Health-related quality of life 2 years after pedicle subtraction osteotomy for sagittal imbalance: a single-center experience of 65 patients.

PURPOSE: Pedicle subtraction osteotomy (PSO) as an invasive procedure with high reoperation and complication rates in an often elderly population has often been questioned. The purpose of our study was to evaluate the impact of PSO for sagittal imbalance (SI) on patient-reported outcomes including self-reported satisfaction and health-related quality of life 2 years postoperatively. METHODS: Consecutive patients who underwent correction of their spinal deformity by thoracolumbar PSO were assessed using self-reporting questionnaires 2 years postoperatively. Outcome was measured by visual analogue scale (VAS) for back and leg pain, Oswestry Disability Index (ODI), and EQ-5D scores. Additionally, a Patient Satisfaction Index (PSI) rated in four grades (A: very satisfied to D: not satisfied), walking range, and the Timed Up and Go (TUG) Test were evaluated. RESULTS: Sixty-five patients were included, and each parameter was assessed preoperatively and 24 months postoperatively. The intervention led to significant improvements in back pain (8.1 ± 1.2 vs. 2.9 ± 1.9; p < 0.001), as well as ODI scores (57.7 ± 13.9 vs. 32.6 ± 18.9; p < 0.001), walking range (589 ± 1676 m vs. 3265 ± 3405 m; p < 0.001), and TUG (19.2 s vs. 9.7 s; p < 0.05). 90.7% of patients (n = 59/65) reported a PSI grade "A" or "B" 24 months postoperatively. CONCLUSION: Patient satisfaction 24 months after PSO for SI is high. Quality of life improved significantly by restoring sagittal balance.

Current trends and outcomes of non-elective neurosurgical care in Central Europe during the second year of the COVID-19 pandemic.

Reflecting the first wave COVID-19 pandemic in Central Europe (i.e. March 16th-April 15th, 2020) the neurosurgical community witnessed a general diminution in the incidence of emergency neurosurgical cases, which was impelled by a reduced number of traumatic brain injuries (TBI), spine conditions, and chronic subdural hematomas (CSDH). This appeared to be associated with restrictions imposed on mobility within countries but also to possible delayed patient introduction and interdisciplinary medical counseling. In response to one year of COVID-19 experience, also mapping the third wave of COVID-19 in 2021 (i.e. March 16 to April 15, 2021), we aimed to reevaluate the current prevalence and outcomes for emergency non-elective neurosurgical cases in COVID-19-negative patients across Austria and the Czech Republic. The primary analysis was focused on incidence and 30-day mortality in emergency neurosurgical cases compared to four preceding years (2017-2020). A total of 5077 neurosurgical emergency cases were reviewed. The year 2021 compared to the years 2017-2019 was not significantly related to any increased odds of 30 day mortality in Austria or in the Czech Republic. Recently, there was a significant propensity toward increased incidence rates of emergency non-elective neurosurgical cases during the third COVID-19 pandemic wave in Austria, driven by their lower incidence during the first COVID-19 wave in 2020. Selected neurosurgical conditions commonly associated with traumatic etiologies including TBI, and CSDH roughly reverted to similar incidence rates from the previous non-COVID-19 years. Further resisting the major deleterious effects of the continuing COVID-19 pandemic, it is edifying to notice that the neurosurgical community´s demeanor to the recent third pandemic culmination keeps the very high standards of non-elective neurosurgical care alongside with low periprocedural morbidity. This also reflects the current state of health care quality in the Czech Republic and Austria.

A simple electrical approach to diagnosing a suspected lead break in patients with implanted vagus nerve stimulators - Technical note.

PURPOSE: Vagus nerve stimulation (VNS) is an effective adjunctive treatment for patients with drug-resistant epilepsy (DRE) or difficult-to-treat depression (DTD). The implanted system consists of a titanium-cased generator and a lead with platinum electrodes, placed around the cervical vagus nerve. In rare cases a lead may break, causing the patient to receive insufficient therapy or no therapy at all, with potentially dangerous consequences. In order to confirm a suspected lead breakage, physicians have the option to perform x-rays. However, x-rays often do not show a clear, unmistakable lead break. In this technical note an additional method to verify lead integrity electrophysiological is described in detail to provide the highest degree of certainty on the integrity of the lead when a broken lead is suspected before proceeding to revision surgery. METHODS: When patients introduce themselves with symptoms indicating a suspected lead breakage, a systematic lead break management is required. This includes, beside the clinical anamneses, performing VNS Therapy® System Diagnostics (SD). If an unacceptable HIGH lead impedance is observed, performing x-rays (anteroposterior and lateral views) may help to confirm a lead breakage. Additionally, EMG recording equipment can be used to analyse the VNS stimulus waveform from the neck for verification of an electrical discontinuity. RESULTS: A differentiated VNS waveform with narrowed pulses or no waveform at all can confirm lead discontinuity. CONCLUSION: This Technical Note describes an easy but underused electrophysiological procedure to be included in the standardized protocol for identifying VNS lead breakage.

