Objective: To assess the prognostic value of MOG antibodies (abs) in the differential diagnosis of acquired demyelinating syndromes (ADS). Methods: Clinical course, MRI, MOG-abs, AQP4-abs, and CSF cells and oligoclonal bands (OCB) in children with ADS and 24 months of follow-up were reviewed in this observational prospective multicenter hospital-based study. Results: Two hundred ten children with ADS were included and diagnosed with acute disseminated encephalomyelitis (ADEM) (n = 60), neuromyelitis optica spectrum disorder (NMOSD) (n = 12), clinically isolated syndrome (CIS) (n = 101), and multiple sclerosis (MS) (n = 37) after the first episode. MOG-abs were predominantly found in ADEM (57%) and less frequently in NMOSD (25%), CIS (25%), or MS (8%). Increased MOG-ab titers were associated with younger age (p = 0.0001), diagnosis of ADEM (p = 0.005), increased CSF cell counts (p = 0.011), and negative OCB (p = 0.012). At 24-month follow-up, 96 children had no further relapses. Thirty-five children developed recurrent non-MS episodes (63% MOG-, 17% AQP4-abs at onset). Seventy-nine children developed MS (4% MOG-abs at onset). Recurrent non-MS episodes were associated with high MOG-ab titers (p = 0.0003) and older age at onset (p = 0.024). MS was predicted by MS-like MRI (p < 0.0001) and OCB (p = 0.007). An MOG-ab cutoff titer ≥1:1,280 predicted a non-MS course with a sensitivity of 47% and a specificity of 100% and a recurrent non-MS course with a sensitivity of 46% and a specificity of 86%. Conclusions: Our results show that the presence of MOG-abs strongly depends on the age at disease onset and that high MOG-ab titers were associated with a recurrent non-MS disease course.

BACKGROUND Due to the redundancy of molecular pathways simultaneously involved in glioblastoma growth and angiogenesis, therapeutic approaches intervening at multiple levels seem particularly appealing. METHODS This prospective, multicenter, single-arm phase II trial was designed to evaluate the antitumor activity of sunitinib, an oral small-molecule inhibitor of several receptor tyrosine kinases, in patients with first recurrence of primary glioblastoma using a continuous once-daily dosing regimen. Patients received a starting dose of sunitinib 37.5 mg, followed by a maintenance dose between 12.5 mg and 50 mg depending on drug tolerability. The primary endpoint was a 6-month progression-free survival (PFS) rate. Secondary endpoints included median PFS, overall survival (OS), safety/toxicity, quality of life, and translational studies on the expression of sunitinib target molecules. RESULTS Forty participants were included in this study, and no objective responses were detected. PFS6 was 12.5%, median PFS 2.2 months, and median OS 9.2 months. Five participants (12.5%) showed prolonged stable disease ≥6 months with a median PFS of 16.0 months (range, 6.4-41.4 mo) and a median OS of 46.9 months (range, 21.2-49.2 mo) for this subgroup. c-KIT expression in vascular endothelial cells (n = 14 participants) was associated with improved PFS. The most common toxicities were fatigue/asthenia, mucositis/dermatitis, dysesthesias, gastrointestinal symptoms, cognitive impairment, leukoctopenia, and thrombocytopenia. Two participants (5%) terminated treatment due to toxicity. CONCLUSION Continuous daily sunitinib showed minimal antiglioblastoma activity and substantial toxicity when given at higher doses. High endothelial c-KIT expression may define a subgroup of patients who will benefit from sunitinib treatment by achieving prolonged PFS. ClinicalTrials.gov Identifier: NCT00535379.

