The novel insulin resistance parameters RBP4 and GLP-1 in patients treated with valproic acid: just a sidestep?

Valproic acid (VPA), as one of the most widely prescribed antiepileptic drugs (AED) for many types of epilepsy in adults and children, is associated with weight gain, alteration of adipocytokine homeostasis, insulin resistance and Non-Alcoholic Fatty Liver Disease (NAFLD). Retinol-binding protein 4 (RBP4) and Glucagon-like peptide-1 (GLP-1) are considered as important new targets in modern type 2 diabetes mellitus therapy linked to insulin resistance, NAFLD and visceral obesity acting via peripheral or central mechanisms. We herein demonstrate the lack of an influence of VPA treatment on RBP4 and GLP-1 in otherwise healthy patients. In summary, the absence of any relationship with RBP4 and GLP-1 concentrations does not suggest a role of these novel insulin resistance parameters as potential regulators of glucose and fat metabolism during VPA-therapy.

Cerebral vasospasm following temporal lobe epilepsy surgery.

OBJECTIVE: Selective amygdalohippocampectomy (AHE) has been associated with postoperative cerebral vasospasm (CVS) in patients with medically intractable temporal lobe epilepsy. The incidence in temporal lobe resection (TLR) is unknown. This retrospective cohort study evaluates the incidence of and risk factors for the development of CVS in patients with TLR and AHE. METHODS: A total of 119 patients were included between 1998 and 2009. All patients were evaluated by standardized preoperative and postoperative transcranial Doppler sonography (TCD) evaluations and neurologic examinations. Postoperative CT scans were evaluated by an independent radiologist and the volume of bleeding within the resection cavity was quantified. RESULTS: Of 107 patients with longitudinal TCD data, 35 (32.7%) developed postoperative CVS. The incidence of CVS did not differ between patients with TLR and AHE. CVS was associated with female gender and a higher bleeding volume in the postoperative CT scan (p = 0.035 and 0.046). Patients with CVS showed a significantly higher incidence of postoperative neurologic signs and symptoms (48.6%) compared to patients without CVS (25%, p = 0.015). The mean length of stay was significantly prolonged in patients with diffuse CVS compared to patients with localized CVS or no CVS (28.8 ± 10.9, 24.2 ± 6.6, and 18.2 ± 6.1 days, p < 0.001). CONCLUSION: CVS is a frequent complication of surgery for temporal lobe epilepsy irrespective of the resection method. Important risk factors for the development of postoperative CVS are female gender and a higher amount of bleeding in the postoperative CT. Patients with CVS more frequently have neurologic signs and symptoms resulting in prolonged hospital stay.

Hippocampal abnormalities in malformations of cortical development: MRI study.

OBJECTIVES: Hippocampal abnormalities may coexist with malformations of cortical development (MCD). This cross-sectional MRI study aimed at categorizing hippocampal abnormalities in a large group of MCD and comparing MCD patients with (group W) and without (group W/O) hippocampal abnormalities. METHODS: Hippocampal anatomy, rotation, size, internal structure, and MRI signal alterations were assessed visually by 3 independent raters in patients with MCD and epilepsy. Four types of hippocampal abnormalities were examined in 220 patients (116 women, mean age 31 +/- 16.6, range 2-76 years): partially infolded/hypoplastic hippocampus (HH), hippocampal sclerosis (HS), malrotated hippocampus (MH), and enlarged hippocampus (EH). The commonest MCD in the cohort were focal cortical dysplasia (27%), polymicrogyria (PMG) (21%), developmental tumors (15%), and periventricular nodular heterotopia (PNH) (14%). RESULTS: Hippocampal abnormalities were seen in 69/220 (31%) patients: HH in 34/69 (49%); HS in 18/69 (26%); MH in 15/69 (22%); and EH in 2/69 (3%). PNH (21/30 [70%]) and PMG (22/47 [47%]) were most commonly associated with hippocampal abnormalities. Compared to the W/O group, patients in the W group had a higher rate of learning disability (W 41/69 [59%] vs W/O 56/151 [37%]; p = 0.003) and delayed developmental milestones (W 36/69 [52%] vs W/O 53/151 [35%]; p = 0.025); groups did not differ otherwise with regard to clinical presentation. HH was associated with symptomatic generalized epilepsies (11/34 [32%]) and high rate of learning disability (27/34 [79%]), neurologic deficits (25/34 [73%]), and delayed developmental milestones (23/34 [68%]). CONCLUSIONS: About a third of patients with malformations of cortical development had hippocampal abnormalities. Patients with hypoplastic hippocampus had the most severe clinical phenotype.

