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Objective: Anterior temporal lobectomy (ATL) and transsylvian selective amygdalohippocampectomy (tsSAHE) are effective treatment strategies for intractable temporal lobe epilepsy but may cause visual field deficits (VFDs) by damaging the optic radiation (OpR). Due to the OpR's considerable variability and because it is indistinguishable from surrounding tissue without further technical guidance, it is highly vulnerable to iatrogenic injury. This imaging study uses a multimodal approach to assess visual outcomes after epilepsy surgery. Methods: We studied 62 patients who underwent ATL (n = 32) or tsSAHE (n = 30). Analysis of visual outcomes was conducted in four steps, including the assessment of (1) perimetry outcome (VFD incidence/extent, n = 44/40), (2) volumetric OpR tractography damage (n = 55), and the (3) relation of volumetric OpR tractography damage and perimetry outcome (n = 35). Furthermore, (4) fixel‐based analysis (FBA) was performed to assess micro‐ and macrostructural changes within the OpR following surgery (n = 36). Results: Altogether, 56% of all patients had postoperative VFDs (78.9% after ATL, 36.36% after tsSAHE, p =.011). VFDs and OpR tractography damage tended to be more severe within the ATL group (ATL vs. tsSAHE, integrity of contralateral upper quadrant: 65% vs. 97%, p =.002; OpR tractography damage: 69.2 mm3 vs. 3.8 mm3, p =.002). Volumetric OpR tractography damage could reliably predict VFD incidence (86% sensitivity, 78% specificity) and could significantly explain VFD extent (R2 =.47, p =.0001). FBA revealed a more widespread decline of fibre cross‐section within the ATL group. Significance: In the context of controversial visual outcomes following epilepsy surgery, this study provides clinical as well as neuroimaging evidence for a higher risk and greater severity of postoperative VFDs after ATL compared to tsSAHE. Volumetric OpR tractography damage is a feasible parameter to reliably predict this morbidity in both treatment groups and may ultimately support personalized planning of surgical candidates. Advanced diffusion analysis tools such as FBA offer a structural explanation of surgically induced visual pathway damage, allowing noninvasive quantification and visualization of micro‐ and macrostructural tract affection. [ABSTRACT FROM AUTHOR]

Objective: To develop language functional MRI (fMRI) methods that accurately predict postsurgical naming decline in temporal lobe epilepsy (TLE). Methods: Forty‐six patients with TLE (25 left) and 19 controls underwent two overt fMRI paradigms (auditory naming and picture naming, both with active baseline conditions) and one covert task (verbal fluency). Clinical naming performance was assessed preoperatively and 4 months following anterior temporal lobe resection. Preoperative fMRI activations were correlated with postoperative naming decline. Individual laterality indices (LI) were calculated for temporal (auditory and picture naming) and frontal regions (verbal fluency) and were considered as predictors of naming decline in multiple regression models, along with other clinical variables (age at onset of seizures, preoperative naming scores, hippocampal volume, age). Results: In left TLE patients, activation of the left posterior inferior temporal gyrus during auditory naming and activation of left fusiform gyrus during picture naming were related to greater postoperative naming decline. Activation LI were the best individual predictors of naming decline in a multivariate regression model. For picture naming, an LI of higher than 0.34 gave 100% sensitivity and 92% specificity (positive predictive value (PPV) 91.6%). For auditory naming, a temporal lobe LI higher than 0.18 identified all patients with a clinically significant naming decline with 100% sensitivity and 58% specificity (PPV: 58.3%). No effect was seen for verbal fluency. Interpretation: Auditory and picture naming fMRI are clinically applicable to predict postoperative naming decline after left temporal lobe resection in individual patients, with picture naming being more specific. [ABSTRACT FROM AUTHOR]

