DBS emergency surgery for treatment of dystonic storm associated with rhabdomyolysis and acute colitis in DYT-GNAO1.

INTRODUCTION: Patients with variants in the GNAO1 gene may present with life-threatening dystonic storm. There is little experience using pallidal deep brain stimulation (DBS) as an emergency treatment in such cases. CASE DESCRIPTION: We report on a 16-year-old girl with a variant in the GNAO1 gene (c.626G > T; p.(Arg209Leu)) who was admitted to the intensive care unit with medically refractory dystonic storm with secondary complications inducing rhabdomyolysis and acute colitis. Emergency pallidal DBS resulted in rapid improvement of dystonic storm and the subsidence of rhabdomyolysis and colitis. There were no further episodes of dystonic storm during follow-up of 2 years. CONCLUSION: Pallidal DBS is a useful treatment option for GNAO1-related dystonic storm with secondary complications which can be performed as an emergency surgery.

Pitfalls in Genetic Diagnostics: Why Phenotyping is Essential.

New genetic testing technologies have revolutionized medicine within the past years. It is foreseeable that the development will continue with the introduction of new techniques. Nevertheless, despite improved technology, an exact clinical description of the phenotype is still necessary and it is important to critically question findings, both before initiating genetic testing and when interpreting the results. We present four brief case vignettes to point out difficulties associated with correctly interpreting genetic findings.

Serotonin and the Brain's Rich Club-Association Between Molecular Genetic Variation on the TPH2 Gene and the Structural Connectome.

The rich club comprises a densely mutually connected set of hub regions in the brain, thought to serve as a processing and integration core. We assessed the impact of normal variation of the tryptophane hydroxylase 2 gene's promotor region (TPH2 rs4570625) on structural connectivity of the rich club pathways by means of a candidate gene association design. Tryptophane hydroxylase 2 (TPH2) is a rate-limiting enzyme in the biosynthesis of serotonin and is known to inhibit, in addition to its role as a trans-synaptic messenger, axonal and dendritic growth. The TPH2 T-variant has been associated with reduced mRNA expression and reduced serotonin levels, which may particularly influence the development of macroscale anatomical connectivity. Here, we show larger mean connectivity in the rich club in carriers of the T-variant, suggesting potential effects of upregulation of neural connectivity growth in this central core system. In addition, by edge-removal statistics, we show that the TPH2-associated higher levels of rich club connectivity are of importance for the functioning of the total structural network. The observed association is speculated to result from an effect of serotonin levels on brain development, potentially leading to stronger structural connectivity in heavily interconnected hubs.

Variation on the dopamine D2 receptor gene (DRD2) is associated with basal ganglia-to-frontal structural connectivity.

Dopaminergic neurotransmission in the mesocortical system is crucial for higher order cognition. Common variation on the dopamine D2 receptor (DRD2) gene has been linked to individual differences in dopaminergic signaling and was also repeatedly associated to cognitive markers. The relationship between dopaminergic genetic variants and neurostructural properties of the mesocortical system, however, has received little attention so far. Recently, the direction of a dopaminergic manipulation was predicted from the integrity of fiber tracts between subcortical areas and the frontal lobes. Fiber tract integrity was therefore proposed as an indicator of baseline dopamine activity. This raises the question whether DRD2 variants that relate to dopamine turnaround are also linked to fiber tract integrity. In the present study we assessed associations between the DRD2 rs6277 polymorphism and subcortical connections from connectome maps derived from diffusion weighted imaging in n=105 healthy volunteers (43 males and 62 females). Carriers of the CC genotype who are characterized by elevated striatal dopamine turnaround showed higher integrity in terms of fractional anisotropy on fiber tracts between the basal ganglia and frontal regions compared to carriers of the CT and TT variant. Our results indicate that structural connectivity could serve as a conceptual link between genetically determined individual differences in dopaminergic activity and effects of dopamine challenges on executive functioning.

