Progesterone and its derivatives for the treatment of catamenial epilepsy: A systematic review.

OBJECTIVE: Catamenial epilepsy (CE) is defined as an increase in seizure frequency during specific phases of the menstrual cycle in women with epilepsy. The treatment usually includes a combination of non-hormonal and hormonal therapies. This systematic review summarizes the available data on the efficacy of progesterone and its derivates to treat CE. METHODS: We performed a systematic search of the literature to identify studies reporting data on the use of progesterone and its derivatives (any type and dose) for the treatment of CE. The main outcome included the efficacy of progesterone and its derivatives on seizure frequency. RESULTS: Nineteen articles (457 patients) were included; four were randomized controlled trials (two comparing progesterone vs placebo and two comparing norethisterone vs placebo). Progesterone was generally administered during the luteal phase (from day 15 to 25) or during perimenstrual exacerbations (from day 23 to 25), with an average dose of 10-30 mg/day to a maximum of 300 mg/day. The therapy, usually well tolerated, was ineffective in the randomized controlled trials; conversely, it was associated with an overall reduction in seizure frequency in case reports and uncontrolled studies. CONCLUSIONS: Although data from uncontrolled studies suggest that hormone therapy with progesterone may be useful in the treatment of CE, its efficacy has not been demonstrated in controlled trials. The possible antiseizure effect of progesterone could be mediated by its active metabolite allopregnanolone, making the plasmatic measurement of these hormones mandatory to evaluate efficacy. Further randomized controlled trials should investigate the efficacy of progesterone and its derivatives, addressing these pharmacological issues.

New anti-seizure medication for elderly epilepsy patients - a critical narrative review.

Introduction: The number of elderly patients with epilepsy is growing in resource rich countries due to demographic changes and increased longevity. Management in these patients is challenging as underlying etiology, co-morbidities, polypharmacy, age-related pharmacokinetic and pharmacodynamic changes need to be considered.Areas covered: Lacosamide, eslicarbazepine acetate, brivaracetam, and perampanel have been approved in the USA and Europe for monotherapy and/or adjunctive treatment of seizures in the last few years. The authors review the pharmacological properties and safety profile of these drugs and provide recommendations for their use in in the elderly.Expert opinion: There are only limited data available on more recent antiseizure medications (ASMs). Drugs with a low risk of interaction (lacosamide, brivaracetam) are preferred choices. Once daily formulations (perampanel and eslicarbazepine acetate) have the advantage of increased compliance. Intravenous formulations (brivaracetam and lacosamide) are useful in emergency situations and in patients who have difficulties to swallow. Dose adjustments are necessary for all ASMs used in the elderly with slow titration and lower target doses than in the regulatory trials. The adverse event profile does not significantly differ from that found in the general adult population.

Decrease in mortality of adult epilepsy patients since 1980: lessons learned from a hospital-based cohort.

BACKGROUND AND PURPOSE: Data on mortality in patients with epilepsy have been available since the 1800s. They consistently show a 2-3-fold increase compared to the general population. Despite major advances in diagnostic tools and treatment options, there is no evidence for a decrease in premature deaths. The temporal trend of mortality in a hospital-based epilepsy cohort over three decades was assessed. METHODS: A hospital-based incidence cohort was recruited from a specialized epilepsy outpatient clinic at Innsbruck Medical University between 1980 and 2007, divided by decade into three cohorts and followed for 5 years after initial epilepsy diagnosis. Deaths and their primary causes were determined using probabilistic record linkage with the Austrian death registry. Age-, sex- and period-adjusted standardized mortality rates (SMRs) were computed in relation to the general population of the same area and grouped according to time of diagnosis. RESULTS: In all, 122 deaths in 4549.9 person-years (1954.5 women, 2595.2 men) were identified. The overall SMR was 2.2 [95% confidence interval (CI) 1.8-2.6] and decreased from 3.0 (95% CI 2.1-4.3) in 1980-1989, to 2.7 (95% CI 2.0-3.5) in 1990-1999 and to 1.4 (95% CI 1.0-2.0) in 2000-2007. CONCLUSIONS: This study indicates a decrease in mortality in newly diagnosed epilepsy patients over the last three decades. This may be due to advances in diagnosis and treatment over the past three decades, including early identification of drug resistance, introduction of new anti-epileptic drugs and establishment of a comprehensive epilepsy surgery programme in this region.

rTMS of the prefrontal cortex has analgesic effects on neuropathic pain in subjects with spinal cord injury.