Summary: Introduction: Medial temporal lobe epilepsy (mTLE) is the most common refractory focal epilepsy in adults. Around 30%‐40% of patients have prominent memory impairment and experience significant postoperative memory and language decline after surgical treatment. BDNF Val66Met polymorphism has also been associated with cognition and variability in structural and functional hippocampal indices in healthy controls and some patient groups. Aims: We examined whether BDNF Val66Met variation was associated with cognitive impairment in mTLE. Methods: In this study, we investigated the association of Val66Met polymorphism with cognitive performance (n = 276), postoperative cognitive change (n = 126) and fMRI activation patterns during memory encoding and language paradigms in 2 groups of patients with mTLE (n = 37 and 34). Results: mTLE patients carrying the Met allele performed more poorly on memory tasks and showed reduced medial temporal lobe activation and reduced task‐related deactivations within the default mode networks in both the fMRI memory and language tasks than Val/Val patients. Conclusions: Although cognitive impairment in epilepsy is the result of a complex interaction of factors, our results suggest a role of genetic factors on cognitive impairment in mTLE. [ABSTRACT FROM AUTHOR]

Interictal generalized epileptiform discharges may impair cognition. We used simultaneous video-electroencephalography and functional imaging to quantify changes, induced by epileptiform discharges, in the task-related activations during a spatial working-memory paradigm. The number of epileptiform discharges increased during the task with its level of complexity, but were not significantly associated with wrong responses during the task. We observed hemodynamic responses in working-memory related frontal-lobe-network, motor-cortex, precuneus, and parietal lobes in the absence of epileptiform discharges. In the presence of epileptiform discharges during the task, task-related hemodynamic changes were seen only in motor-cortex, precuneus, and parietal lobes. These findings suggest that generalized epileptiform discharges during a high demanding working memory task may change the working memory-related hemodynamic responses in frontal-lobe-network. Hum Brain Mapp 34:2910-2917, 2013. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Purpose: Focal epilepsies are often associated with structural and functional changes that may extend beyond the area of seizure onset. In this study we investigated the functional anatomy of memory in patients with frontal lobe epilepsy (FLE), focusing on the local and remote effects of FLE on the networks supporting memory encoding. Methods: We studied 32 patients with drug-resistant FLE and 18 controls using a functional magnetic resonance imaging (fMRI) memory encoding paradigm. Key Findings: During encoding of stimuli, patients with FLE recruited more widely distributed areas than healthy controls, in particular within the frontal lobe contralateral to the seizure onset. Normal memory performance was associated with increased recruitment of frontal areas, and conversely a poor performance was associated with an absence of this increased recruitment and decreased activation in mesial temporal lobe areas. Significance: In patients with FLE, recruitment of wider areas, particularly in the contralateral frontal lobe, appears to be an effective compensatory mechanism to maintain memory function. Impaired hippocampal activation is relatively rare and, in turn, associated with poor recognition memory. [ABSTRACT FROM AUTHOR]

Summary Purpose: Anterior temporal lobe resection (ATLR) controls seizures in up to 70% of patients with intractable temporal lobe epilepsy (TLE) but, in the language dominant hemisphere, may impair language function, particularly naming. Functional reorganization can occur within the ipsilateral and contralateral hemispheres. We investigated reorganization of language in left-hemisphere-dominant patients before and after ATLR; whether preoperative functional magnetic resonance imaging (fMRI) predicts postoperative naming decline; and efficiency of postoperative language networks. Methods: We studied 44 patients with TLE due to unilateral hippocampal sclerosis (24 left) on a 3T GE-MRI scanner. All subjects performed language fMRI and neuropsychological testing preoperatively and again 4 months after left or right ATLR. Key Findings: Postoperatively, individuals with left TLE had greater bilateral middle/inferior frontal fMRI activation and stronger functional connectivity from the left inferior/middle frontal gyri to the contralateral frontal lobe than preoperatively, and this was not observed in individuals with right TLE. Preoperatively, in left and right TLE, better naming correlated with greater preoperative left hippocampal and left frontal activation for verbal fluency (VF). In left TLE, stronger preoperative left middle frontal activation for VF was predictive of greater decline in naming after ATLR. Postoperatively, in left TLE with clinically significant naming decline, greater right middle frontal VF activation correlated with better postoperative naming. In patients without postoperative naming decline, better naming correlated with greater activation in the remaining left posterior hippocampus. In right TLE, naming ability correlated with left hippocampal and left and right frontal VF activation postoperatively. Significance: In left TLE, early postoperative reorganization to the contralateral frontal lobe suggests multiple systems support language function. Postoperatively, ipsilateral recruitment involving the posterior hippocampal remnant is important for maintaining language, and reorganization to the contralateral hemisphere is less effective. Preoperative left middle frontal activation for VF was predictive of naming decline in left TLE after ATLR. [ABSTRACT FROM AUTHOR]