Presurgical entorhinal cortex volume and postoperative seizure outcome in temporal lobe epilepsy.

BACKGROUND: Although temporal lobe surgery is an effective treatment for patients with intractable mesial temporal lobe epilepsy (mTLE), a third of patients will continue to experience seizures at 2 years after surgery. The reasons are unknown. One suggestion is that patients with abnormalities of the entorhinal cortex might have a subtype of mTLE that is resistant to surgery. We investigated the association between presurgical entorhinal cortex volume and postoperative outcome in patients with mTLE. METHODS: 78 patients with intractable mTLE and unilateral hippocampal sclerosis underwent comprehensive presurgical evaluation at the Department of Epileptology, University Hospital Bonn, Germany. Patients and 76 age-matched healthy controls received an MP-RAGE T1-weighted MRI. We determined left and right entorhinal cortex volume, masked to participant identity, using rigorous manual techniques. All patients had complex partial seizures, underwent amygdalohippocampectomy, and received postoperative outcome assessment. FINDINGS: There was a significant effect of group (controls, left mTLE, right mTLE) on the volume of the left (univariate ANOVA F=29·6, p<0·001) and right (F=8·3, p<0·001) entorhinal cortex, and entorhinal asymmetry (F=92·6, p<0·001). Post-hoc analysis with Bonferroni correction revealed that patients with left (p<0·001) and right (p=0·01) mTLE had significantly reduced volume of the ipsilateral entorhinal cortex relative to controls, and patients with right mTLE also had volume reduction of the contralateral entorhinal cortex (p=0·01). We found no significant differences in entorhinal cortex volumes and clinical data between patients (n=48, 62%) surgically rendered seizure free (ILAE I-II) and patients (n=30, 38%) with persistent seizures (ILAE III-VI). INTERPRETATION: These data indicate that gross atrophy of the entorhinal cortex is not a predictor of postoperative outcome in patients with intractable mTLE. We are evaluating whether alterations in entorhinal cortex connectivity and extent of resection are related to postoperative outcome in our series of patients. FUNDING: This work was supported by a UK Medical Research Council grant awarded to SSK.

Thalamotemporal alteration and postoperative seizures in temporal lobe epilepsy.

OBJECTIVE: There are competing explanations for persistent postoperative seizures after temporal lobe surgery. One is that 1 or more particular subtypes of mesial temporal lobe epilepsy (mTLE) exist that are particularly resistant to surgery. We sought to identify a common brain structural and connectivity alteration in patients with persistent postoperative seizures using preoperative quantitative magnetic resonance imaging and diffusion tensor imaging (DTI). METHODS: We performed a series of studies in 87 patients with mTLE (47 subsequently rendered seizure free, 40 who continued to experience postoperative seizures) and 80 healthy controls. We investigated the relationship between imaging variables and postoperative seizure outcome. All patients had unilateral temporal lobe seizure onset, had ipsilateral hippocampal sclerosis as the only brain lesion, and underwent amygdalohippocampectomy. RESULTS: Quantitative imaging factors found not to be significantly associated with persistent seizures were volumes of ipsilateral and contralateral mesial temporal lobe structures, generalized brain atrophy, and extent of resection. There were nonsignificant trends for larger amygdala and entorhinal resections to be associated with improved outcome. However, patients with persistent seizures had significant atrophy of bilateral dorsomedial and pulvinar thalamic regions, and significant alterations of DTI-derived thalamotemporal probabilistic paths bilaterally relative to those patients rendered seizure free and controls, even when corrected for extent of mesial temporal lobe resection. INTERPRETATION: Patients with bihemispheric alterations of thalamotemporal structural networks may represent a subtype of mTLE that is resistant to temporal lobe surgery. Increasingly sensitive multimodal imaging techniques should endeavor to transform these group-based findings to individualize prediction of patient outcomes.

Distinct white matter integrity in glutamic acid decarboxylase and voltage-gated potassium channel-complex antibody-associated limbic encephalitis.