Anidulafungin and Micafungin Concentrations in Cerebrospinal Fluid and in Cerebral Cortex.

Anidulafungin and micafungin were quantified in cerebrospinal fluid (CSF) of critically ill adults and in cerebral cortex of deceased patients. In CSF, anidulafungin levels (<0.01 to 0.66 µg/ml) and micafungin levels (<0.01 to 0.16 µg/ml) were lower than those in plasma concentrations (0.77 to 5.07 and 1.21 to 8.70 µg/ml, respectively) drawn simultaneously. In cerebral cortex, anidulafungin and micafungin levels were 0.21 to 2.34 and 0.18 to 2.88 µg/g, respectively. Thus, MIC values of several pathogenic Candida strains exceed concentrations in CSF and in brain.

Symptomatic hemiparkinsonism due to extensive middle and posterior fossa arachnoid cyst: case report.

INTRODUCTION: Intracranial neoplasms are an uncommon cause of symptomatic parkinsonism. We here report a patient with an extensive middle and posterior fossa arachnoid cyst presenting with parkinsonism that was treated by neurosurgical intervention. METHODS: Retrospective chart review and clinical examination of the patient. CASE REPORT: This 55-year-old male patient with hemiparkinsonism and recurrent bouts of headaches was first diagnosed in 1988. CT scans revealed multiple cystic lesions compressing brainstem and basal ganglia, which were partially resected. Subsequently, the patient was free of complaints for 20 years. In 2009 the patient presented once more with severe unilateral tremor and thalamic pain affecting the right arm. Despite symptomatic treatment with L-Dopa and pramipexole symptoms worsened over time. In 2014 there was further progression with increasing hemiparkinsonism, hemidystonia, unilateral thalamic pain and pyramidal signs. Repeat CT scanning revealed a progression of the cysts as well as secondary hydrocephalus. Following repeat decompression of the brainstem and fenestration of all cystic membranes parkinsonism improved with a MDS- UPDRS III score reduction from 39 to 21. Histology revealed arachnoid cystic material. CONCLUSION: We report on a rare case of recurrent symptomatic hemiparkinsonism resulting from arachnoid cysts.

Diagnostic and therapeutic approach in adult patients with traumatic brain injury receiving oral anticoagulant therapy: an Austrian interdisciplinary consensus statement.

There is a high degree of uncertainty regarding optimum care of patients with potential or known intake of oral anticoagulants and traumatic brain injury (TBI). Anticoagulation therapy aggravates the risk of intracerebral hemorrhage but, on the other hand, patients take anticoagulants because of an underlying prothrombotic risk, and this could be increased following trauma. Treatment decisions must be taken with due consideration of both these risks. An interdisciplinary group of Austrian experts was convened to develop recommendations for best clinical practice. The aim was to provide pragmatic, clear, and easy-to-follow clinical guidance for coagulation management in adult patients with TBI and potential or known intake of platelet inhibitors, vitamin K antagonists, or non-vitamin K antagonist oral anticoagulants. Diagnosis, coagulation testing, and reversal of anticoagulation were considered as key steps upon presentation. Post-trauma management (prophylaxis for thromboembolism and resumption of long-term anticoagulation therapy) was also explored. The lack of robust evidence on which to base treatment recommendations highlights the need for randomized controlled trials in this setting.

Immediate Versus Delayed Surgical Treatment of Lumbar Disc Herniation for Acute Motor Deficits: The Impact of Surgical Timing on Functional Outcome.

