The connectivity-based architecture of the human piriform cortex.

The anatomy of the human piriform cortex (PC) is poorly understood. We used a bimodal connectivity-based-parcellation approach to investigate subregions of the PC and its connectional differentiation from the amygdala. One hundred (55 % female) genetically unrelated subjects from the Human Connectome Project were included. A region of interest (ROI) was delineated bilaterally covering PC and amygdala, and functional and structural connectivity of this ROI with the whole gray matter was computed. Spectral clustering was performed to obtain bilateral parcellations at granularities of k = 2-10 clusters and combined bimodal parcellations were computed. Validity of parcellations was assessed via their mean individual-to-group similarity per adjusted rand index (ARI). Individual-to-group similarity was higher than chance in both modalities and in all clustering solutions. The amygdala was clearly distinguished from PC in structural parcellations, and olfactory amygdala was connectionally more similar to amygdala than to PC. At higher granularities, an anterior and ventrotemporal and a posterior frontal cluster emerged within PC, as well as an additional temporal cluster at their boundary. Functional parcellations also showed a frontal piriform cluster, and similar temporal clusters were observed with less consistency. Results from bimodal parcellations were similar to the structural parcellations. Consistent results were obtained in a validation cohort. Distinction of the human PC from the amygdala, including its olfactory subregions, is possible based on its structural connectivity alone. The canonical fronto-temporal boundary within PC was reproduced in both modalities and with consistency. All obtained parcellations are freely available.

[Epilepsy and Pregnancy]. / Epilepsie und Schwangerschaft.

BACKGROUND: On average, female patients with epilepsy have 0.9 children, which is below the birth rate of healthy women. One reason is insufficient counselling. OBJECTIVES: To summarize the current data relevant to counselling pregnant women with epilepsy. MATERIALS AND METHODS: Discussion of research and recommendations concerning seizure control during pregnancy, pregnancy and birth complications, congenital malformations, and breastfeeding. RESULTS: Changes in seizure frequency during pregnancy are variable and partly due to changes in the serum concentrations of antiepileptic drugs. Epilepsy patients have a slightly higher risk for some pregnancy and birth complications including spontaneous abortion, pre- and postpartum bleeding, induction of labour, and caesarean section. In particular, the administration of valproic acid can lead to congenital malformations and a lower IQ of the child. Folic acid seems to have a protective effect. Data concerning breastfeeding are insufficient. CONCLUSIONS: If possible, epilepsy patients should be treated with a low-dose monotherapy during pregnancy and valproic acid should be avoided. Treatment with lamotrigine requires frequent control of serum concentration. Supplementary folic acid (5 mg daily dose) is recommended. Epilepsy is not an indication for a caesarean section.

[New aspects in the field of epilepsy]. / Neues auf dem Gebiet der Epilepsien.

Regarding epilepsy several new developments can be reported. The International League Against Epilepsy (ILAE) has suggested a new definition of epilepsy, for the first time including a definition of epilepsy resolution. Progress in the diagnosis relates to new genetic findings, improvements in magnetic resonance imaging (MRI) and the increasing use of stereo electroencephalograms (sEEG). Regarding treatment there are new clinically relevant data on the pathophysiology and prevention of sudden unexpected death in epilepsy (SUDEP). Zonisamide has been approved by the European Medicines Agency (EMA) for monotherapy in adults with focal seizures and combination therapy in children aged ≥ 6 years. Retigabin and perampanel have been approved but are currently taken off the market in Germany (only) because the Gemeinsamer Bundesausschuss (GBA, Joint Federal Committee) did not find any additional therapeutic value as compared to lamotrigine due to a lack of data. A decision regarding a new application for perampanel is pending. Regarding surgical treatment novel ablation techniques (e.g. stereotactic radiofrequency and laser ablation as well as focussed ultrasound ablation) and brain stimulation paradigms are under investigation. Experimental studies, generously supported by the European Union (EU) and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) are focusing on (opto-)genetic (e.g. using lentoviral transfection), epigenetic (e.g. micro-RNA-related) approaches and on the investigation of neuronal micronetworks.

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.

Intraoperative ultrasound in malformations of cortical development.