OBJECTIVE: Autoantibodies against glutamic acid decarboxylase (GAD) and the voltage-gated potassium channel (VGKC) complex are associated with distinct subtypes of limbic encephalitis regarding clinical presentation, response to therapy, and outcome. The aim of this study was to investigate white matter changes in these two limbic encephalitis subtypes by means of diffusion tensor imaging (DTI). METHODS: Diffusion data were obtained in 14 patients with GAD antibodies and 16 patients with VGKC-complex antibodies and compared with age- and gender-matched control groups. Voxelwise statistical analysis was carried out using tract-based spatial statistics. The results were furthermore compared with those of 15 patients with unilateral histologically confirmed hippocampal sclerosis and correlated with verbal and figural memory performance. RESULTS: We found widespread changes of fractional anisotropy and all diffusivity parameters in GAD-associated limbic encephalitis, whereas no changes were found in VGKC-complex-associated limbic encephalitis. The changes observed in the GAD group were even more extensive when compared against those of the hippocampal sclerosis group, although the disease duration was markedly shorter in patients with GAD antibodies. Correlation analysis revealed areas with a trend toward a negative correlation of diffusivity parameters with figural memory performance located mainly in the right temporal lobe in the GAD group as well. SIGNIFICANCE: The present study provides further evidence that, depending on the associated antibody, limbic encephalitis features clearly distinct imaging characteristics by showing widespread white matter changes in GAD-associated limbic encephalitis and preserved white matter integrity in VGKC-complex-associated limbic encephalitis. Furthermore, our results contribute to a better understanding of the specific pathophysiologic properties in these two subforms of limbic encephalitis by revealing that patients with GAD antibodies show widespread affections of white matter across various regions of the brain. In contrast to this, the inflammatory process seems to be more localized in VGKC-complex-associated limbic encephalitis, primarily affecting mesiotemporal gray matter.

Morphometric MRI alterations and postoperative seizure control in refractory temporal lobe epilepsy.

Refractory mesial temporal lobe epilepsy (mTLE) is a debilitating condition potentially amenable to resective surgery. However, between 40 and 50% patients continue to experience postoperative seizures. The development of imaging prognostic markers of postoperative seizure outcome is a crucial objective for epilepsy research. In the present study, we performed analyses of preoperative cortical thickness and subcortical surface shape on MRI in 115 of patients with mTLE and radiologically defined hippocampal sclerosis being considered for surgery, and 80 healthy controls. Patients with excellent (International League Against Epilepsy outcome (ILAE) I) and suboptimal (ILAE II-VI) postoperative outcomes had a comparable distribution of preoperative atrophy across the cortex, basal ganglia, and amygdala. Conventional volumetry of whole hippocampal and extrahippocampal subcortical structures, and of global gray and white matter, could not differentiate between patient outcome groups. However, surface shape analysis revealed localized atrophy of the thalamus bilaterally and of the posterior/lateral hippocampus contralateral to intended resection in patients with persistent postoperative seizures relative to those rendered seizure free. Data uncorrected for multiple comparisons also revealed focal atrophy of the ipsilateral hippocampus posterior to the margins of resection in patients with persistent seizures. This data indicates that persistent postoperative seizures after temporal lobe surgery are related to localized preoperative shape alterations of the thalamus bilaterally and the hippocampus contralateral to intended resection. Imaging techniques that have the potential to unlock prognostic markers of postoperative outcome in individual patients should focus assessment on a bihemispheric thalamohippocampal network in prospective patients with refractory mTLE being considered for temporal lobe surgery.

Brain tumors in children with refractory seizures­a long-term follow-up study after epilepsy surgery.