STUDY DESIGN: Repetitive transcranial magnetic stimulation study. OBJECTIVES: The analgesic effects of repetitive transcranial magnetic stimulation (rTMS) in chronic pain have been the focus of several studies. In particular, rTMS of the premotor cortex/dorsolateral prefrontal cortex (PMC/DLPFC) changes pain perception in healthy subjects and has analgesic effects in acute postoperative pain, as well as in fibromyalgia patients. However, its effect on neuropathic pain in patients with traumatic spinal cord injury (SCI) has not been assessed. SETTING: Merano (Italy) and Salzburg (Austria). METHODS: In this study, we performed PMC/DLPFC rTMS in subjects with SCI and neuropathic pain. Twelve subjects with chronic cervical or thoracic SCI were randomized to receive 1250 pulses at 10 Hz rTMS (n=6) or sham rTMS (n=6) treatment for 10 sessions over 2 weeks. The visual analog scale, the sensory and affective pain rating indices of the McGill Pain Questionnaire (MPQ), the Hamilton Depression Rating Scale and the Hamilton Anxiety Rating Scale were used to assed pain and mood at baseline (T0), 1 day after the first week of treatment (T1), 1 day (T2), 1 week (T3) and 1 month (T4) after the last intervention. RESULTS: Subjects who received active rTMS had a statistically significant reduction in pain symptoms in comparison with their baseline pain, whereas sham rTMS participants had a non-significant change in daily pain from their baseline pain. CONCLUSION: The findings of this preliminary study in a small patient sample suggest that rTMS of the PMC/DLPFC may be effective in relieving neuropathic pain in SCI patients.

Perampanel in patients with refractory and super-refractory status epilepticus in a neurological intensive care unit.

INTRODUCTION: In refractory status epilepticus (SE), because of subcellular maladaptive changes, GABAergic drugs are no longer effective, and the excitatory neurotransmitter glutamate (Glu) plays a major role in seizure perpetuation. Perampanel (PER, licensed since 09/2012) is the first orally active noncompetitive AMPA receptor antagonist for adjunctive treatment of refractory focal epilepsy. METHODS: We analyzed treatment response, seizure outcome, and adverse effects of add-on treatment with perampanel in patients with refractory status epilepticus in the Neurological Intensive Care Unit (NICU), Salzburg, Austria between 09/2012 and 11/2014 by retrospective chart review. RESULTS: Twelve patients (75% women) with refractory status epilepticus were treated with PER administered per nasogastric tube between 09/2012 and 11/2014. Median age was 75 years [range: 60-91]. The most frequent SE type was nonconvulsive SE (NCSE) with (5/12, 42%) and without coma (6/12, 50%). In seven patients (58%), SE arose de novo, with an acute symptomatic cause in five patients (42%). Cerebrovascular diseases (4/12, 33%) and cerebral tumors (4/12, 33%) were the most common etiologies. Perampanel was given after a median number of four antiepileptic drugs [range: 2-7] and a median time of 1.5 days [range: 0.8-18.3]. In one patient (8%), clinical improvement was observed within 24h and EEG improvement within 60 h after administration of PER, while in another patient (8%), clinical and EEG improvement was observed more than 48 h after administration. Median initial dose was 4 mg [range: 2-12; SD: 4.11], titrated up to a median of 12 mg [range: 4-12] in steps of 2 to 4 mg per day. No adverse effects were reported regarding cardiorespiratory changes or laboratory parameters. Outcomes after SE were moderate disability in five patients (42%), death in three patients (25%), and persistent vegetative state in two patients (17%). CONCLUSION: Though glutamate plays a major role in seizure perpetuation, the noncompetitive AMPA receptor antagonist PER could only ameliorate seizure activity in a few patients with refractory SE. The long duration of SE before the administration of PER via nasogastric tube, as well as relatively low doses of PER, might be responsible for the modest result. Perampanel was well tolerated, and no adverse events were reported. This article is part of a Special Issue entitled Status Epilepticus.

Limbic encephalitis due to GABAB and AMPA receptor antibodies: a case series.