Integration of multimodality imaging and surgical navigation in the management of patients with refractory epilepsy. A pilot study using a new minimally invasive reference and head-fixation system.

OBJECTIVE: To review the experience with a new system (VBH system) for minimally invasive frameless stereotactic guidance, acting as a common platform to provide multimodal image integration and surgical navigation in a consecutive series of 25 patients who underwent surgery for drug-resistant seizures. METHODS: The usefulness of the VBH system for integrating all images to produce one dataset and for intraoperative instrument guidance and navigation was judged semiquantitatively in a three-tiered scale (+, ++, +++). Seizure outcome was classified according to Engel. RESULTS: The presurgical evaluation extended over 21.2 months (mean). A total of 141 registrations of images were performed (mean 5.6 per patient, range: 2 to 16). In 19 (76%) of 25 patients structural data fused with functional data were used for the presurgical workup. Six patients proceeded directly to navigated resection. Nineteen patients (76%) underwent invasive recording, of whom 13 underwent resective surgery. In seven patients (28%) the combination of multimodal image fusion and intra-operative stereotactic guidance was judged "essential" (+++) to remove the epileptogenic zone. Integration of all images to form one dataset was "essential" (+++) for decision making in 15 and "helpful" (++) in 4 patients (overall 76% of patients). Intraoperative use of frameless neuronavigation was "essential" (+++) in ten and "helpful" (++) in all remaining patients. Eighty percent of the patients achieved satisfactory seizure outcome after 1 year. CONCLUSION: The VBH system is a safe and effective non-invasive tool for repetitive imaging, multimodal image fusion and frameless stereotactic surgical navigation in candidates for epilepsy surgery.

Non-alcoholic fatty liver disease (NAFLD), insulin resistance and lipid profile in antiepileptic drug treatment.

PURPOSE: Patients undergoing long-term treatment with valproic acid (VPA) are prone to develop different features of the metabolic syndrome (MS). The aim of the present study was to evaluate the occurrence of non-alcoholic fatty liver disease (NAFLD), insulin resistance (IR) and a pro-atherogenic lipid profile in patients undergoing VPA, carbamazepine (CBZ) and lamotrigine (LTG) monotherapy compared to healthy controls. METHODS: Abdominal ultrasound as well as measurement of serum fasting insulin and glucose, serum lipids and liver function parameters were performed in VPA (n=23), CBZ (n=22) and LTG (n=23) treated non-diabetic and non-obese epileptic patients compared to healthy controls (n=16). RESULTS: Ultrasound measurement demonstrated characteristics of fatty liver disease in 60.9% of VPA, in 22.7% of CBZ, in 8.7% of LTG treated patients and in 12.5% of the healthy controls, with highest level of steatosis seen in VPA treated patients. In addition, patients on VPA monotherapy showed a higher body-mass index (BMI) when compared to LTG treated patients and controls (p

Electroclinical and imaging findings in ulegyria and epilepsy: a study on 25 patients.

PURPOSE: Ulegyria refers to cerebral cortex scarring, which results from a perinatal ischaemic brain injury. It presents with a characteristic gyral pattern: small circumvolutions with atrophy at sulci bottom and spared apex. Ulegyria is frequently associated with epilepsy, cerebral palsy and mental disability. We analysed electroclinical and MRI features in patients with ulegyria and epilepsy. PATIENTS AND METHODS: We reviewed 25 patients (14 males/11 females) with ulegyria and epilepsy from the database (about 5000 patients with epilepsy) of our unit. Patients were examined clinically, underwent high resolution MRI, EEG recordings, positron emission tomography, single photon emission computed tomography and neuropsychological testing. Two patients with refractory seizures underwent epilepsy surgery. RESULTS: Mean age of patients was 34 years (5-66) at the reassessment time. The majority (16/25, 64%) had a history of perinatal asphyxia. 15 patients had delayed developmental milestones; 20 had learning disabilities and five patients were severely disabled. Mean age at seizure onset was 4.2 years (1-18). 17 patients (68%) had medically intractable epilepsy. 11 patients (44%) had occipital lobe seizures. The majority (n = 24, 96%) had parieto-occipital lesions on MRI. In 13 patients (52%), ulegyria was bilateral. 12 patients (48%) had hippocampal sclerosis. Two patients underwent epilepsy surgery with an excellent postoperative outcome (Engel class IA and IC). CONCLUSION: Patients with ulegyria often have a history of perinatal asphyxia and present with pharmacoresistant seizures. Their presurgical assessment is complicated because of frequent dual pathology (hippocampal sclerosis) and bilateral lesions.