STUDY DESIGN: A retrospective cohort study. OBJECTIVE: The aim of the study was to assess the impact of time to surgery in patients with motor deficits (MDs) on their functional outcome. The current single-center study presents results of emergency surgery for LDH in a group of patients with acute paresis in a "real-world" setting. SUMMARY OF BACKGROUND DATA: MDs are a frequent symptom of lumbar disc herniation (LDH). Although surgery within 48 hours has been recommended for cauda-equina syndrome, the best timing of surgery for acute MDs continues to be debated. The effect of early surgery has been proposed but remains to be unproven. METHODS: A total of 330 patients with acute paresis caused by LDH acutely referred to our department and surgically treated using microsurgical discectomy from January 2013 to December 2015 were included. Based on the duration of MD and surgical timing, all patients were classified into two categories: Group I included all patients with paresis <48 hours and Group II included all patients with paresis >48 hours. Patient demographics, LDH/clinical/treatment characteristics, and outcomes were collected prospectively.Severity of paresis [Medical Research Council (MRC) Grade 0-4], surgery-related complications, functional recovery of motor/sensory deficits, sciatica, retreatment/recurrence rates, and overall neurological outcome were analyzed. RESULTS: Group I showed significantly faster recovery of moderate/severe paresis (MRC 0-3) at discharge, and 6-weeks/3-months follow up (P ≤ 0.001), whereas there were no significant differences in recovery for mild paresis (MRC 4). Sensory deficits also recovered substantially faster in Group I at 6-weeks (P = 0.003) and 3-months follow up (P = 0.045). Body mass index, preoperative MRC-grade, and duration of MDs were identified as significant predictors for recovery of paresis at all follow ups with substantial impact on patient reported outcomes including sciatica and/or dermatomal sensory deficits. CONCLUSION: Given the superior rates of neurological recovery of acute moderate/severe MDs, immediate surgery should be the primary option. However, a prospective randomized clinical trial is needed to confirm the superiority of emergency surgery. LEVEL OF EVIDENCE: 3.

Brain temperature but not core temperature increases during spreading depolarizations in patients with spontaneous intracerebral hemorrhage.

Spreading depolarizations (SDs) are highly active metabolic events, commonly occur in patients with intracerebral hemorrhage (ICH) and may be triggered by fever. We investigated the dynamics of brain-temperature (Tbrain) and core-temperature (Tcore) relative to the occurrence of SDs. Twenty consecutive comatose ICH patients with multimodal electrocorticograpy (ECoG) and Tbrain monitoring of the perihematomal area were prospectively enrolled. Clusters of SDs were defined as ≥2 SDs/h. Generalized estimating equations were used for statistical calculations. Data are presented as median and interquartile range. During 3097 h (173 h [81-223]/patient) of ECoG monitoring, 342 SDs were analyzed of which 51 (15%) occurred in clusters. Baseline Tcore and Tbrain was 37.3℃ (36.9-37.8) and 37.4℃ (36.7-37.9), respectively. Tbrain but not Tcore significantly increased 25 min preceding the onset of SDs by 0.2℃ (0.1-0.2; p < 0.001) and returned to baseline 35 min following SDs. During clusters, Tbrain increased to a higher level (+0.4℃ [0.1-0.4]; p = 0.006) when compared to single SDs. A higher probability (OR = 36.9; CI = 36.8-37.1; p < 0.001) of developing SDs was observed during episodes of Tbrain ≥ 38.0℃ (23% probability), than during Tbrain ≤ 36.6℃ (9% probability). Spreading depolarizations - and in particular clusters of SDs - may increase brain temperature following ICH.

Severe head injury in very old patients: to treat or not to treat? Results of an online questionnaire for neurosurgeons.

Due to the aging population, neurosurgeons are confronted with an increasing number of very old patients suffering from traumatic brain injury. Many of these patients present with an acute subdural hematoma. There is a lack of data on neurosurgical decision-making in elderly people. We investigated the importance of imaging criteria, patients' wishes, their surrogates' wishes, and patient demographics on treatment decisions chosen by neurosurgeons. An online questionnaire was sent to all German neurosurgical units via the German Society of Neurosurgery (DGNC). The survey was based on the reported case of an unconscious 81-year-old patient with an acute subdural hematoma and consisted of 13 questions. Of these questions, nine addressed indication and treatment plan and four evaluated the neurosurgeon's interest in gathering additional information on the patient's social environment and supposed patient's wishes or advance directive. Eighty-five percent of the interviewed neurosurgeons would perform an emergency operation in the presented case. Midline shift (84%), hematoma thickness (81%), and time between traumatic injury and treatment (81%) were considered to be the most important factors for surgical treatment. Gathering information on the social environment of the patient (66%) and discussion with family members (57%) were felt to be either unimportant. Neurosurgeons in Central Europe tend to treat acute subdural hematoma in very old patients based on imaging findings and according to mechanistic views. Social circumstances and patient wishes are considered to be less important. Education of the medical profession and the general public should aim to bring these factors into focus in the decision-making process.

