Societal costs and quality of life analysis in patients undergoing resective epilepsy surgery: A one-year follow-up.

Although effectiveness of Resective Epilepsy Surgery (RES) for patients with drug-resistant epilepsy (DRE) is widely proven, research on the impact of societal costs (SC) is lacking. The aim of this study is to provide both clinical and economic outcomes of RES by offering an overview of treatment effectiveness as well as SC of RES in a cohort of 30 Dutch DRE patients. This project serves as a pilot project to offer an up-to-date model for larger cost-effectiveness studies. Medical consumption, productivity losses, disease-specific and generic health-related quality of life (QoL), and seizure frequency were assessed before and 3-, 6-, and 12-months post-surgery with validated questionnaires. Linear mixed models, ANOVAs, and logistic regressions were performed. SC for the first year after RES entailed €54,376 and decreased over time. Moreover, 50% of patients experienced a clinically important increase in disease-specific QoL and 53% of patients in generic health-related QoL. Lastly, 73% of patients reached seizure freedom 12 months postoperative. Seizure reduction was correlated with increase in disease-specific QoL. Within one year after surgery, RES leads to reduction in SC and improvements in QoL over time. Future research should encompass longer follow-up periods, larger sample size, and a cost-effectiveness analysis with a comparator.

Value of ultra-high field MRI in patients with suspected focal epilepsy and negative 3 T MRI (EpiUltraStudy): protocol for a prospective, longitudinal therapeutic study.

PURPOSE: Resective epilepsy surgery is a well-established, evidence-based treatment option in patients with drug-resistant focal epilepsy. A major predictive factor of good surgical outcome is visualization and delineation of a potential epileptogenic lesion by MRI. However, frequently, these lesions are subtle and may escape detection by conventional MRI (≤ 3 T). METHODS: We present the EpiUltraStudy protocol to address the hypothesis that application of ultra-high field (UHF) MRI increases the rate of detection of structural lesions and functional brain aberrances in patients with drug-resistant focal epilepsy who are candidates for resective epilepsy surgery. Additionally, therapeutic gain will be addressed, testing whether increased lesion detection and tailored resections result in higher rates of seizure freedom 1 year after epilepsy surgery. Sixty patients enroll the study according to the following inclusion criteria: aged ≥ 12 years, diagnosed with drug-resistant focal epilepsy with a suspected epileptogenic focus, negative conventional 3 T MRI during pre-surgical work-up. RESULTS: All patients will be evaluated by 7 T MRI; ten patients will undergo an additional 9.4 T MRI exam. Images will be evaluated independently by two neuroradiologists and a neurologist or neurosurgeon. Clinical and UHF MRI will be discussed in the multidisciplinary epilepsy surgery conference. Demographic and epilepsy characteristics, along with postoperative seizure outcome and histopathological evaluation, will be recorded. CONCLUSION: This protocol was reviewed and approved by the local Institutional Review Board and complies with the Declaration of Helsinki and principles of Good Clinical Practice. Results will be submitted to international peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: www.trialregister.nl : NTR7536.

Myasthenia gravis after glioblastoma resection: paraneoplastic syndrome or coincidence? A unique case report and review of the literature.

Paraneoplastic neurological syndromes (PNS) can manifest with every type of malignancy. A well-known syndrome is myasthenia gravis (MG) in combination with thymomas. No association between primary brain tumors and neuromuscular disorders has been described. Here, we present a case of a 65-year-old patient who developed MG, following an uncomplicated, gross-total resection of a glioblastoma. To our knowledge, this is the first case describing the onset of MG during the early postoperative phase after glioblastoma resection. Current criteria of PNS are insufficient when the neurological syndrome is diagnosed at the time of a malignancy or shortly thereafter and should be revisited.

Ultra-high field magnetic resonance imaging in human epilepsy: A systematic review.