PURPOSE: Epilepsy surgery is an established treatment option for medically refractory epilepsy. Brain tumors, besides dysplasias, vascular malformations, and other lesions, can cause refractory epilepsy. Long-term epilepsy-associated brain tumors, even though mostly benign, are neoplastic lesions and thus have to be considered as both epileptic and oncological lesions. METHODS: We retrospectively analyzed epileptological and oncological long-term follow-up (FU) in pediatric patients who underwent brain surgery for refractory epilepsy and whose histology showed a tumor as underlying cause (n = 107, mean FU 119 months). RESULTS: At last available outcome, 82.2% of patients were seizure free (International League Against Epilepsy (ILAE) class 1) and seizure outcome was stable over more than 14 years. Fifty-four percent of the patients were without anti-epileptic drugs (AEDs) at last available outcome; 96.2% of the tumors were classified WHO grade I and II and 3.7% were malignant (WHO grade III). Adjuvant treatment was administered in 5.7%; 2.9% had relapse and one patient died (tumor-related mortality = 1.4%). After surgery, 91% of the patients attended regular school/university and/or professional training. CONCLUSIONS: This study shows that epileptological outcome within this group is promising and stable and oncological outcome has a very good prognosis. However, oncological FU must not be dismissed as a small percentage of patients who suffer from malignant tumors and adjuvant treatment, relapse, and mortality have to be considered.

In vivo mapping of hippocampal subfields in mesial temporal lobe epilepsy: relation to histopathology.

A particularly popular automated magnetic resonance imaging (MRI) hippocampal subfield mapping technique is the one described by Van Leemput et al. (2009: Hippocampus 19:549-557) that is currently distributed with FreeSurfer software. This method assesses the probabilistic locations of subfields based on a priori knowledge of subfield topology determined from high-field MRI. Many studies have applied this technique to conventionally acquired T1-weighted MRI data. In the present study, we investigated the relationship between this technique applied to conventional T1-weighted MRI data acquired at 3 T and postsurgical hippocampal histology in patients with medically intractable mesial temporal lobe epilepsy (mTLE) and hippocampal sclerosis (HS). Patients with mTLE (n = 82) exhibited significant volume loss of ipsilateral CA1, CA2-3, CA4-dentate gyrus (DG), subiculum, and fimbria relative to controls (n = 81). Histopathological analysis indicated that the most significant neuronal loss was observed in CA1, then CA4 and CA3, and more subtle neuronal loss in CA2, consistent with classical HS. Neuronal density of CA1 significantly correlated with MRI-determined volume of CA1, and increasingly so with CA2-3 and CA4-DG. Patients with increased HS based on histopathology had greater volume loss of the ipsilateral hippocampal regions on MRI. We conclude by suggesting that whilst time efficient and fully reproducible when applied to conventional single acquisition sequences, the use of the automated subfield technique described here may necessitate the application to multiacquisition high-resolution MR sequences for accurate delineation of hippocampal subfields.

Safety, feasibility and complications during resective pediatric epilepsy surgery: a retrospective analysis.

BACKGROUND: Resective epilepsy surgery is an established and effective method to reduce seizure burden in drug-resistant epilepsy. It was the objective of this study to assess intraoperative blood loss, transfusion requirements and the degree of hypothermia of pediatric epilepsy surgery in our center. METHODS: Patients were identified by our epilepsy surgery database, and data were collected via retrospective chart review over the past 25 years. Patients up to the age of 6 years were included, and patients with insufficient data were excluded. RESULTS: Forty-five patients with an age of 3.2 ± 1.6 (mean ± SD) years and a body weight of 17 [14; 21.5] kg (median [25%, 75% percentile]) were analysed. Duration of surgery was 3 h 49 min ± 53 min, which was accompanied by an intraoperative blood loss of 150 [90; 300] ml. This corresponded to 11.7 [5.2; 21.4] % of estimated total blood volume, ranging from 0 to 75%. A minimal haemoglobin count of 8.8 ± 1.4 g/dl was measured, which was substituted with erythrocyte concentrate (100 [0; 250] ml) in 23 patients. Body core temperature dropped from 36.0 ± 0.7°C at baseline to a minimum of 35.7 ± 0.7°C, and increased significantly (p < 0.001) thereafter to 37.1 ± 0.7°C until the end of surgery. A significant (p = 0.0003) correlation between duration of surgery and blood loss (Pearson r = 0.52) was observed. However, age, minimal body temperature or number of antiepileptic drugs seemed to have no impact on blood loss. CONCLUSION: Resective epilepsy surgery is a safe procedure even in the pediatric population, however it is associated with significant blood loss especially during long surgical procedures.