Refractory intracranial hypertension in traumatic brain injury: Proposal for a novel score to assess the safety of lumbar cerebrospinal fluid drainage.

BACKGROUND: Cerebrospinal fluid (CSF) drainage via ventricular puncture is an established therapy of elevated intracranial pressure (ICP). In contrast, lumbar CSF removal is believed to be contraindicated with intracranial hypertension. METHODS: We investigated the safety and efficacy of lumbar CSF drainage to decrease refractory elevated ICP in a small cohort of patients with traumatic brain injury (TBI). A score (0-8 points) was used to assess computed tomography (CT) images for signs of herniation and for patency of the basal cisterns. All patients received lumbar CSF drainage either as a continuous drainage or as a single lumbar puncture (LP). Type and method of CSF drainage, mean ICP 24 h prior and after CSF removal, and adverse events were documented. Outcome was assessed after 3 months (with dichotomized Glasgow outcome scale). RESULTS: Eight patients were evaluated retrospectively. n = 5 suffered a moderate, n = 2 a severe TBI (one Glasgow coma score not documented). The CT score was ≥5 in all patients prior to LP and decreased after puncture without clinical consequences in two patients. The amount of CSF removal did not correlate with score changes (P = 0.45). CSF drainage led to a significant reduction of mean ICP (from 22.3 to 13.9 mmHg, P = 0.002). Continuous drainage was more effective than a single LP. Three of eight patients reached a favorable outcome. CONCLUSIONS: Lumbar CSF removal for the treatment of intracranial hypertension is effective and safe, provided the basal cisterns are discernible, equivalent to ≥5 points in the proposed new score. The score needs further validation.

The Volume of the Third Ventricle as a Prognostic Marker for Shunt Dependency After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Hydrocephalus is a common sequelae of aneurysmal subarachnoid hemorrhage (aSAH). However, in daily routine it is difficult to predict a patient's need for ventricular shunt placement in the course of the disease. OBJECTIVE: The purpose of this study was to identify radiologic predictors for development of a shunt-dependent hydrocephalus after aSAH. METHODS: A cohort of 217 patients with aSAH with adequate pretreatment computed tomography (CT) imaging was retrospectively reviewed. All variables, including demographic data, treatment, and initial CT imaging were gathered and grading was performed using Hunt and Hess, Graeb, LeRoux, and modified Fisher scores. Analysis of the radiographic parameters consisted of straight measurement and three-dimensional volumetry using manual segmentation. Univariate and multivariate statistical analyses were performed to identify predictive parameters. RESULTS: Of 217 patients, 36 (17.5%) required a ventricular shunt (VS). A receiver operating characteristic analysis between the volume of the third ventricle and shunt-dependent hydrocephalus showed a significant cutoff at a volume of 2.3 cm3 with a 4.3-fold higher risk for shunt dependency (P < 0.001). However, the treatment modality and classification according to the mentioned scores were not associated with the need for VS after aSAH. In univariate and multivariate analysis, the volume of the third ventricle on admission remained a significant prognostic marker for the need of a VS. CONCLUSIONS: Our data suggest that the volume of the third ventricle in the initial CT is a strong predictor for shunt dependency after aSAH.

"I am not afraid of death"-a survey on preferences concerning neurosurgical interventions among patients over 75 years.

INTRODUCTION: Treatment decisions in elderly patients with traumatic brain injury (TBI) are mainly determined by trauma severity and patient age. The aim of this study was to explore personal preferences of potential patients regarding life-prolonging neurosurgical interventions by interviewing ambulatory, autonomous elderly people. METHODS: One hundred consecutive patients older than 75 years frequenting the outpatient clinic of the Department of Neurosurgery were interviewed about their attitudes regarding the hypothetical case of an 81-year-old patient with TBI and a space-occupying acute subdural hematoma (aSDH) using a 21-point questionnaire. RESULTS: Fifty-one percent of the consulted persons declined life-prolonging surgical measures. If surgery was associated with physical disability, 68% of the people wished no surgery. In case of cognitive impairment after surgery, 91% were against any surgical intervention. The majority feared being a burden to relatives (76%) and becoming unable to master an independent life (75%). Four-fifths of the interviewed patients (82%) were not afraid of death. CONCLUSIONS: The majority of elderly patients only consent to surgical measures if no relevant disabilities are involved and if they can return to their previous life. These findings need consideration in case of life-threatening neurosurgical emergencies as well as in the surgical treatment of elderly patients in general.