Patients with focal epilepsy that is refractory to medical treatment are often considered candidates for resective surgery. Magnetic resonance imaging (MRI) has a very important role in the presurgical work-up of these patients, but is unremarkable in about one-third of cases. These patients are often deferred from surgery or have a less positive outcome if surgery is eventually undertaken. The aim of this study was to evaluate our recently described voxel-based technique using routine T2-FLAIR (fluid-attenuated inversion-recovery) scans in MRI-negative patients and to compare the results with video-EEG (electroencephalography) telemetry (VT) findings. We identified 70 epilepsy patients with refractory focal seizures who underwent VT and had a normal routine MRI. T2-FLAIR scans were bias-corrected, and intensity and spatially normalized (nFSI) using Statistical Parametric Mapping 5 (SPM5) as previously described. Individual scans were then compared against a set of 25 normal controls using a voxel-based method. SPM5 identified 10 patients with suprathreshold clusters (14.3%). In 50% of these there was concordance between the lobe of the most significant cluster and the presumed lobe of seizure onset, as defined by VT. All cases were concordant with respect to lateralization of the putative focus. Using nFSI we identified focal structural cerebral abnormalities in 11.4% of patients with refractory focal seizures, and normal conventional MRI, that were fully or partially concordant with scalp VT. This voxel-based analysis of FLAIR scans, which are widely available, could provide a useful tool in the presurgical evaluation of epilepsy patients. Ongoing work is to compare these imaging findings with the results of intracranial EEG and histology of surgical resections. [ABSTRACT FROM AUTHOR]

Anterior temporal lobe resections (ATLR) benefit 70% of patients with refractory mesial temporal lobe epilepsy (TLE), but may be complicated by emotional disturbances. We used functional magnetic resonance imaging (fMRI) to investigate the role of the amygdala in processing emotions in TLE and whether this may be a potential preoperative predictive marker for emotional disturbances following surgery. We studied 54 patients with refractory mesial TLE due to hippocampal sclerosis (28 right, 26 left) and 21 healthy controls using a memory encoding fMRI paradigm, which included viewing fearful and neutral faces. Twenty-one TLE patients (10 left, 11 right) subsequently underwent ATLR. Anxiety and depression were assessed preoperatively and 4 months postoperatively using the Hospital Anxiety and Depression Scale. On viewing fearful faces, healthy controls demonstrated left lateralized, while right TLE patients showed bilateral amygdala activation. Left TLE patients had significantly reduced activation in left and right amygdalae compared to controls and right TLE patients. In right TLE patients, left and right amygdala activation was significantly related to preoperative anxiety and depression levels, and preoperative right amygdala activation correlated significantly with postoperative change of anxiety and depression scores, characterized by greater increases in anxiety and depression in patients with greater preoperative activation. No such correlations were seen for left TLE patients. The fearful face fMRI paradigm is a reliable method for visualizing amygdala activation in controls and patients with mesial TLE. Activation of the right amygdala preoperatively was predictive of emotional disturbances following right ATLR. [ABSTRACT FROM AUTHOR]