Progressive fiber tract affections after temporal lobe surgery.

SUMMARY: Several studies reported changes in white matter architecture following temporal lobe surgery in patients with temporal lobe epilepsy (TLE) at short intervals after surgery. We investigated 20 patients with left-sided TLE using diffusion-imaging at two time points, that is, at 3-6 months and 12 months after surgery, to investigate postsurgical plasticity. We observed a loss of fiber tract integrity mainly in fiber tracts of the ipsilateral temporal lobe. Our data show that the remodeling of brain connectivity after surgical interventions continues for longer time periods. The functional implications of these plastic changes will have to be explored.

Quantitative FLAIR analysis indicates predominant affection of the amygdala in antibody-associated limbic encephalitis.

PURPOSE: Limbic encephalitis is an autoimmune-mediated disease leading to temporal lobe epilepsy, mnestic deficits, and affective disturbances. Magnetic resonance imaging (MRI) usually shows signal and volume changes of the temporomesial structures. However, these abnormalities may be subtle, thereby hampering the diagnosis by conventional visual assessment. In the present study we evaluated the diagnostic value of a fully automated MRI postprocessing technique in limbic encephalitis and hippocampal sclerosis. METHODS: The MRI postprocessing was based largely on a recently described method allowing for an observer-independent quantification of the fluid-attenuated inversion recovery (FLAIR) signal intensities of amygdala and hippocampus. A 95% confidence region was calculated from the FLAIR intensities of 100 healthy controls. We applied this analysis to the MRI data of 39 patients with antibody-associated limbic encephalitis and 63 patients with hippocampal sclerosis. Moreover, the results were compared to those of visual assessment by an experienced neuroradiologist. KEY FINDINGS: The method detected limbic encephalitis and hippocampal sclerosis with a high sensitivity of 85% and 95%, respectively. The detection rate of the automated approach in limbic encephalitis was significantly superior to visual analysis (85% vs. 51%; p = 0.001), whereas no statistically significant difference for the detection rate in hippocampal sclerosis was found. Patients with limbic encephalitis had significantly higher absolute intensity values of the amygdala and a significantly higher percentage fell outside of the amygdalar confidence region compared to those with hippocampal sclerosis (79% vs. 27%; p < 0.001), whereas we found opposite results in the hippocampal analysis (38% vs. 95%; p < 0.001). SIGNIFICANCE: The FLAIR analysis applied in this study is a powerful tool to quantify signal changes of the amygdala and hippocampus in limbic encephalitis and hippocampal sclerosis. It significantly increases the diagnostic sensitivity in limbic encephalitis in comparison to conventional visual analysis. Furthermore, the method provides an interesting insight into the distinct properties of these two disease entities on MRI, indicating a predominant affection of the amygdala in limbic encephalitis, whereas the affection of the hippocampus is far less pronounced when compared to hippocampal sclerosis.

Automated 3D MRI volumetry reveals regional atrophy differences in Rasmussen encephalitis.

