Katja Menzler

Men and women are different: Diffusion tensor imaging reveals sexual dimorphism in the microstructure of the thalamus, corpus callosum and cingulum

INTRODUCTION Numerous magnetic resonance imaging (MRI) studies have addressed the question of morphological differences of the brain of men and women, reporting conflicting results regarding brain size and the ratio of gray and white matter. In the present study, we used diffusion tensor imaging (DTI) to delineate sex differences of brain white matter. METHODS We investigated brain microstructure in 25 male and 25 female healthy subjects using a 3T MRI scanner. Whole-head DTI scans were analyzed without a-priori hypothesis using Tract-Based Spatial Statistics (TBSS) calculating maps of fractional anisotropy (FA), radial diffusivity (RD, a potential marker of glial alteration and changes in myelination) and axial diffusivity (AD, a potential marker of axonal changes). RESULTS DTI revealed regional microstructural differences between the brains of male and female subjects. Those were prominent in the thalamus, corpus callosum and cingulum. Men showed significantly (p<0.0001) higher values of fractional anisotropy and lower radial diffusivity in these areas, suggesting that the observed differences are mainly due to differences in myelination. DISCUSSION As a novel finding we showed widespread differences in thalamic microstructure that have not been described previously. Additionally, the present study confirmed earlier DTI studies focusing on sexual dimorphism in the corpus callosum and cingulum. All changes appear to be based on differences in myelination. The sex differences in thalamic microstructure call for further studies on the underlying cause and the behavioral correlates of this sexual dimorphism. Future DTI group studies may carefully control for gender to avoid confounding.

Invasive EEG studies in tumor-related epilepsy: When are they indicated and with what kind of electrodes?

Patients with tumor‐related epilepsy (TRE) represent an important proportion of epilepsy surgery cases. Recently established independent negative predictors of postoperative seizure outcome are long duration of epilepsy, presence of generalized tonic–clonic seizures, and incomplete tumor resection. In temporal lobe cases, additional hippocampectomy or corticectomy may further improve outcome. Invasive electroencephalography (EEG) recordings (IEEG) may be indicated to guide the resection by defining eloquent cortex (EC) or to determine the extent of potentially magnetic resonance imaging (MRI)–negative epileptogenic tissue. In fact, invasive recordings are reportedly used in up to 10% of patients who are undergoing epilepsy surgery for TRE. Following careful consideration of the concepts underlying epilepsy surgery, the current use of IEEG, and the predictors of outcome in extratemporal and temporal tumors in TRE, we postulate the following> (1) In patients with extratemporal TRE, IEEG is necessary only if the MRI lesion (and if feasible a rim around it) cannot be completely resected because of adjacent or overlapping EC. In these cases, EC should be mapped to determine its relationships to the lesion, the irritative, and seizure‐onset zones in order to maximize the extent of the lesionectomy. (2) In patients with nondominant temporal TRE, data suggest that if epileptogenic tumors (ETs) are encroaching on mesial temporal structures, if epilepsy duration is long, and seizures are frequent and disabling, these structures should be included in the resection. (3) In patients with dominant temporal TRE, we suggest leaving the mesial structures in place if they are functionally and structurally intact and to consider resecting these structures only if they are structurally and functionally abnormal. There is insufficient evidence justifying the use of IEEG to define the extent of the epileptogenic zone in such cases. This should be reserved for cases where an initial lesionectomy has failed.

In vivo demonstration of microstructural brain pathology in progressive supranuclear palsy: A DTI study using TBSS

We investigated DTI changes, potentially indicating alterations of microstructure and brain tissue integrity in 13 patients with probable progressive supranuclear palsy (PSP, Richardson syndrome) at stage III or less and 10 age‐matched controls using a whole brain analysis of diffusion tensor imaging (DTI) data. DTI images were analyzed using tract‐based spatial statistics, a hypothesis‐free technique. Fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD) were determined. In patients with PSP, significant increases in FA (P < 0.0001), an unspecific measure of microstructural tissue integrity, were found in the cerebellum and in the superior cerebellar peduncle bilaterally, in the fornix, the body of the corpus callosum and the olfactory region, when compared with age‐matched healthy controls. Further, regional reductions in AD (P < 0.0001), an indicator of altered axonal integrity, were observed in the pons, the right substantia nigra and the cerebellar white matter bilaterally. Significant increases in RD (P < 0.0001), a potential measure of altered myelin integrity, occurred bilaterally in the superior cerebellar peduncle, the cerebellar white matter, the vermis of the cerebellum, the fornix, the body of the corpus callosum, and the olfactory region. RD values in the superior cerebellar peduncle discriminated patients with PSP and controls with high sensitivity (0.92) and specificity (1.0). The findings are supported by neuropathological studies. Our data suggest the usefulness of this clinically available new technique as a possible tool for differential diagnosis.