Neurocysticercosis (NCC) is a major cause of epilepsy in regions where pigs are free-ranging and hygiene is poor. Pork production is expected to increase in the next decade in sub-Saharan Africa, hence NCC will likely become more prevalent. In this study, people with epilepsy (PWE, n=212) were followed up 28.6 months after diagnosis of epilepsy. CT scans were performed, and serum and cerebrospinal fluid (CSF) of selected PWE were analysed. We compared the demographic data, clinical characteristics, and associated risk factors of PWE with and without NCC. PWE with NCC (n=35) were more likely to be older at first seizure (24.3 vs. 16.3 years, p=0.097), consumed more pork (97.1% vs. 73.6%, p=0.001), and were more often a member of the Iraqw tribe (94.3% vs. 67.8%, p=0.005) than PWE without NCC (n=177). PWE and NCC who were compliant with anti-epileptic medications had a significantly higher reduction of seizures (98.6% vs. 89.2%, p=0.046). Other characteristics such as gender, seizure frequency, compliance, past medical history, close contact with pigs, use of latrines and family history of seizures did not differ significantly between the two groups. The number of NCC lesions and active NCC lesions were significantly associated with a positive antibody result. The electroimmunotransfer blot, developed by the Centers for Disease Control and Prevention, was more sensitive than a commercial western blot, especially in PWE and cerebral calcifications. This is the first study to systematically compare the clinical characteristics of PWE due to NCC or other causes and to explore the utility of two different antibody tests for diagnosis of NCC in sub-Saharan Africa.

The purpose of this study is to evaluate apparent diffusion coefficient (ADC) maps to distinguish anti-vascular and anti-tumor effects in the course of anti-angiogenic treatment of recurrent high-grade gliomas (rHGG) as compared to standard magnetic resonance imaging (MRI).This retrospective study analyzed ADC maps from diffusion-weighted MRI in 14 rHGG patients during bevacizumab/irinotecan (B/I) therapy. Applying image segmentation, volumes of contrast-enhanced lesions in T1 sequences and of hyperintense T2 lesions (hT2) were calculated. hT2 were defined as regions of interest (ROI) and registered to corresponding ADC maps (hT2-ADC). Histograms were calculated from hT2-ADC ROIs. Thereafter, histogram asymmetry termed "skewness" was calculated and compared to progression-free survival (PFS) as defined by the Response Assessment Neuro-Oncology (RANO) Working Group criteria.At 8-12 weeks follow-up, seven (50%) patients showed a partial response, three (21.4%) patients were stable, and four (28.6%) patients progressed according to RANO criteria. hT2-ADC histograms demonstrated statistically significant changes in skewness in relation to PFS at 6 months. Patients with increasing skewness (n = 11) following B/I therapy had significantly shorter PFS than did patients with decreasing or stable skewness values (n = 3, median percentage change in skewness 54% versus -3%, p = 0.04).In rHGG patients, the change in ADC histogram skewness may be predictive for treatment response early in the course of anti-angiogenic therapy and more sensitive than treatment assessment based solely on RANO criteria.

Prominent leukoaraiosis is common in the clinical routine setting. In addition to microatheroma and hypertensive small vessel disease (lipohyalinosis), a large number of rare but clinically relevant differential diagnoses have to be considered. A man in his 60s presented with left pontine infarction and subsequent rapidly deteriorating leukoaraiosis associated with dementia. Standard non-invasive examination did not enable the correct diagnosis to be obtained. A brain biopsy sample revealed a combination of diffuse infiltrating and intravascular large B cell central nervous system (CNS) lymphoma, which has not previously been described in literature. Despite immediate treatment with state of the art chemotherapy, the patient died 3 months after the onset of symptoms. Diffuse infiltrating and intravascular primary CNS lymphoma is a rare cause of rapidly progressive leukoencephalopathy and stroke mediated by neoplastic microvessel occlusion and inflammatory tissue damage. This report intends to increase awareness among neurologists and other stroke physicians about this disease in order to accelerate diagnosis and initiation of treatment.

Reversible cerebral vasoconstriction syndrome is recognized increasingly as a complication of the postpartum period. Our series of four cases illustrates its phenotypical variability, summarizes the diagnostic work-up, and outlines potential treatment strategies for this usually benign but sometimes disabling and life-threatening disease.