PURPOSE: Malformations of cortical development (MCD) are a common cause of medically refractory focal epilepsy. However, the intraoperative definition of MCD can be challenging. In this study we assess the feasibility of intraoperative ultrasound (IOUS) for the intraoperative localization of MCD. MATERIALS AND METHODS: Five epilepsy patients with at least one suspected lesion of MCD were operated with the aid of IOUS. IOUS was compared to preoperative MRI and histopathology. RESULTS: In three cases of focal cortical dysplasia (FCD) type IIB and one case of periventricular heterotopia, the lesions could be delineated well on IOUS and the configuration of the lesion corresponded to the appearance on MRI. However, only one of two FCD type I lesions could be detected on IOUS. CONCLUSION: IOUS can be helpful in defining FCD IIB as well as periventricular heterotopia intraoperatively, but this seems to be more difficult in FCD type I.

Stiripentol in the treatment of adults with focal epilepsy- a retrospective analysis.

OBJECTIVES: The aim of the present study was to evaluate the safety and efficacy of the add-on treatment of stiripentol (STP) in adult patients with severely pharmacoresistant focal or multifocal epilepsy. METHODS: Data on adult patients treated with STP from March 2007 to July 2020 and with at least one clinical follow-up (FU) were retrospectively reviewed. Data on tolerability, efficacy and concomitant medication were evaluated at baseline, 6 months (5.5 ± 1.6 months (mean ± SD)) and 12 months (13.1 ± 3.9 months (mean ± SD)). RESULTS: Data of 22 patients (54.5% male, mean age 34.4 ± 17.79 years (mean ± SD), including mean duration of epilepsy 17.6 ± 25.5 years (mean ± SD), median seizure frequency 30 ± 20 (median ± MAD) per month, and 63.6% being severely intellectually disabled, with 3 to 18 previous anti-seizure-drugs (ASD), were collected. After 6 months, 72.7% of the patients were still taking STP, and 31% of the patients were responders, including 13% who were seizure-free. The 12-month retention rate was 54.4 %, the response rate was 36.4% and 13.6% of patients were seizure-free at the 12-month FU. Reasons for discontinuation were increased seizure frequency, hyperammonaemia and encephalopathy. CONCLUSION: STP seems to be a useful option in the treatment of patients with severely pharmacoresistant epilepsy. Prospective trials are necessary to examine the efficacy of STP in adult patients with pharmacoresistant focal epilepsy.

Test-retest reliability of single and paired pulse transcranial magnetic stimulation parameters in healthy subjects.

OBJECTIVE: To determine the influence of different factors on test-retest reliability of frequently used transcranial magnetic stimulation (TMS) parameters while controlling for potential confounders in healthy subjects. METHODS: TMS was applied in 93 healthy volunteers (61% male) twice (mean retest interval of 34.0 ± 25.6 (SD) days) between 7 am and 2 pm by four investigators (sessions n investigator A=47, investigator B=95, investigator C=28, investigator D=16). Women were assessed in their follicular phase. Test stimulus (TS), resting motor threshold (RMT), short latency intracortical inhibition (SICI), intracortical facilitation (ICF) and cortical silent period (SCP) were analyzed. RESULTS: Good test-retest reliabilities were observed for TS (r=.880) and RMT (r=.826), moderate for visual and automated analyzed CSP durations (resp. r=.466, r=.486), and poor for ICF (r=-.159). Reliable change indexes are reported. Gender (e.g. automated CSP women: r=.538 vs. men: r=.422), re-test interval and method of CSP-analysis did not influence reliabilities. CONCLUSIONS: In a large sample of healthy volunteers we found good to moderate test-retest reliabilities in all but one TMS-parameter. Automated analysis of the CSP did not prove to be more reliable than visual determination. SIGNIFICANCE: This study contains analyses of re-test reliability in TMS considering several confounding factors. For the first time it presents reliable change indices for all frequently used TMS parameters.

Perioperative changes in cortical excitability, mood, and quality of life in patients with primary hyperparathyroidism: a pilot study using transcranial magnetic stimulation.