PURPOSE: Rasmussen encephalitis is a chronic immune-mediated disease leading to unilateral atrophy on magnetic resonance imaging (MRI) and progressive neurologic deficits. Until now, quantitative parameters describing the course of the disease on MRI require manual intervention and are, therefore, time-consuming and observer-dependent. Furthermore, regional atrophy differences cannot be evaluated with the previously published methods. In this study we present a fully automated volumetric approach applied to serial MRI scans of 12 patients with Rasmussen encephalitis. METHODS: We retrospectively analyzed 12 patients with Rasmussen encephalitis with a disease onset between 2001 and 2008. All patients underwent a total of 66 serial MRI scans including a three-dimensional T(1) data set. The volumetric analysis was based on standard procedures of the freely available software FMRIB Software Library (FSL) and required about 45 min per scan. Furthermore, planimetric analyses were performed on 51 scans as described previously. KEY FINDINGS: The relative and absolute volume loss of the affected hemisphere was significantly higher compared to the unaffected hemisphere. Referring to regional atrophy differences our results show that the frontal lobe and the insula were preferentially involved in the atrophic process. The degree of hemispheric, parietal, and occipital atrophy was negatively correlated with the age at disease onset, indicating a more aggressive and outspread disease in young children compared to adolescents. Volumetric hemispheric ratio and planimetric hemispheric ratio correlated significantly, but planimetric hemispheric ratio underestimated the real degree of hemiatrophy, especially in patients with predominant affections outside the frontoinsular region. SIGNIFICANCE: The volumetric analysis presented here offers a precise assessment of the disease progression in Rasmussen encephalitis in an observer-independent and time-efficient manner and gives an interesting insight into the course of the disease on MRI. The degree of atrophy evaluated with this method correlates with clinical parameters and is comparable to atrophy rates in patients receiving immunotherapy in preceding planimetric MRI studies.

The brain in myotonic dystrophy 1 and 2: evidence for a predominant white matter disease.

Myotonic dystrophy types 1 and 2 are progressive multisystemic disorders with potential brain involvement. We compared 22 myotonic dystrophy type 1 and 22 myotonic dystrophy type 2 clinically and neuropsychologically well-characterized patients and a corresponding healthy control group using structural brain magnetic resonance imaging at 3 T (T(1)/T(2)/diffusion-weighted). Voxel-based morphometry and diffusion tensor imaging with tract-based spatial statistics were applied for voxel-wise analysis of cerebral grey and white matter affection (P(corrected) < 0.05). We further examined the association of structural brain changes with clinical and neuropsychological data. White matter lesions rated visually were more prevalent and severe in myotonic dystrophy type 1 compared with controls, with frontal white matter most prominently affected in both disorders, and temporal lesions restricted to myotonic dystrophy type 1. Voxel-based morphometry analyses demonstrated extensive white matter involvement in all cerebral lobes, brainstem and corpus callosum in myotonic dystrophy types 1 and 2, while grey matter decrease (cortical areas, thalamus, putamen) was restricted to myotonic dystrophy type 1. Accordingly, we found more prominent white matter affection in myotonic dystrophy type 1 than myotonic dystrophy type 2 by diffusion tensor imaging. Association fibres throughout the whole brain, limbic system fibre tracts, the callosal body and projection fibres (e.g. internal/external capsules) were affected in myotonic dystrophy types 1 and 2. Central motor pathways were exclusively impaired in myotonic dystrophy type 1. We found mild executive and attentional deficits in our patients when neuropsychological tests were corrected for manual motor dysfunctioning. Regression analyses revealed associations of white matter affection with several clinical parameters in both disease entities, but not with neuropsychological performance. We showed that depressed mood and fatigue were more prominent in patients with myotonic dystrophy type 1 with less white matter affection (early disease stages), contrary to patients with myotonic dystrophy type 2. Thus, depression in myotonic dystrophies might be a reactive adjustment disorder rather than a direct consequence of structural brain damage. Associations of white matter affection with age/disease duration as well as patterns of cerebral water diffusion parameters pointed towards an ongoing process of myelin destruction and/or axonal loss in our cross-sectional study design. Our data suggest that both myotonic dystrophy types 1 and 2 are serious white matter diseases with prominent callosal body and limbic system affection. White matter changes dominated the extent of grey matter changes, which might argue against Wallerian degeneration as the major cause of white matter affection in myotonic dystrophies.

Multi-scale image analysis and prediction of visual field defects after selective amygdalohippocampectomy.