BACKGROUND: Two novel antibodies (abs) directed to γ-aminobutyric acid B receptor (GABA(B)R) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) in patients with limbic encephalitis (LE) were first described by the Philadelphia/Barcelona groups and confirmed by the Mayo group. We present a novel series for further clinical and paraclinical refinement. METHODS: Serum and cerebrospinal fluid samples from a diagnostic laboratory were selected if found to be positive for GABA(B)R or AMPAR abs within a broad antineuronal ab panel. Data were retrospectively compiled. RESULTS: In 10 patients, we detected abs to GABA(B)R. Median age was 70 years. Five of them were diagnosed with small cell lung cancer (SCLC). Intrathecal GABA(B)R ab synthesis was found in all six patients with sufficient data available (median ab-index: 76.8). On MRI, we found bilateral mediotemporal and in two cases cortical abnormalities. EEG revealed encephalopathy, partly with epileptiform discharges. Five patients received immunotherapy, two patients tumour treatment and three both therapies. Three patients died, in five patients cognitive functions declined, one patient improved slightly and one patient fully recovered. AMPAR abs were detected in three patients with mnestic disturbances. Median age was 60.7 years. The only female patient was diagnosed with ovarian cancer. None of the patients had intrathecal ab synthesis. MRI findings showed bilateral mediotemporal abnormalities. EEG was normal in all patients. Two of the three immunologically treated patients improved, one patient stabilised on a low level. DISCUSSION: GABA(B)R and AMPAR abs are well associated with LE. GABA(B)R abs lead to severe clinical, neuroradiological and EEG abnormalities with poorer outcome.

[Quality guidelines for presurgical epilepsy diagnosis and operative epilepsy therapy: 1st revised version]. / Qualitätsleitlinien für prächirurgische Epilepsiediagnostik und operative Epilepsietherapie : 1. Neufassung.

In patients with pharmacorefractory epilepsy, preoperative epilepsy evaluation and subsequent epilepsy surgery lead to a significant improvement of seizure control, proportion of seizure-free patients, quality of life and social participation. The aims of preoperative epilepsy evaluation are to define the chance of complete seizure freedom and the likelihood of inducing new neurological deficits in a given patient. As epilepsy surgery is an elective procedure quality standards are particularly high. As detailed in the first edition of these practice guidelines, quality control relates to seven different domains: (1) establishing centres with a sufficient number of sufficiently and specifically trained personnel, (2) minimum technical standards and equipment, (3) continuing medical education of employees, (4) surveillance by trained personnel during the video electroencephalography (EEG) monitoring (VEM), (5) systematic acquisition of clinical and outcome data, (6) the minimum number of preoperative evaluations and epilepsy surgery procedures and (7) cooperation of epilepsy centres. In the first edition of these practice guidelines published in 2000 it was defined which standards were desirable and that their implementation should be aimed for. These standards related especially to the certification required for different groups of medical doctors involved and to the minimum numbers of procedures required. In the subsequent decade quite a number of colleagues have been certified by the trinational Working Group (Arbeitsgemeinschaft, AG) for Presurgical Epilepsy Diagnosis and Operative Epilepsy Treatment (http://www.ag-epilepsiechirurgie.de) and therefore, on 8 May 2013 the executive board of the AG decided to now make these standards obligatory.

Comparison of endovascular treatment versus conservative medical treatment in patients with acute basilar artery occlusion.

INTRODUCTION: Basilar artery occlusion (BAO) causes mortality up to 90%. METHODS: A total of 99 patients with BAO received either endovascular (endovascular mechanical recanalization and/or intra-arterial with optional intravenous thrombolysis [IVT] as bridging concept) or conservative medical treatment (IVT and/or medical oral therapy). Outcome parameters were measured in accordance with the thrombolysis in cerebral infarction (TICI), National Institutes of Health Stroke Scale (NIHSS), and modified Rankin Scale (mRS) scores. RESULTS: In all, 78% underwent endovascular and 22% conservative medical treatment. The NIHSS at admission was 20 in both the groups. Postprocedurally, 36% (95% confidence interval: 26%-48%) of the endovascular group and 9% (21%-64%) of the conservative group reached TICI 3 (P = .017). In all, 30% of the endovascular group and 9% of the conservative group were documented with TICI 2b (P = .057). At 90 days follow-up, 45% (31%-60%) of the endovascular-treated patientsand no patient (0%-25%) of the conservative-treated group reached mRS ≤2 (P = .012). CONCLUSION: Endovascular treatment of BAO provides a better chance to survive this severe condition with good clinical outcome.