Postoperative Thromboembolic Prophylaxis with Low-Molecular-Weight Heparin and Risk of Rebleeding in Patients with Chronic Subdural Hematomas: A Comparative Retrospective Cohort Study.

OBJECTIVE: Early postoperative administration of low-molecular-weight heparin (LMWH) to prevent thromboembolic events in patients with chronic subdural hematoma (CSDH) is controversial. Our goal was to investigate impact of early postoperative LMWH administration on recurrence rate of CSDHs. METHODS: Retrospective review was performed of 136 patients with CSDHs who were operated on during an 18-month period. Early postoperative administration of LMWH was at the discretion of the treating surgeon. This resulted in patients treated (heparin [H] group) or not treated with LMWH (no heparin [NH] group). All patients underwent imaging 4 weeks after surgery or earlier in cases of deterioration. The primary outcome variable was reoperation. Secondary outcomes were reoperation, important residual hematoma (defined as hematoma depth of more than one third of original size), and incidence of thromboembolic complications. Relative risk and absolute risk reduction were calculated. RESULTS: We included 105 patients, 50 (47.6%) in the NH group and 55 (52.4%) in the H group. Nine patients (18%) in the NH group and 6 patients (10.9%) in the H group required secondary surgery (relative risk 0.61, 95% confidence interval 0.23-1.58, P = 0.404, absolute risk reduction 0.07). Eleven patients (22%) in the NH group and 15 patients (27.3%) in the H group presented with important residual hematoma or underwent surgery for hematoma recurrence (relative risk 1.24, 95% confidence interval 0.63-2.44, P = 0.532, absolute risk reduction -0.05). CONCLUSIONS: Our data provide preliminary evidence that early postoperative administration of LWMH does not increase risk of clinically relevant recurrence of CSDHs.

Reconstruction of large cranial defects with poly-methyl-methacrylate (PMMA) using a rapid prototyping model and a new technique for intraoperative implant modeling.

BACKGROUND: Reconstruction of large cranial defects after craniectomy can be accomplished by free-hand poly-methyl-methacrylate (PMMA) or industrially manufactured implants. The free-hand technique often does not achieve satisfactory cosmetic results but is inexpensive. In an attempt to combine the accuracy of specifically manufactured implants with low cost of PMMA. METHODS: Forty-six consecutive patients with large skull defects after trauma or infection were retrospectively analyzed. The defects were reconstructed using computer-aided design/computer-aided manufacturing (CAD/CAM) techniques. The computer file was imported into a rapid prototyping (RP) machine to produce an acrylonitrile-butadiene-styrene model (ABS) of the patient's bony head. The gas-sterilized model was used as a template for the intraoperative modeling of the PMMA cranioplasty. Thus, not the PMMA implant was generated by CAD/CAM technique but the model of the patients head to easily form a well-fitting implant. Cosmetic outcome was rated on a six-tiered scale by the patients after a minimum follow-up of three months. RESULTS: The mean size of the defect was 74.36cm2. The implants fitted well in all patients. Seven patients had a postoperative complication and underwent reoperation. Mean follow-up period was 41 months (range 2-91 months). Results were excellent in 42, good in three and not satisfactory in one patient. Costs per implant were approximately 550 Euros. CONCLUSION: PMMA implants fabricated in-house by direct molding using a bio-model of the patients bony head are easily produced, fit properly and are inexpensive compared to cranial implants fabricated with other RP or milling techniques.

Spreading depolarizations in patients with spontaneous intracerebral hemorrhage: Association with perihematomal edema progression.