RATIONALE: Resective epilepsy surgery is an evidence-based curative treatment option for patients with drug-resistant focal epilepsy. The major preoperative predictor of a good surgical outcome is detection of an epileptogenic lesion by magnetic resonance imaging (MRI). Application of ultra-high field (UHF) MRI, i.e. field strengths ≥ 7 Tesla (T), may increase the sensitivity to detect such a lesion. METHODS: A keyword search strategy was submitted to Pubmed, EMBASE, Cochrane Database and clinicaltrials.gov to select studies on UHF MRI in patients with epilepsy. Follow-up study selection and data extraction were performed following PRISMA guidelines. We focused on I) diagnostic gain of UHF- over conventional MRI, II) concordance of MRI-detected lesion, seizure onset zone and surgical decision-making, and III) postoperative histopathological diagnosis and seizure outcome. RESULTS: Sixteen observational cohort studies, all using 7T MRI were included. Diagnostic gain of 7T over conventional MRI ranged from 8% to 67%, with a pooled gain of 31%. Novel techniques to visualize pathological processes in epilepsy and lesion detection are discussed. Seizure freedom was achieved in 73% of operated patients; no seizure outcome comparison was made between 7T MRI positive, 7T negative and 3T positive patients. 7T could influence surgical decision-making, with high concordance of lesion and seizure onset zone. Focal cortical dysplasia (54%), hippocampal sclerosis (12%) and gliosis (8.1%) were the most frequently diagnosed histopathological entities. SIGNIFICANCE: UHF MRI increases, yet variably, the sensitivity to detect an epileptogenic lesion, showing potential for use in clinical practice. It remains to be established whether this results in improved seizure outcome after surgical treatment. Prospective studies with larger cohorts of epilepsy patients, uniform scan and sequence protocols, and innovative post-processing technology are equally important as further increasing field strengths. Besides technical ameliorations, improved correlation of imaging features with clinical semiology, histopathology and clinical outcome has to be established.

Visual field deficits after epilepsy surgery: a new quantitative scoring method.

BACKGROUND: Anterior temporal lobectomy (ATL) as a treatment for drug-resistant temporal lobe epilepsy (TLE) frequently causes visual field deficits (VFDs). Reported VFD encompasses homonymous contralateral upper quadrantanopia. Its reported incidence ranges from 15 to 90%. To date, a quantitative method to evaluate postoperative VFD in static perimetry is not available. A method to quantify postoperative VFD, which allows for comparison between groups of patients, was developed. METHODS: Fifty-five patients with drug-resistant TLE, who underwent ATL with pre- and postoperative perimetry, were included. Temporal lobe resection length was measured on postoperative MRI. Percentage VFD was calculated for the total visual field, contralateral upper quadrant, or other three quadrants combined. RESULTS: Patients were divided into groups by resection size (< 45 and ≥ 45 mm) and side of surgery (right and left). We found significant higher VFD in the ≥ 45 vs. < 45 mm group (2.3 ± 4.4 vs. 0.7 ± 2.4%,p = 0.04) for right-sided ATL. Comparing VFD in both eyes, we found more VFD in the right vs. left eye following left-sided ATL (14.5 ± 9.8 vs. 12.9 ± 8.3%, p = 0.03). We also demonstrated significantly more VFD in the < 45 mm group for left- vs. right-sided surgery (6.7 ± 6.7 vs. 13.1 ± 7.0%, p = 0.016). A significant quantitative correlation between VFD and resection size for right-sided ATL was shown (r = 0.52, p < 0.01). CONCLUSIONS: We developed a new quantitative scoring method for the assessment of postoperative visual field deficits after temporal lobe epilepsy surgery and assessed its feasibility for clinical use. A significant correlation between VFD and resection size for right-sided ATL was confirmed.

In vivo assessment of the human cerebral microcirculation and its glycocalyx: A technical report.

INTRODUCTION: The cerebral microcirculation and its glycocalyx, a matrix coating the luminal endothelium, are key regulators of capillary permeability and cerebral blood flow. Microvascular abnormalities are described in several neurological disorders. However, assessment of the cerebral microcirculation and glycocalyx has mainly been performed ex vivo. NEW METHOD: Here, the technical feasibility of in vivo assessment of the human cerebral microcirculation and its glycocalyx using sidestream dark field (SDF) imaging is discussed. Intraoperative assessment requires the application of a sterile drape covering the camera (slipcover). First, sublingual measurements with and without slipcover were performed in a healthy control to assess the impact of this slipcover. Subsequently, using SDF imaging, the sublingual (reference), cortical, and hippocampal microcirculation and glycocalyx were evaluated in patients who underwent resective brain surgery as treatment for drug-resistant temporal lobe epilepsy. Finally, vessel density, and the perfused boundary region (PBR), a validated gauge of glycocalyx health, were calculated using GlycoCheck© software. RESULTS: The addition of a slipcover affects vessel density and PBR values in a control subject. The cerebral measurements in five patients were more difficult to obtain than the sublingual ones. This was probably at least partly due to the introduction of a sterile slipcover. Results on vessel density and PBR showed similar patterns at all three measurement sites. COMPARISON WITH EXISTING METHODS: This is the first report on in vivo assessment of the human cerebrovascular glycocalyx. Assessment of the glycocalyx is an additional application of in vivo imaging of the cerebral microcirculation using SDF technique. This method enables functional analysis of the microcirculation and glycocalyx, however the addition of a sterile slipcover affects the measurements. CONCLUSIONS: SDF imaging is a safe, quick, and straightforward technique to evaluate the functional cerebral microcirculation and glycocalyx. Because of their eminent role in cerebral homeostasis, this method may significantly add to research on the role of vascular pathophysiology underling various neurological disorders.