Glatiramer acetate attenuates the pro-migratory profile of adhesion molecules on various immune cell subsets in multiple sclerosis.

An altered expression pattern of adhesion molecules (AM) on the surface of immune cells is a premise for their extravasation into the central nervous system (CNS) and the formation of acute brain lesions in multiple sclerosis (MS). We evaluated the impact of glatiramer acetate (GA) on cell-bound and soluble AM in the peripheral blood of patients with relapsing-remitting MS (RRMS). Fifteen patients treated de novo with GA were studied on four occasions over a period of 12 months. Surface levels of intracellular cell adhesion molecule (ICAM)-1, ICAM-3, lymphocyte function-associated antigen (LFA)-1 and very late activation antigen (VLA)-4 were assessed in T cells (CD3(+) CD8(+) , CD3(+) CD4(+) ), B cells, natural killer (NK) cells, natural killer T cells (NK T) and monocytes by five-colour flow cytometry. Soluble E-selectin, ICAM-1, ICAM-3, platelet endothelial cell adhesion molecule (PECAM)-1, P-selectin and vascular cell adhesion molecule (VCAM)-1 were determined with a fluorescent bead-based immunoassay. The pro-migratory pattern in RRMS was verified by comparison with healthy controls and was characterized by up-regulation of LFA-1 (CD3(+) CD4(+) T cells, B cells), VLA-4 (CD3(+) CD8(+) T cells, NK cells), ICAM-1 (B cells) and ICAM-3 (NK cells). Effects of GA treatment were most pronounced after 6 months and included attenuated levels of LFA-1 (CD3(+) CD4(+) ) and VLA-4 (CD3(+) CD4(+) , CD3(+) CD8(+) , NK, NK T, monocytes). Further effects included lowering of ICAM-1 and ICAM-3 levels in almost all immune cell subsets. Soluble AM levels in RRMS did not differ from healthy controls and remained unaltered after GA treatment. The deregulated pro-migratory expression profile of cell-bound AM is altered by GA treatment. While this alteration may contribute to the beneficial action of the drug, the protracted development and unselective changes indicate more secondary immune regulatory phenomena related to these effects.

Clinical characteristics, risk factors and pre-surgical evaluation of post-infectious epilepsy.

BACKGROUND AND PURPOSE: Epilepsy is a frequent complication of central nervous system (CNS) infections. Post-infectious epilepsy is commonly refractory to medical treatment and plays a pivotal role for the poor long-term outcome of CNS infections. OBJECTIVES: To provide an overview of clinical characteristics and risk factors of seizures associated with CNS infections. In addition, to summarize the state of the art of anticonvulsive treatment and the pre-surgical evaluation process in refractory cases. METHODS: A comprehensive literature search for articles published between January 1970 and December 2011 was carried out. RESULTS: The occurrence of seizures during the acute course of meningitis, encephalitis and brain abscess is the main risk factor for the development of post-infectious epilepsy. There is a shortage of trials evaluating the efficacy of prophylactic and symptomatic treatment during the course of acute infection. Moreover, there are no randomized-controlled trials studying anticonvulsive drugs and their combinations for the management of post-infectious epilepsy. In a selected group of patients, however, medically refractory focal epilepsy is potentially curable by surgery. CONCLUSIONS: Further studies are required to improve the pathogenetic understanding of post-infectious epilepsy in order to develop preventive measures as well as to evaluate additional medical and surgical treatment strategies for the patients currently not considered for surgery.

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.

Isolated leptomeningeal infiltration of a primary CNS B-cell lymphoma diagnosed by flow cytometry and confirmed by necropsy.

BACKGROUND: The diagnosis of the isolated leptomeningeal involvement of a primary central nervous system B-cell lymphoma without parenchyma lesions may be difficult. Patients with leptomeningeal meningeosis lymphomatosa can present with various neurologic deficits. AIMS OF THE STUDY: To demonstrate the impact of cerebrospinal fluid (CSF) flow cytometry in the diagnosis of an isolated leptomeningeal manifestation of B-cell lymphoma by presenting an interesting case report. METHODS: Flow cytometric analysis of B-cell monoclonality of the CSF was performed as complementary diagnostic procedure in addition to CSF cytology. Final diagnosis was confirmed by necropsy. RESULTS: We suspected isolated leptomeningeal manifestation of B-cell lymphoma with palsy of the VI and VII cranial nerves in a 79-year-old male, because of mononuclear pleocytosis in CSF. Interestingly, the decisive diagnostic hint was given by implementation of flow cytometry of the CSF. Diagnosis was confirmed by postmortem autopsy. CONCLUSION: Our case shows that flow cytometry of the CSF in addition to conventional CSF cytology has the potential to accelerate diagnosis of lymphomeningeal infiltration of B-cell lymphoma.