Outcome of adult patients with temporal lobe tumours and medically refractory focal epilepsy.

BACKGROUND: Tumours are a well-recognized cause of medically intractable epilepsies. Tumours represent the primary pathology in 10%-30% of patients undergoing surgical treatment for chronic epilepsy. This study examines the surgical and epileptological outcome of adults with temporal lobe tumoural epilepsy treated within a comprehensive epilepsy surgery programme. METHODS: Between 1999 and 2004, 99 consecutive patients have been operated for intractable temporal lobe epilepsy (TLE). Among these, 14 adult patients exhibited temporal lobe neoplasms associated with TLE. Every patient underwent a comprehensive presurgical evaluation including video-EEG monitoring, MRI, interictal PET scan, ictal SPECT and neuropsychological testing. Surgical strategies were determined in an interdisciplinary seizure conference and tailored to the findings of the presurgical evaluation. All patients were available for follow up at regular intervals after 3, 6, 12 months and yearly thereafter. Epileptological outcome was classified according to Engel [10] and the ILAE (International League Against Epilepsy)/systems [33]. FINDINGS: The surgical procedures performed were temporal lobe resection in 3 patients, extended lesionectomy in 4 and extended lesionectomy with resection of the temporomesial structures in 7. One patient with an astrocytoma grade III underwent a second and third operation for recurrent disease. Histological results: Astrocytoma 5 patients, ganglioglioma/gangliocytoma 5, oligodendroglioma 2, ependymoma 1 and dysembryoplastic neuroepithelial tumour (DNET) 1. Postoperative follow-up was performed after 12-74 months (mean 31). The outcome according to the Engel classification indicated class IA in 9 patients, class IC in 3, and 1 each in classes IIIA and IVA. Epileptological outcome according to the ILAE classification indicated class 1 (12 patients) and class 4 (2 patients). Surgical mortality was zero and mild permanent neurological deficits due to surgery were seen in 2 patients. Postoperatively 3 patients showed a homonymous quadrantanopia. CONCLUSIONS: Patients with drug resistant epilepsy and temporal lobe tumours should undergo evaluation in dedicated epilepsy surgery programmes.

Unilateral polymicrogyria with ipsilateral cerebral hemiatrophy: a distinct syndrome?

INTRODUCTION: There are sporadic reports of unilateral polymicrogyria with ipsilateral hemiatrophic cerebri associated with epilepsy, focal neurological deficit and mental retardation. The mechanisms which cause this condition are not well understood. The aim of our study was to delineate further, clinical and neuroimaging features of this malformation of cortical development and to explore its possible etiological background. PATIENTS AND METHODS: Four patients (two males and two females), aged from 23 to 31 years (mean age range 27.5 years) were evaluated. Subjects underwent clinical, electrophysiological, neuropsychological and high resolution magnetic resonance imaging assessment. RESULTS: No significant perinatal event or exposure to intrauterine infection was noted. None suffered from birth asphyxia or ischemic injury. The parents of two patients were first cousins. Every subject had delayed developmental milestones, mental disability and congenital, non-progressive, spastic hemiparesis. They had epilepsy with seizure-onset ranging from three months to 17 years (mean 6.8 years); two had intractable seizures. In all patients, unilateral, right-sided polymicrogyria was associated with ipsilateral cerebral hemiatrophy. Polymicrogyria involved mainly anterior perisylvian areas; occipital regions were relatively spared. CONCLUSION: The evaluated patients showed homogenous clinical and neuroimaging characteristics. We support the idea that the disorder could constitute a clinical entity with an underlying genetic cause.

Transient and permanent magnetic resonance imaging abnormalities after complex partial status epilepticus.