Protocol for intraoperative assessment of the human cerebrovascular glycocalyx.

INTRODUCTION: Adequate functioning of the blood-brain barrier (BBB) is important for brain homoeostasis and normal neuronal function. Disruption of the BBB has been described in several neurological diseases. Recent reports suggest that an increased permeability of the BBB also contributes to increased seizure susceptibility in patients with epilepsy. The endothelial glycocalyx is coating the luminal side of the endothelium and can be considered as the first barrier of the BBB. We hypothesise that an altered glycocalyx thickness plays a role in the aetiology of temporal lobe epilepsy (TLE), the most common type of epilepsy. Here, we propose a protocol that allows intraoperative assessment of the cerebrovascular glycocalyx thickness in patients with TLE and assess whether its thickness is decreased in patients with TLE when compared with controls. METHODS AND ANALYSIS: This protocol is designed as a prospective observational case-control study in patients who undergo resective brain surgery as treatment for TLE. Control subjects are patients without a history of epileptic seizures, who undergo a craniotomy or burr hole surgery for other indications. Intraoperative glycocalyx thickness measurements of sublingual, cortical and hippocampal microcirculation are performed by video microscopy using sidestream dark-field imaging. Demographic details, seizure characteristics, epilepsy risk factors, intraoperative haemodynamic parameters and histopathological evaluation are additionally recorded. ETHICS AND DISSEMINATION: This protocol has been ethically approved by the local medical ethical committee (ID: NL51594.068.14) and complies with the Declaration of Helsinki and principles of Good Clinical Practice. Informed consent is obtained before study enrolment and only coded data will be stored in a secured database, enabling an audit trail. Results will be submitted to international peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: NTR5568.

The influence of neuropathology on brain inflammation in human and experimental temporal lobe epilepsy.

It is unclear to what extent neuropathological changes contribute to brain inflammation observed in temporal lobe epilepsy (TLE). Here, we compared cytokine levels between histopathologically-confirmed sclerotic hippocampi and histopathologically-confirmed normal hippocampi from TLE patients. We analyzed a similar cytokine panel in the hippocampi of amygdala-kindled rats and we evaluated neuropathological changes by immunohistochemistry. In TLE patients, cytokine levels were not significantly different between sclerotic and non-sclerotic hippocampi. Though kindling resulted in increased astrocyte activation, cytokine levels and microglia activation were unchanged. These results suggest that the chronic epileptic state in TLE can also occur in the absence of intracerebral inflammation. Highlights.

Surgery for temporal lobe epilepsy after cerebral malaria.

The most common indication for epilepsy surgery is temporal lobe epilepsy (TLE) which usually is divided into two categories, mesial and lateral TLE. The commonest pathology underlying mesial temporal lobe epilepsy (MTLE) is mesial temporal sclerosis (MTS); we report on a 50-year-old male patient, who contracted cerebral malaria and developed MTLE shortly thereafter. Magnetic resonance imaging (MRI) showed MTS. Surgical treatment was an anteromedial temporal lobe resection with amygdalohippocampectomy. The patient is seizure free, 36 months after surgical treatment. This is the first report describing MTLE-onset subsequent to cerebral malaria and discussing the potential pathophysiological relationship between cerebral malaria and MTS.

[Parinaud's syndrome as a sign of acute obstructive hydrocephalus: recovery after acute ventriculostomy]. / Het syndroom van Parinaud als teken van acute obstructieve hydrocefalus: herstel na acute ventriculostomie.

Paresis or palsy of upward vertical gaze, pupillary light-near dissociation and nystagmus retractorius with convergence, were present in a boy aged 16 years and a woman aged 30 years with an obstructive hydrocephalus due to an aqueductal stenosis as a consequence of a bacterial meningitis and in a woman aged 26 years and a man aged 47 years with an outlet obstruction of the fourth ventricle after a posterior fossa operation for a tumour in the fourth ventricle. All of the patients were suspected of having a drain dysfunction. They all underwent a third-ventriculocisternostomy after which their symptoms (partially) resolved. The presenting symptoms stated are the classical triad of Parinaud's syndrome. In addition to these there are less frequent symptoms such as bilateral eyelid retraction (Collier's sign) and convergence spasms. The syndrome is rare but has a significant mortality risk and a high morbidity rate if an obstructive hydrocephalus is not diagnosed and treated. An MRI scan of the cerebrum to detect obstructive hydrocephalus with dilation of the aqueduct is the diagnostic of choice. For an obstructive hydrocephalus with dilation of the aqueduct a third-ventriculocisternostomy is the treatment of choice.