Pathophysiologic mechanisms of secondary brain injury after intracerebral hemorrhage and in particular mechanisms of perihematomal-edema progression remain incompletely understood. Recently, the role of spreading depolarizations in secondary brain injury was established in ischemic stroke, subarachnoid hemorrhage and traumatic brain injury patients. Its role in intracerebral hemorrhage patients and in particular the association with perihematomal-edema is not known. A total of 27 comatose intracerebral hemorrhage patients in whom hematoma evacuation and subdural electrocorticography was performed were studied prospectively. Hematoma evacuation and subdural strip electrode placement was performed within the first 24 h in 18 patients (67%). Electrocorticography recordings started 3 h after surgery (IQR, 3-5 h) and lasted 157 h (median) per patient and 4876 h in all 27 patients. In 18 patients (67%), a total of 650 spreading depolarizations were observed. Spreading depolarizations were more common in the initial days with a peak incidence on day 2. Median electrocorticography depression time was longer than previously reported (14.7 min, IQR, 9-22 min). Postoperative perihematomal-edema progression (85% of patients) was significantly associated with occurrence of isolated and clustered spreading depolarizations. Monitoring of spreading depolarizations may help to better understand pathophysiologic mechanisms of secondary insults after intracerebral hemorrhage. Whether they may serve as target in the treatment of intracerebral hemorrhage deserves further research.

Opening the Internal Hematoma Membrane Does Not Alter the Recurrence Rate of Chronic Subdural Hematomas: A Prospective Randomized Trial.

BACKGROUND: Factors determining the recurrence of chronic subdural hematomas (CSDHs) are not clear. Whether opening the so-called internal hematoma membrane is useful has not been investigated. OBJECTIVE: To investigate whether splitting the inner hematoma membrane influences the recurrence rate in patients undergoing burr-hole craniotomy for CSDH. METHODS: Fifty-two awake patients undergoing surgery for 57 CSDHs were prospectively randomized to either partial opening of the inner hematoma membrane (group A) or not (group B) after enlarged burr-hole craniotomy and hematoma evacuation. Drainage was left in situ for several days postoperatively. Groups were comparable with regard to demographic, clinical, and imaging variables. Outcome was assessed after 3-6 weeks for the combined outcome variable of reoperation or residual hematoma of one third or more of the original hematoma thickness. RESULTS: Fourteen patients underwent reoperation for clinical deterioration or residual hematoma during follow-up (n = 6 in group A, 21%; n = 8 in group B, 28 %) (P = 0.537). Residual hematoma of ≥ one third not requiring surgery was present in 7 patients in group A (25%) and 10 patients in group B (36%) (P = 0.383). The overall cumulative failure rate (reoperation or hematoma thickness ≥ one third) was 13/28 (46%) in group A and 18/28 in group B (P = 0.178; relative risk, 0.722 [95% confidence interval, 0.445-1.172]; absolute risk reduction -16% [95% confidence interval, -38% to 8%]). CONCLUSIONS: Opening the internal hematoma membrane does not alter the rate of patients requiring revision surgery and the number of patients showing a marked residual hematoma 6 weeks after evacuation of a CSDH.

Remote ischemic preconditioning in the prevention of ischemic brain damage during intracranial aneurysm treatment (RIPAT): study protocol for a randomized controlled trial.

BACKGROUND: The treatment of intracranial aneurysms may be associated with cerebral ischemia. We hypothesize that pre-interventional remote ischemic preconditioning (RIPC) reduces ischemic cerebral tissue damage in patients undergoing elective intracranial aneurysm treatment. METHODS/DESIGN: This study is a single-center, prospective, randomized, double-blind explorative trial. Patients with an unruptured intracranial aneurysm admitted to Innsbruck Medical University Hospital for coiling or clipping will be consecutively randomized to either the intervention group (= RIPC by inflating an upper extremity blood-pressure cuff for 3 x 5 min to 200 mmHg) or the control group after induction of anesthesia. Participants will be randomized 1:1 to either the preconditioning group or the sham group using a random allocation sequence and block randomization. The precalculated sample size is n = 24 per group. The primary endpoint is the area-under-the-curve concentration of serum biomarkers (S100B, NSE, GFAP, MMP9, MBP, and cellular microparticles) in the first five days after treatment. Secondary endpoints are the number and volume of new ischemic lesions in magnetic resonance imaging and clinical outcome evaluated with the National Institutes of Health Stroke Scale, the modified Rankin Scale, and neuropsychological tests at six and twelve months. All outcome variables will be determined by observers blinded to group allocation. This study was approved by the local institutional Ethics Committee (UN5164), version 3.0 of the study protocol, dated 20 October 2013. DISCUSSION: This study uses the elective treatment of intracranial aneurysms as a paradigmatic situation to explore the neuroprotective effects of RIPC. If effects are demonstrable in this pilot trial, a larger, prospective phase III trial will be considered.

Calcium-binding proteins in focal cortical dysplasia.