An increasing number of patients undergo epilepsy surgery. The rocess of decision-making is complex and based on an individal approach. So far there is no firm data whether concomitant e.g. demyelinating) diseases can influence the postoperative outome [1]. Vice versa, no robust studies on the effects of central ervous surgery upon demyelinating diseases are available and he evidence is anecdotal. We report the case of a patient sufferng from medically intractable temporal lobe epilepsy (TLE), who eveloped primary progressive multiple sclerosis (MS) soon after pilepsy surgery.We describe the clinical features and discuss posible relationships.

P>Purpose:In temporal lobe epilepsies an asymmetric termination (AST) of the clonic phase of secondary generalized tonic-clonic seizures (sGTCS) reliably lateralizes the side of seizure onset. The last clonic activity occurs ipsilateral to the side of the seizure onset zone. We compared the prevalence and lateralizing value of AST in sGTCS of frontal and temporal lobe origin as well as in primary generalized tonic-clonic seizures (pGTCS).Methods:We analyzed 177 seizures in 84 consecutive patients. Forty-one patients had temporal lobe epilepsy (TLE), 24 frontal lobe epilepsy (FLE), and 19 had nonfocal (primary) generalized epilepsies (GE). All patients underwent intensive video-EEG (electroencephalography) monitoring, high-resolution magnetic resonance imaging (MRI), neuropsychological testing, and single photon emission computed tomography/positron emission tomography (SPECT/PET) when feasible. Two investigators blinded for diagnosis, EEG, and imaging data assessed frequency and side of the last clonic jerk.Results:AST occurred in 63% of patients with TLE (47% of seizures), in 71% with FLE (60% of seizures), and in 42% with GE (21% of seizures). These results were not significant for patients, but significant for seizures in TLE versus GE and in FLE versus GE (p < 0.001). The positive predictive value (PPV) for the side of seizure onset was 74% (p = 0.003) in TLE and 75% (p = 0.008) in FLE.Discussion:AST in sGTCS lateralizes the side of seizure onset in TLE and in FLE to the ipsilateral hemisphere with a high PPV. However, AST was also observed in GE. Therefore, asymmetric clinical signs should not inevitably lead to the assumption of focal epilepsy syndromes.

Summary Purpose: In developing countries, neurocysticercosis (NCC) is a common cause of epilepsy. Most of the work on NCC and epilepsy has been compiled in Latin America. To date, comprehensive neuroimaging studies are missing in sub‐Saharan Africa. Methods: In our study, we interviewed 212 people with epilepsy (PWE) and performed cerebral computed tomography (CT) at the Haydom Lutheran Hospital in northern Tanzania. Control cerebral CT scans were selected from 198 consecutive individuals without epilepsy. Sera of PWE with lesions indicating NCC (n = 20), PWE without NCC lesions (n = 20), and healthy individuals (n = 20), as well as cerebrospinal fluid (CSF) samples of PWE with NCC lesions (n = 11) were investigated for anticysticercal antibodies. Results: Definite NCC lesions were present in five (2.4%), lesions highly suggestive of NCC in 24 (11.3%), and lesions compatible with NCC in nine (4.2%) PWE. This compares to two (1.0%) people with definite NCC lesions, two (1.0%) with lesions highly suggestive of, and six (2.9%) with lesions compatible with NCC in the control group. NCC lesions were significantly more frequent in PWE compared to controls (p < 0.0001). CT results, and serum and CSF analysis taken together, we diagnosed 22 (10.4%) individuals with probable and 7 (3.3%) with definitive NCC in our cohort of PWE. Conclusion: For the first time in sub‐Saharan Africa, we give evidence within a large‐scale neuroimaging study that NCC, a so far neglected infectious disease, represents a major cause of epilepsy.

