlier, then suddenly developed a grand mal seizure due to posterior reversible encephalopathy syndrome diagnosed by magnetic resonance imaging of the brain. In an effort to reduce her tacrolimus dose, an alternative immunosuppressant regimen combining tacrolimus and sirolimus was used. RESULTS: After the modification of her immunosuppressant regimen, there was rapid clinical improvement with no further seizures. Her brain findings had resolved on magnetic resonance imaging 2 months later. Over the next 6 months, allograft function remained stable and surveillance transbronchial biopsies found no allograft rejection on the combined sirolimus and tacrolimus therapy. CONCLUSIONS: Tacrolimus-associated neurotoxicity resolved in a lung transplant recipient with a combined tacrolimus and sirolimus regimen. This combined therapy appears to be an effective alternative for lung transplant recipients that allow them to receive the benefits of both drugs but at lower doses, which reduces the risk for adverse effects.

Disruption of the blood-brain barrier after generalized tonic-clonic seizures correlates with cerebrospinal fluid MMP-9 levels.

BACKGROUND: Increasing evidence suggests seizures cause blood-brain barrier (BBB) dysfunction including decreased seizure threshold and higher onset potential of future seizures. However, the mechanisms underlying BBB damage in seizures remains poorly understood. Evidence in human and animal models shows BBB disruption is associated with activation of matrix metalloproteinase-9 (MMP-9) after cerebral ischemia and inflammation. The objective of this study was to determine whether MMP-9 concentrations in cerebral spinal fluid (CSF) are associated with BBB disruption in patients after epileptic seizures. METHODS: Thirty-one patients with generalized tonic-clonic (GTC) seizures were included in the study: 20 had recurrent GTC seizures (RS), and 11 had a single GTC seizure (SS) episode. Twenty-five adult non-seizure patients were used as controls. CSF samples were collected by lumbar puncture within 24 h after seizure cessation (range: 3-15 h, mean 6.2 h). CSF MMP-9 levels were determined by an enzyme-linked immunosorbent assay (ELISA). MMP enzyme activity was measured by gelatin zymography. The CSF/serum albumin ratio (albumin quotient, QAlb) was used as a measure of blood-brain barrier permeability. RESULTS: We found significantly higher CSF MMP-9 concentrations in seizure patients compared with controls (P < 0.001). CSF MMP-9 levels and QAlb values were higher in RS patients compared with SS and controls. Moreover, CSF MMP-9 concentration showed strong correlation between QAlb values (r = 0.76, P < 0.0001) and between CSF leukocyte counts (r = 0.77, P < 0.0001) in patients after seizures. Gelatin zymography showed MMP-9 proteolytic activity only in GTC seizure patients. CONCLUSIONS: Our results suggest MMP-9 plays a role in BBB dysfunction, characterized by invasion of leukocytes into the CSF during seizures.

Expressional analysis of inwardly rectifying Kir4.1 channels in Noda epileptic rat (NER).

The inwardly rectifying potassium channel subunit Kir4.1 is expressed in brain astrocytes and involved in spatial K(+) buffering, regulating neural activity. To explore the pathophysiological alterations of Kir4.1 channels in epileptic disorders, we analyzed interictal expressional levels of Kir4.1 in the Noda epileptic rat (NER), a hereditary animal model for generalized tonic-clonic (GTC) seizures. Western blot analysis showed that Kir4.1 expression in NERs was significantly reduced in the occipito-temporal cortical region and thalamus. However, the expression of Kir5.1, another Kir subunit mediating spatial K(+) buffering, remained unaltered in any brain regions examined. Immunohistochemical analysis revealed that Kir4.1 was primarily expressed in glial fibrillary acidic protein (GFAP)-positive astrocytes (somata) and foot processes clustered around neurons proved with anti-neuronal nuclear antigen (NeuN) antibody. In NERs, Kir4.1 expression in astrocytic processes was region-selectively diminished in the amygdaloid nuclei (i.e., medial amygdaloid nucleus and basomedial amygdaloid nucleus) while Kir4.1 expression in astrocytic somata was unchanged. Furthermore, the amygdala regions with reduced Kir4.1 expression showed a marked elevation of Fos protein expression following GTC seizures. The present results suggest that reduced activity of astrocytic Kir4.1 channels in the amygdala is involved in limbic hyperexcitability in NERs.

Developmental venous anomaly with contralateral impaired venous drainage in a 17-year-old male. A case report.

Developmental venous anomalies (DVA) drain normal neural tissue and are mostly discovered incidentally. We describe a young patient with a left hemisphere superficial to deep DVA and right hemisphere venous outflow restriction presenting with a seizure. The right hemisphere drainage variation is not typical of a DVA but represents another drainage pattern on the border of normality.

Siblings with refractory occipital epilepsy showing localized network activity on EEG-fMRI.

The benign occipital epilepsies of childhood include Panayiotopoulos and Gastaut syndromes; a third syndrome, idiopathic photosensitive occipital epilepsy may also begin in childhood or adolescence. We describe siblings with occipital epilepsy characterized by refractory, frequent, brief visual seizures and normal magnetic resonance imaging (MRI). Electroencephalography (EEG) with functional MRI (fMRI) supports localization of interictal epileptiform activity to the occipital lobes. Our hypothesis is that the siblings share a genetic focal epilepsy arising from a localized occipital network. Although they share many features of Gastaut syndrome, their refractory ongoing seizures in adolescence is unusual and likely due to underlying genetic determinants.

Dendritic, axonal, and spinal pathology of the Purkinje cells and the neurons of the dentate nucleus after long-term phenytoin administration: a case report.

Phenytoin is a commonly prescribed anticonvulsant drug; however, there is evidence that long-term administration is related to cerebellar ataxia, cerebellar atrophy, loss of Purkinje cells, and hyperplasia of Bergman glia cells. The aim of the present study was to detect and describe any possible alterations of the Purkinje cells, and neurons of the dentate nucleus, as those can be seen with the use of silver impregnation techniques, such as Golgi and Nauta method. The study was performed on a 7-year-old boy who was under phenytoin treatment for more than 3.5 years and had clinical manifestations of cerebellar ataxia. Golgi silver impregnation technique revealed substantial loss of dendritic spines and tertiary dendritic branches, both on the Purkinje cells and the neurons of the dentate nucleus, whereas the Nauta method demonstrated swollen and degenerated axons of Purkinje cells.