OBJECTIVE: Serum calcium (Ca(2)(+)) and parathyroid hormone (PTH), amongst others, modify cortical excitability. Alterations in cortical excitability were shown in patients with epilepsy as well as hyper- or hypoparathyroidism. In patients with primary hyperparathyroidism (pHPT), preoperative elevated serum calcium and parathyroidectomy (PTx) may affect mood and quality of life. We hypothesized that perioperative changes in Ca(2)(+) and PTH in pHPT will affect cortical excitability and improve subjective health. DESIGN AND METHODS: Transcranial magnetic stimulation (TMS) was performed before and after surgery in 15 pHPT patients. We measured resting motor threshold, cortical silent period (CSP), short intracortical inhibition, and intracortical facilitation. Health questionnaires were administered before, 1 day and 6 months after PTx, along with the disease-specific Pasieka's parathyroid assessment of symptoms (PAS), which was, to our knowledge, its first use in German. RESULTS: SURGERY WAS SUCCESSFUL IN ALL PATIENTS. TMS-MEASUREMENTS REMAINED UNCHANGED WHEN ANALYZING ALL PATIENTS IN THIS PILOT STUDY. POSTOPERATIVELY, DEPRESSION DECLINED (P=0.05) AND QUALITY OF LIFE IMPROVED SIGNIFICANTLY (P=0.001) IN THE SF-36-SUBSCALES: vitality, social functioning, mental health and subjective health transition (post-hoc analysis). The PAS proved early relief of disease-specific symptoms (P<0.001). CONCLUSIONS: We found unchanged cortical excitability comparing pre- and post-PTx in this pilot study. Mood and quality of life improved postoperatively. The German PAS is valuable in detecting disease-specific changes early after PTx.

Effects of transcranial direct current stimulation on pain perception and working memory.

Previous studies have shown that non-invasive stimulation of the dorsolateral prefrontal cortex (DLPFC) could modulate experimentally induced pain and working memory (WM) in healthy subjects. However, the two aspects have never been assessed concomitantly. The present study was set up to investigate the effects of transcranial direct current stimulation (tDCS) of the DLPFC on thermal pain and WM in the same population of healthy volunteers. In a randomized and balanced order of different sessions separated by 1 week, 20 min of 2 mA anodal, cathodal or sham tDCS were applied to the left or right DLPFC in two separate experiments. Twelve healthy volunteers were enrolled for each stimulated hemisphere. Warm and cold detection thresholds, heat and cold pain thresholds as well as heat pain tolerance thresholds were measured before, during and following tDCS. WM was assessed by a 2-back task applied once during cortical stimulation. Anodal tDCS of the right DLPFC led to an increase of tolerance to heat pain. The 2-back task revealed fewer outliers during cathodal tDCS of the left DLPFC. The present data show an involvement of the DLPFC in the processing of pain and WM. There was no correlation between these findings, suggesting that the analgesic effects of cortical stimulation are not associated with cognitive processing. However, this conclusion is difficult to affirm because of some limitations of the study regarding the parameters of stimulation or a ceiling effect of the 2-back task for instance.

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.

Evaluation of MRI criteria (1.5 T) for the diagnosis of hippocampal sclerosis in healthy subjects.

PURPOSE: The presence of hippocampal sclerosis (HS) on MRI has a great impact on the clinical evaluation and counselling of patients with temporal lobe epilepsy (TLE) and is considered as a key criterion for the decision to recommend epilepsy surgery. However, neuropathological studies describe evidence of HS in up to 10% of non-epileptic individuals, questioning the impact of this MRI finding in patients with TLE. We evaluated the prevalence of HS on MRI in the general population. METHODS: 100 healthy subjects and 10 patients with TLE due to HS were investigated in a prospective study using a specific protocol for the detection of hippocampal pathology (coronal FLAIR, coronal T2 TSE and a T1 weighted 3D SPGR sequence). RESULTS: HS was detected in none of the healthy subjects (95% confidence interval=0-3.6%), but in all patients. Inter-rater agreement was perfect for presence of HS. Thirty-three subjects had an unilaterally enlarged temporal horn as an isolated secondary criterion for HS and inter-rater agreement was slight for this point. Incidental pathological findings were detected in two patients (2%): one had a low grade astrocytoma (1%), one an aneurysm of the posterior communicating artery (1%). CONCLUSIONS: HS was not diagnosed in healthy subjects, supporting its impact on the evaluation of patients with temporal lobe epilepsy. An unilateral enlarged temporal horn that occurred in one third of the healthy subjects should not be considered as a pathologic finding or even as a marker for HS.