Cavernoma-related epilepsy: Review and recommendations for management - Report of the Surgical Task Force of the ILAE Commission on Therapeutic Strategies

Cerebral cavernous malformations (CCMs) are well‐defined, mostly singular lesions present in 0.4–0.9% of the population. Epileptic seizures are the most frequent symptom in patients with CCMs and have a great impact on social function and quality of life. However, patients with CCM‐related epilepsy (CRE) who undergo surgical resection achieve postoperative seizure freedom in only about 75% of cases. This is frequently because insufficient efforts are made to adequately define and resect the epileptogenic zone. The Surgical Task Force of the Commission on Therapeutics of the International League Against Epilepsy (ILAE) and invited experts reviewed the pertinent literature on CRE. Definitions of definitive and probable CRE are suggested, and recommendations regarding the diagnostic evaluation and etiology‐specific management of patients with CRE are made. Prospective trials are needed to determine when and how surgery should be done and to define the relations of the hemosiderin rim to the epileptogenic zone.

Diffusion tensor imaging in episodic cluster headache.

Background.— Cluster headache (CH) is a rare headache disorder with severe unilateral headache bouts and autonomic symptoms. The pathophysiology of CH is not completely understood. Using a voxel‐based morphometric paradigm or functional imaging, a key role of the hypothalamus and the pain matrix could be demonstrated during CH episodes. However, there are no diffusion tensor imaging (DTI) data investigating the white matter microstructure of the brain in patients with CH. Therefore, we used DTI to delineate microstructural changes in patients with CH in a headache‐free state.

Comparing the neural correlates of affective and cognitive theory of mind using fMRI: Involvement of the basal ganglia in affective theory of mind.

Theory of Mind (ToM) is the ability to infer other people’s mental states like intentions or desires. ToM can be differentiated into affective (i.e., recognizing the feelings of another person) and cognitive (i.e., inferring the mental state of the counterpart) subcomponents. Recently, subcortical structures such as the basal ganglia (BG) have also been ascribed to the multifaceted concept ToM and most BG disorders have been reported to elicit ToM deficits. In order to assess both the correlates of affective and cognitive ToM as well as involvement of the basal ganglia, 30 healthy participants underwent event-related fMRI scanning, neuropsychological testing, and filled in questionnaires concerning different aspects of ToM and empathy. Directly contrasting affective (aff) as well as cognitive (cog) ToM to the control (phy) condition, activation was found in classical ToM regions, namely parts of the temporal lobe including the superior temporal sulcus, the supplementary motor area, and parietal structures in the right hemisphere. The contrast aff > phy yielded additional activation in the orbitofrontal cortex on the right and the cingulate cortex, the precentral and inferior frontal gyrus and the cerebellum on the left. The right BG were recruited in this contrast as well. The direct contrast aff > cog showed activation in the temporoparietal junction and the cingulate cortex on the right as well as in the left supplementary motor area. The reverse contrast cog > aff however did not yield any significant clusters. In summary, affective and cognitive ToM partly share neural correlates but can also be differentiated anatomically. Furthermore, the BG are involved in affective ToM and thus their contribution is discussed as possibly providing a motor component of simulation processes, particularly in affective ToM.

DTI reveals hypothalamic and brainstem white matter lesions in patients with idiopathic narcolepsy

BACKGROUND Symptomatic narcolepsy is often related to hypothalamic, pontine, or mesencephalic lesions. Despite evidence of disturbances of the hypothalamic hypocretin system in patients with idiopathic narcolepsy, neuroimaging in patients with idiopathic narcolepsy revealed conflicting results and there is limited data on possible structural brain changes that might be associated with this disorder. METHODS We investigated with diffusion tensor imaging (DTI) whether microstructural abnormalities in the brain of eight patients with idiopathic narcolepsy with cataplexy are detectable compared to 12 healthy controls using a 1.5T MRI scanner. Whole-head DTI scans were analyzed without an a priori hypothesis. Voxelwise statistical analysis of fractional anisotropy (FA) data was performed using Tract-Based Spatial Statistics (TBSS), a non-linear analysis approach. RESULTS Patients with narcolepsy showed microstructural white matter changes in the right hypothalamus as well as in the left mesencephalon, pons, and medulla oblongata. Additionally, areas in the left temporal lobe, the pre- and postcentral gyrus, the frontal and parietal white matter, the corona radiata, the right internal capsule, and the caudate nucleus had altered microstructure in patients with narcolepsy. CONCLUSIONS Our study shows widespread microstructural white matter changes that are not visible on conventional MRI scans in patients with idiopathic narcolepsy. In support of the evidence from patients with symptomatic narcolepsy, we found microstructural changes in the hypothalamus, mesencephalon, pons, and medulla oblongata. Changes are in accordance with disturbances of the hypothalamic hypocretin system and its projections to mesencephalic and pontine areas regulating REM sleep.