Neurodevelopmental changes regarding interference and magnitude processing were assessed in 3 age groups (children, n = 10; young adults, n = 11; elderly participants, n = 9) by using an functional magnetic resonance imaging version of the numerical Stroop task. Behaviorally, comparable distance and size congruity effects were found in all 3 age groups. Distance effects were most pronounced in the more difficult numerical task, whereas size congruity effects were comparable across tasks. In response to interference, an age-linear trend in the pattern of activation in left and right prefrontal and left middle temporal regions of the brain was observed. This implicates that with increasing age interference control requires increasing effort (possible explanations for children's relatively lower interference effects are provided). In contrast, the distance effect produced a negative linear trend in right prefrontal, supplementary motor area, and intraparietal cortex. This suggests that relative to old adults, children and young adults had to recruit a larger network upon processing magnitude. The latter findings are even more remarkable considering that the behavioral effects were similar across groups. In summary, the developmental trajectories of interference control and magnitude processing differ, although these cognitive functions activate partially overlapping brain regions.

Abnormalities of deep cerebellar nuclei in Joubert syndrome have been previously reported only in rare autopsy cases. Epilepsy in association with Joubert syndrome is also rarely reported. In two new cases of patients with Joubert syndrome, bilateral hypoplasia of deep cerebellar nuclei was detected in vivo by magnetic resonance imaging. One of the patients had drug-resistant epilepsy. Both patients received clinical examination, electroencephalography, neuropsychologic testing, and high-resolution magnetic resonance imaging (1.5 T). Patient 1, a 7-year-old boy, had muscular hypotonia, periodic tachypnea, mild ataxia, global developmental delay, exotropia, and polydactyly. Patient 2, a 23-year-old woman, had muscular hypotonia, epilepsy with pharmacoresistant generalized tonic-clonic seizures, learning disability, esotropia, and mild gait ataxia. Abnormalities of deep cerebellar nuclei might contribute to the pathophysiology of epilepsy in patients with Joubert syndrome.

In developing countries, especially Latin America, neurocysticercosis (NCC) is a common cause of epilepsy. Recently, neurotoxocariasis has also been implicated in the pathogenesis of epilepsy. In sub-Saharan Africa data on parasitic disease and epilepsy are scarce. We therefore conducted a study in a rural hospital in northern Tanzania and analysed serum samples for anticysticercal and antitoxocaral antibodies for 40 people with epilepsy (PWE), 20 of whom had confirmed NCC on cranial computed tomography (CT) and 20 healthy individuals. Cerebrospinal fluid (CSF) of 11 PWE with NCC lesions on cranial CT was also investigated. Antibodies were determined using ELISA and Western blot. Six PWE with NCC lesions showed anticysticercal antibodies in serum. Of those, five had active lesions. Anticysticercal antibodies were significantly more frequent in PWE with active NCC than in those with inactive NCC (P<0.01). CSF samples were positive for anticysticercal antibodies in five patients, of whom four had active lesions on cranial CT. Antitoxocaral antibodies were detected in sera of 11 (55%) PWE with NCC lesions, of eight (40%) PWE without lesions on cranial CT and of eight (40%) controls. In our study anticysticercal antibodies in both serum and CSF were associated with active NCC in PWE, whereas there was no relationship between antitoxocaral antibodies and epilepsy.

Aim of this functional magnetic resonance imaging (fMRI) study was to dissociate normal aging and minimal cognitive impairment (MCI) concerning magnitude processing and interference control. We examined the neural correlates of a numerical Stroop task in elderly individuals with and without MCI. Fifteen elderly participants (six patients with MCI and nine controls) were subjected to a numerical Stroop task requiring numerical/physical magnitude classifications while inhibiting task-irrelevant stimulus dimensions. Effects of distance and congruity were examined. Behaviourally, robust distance and congruity effects were observed in both groups and tasks. Imaging baseline conditions revealed stronger and more distributed activations in MCI patients relative to controls which could not be explained by the higher error rates committed by patients. Across tasks, conjunction analysis revealed highly significant activations in intra-parietal and prefrontal regions suggesting that both groups recruit comparable brain regions upon processing magnitude and interference, respectively. MCI patients exhibited stronger pre-/postcentral and thalamic activations, possibly reflecting more effortful response-selection processes or alternatively, deficient inhibitory control. Moreover, MCI patients exhibited additional activations in fronto-parietal (magnitude) and occipital/cerebellar (congruity) regions. To summarize, though MCI patients needed to recruit more distributed activation patterns conjunction analysis revealed common activation sites in response to magnitude processing and interference control.