Selective amygdalohippocampectomy is an effective treatment for patients with therapy-refractory temporal lobe epilepsy but may cause visual field defect (VFD). Here, we aimed to describe tissue-specific pre- and postoperative imaging correlates of the VFD severity using whole-brain analyses from voxel- to network-level. Twenty-eight patients with temporal lobe epilepsy underwent pre- and postoperative MRI (T1-MPRAGE and Diffusion Tensor Imaging) as well as kinetic perimetry according to Goldmann standard. We probed for whole-brain gray matter (GM) and white matter (WM) correlates of VFD using voxel-based morphometry and tract-based spatial statistics, respectively. We furthermore reconstructed individual structural connectomes and conducted local and global network analyses. Two clusters in the bihemispheric middle temporal gyri indicated a postsurgical GM volume decrease with increasing VFD severity (FWE-corrected p < 0.05). A single WM cluster showed a fractional anisotropy decrease with increasing severity of VFD in the ipsilesional optic radiation (FWE-corrected p < 0.05). Furthermore, patients with (vs. without) VFD showed a higher number of postoperative local connectivity changes. Neither in the GM, WM, nor in network metrics we found preoperative correlates of VFD severity. Still, in an explorative analysis, an artificial neural network meta-classifier could predict the occurrence of VFD based on presurgical connectomes above chance level.

Widespread affections of large fiber tracts in postoperative temporal lobe epilepsy.

Temporal lobe epilepsy with hippocampus sclerosis (HS) is the most frequent focal epilepsy and often refractory to anticonvulsant therapy. Secondary structural damage has been reported in several studies of temporal lobe epilepsy and unilateral hippocampal sclerosis. Applying diffusion tensor imaging (DTI) we investigated alterations in white matter following temporal lobe surgery in patients with medial temporal lobe epilepsy. We examined 40 patients who underwent surgery at our hospital for HS between 1996 and 2006 with diffusion tensor imaging (DTI). Images were obtained at a 3 T MRI scanner employing 60 gradient directions. Tract-based spatial statistics (TBSS), a novel voxel-based approach, was applied to analyze the data. Both patients with left- as well as right-sided surgery exhibited widespread degradation of fractional anisotropy (FA) in main fiber tracts not limited to the respective temporal lobe such as the uncinate fasciculus, the fronto-occipital fasciculus, the superior longitudinal fasciculus, the corpus callosum and the corticospinal tract on the respective hemisphere. Patients with left-hemispheric surgery showed more widespread affections ipsilaterally and also FA decrease in the contralateral inferior longitudinal fasciculus. DTI demonstrates widespread clusters of abnormal diffusivity and anisotropy in prominent white matter tracts linking mesial temporal lobe structures with other brain areas. Alterations in the ipsilateral mesial temporal lobe can be attributed to be a result of surgery, whereas extratemporal FA decrease is more likely the result of the underlying seizure disorder.

Tracking the brain in myotonic dystrophies: A 5-year longitudinal follow-up study.

OBJECTIVES: The aim of this study was to examine the natural history of brain involvement in adult-onset myotonic dystrophies type 1 and 2 (DM1, DM2). METHODS: We conducted a longitudinal observational study to examine functional and structural cerebral changes in myotonic dystrophies. We enrolled 16 adult-onset DM1 patients, 16 DM2 patients, and 17 controls. At baseline and after 5.5 ± 0.4 years participants underwent neurological, neuropsychological, and 3T-brain MRI examinations using identical study protocols that included voxel-based morphometry and diffusion tensor imaging. Data were analyzed by (i) group comparisons between patients and controls at baseline and follow-up, and (ii) group comparisons using difference maps (baseline-follow-up in each participant) to focus on disease-related effects over time. RESULTS: We found minor neuropsychological deficits with mild progression in DM1 more than DM2. Daytime sleepiness was restricted to DM1, whereas fatigue was present in both disease entities and stable over time. Comparing results of cross-sectional neuroimaging analyses at baseline and follow-up revealed an unchanged pattern of pronounced white matter alterations in DM1. There was mild additional gray matter reduction in DM1 at follow-up. In DM2, white matter reduction was of lesser extent, but there were some additional alterations at follow-up. Gray matter seemed unaffected in DM2. Intriguingly, longitudinal analyses using difference maps and comparing them between patients and controls did not reveal any significant differences of cerebral changes over time between patients and controls. CONCLUSION: The lack of significant disease-related progression of gray and white matter involvement over a period of five years in our cohort of DM1 and DM2 patients suggests either a rather slowly progressive process or even a stable course of cerebral changes in middle-aged adult-onset patients. Being the first longitudinal neuroimaging trial in DM1 and DM2, this study provides useful additional information regarding the natural history of brain involvement.