Epileptogenicity of cavernomas depends on (archi-) cortical localization.

BACKGROUND:Patients with cerebral cavernomas have an estimated risk of the development of epilepsy of 1.5% to 2.4% per patient-year. OBJECTIVE:To clarify the predictive value of different risk factors for epilepsy in patients with supratentorial cavernomas. METHODS:We retrospectively analyzed data of 109 patients with supratentorial cavernomas. The correlation of epilepsy with the variables of single or multiple cavernomas, sex, age, side, cortical involvement, mesiotemporal archicortical vs neocortical involvement, lobar location of neocortical cavernomas, the presence of a hemosiderin rim and of edema, and the maximal diameters of cavernoma, hemosiderin rim, and edema, if present, were calculated using univariate and multivariate penalized likelihood logistic regression models. RESULTS:Cortical involvement was the most relevant risk factor for epilepsy (P < .0001). No patient with a subcortical cavernoma presented with epilepsy. Epilepsy was more common in patients with mesiotemporal archicortical cavernomas than in patients with neocortical cavernomas (P = .02), whereas the lobar location of neocortical cavernomas was not significantly associated with the risk of the development of epilepsy. In the multivariate analysis, a greater diameter of the cavernoma, the absence of edema, and localization in the left hemisphere were also associated with the occurrence of epilepsy (P < .05). CONCLUSION:The epileptogenicity of supratentorial cavernomas depends on cortical, especially mesiotemporal archicortical, involvement. Exclusively subcortical cavernomas are highly unlikely to cause epilepsy. This information is helpful in counseling patients with cavernomas regarding their risk of epileptic seizures and in patients with multiple cavernomas and epilepsy to generate a valid hypothesis of which cavernoma may cause epilepsy.

The role of underlying structural cause for epilepsy classification: Clinical features and prognosis in mesial temporal lobe epilepsy caused by hippocampal sclerosis versus cavernoma

Purpose:  The recent “Report of the ILAE Commission on Classification and Terminology” recommends an epilepsy classification that gives more emphasis to the underlying structural or metabolic cause rather than to the localization of the epileptogenic zone. The aim of the present study was to investigate differences in clinical features, treatment response, and prognosis in patients with mesial temporal lobe epilepsy (MTLE) caused by hippocampal sclerosis (MTLE‐HS) or singular mesiotemporal cavernomas (MTLE‐C) in order to evaluate the impact of underlying pathology on the course of the disease while controlling for localization.

At-home tDCS of the left dorsolateral prefrontal cortex improves visual short-term memory in mild vascular dementia

OBJECTIVES Previous studies have shown that anodal transcranial direct current stimulation (tDCS) of the left dorsolateral prefrontal cortex (DLPFC) led to an improvement of various cognitive functions in patients with Alzheimer dementia, early affected by short-term memory deficits. Since this approach has not been evaluated in the context of vascular dementia, which rather affects the velocity of cognitive responses, we aimed at improving these functions by applying repetitive sessions of anodal tDCS. METHODS Four 20-minute sessions of 2mA anodal or sham at-home tDCS were applied to the left DLPFC in a single-blinded randomised study of 21 patients with mild vascular dementia, with parallel-group design. The effect of tDCS on cognitive testing was assessed up to two weeks beyond the stimulation time. RESULTS A similar clinically meaningful improvement of various cognitive and behavioral dysfunction characteristics could be observed following either active or sham tDCS, whereas visual recall, and reaction times in the n-back task as well as in the go/no-go test improved only in the active tDCS group. CONCLUSIONS In patients with mild vascular dementia, anodal tDCS of the left DLPFC is able to produce additional effects to cognitive training on visual short-term memory, verbal working memory, and executive control.