The purpose of this study was to evaluate the accuracy of stereotactic electrode placement in patients undergoing deep brain stimulation by using pre- and postoperative computed tomography (CT). Twenty-three patients with movement disorders (Parkinson's disease (n=7), tremor (n=9), dystonia (n=7)) treated with bilateral deep brain stimulation (DBS) (overall 46 target points) were investigated. The target point of the electrode was planned stereotactically in combination with a preoperative stereotactic helical computed tomography (CT). A postoperative CT, which was carried out still in the operating room while the patient had the stereotactic frame on the head, was performed in order to control the position of the electrodes in relation to the previously planned target point. The position of the four electrode contacts was measured according to the Talairach space (AC-PC line) and compared with the coordinates of the planned target point. The mean spatial distance of planned target perpendicular to the electrode was 1.32+/-0.75mm. These results show the high accuracy of stereotactic implantation of DBS electrodes assisted by pre- and postoperative image fusion with computed tomography (CT).

Summary Nocturnal hypermotor seizures (NHSs) suggest seizure onset in the frontal lobe. We present a patient with NHSs and insular seizure onset who underwent successful surgical treatment. A 29‐year‐old right‐handed man suffered from intractable NHSs since the age of 12 years. High‐resolution MRI, [ 18 F]FDG‐PET, and neuropsychological examination gave normal results, ictal EEG was obscured by artifacts. Ictal [ 99m Tc]HMPAO‐SPECT revealed hyperperfusion in the right anterior part of the insula and right frontal operculum. The seizure onset zone was localized in the right anterior insula based on invasive recordings. Electrical stimulation in that area elicited habitual seizures. A limited resection of the anterior part of the right insula and the right frontal operculum was performed rendering the patient seizure‐free (follow‐up 1 year). To our knowledge, this is the first reported nonlesional patient with an insular seizure onset and NHSs who underwent successful epilepsy surgery.

NGUYEN, VAN ANH MD; WILHELM, MANUEL MD; HÖNLINGER, BETTINA MD; GOTWALD, THADDÄUS MD; SEPP, NORBERT MD Author Information

Forestier's disease is a systemic rheumatologic abnormality of unknown etiology, characterized by a flowing ossification of the anterior ligament of the spine. In this case study we report on an atypical appearance of Forestier's disease in a 72-year-old woman.This patient had a one-month history of rapidly progressing dysphonia and dyspnea and at the time of admission was unable to eat. She had been operated for gastric and colon carcinoma seventeen months earlier. Total body CT scans showed a flowing ossification of the anterior ligament between levels C2 and C7 and an osteophyte protruding in the ventral direction at level C2. Before the osteophyte's removal, a tumor screening was conducted to exclude the presence of distant metastases or occult malignancy. Resection of the large osteophyte was performed via a typical ventral -cervical approach with horizontal skin incision. Six months after the procedure, the patient experienced distinct improvement of her condition and was able to eat both pulpy and solid foods again.In this case example, a rapidly progressive dysphagia was not caused by secondary malignancy, as initially speculated, but resulted from a ventral -cervical osteophyte, considered a rare cause for acute development of severe dysphagia. Early diagnosis of Forestier's disease in this patient led to immediate surgical intervention, which proved to be adequate treatment and enabled the patient to make a good recovery.