To investigate the frequency of mutations in the Leucine-Rich Repeat Kinase 2 gene (LRRK2) in a sample of Austrian Parkinson's disease (PD) patients, we sequenced the complete coding region in 16 patients with autosomal dominant PD. Furthermore, we sequenced exons 31, 35, and 41 additionally in 146 patients with idiopathic PD and 30 patients with dementia with Lewy bodies. Furthermore, all 192 patients were screened for 21 putative LRRK2 mutations. While the most common mutation G2019S and the risk variant G2385R were not found in our samples, we detected a novel missense mutation (S973N) in a patient with familial, late-onset and dopa-responsive PD. [ABSTRACT FROM AUTHOR]

Purpose: We systematically analyzed the lateralizing value of clinical seizure semiology in patients with frontal lobe epilepsy (FLE). Methods: We studied the incidence, positive predictive value (PPV), and the lateralizing significance of various clinical symptoms in 228 seizures (s) of 31 patients (p) with medically refractory FLE (17 with left-sided and 14 with right-sided seizure onset). Seizures recorded during prolonged video-EEG monitoring were assessed by two independent reviewers blinded for the patient's clinical data. Analysis was performed both for patients and seizures. Results: Version [16 p (52%); PPV, 94%; p = 0.001; 47 s (21%); PPV, 75%; p = 0.001], unilateral clonic movements [16 p (52%); PPV, 81%; p = 0.021; 32 s (14%); PPV, 81%; p = 0.001], unilateral dystonic posturing [eight p (26%); PPV, 75%; p = 0.289; 46 s (20%); PPV, 80%; p = 0.001], unilateral tonic posturing [10 p (32%); PPV, 80%; p = 0.109; 19 s (7.4%); PPV, 79%; p = 0.019], and unilateral grimacing [10 p (32%); PPV, 100%; p = 0.002; 19 s (8%); PPV, 100%; p = 0.001] were of lateralizing significance, indicating a contralateral seizure onset. Asymmetric ending [five p (16%); PPV, 80%; p = 0.375; nine s (4%); PPV, 89%; p = 0.039] after secondarily generalized tonic–clonic seizures was significantly associated with an ipsilateral seizure onset. Pure ictal vocalizations occurred significantly more frequently in seizures of right hemispheric onset [13 p (42%); PPV, 62%; p = 0.581; 63 s (28%); PPV, 73%; p = 0. 001], whereas in individual patients, this symptom showed no lateralizing significance. The remaining clinical symptoms (figure 4 sign, unilateral hand automatisms, early head turning, postictal nose wiping, and unilateral eye blinking) were not of lateralizing significance in our patients. The results of clinical seizure lateralization corresponded with the final lateralization of the seizure-onset zone in 81% of our patients. Conclusions: Clinical seizure semiology can provide correct information on the lateralization of the seizure-onset zone in >80% of patients with medically refractory frontal lobe epilepsy. [ABSTRACT FROM AUTHOR]

Objective.—To evaluate the efficacy of topiramate in the treatment of migraine aura. Antiepileptic drugs may be useful in migraine prevention through such mechanisms as acting directly on the nociceptive system or by modulating the biochemical phenomena of aura. Topiramate acts directly on N-methyl- d-aspartate and amino-3-hydroxy-5-methylisoxazole-4-propionic acid/kainate glutamate receptors and modulates calcium ion channel activity by inhibiting high-voltage–activated L-type calcium ion channels. Methods.—Twelve patients with migraine with aura were enrolled in an open-label study and treated with topiramate for 6 months. The dose of topiramate was increased weekly by 25 mg up to a daily dose of 100 mg after 4 weeks. Results.—In all 12 patients after 6 months of treatment, topiramate did not statistically influence aura frequency ( P= .317) or duration ( P= .480) compared with baseline. Mild to moderate side effects were observed, but they did not interfere with treatment. Consistent with previous observations, migraine frequency as well as headache intensity and duration improved statistically significantly. Conclusion.—Topiramate is not effective in preventing migraine aura. [ABSTRACT FROM AUTHOR]