OBJECTIVE: Alterations in γ-aminobutyric acid (GABA)-ergic cortical neurons have been reported in focal cortical dysplasia (FCD)Ia/IIIa, a malformation of cortical development associated with drug-resistant epilepsy. We compared numbers of neurons containing calcium-binding proteins parvalbumin (PV), calbindin (CB), and calretinin (CR) and densities of respective fibers in lateral temporal lobe surgical specimens of 17 patients with FCD with 19 patients who underwent anterior temporal lobe resection due to nonlesional temporal lobe epilepsy (non-FCD) as well as with 7 postmortem controls. METHODS: PV-, CB-, and CR-immunoreactive (IR) neurons were quantitatively investigated with use of two-dimensional cell counting and densitometry (reflecting mainly IR fibers) in cortical layers II, IV, and V. RESULTS: Numbers of PV-IR neurons, ratios of PV-containing to Nissl-stained neurons (correcting for eventual cell loss), and densities of PV-IR were higher in layer II of the cortex of FCD compared to non-FCD patients. Similarly, densities of CB-IR and CR-IR were also higher in layers II and V, respectively, of FCD than of non-FCD patients. Comparison with postmortem controls revealed significant higher cell numbers and fiber labeling for all three calcium-binding proteins in FCD cortex, whereas numbers of Nissl-stained neurons did not vary between FCD, non-FCD, and postmortem controls. In non-FCD versus postmortem controls, ratios of calcium-binding protein-IR cells to Nissl-stained neurons were unchanged in most instances except for increased CB/Nissl ratios and CB-IR densities in all cortical layers. SIGNIFICANCE: Increased numbers of PV neurons and fiber labeling in FCD compared to nondysplastic epileptic temporal neocortex and postmortem controls may be related to cortical malformation, whereas an increased number of CB-IR neurons and fiber labeling both in FCD and non-FCD specimens compared with postmortem controls may be associated with ongoing seizure activity. The observed changes may represent increased expression of calcium-binding proteins and thus compensatory mechanisms for seizures and neuronal loss in drug-resistant epilepsy.

Midbrain-hindbrain malformations in patients with malformations of cortical development and epilepsy: a series of 220 patients.

Midbrain-hindbrain malformations (MHM) may coexist with malformations of cortical development (MCD). This study represents a first attempt to investigate the spectrum of MHM in a large series of patients with MCD and epilepsy. We aimed to explore specific associations between MCD and MHM and to compare two groups of patients: MCD with MHM (wMHM) and MCD without MHM (w/oMHM) with regard to clinical and imaging features. Two hundred and twenty patients (116 women/104 men, median age 28 years, interquartile range 20-44 years at the time of assessment) with MCD and epilepsy were identified at the Departments of Neurology and Pediatrics, Innsbruck Medical University, Austria. All underwent high-resolution MRIs (1.5-T) between 01.01.2002 and 31.12.2011. Midbrain-hindbrain structures were visually assessed by three independent raters. MHM were seen in 17% (38/220) of patients. The rate of patients wMHM and w/oMHM differed significantly (p=0.004) in three categories of MCD (category I - to abnormal neuronal proliferation; category II - to abnormal neuronal migration; and category III - due to abnormal neuronal late migration/organization): MCD due to abnormal neuronal migration (31%) and organization (23%) were more commonly associated with MHM compared to those with MCD due to abnormal neuronal proliferation (9%). Extensive bilateral MCD were seen more often in patients wMHM compared to those w/oMHM (63% vs. 36%; p=0.004). In wMHM group compared to w/oMHM group there were higher rates of callosal dysgenesis (26% vs. 4%; p<0.001) and hippocampal abnormalities (52% vs. 27%; p<0.001). Patients wMHM were younger (median 25 years vs. 30 years; p=0.010) at the time of assessment and had seizure onset at an earlier age (median 5 years vs. 12 years; p=0.043) compared to those w/oMHM. Patients wMHM had higher rates of learning disability (71% vs. 38%; p<0.001), delayed developmental milestones (68% vs. 35%; p<0.001) and neurological deficits (66% vs. 47%; p=0.049) compared to those w/oMHM. The groups (wMHM and w/oMHM) did not differ in their response to antiepileptic treatment, seizure outcome, seizure types, EEG abnormalities and rate of status epilepticus. Presence of MHM in patients with MCD and epilepsy is associated with severe morphological and clinical phenotypes.