Epileptic seizures, especially status epilepticus can produce MRI changes. In contrast to convulsive status epilepticus (CSE), permanent parenchymal loss is not well documented with nonconvulsive status epilepticus (NCSE) and the observed MRI changes are transient. We describe a patient with non-lesional right-sided temporal lobe epilepsy with complex partial seizures and repeated episodes of untreated complex partial status epilepticus (CPSE). Diffusion-weighted MRI exhibited marked and extended signal changes within the right temporal, frontal, insular and cingulate regions. The affected areas are considered propagation pathways of temporal lobe epilepsies. After admission, the patient was treated with i.v. antiepileptic drugs. Behavioral, EEG and MRI signal changes resolved. An atrophy of the right temporal lobe not seen in the pre-status MRI examinations was observed 6 weeks after the resolution of MRI hyperintensities. Prior episodes of CPSE had been correctly treated and remained without permanent brain damage. This case report is in favour of immediate and aggressive treatment of partial NCSE in order to avoid irreversible parenchymal loss.

Gyratory seizures revisited: a video-EEG study.

PURPOSE: Gyratory seizures (GSs) have been rarely described in generalized as well as in focal epilepsies. They were defined as a rotation around the body axis during a seizure for at least 180 degrees. The mechanisms of generation are unknown and have been discussed controversially. The aim of this investigation was to further delineate seizure semiology and assess a possible lateralizing and localizing value of GSs. METHODS: The authors screened 277 consecutive patients with intractable epilepsies referred to a University Hospital for presurgical evaluation between 1998 and 2004 for GSs: 169 had temporal lobe epilepsy (TLE), 47 frontal lobe epilepsy (FLE), 38 generalized epilepsies (GE), and 23 had extratemporal or multifocal epilepsy. RESULTS: Twelve patients showed gyratory movements in 17 seizures. Eight had FLE and four TLE (p < 0.001). In 58% (7/12), the gyratory movement was initiated by a forced versive movement of the head followed by a rotation toward the contralateral side of seizure onset. In 42% (5/12), the gyratory movement was not preceded by a forced head version. In these seizures, the direction of the rotation was toward the side of seizure onset. CONCLUSIONS: The direction of rotation lateralizes seizure onset zone in focal epilepsy depending on the seizure evolution: 1) gyratory seizures (GSs) starting with a forced version of the head ensuing into a body rotation lateralize seizure onset zone contralateral to the direction of rotation. 2) In GSs without a preceding gyratory forced head version, the direction of rotation is toward the side of seizure onset. GSs occur more frequently in frontal lobe epilepsy than temporal lobe epilepsy, while none of our patients with GSs had generalized epilepsies.

Peri-ictal water drinking lateralizes seizure onset to the nondominant temporal lobe.

The authors describe seven patients with medically refractory temporal lobe epilepsy whose seizures were associated with peri-ictal water drinking behavior. Presurgical evaluation, including video-EEG monitoring, MRI, SPECT, and neuropsychological testing, revealed a seizure onset in the nondominant temporal lobe. All patients had an excellent outcome after epilepsy surgery. Peri-ictal water drinking may represent a lateralizing sign indicating seizure onset in the nondominant temporal lobe.

Asymmetric termination of secondarily generalized tonic-clonic seizures in temporal lobe epilepsy.

In patients with secondarily generalized tonic-clonic seizures (sGTCS) an asymmetric termination of the clonic phase can be observed. The authors systematically analyzed this phenomenon in patients with temporal lobe epilepsy (TLE). Thirty-nine sGTCS from 29 patients with TLE who underwent successful epilepsy surgery were analyzed, in addition to a prospectively collected group of 28 patients with TLE who had 35 sGTCS. The clonic phase of sGTCS did not end synchronously in 65.7% of all patients and in 59.4% of all seizures. In 79.3% to 80% this was ipsilateral to the hemisphere of seizure onset, and there was excellent interobserver agreement.

Reaction kinetics in biofilms.

A novel in situ microtechnique allows evaluating parameters of diffusion-controlled reactions in biofilms. A microprobe, 15 mum in diameter, was used to simultaneously measure the dissolved oxygen concentration and the optical density at different depths in a submerged biofilm. Based on the results, the biofilm diffusion coefficient for dissolved oxygen, D(f) the dissolved oxygen flux through the biofilm surface, J(02), and the half velocity coefficient, K(s), have been calculated.