Cerebral localized marginal zone lymphoma presenting as hypothalamic-pituitary region disorder.

INTRODUCTION: Marginal zone B-cell lymphoma is a rare disease which can be considerably difficult to recognize and diagnose when signs of systemic involvement are absent. CASE PRESENTATION: We report the case of a 57-year-old woman with initial olfactory disturbance, followed by psychosis, diabetes insipidus and hypothalamic eating disorder as an uncommon clinical presentation of marginal zone B-cell lymphoma. CONCLUSION: Marginal zone B-cell lymphoma should be considered as a potential differential diagnosis in patients with hypothalamic disturbances.

Association between structural abnormalities and fMRI response in the amygdala in patients with temporal lobe epilepsy.

OBJECTIVE: The goal of this study was to investigate whether dysplastic amygdalae show an impaired response as revealed by functional MRI (fMRI). METHODS: A fearful face fMRI paradigm using video sequences, as we have recently applied, was used in 25 patients with temporal lobe epilepsy (TLE): 24 had mesial TLE (14 right-, nine left-sided, one bilateral); one left lateral neocortical TLE. T1-, T2-weighted and fluid attenuated inversion recovery (FLAIR) MRI sequences were assessed for the detection and categorisation of structural amygdalar abnormalities according to size and MR signal intensity. Of the 25 patients, five patients had probable dysplastic amygdala (pDA): two right- and three left-sided. RESULTS: A fearful face paradigm led to significant amygdalar activation in all but one patient (p<0.05). In 15 (60%) of the patients amygdalar activation was found contralateral and in four (16%) ipsilateral to the side of seizure onset. Bilateral amygdalar activation was registered in five (20%) patients. In two patients with right-sided and one with left-sided pDA, fMRI activation was observed only in the contralateral amygdala. In two out of three patients with left-sided pDA we found significant ipsilateral amygdalar fMRI-responses. CONCLUSION: Unilateral pDA does not necessarily affect the amygdalar fMRI BOLD-response.

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.

Flexibility of head positioning and head fixation provided by a novel system for non-invasive maxillary fixation and frameless stereotaxy: technical note.

OBJECTIVE: The aim of this study was to demonstrate the flexibility in patient positioning and head fixation provided by a newly developed, minimally invasive upper jaw fixation device in combination with standard navigation software. TECHNIQUE: The Vogele-Bale-Hohner (VBH) headholder and the Stereotactic Intervention and Planning Laboratory (SIP-Lab) Innsbruck reference frame, were applied in epilepsy surgery requiring stereotactic guidance. The system can be adapted to various positioning and instrument guidance requirements. Instrument holders can be fixed either to a base plate or directly to the mouthpiece. When used together with a head clamp and a stabilizing arm, there are no restrictions on patient positioning. When used with the non-invasive headholder, only the supine position is well-suited for use with the described guidance instrumentation. The system can also be used with the head placed on the horseshoe headholder without altering navigation support. CONCLUSION: The VBH mouthpiece combined with an external registration frame is a flexible tool that permits patient positioning and neuronavigation with the head either fixed with a head clamp, or restrained non-invasively with a headholder, or not fixed at all. This might be advantageous within the context of epilepsy surgery.

Tuberous sclerosis complex with unilateral perisylvian polymicrogyria and contralateral hippocampal sclerosis - a case report.

Malformations of cortical development (MCD) encompass a wide spectrum of brain disorders. Although rare, the combination of certain MCD may occur. We report a rare case of combination of three distinct cerebral pathologies: tuberous sclerosis, polymicrogyria and hippocampal sclerosis in a patient with intractable epilepsy. Ictal EEG and ictal SPECT suggested right perisylvian area as a seizure onset zone. However, on MRI multiple potentially epileptogenic lesions were identified. The neurobiological background of the coexistence of different types of malformations of cortical development remains enigmatic.