Structural connectivity changes in temporal lobe epilepsy: Spatial features contribute more than topological measures.

BACKGROUND: Previous studies reported reduced volumes of many brain regions for temporal lobe epilepsy (TLE). It has also been suggested that there may be widespread changes in network features of TLE patients. It is not fully understood, however, how these two observations are related. METHODS: Using magnetic resonance imaging data, we perform parcellation of the brains of 22 patients with left TLE and 39 non-epileptic controls. In each parcellated region of interest (ROI) we computed the surface area and, using diffusion tensor imaging and deterministic tractography, infer the number of streamlines and their average length between each pair of connected ROIs. For comparison to previous studies, we use a connectivity 'weight' and investigate how ROI surface area, number of streamlines & mean streamline length contribute to such weight. RESULTS: We find that although there are widespread significant changes in surface area and position of ROIs in patients compared to controls, the changes in connectivity are much more subtle. Significant changes in connectivity weight can be accounted for by decreased surface area and increased streamline count. CONCLUSION: Changes in the surface area of ROIs can be a reliable biomarker for TLE with a large influence on connectivity. However, changes in structural connectivity via white matter streamlines are more subtle with a relatively lower influence on connection weights.

Neuropsychological outcome after epilepsy surgery in patients with bilateral Ammon's horn sclerosis.

OBJECT: The purpose of this study was to retrospectively assess the objective and subjective neuropsychological outcome after epilepsy surgery in patients with bilateral Ammon's horn sclerosis (AHS). METHODS: Memory and executive functions were evaluated at baseline and at follow-up in 11 surgically treated patients and compared with 8 pharmacologically treated patients with temporal lobe epilepsy and bilateral AHS. The median follow-up duration was 16 months in the surgically treated patients and 80.5 months in the pharmacologically treated group. Subjective outcome was evaluated by questionnaires and included mood, quality of life, subjective memory, and activities of daily living. RESULTS: At the follow-up assessment, 82% of the surgically treated patients as opposed to 0% of the nonsurgery patients were seizure free. In the surgical group, nonverbal memory performance did not change significantly in any patient after surgery, but there was a floor effect in 55% of the surgical patients. Regarding verbal memory, 9% of the surgical patients improved while 73% declined, despite severe impairments already evident at baseline. In the nonsurgery control group, 13% of the patients declined in nonverbal memory (floor effect in 63%) and 25% declined in verbal memory (floor effect in 25%) at follow-up. None of the controls improved at follow-up. Executive functions remained unchanged on an impaired level in both groups. At follow-up, the patient groups did not differ significantly with respect to mood, quality of life, subjective memory, or activities of daily living. However, in most aspects, surgically treated patients reported a slightly better subjective outcome than pharmacologically treated patients and a significantly improved quality of life. CONCLUSIONS: These results suggest that beyond benefits concerning seizure control, surgically treated patients with bilateral AHS, despite already poor baseline performance, are still at risk for severe postoperative decline in memory. In the light of predominantly minor benefits on a subjective level, the findings put the overall outcome of epilepsy surgery in bilateral AHS patients into perspective.