Non-invasive vagus nerve stimulation in epilepsy patients enhances cooperative behavior in the prisoner's dilemma task

The vagus nerve constitutes a key link between the autonomic and the central nervous system. Previous studies provide evidence for the impact of vagal activity on distinct cognitive processes including functions related to social cognition. Recent studies in animals and humans show that vagus nerve stimulation is associated with enhanced reward-seeking and dopamine-release in the brain. Social interaction recruits similar brain circuits to reward processing. We hypothesize that vagus nerve stimulation (VNS) boosts rewarding aspects of social behavior and compare the impact of transcutaneous VNS (tVNS) and sham stimulation on social interaction in 19 epilepsy patients in a double-blind pseudo-randomized study with cross-over design. Using a well-established paradigm, i.e., the prisoner's dilemma, we investigate effects of stimulation on cooperative behavior, as well as interactions of stimulation effects with patient characteristics. A repeated-measures ANOVA and a linear mixed-effects model provide converging evidence that tVNS boosts cooperation. Post-hoc correlations reveal that this effect varies as a function of neuroticism, a personality trait linked to the dopaminergic system. Behavioral modeling indicates that tVNS induces a behavioral starting bias towards cooperation, which is independent of the decision process. This study provides evidence for the causal influence of vagus nerve activity on social interaction

Normal regional brain iron concentration in restless legs syndrome measured by MRI

Susanne Knake1, Johannes T Heverhagen2, Katja Menzler1, Boris Keil2, Wolfgang H Oertel1, Karin Stiasny-Kolster11Department of Neurology, Center of Nervous Diseases, 2Department of Radiology, Philipps University, Marburg, GermanyAbstract: Using a T2* gradient echo magnetic resonance imaging (MRI) sequence, regional T2 signal intensity (SI) values, a surrogate marker for T2 values, were determined in 12 regions of interest (substantia nigra, pallidum, caudate head, thalamus, occipital white matter, and frontal white matter bilaterally) and in two reference regions (cerebrospinal fluid and bone) in 12 patients suffering from moderate to severe idiopathic restless legs syndrome (RLS; mean age 58.5 ± 8.7 years) for 12.1 ± 9.1 years and in 12 healthy control subjects (mean age 56.8 ± 10.6 years). Iron deposits shorten T2 relaxation times on T2-weighted MRI. We used regional T2* SI to estimate regional T2-values. A T2-change ratio was calculated for each region of interest relative to the reference regions. We did not find significant differences in any of the investigated brain regions. In addition, serum measures involved in iron metabolism did not correlate with T2 SI values. We could not replicate earlier findings describing reduced regional brain iron concentrations in patients with RLS. Our results do not support the view of substantially impaired regional brain iron in RLS.Keywords: restless legs syndrome, pathophysiology, iron, MRI, substantia nigr

Treatment of refractory and superrefractory status epilepticus with topiramate: A cohort study of 106 patients and a review of the literature

Objective: Novel treatments are needed to control treatment‐resistant status epilepticus (SE). We present a summary of clinical cases where oral topiramate (TPM) was used in refractory SE (RSE) and superrefractory SE (SRSE). Methods: A review of medical records was carried out to detect TPM administration in SE patients treated in Frankfurt and Marburg between 2011 and 2016. The primary outcome question concerned SE resolution after TPM initiation. Results: In total, TPM was used in 106 of 854 patients having a mean age of 67.4 ± 18.1 years, 61 of whom were female (57.5%). The median latency from SE onset to TPM initiation was 8.5 days. Patients with SE had previously failed a median of five other antiepileptic drugs. The median initial TPM dose was 100 mg/d, which was uptitrated to a median maintenance dose of 400 mg/d. Treatment with TPM was continued for a median time of 12 days. TPM was the last drug provided to 42 of 106 (39.6%) patients, with a resultant response attributed to TPM observed in 29 of 106 (27.4%) patients. A response was attributed to TPM in 21 (31.8%) of 66 RSE cases and eight (20%) of 40 SRSE cases. Treatment‐emergent adverse events were attributed to TPM usage in two patients, one each with pancreatitis and hyperchloremic acidosis, and in 38 patients (35.8%), hyperammonemia was seen. Thirty‐four of these patients received a combination of TPM and valproate and/or phenobarbital. The intrahospital mortality rate was 22.6% (n = 24). Significance: The rate of SE cessation attributed to TPM treatment (27.4%) represents a relevant response given the late treatment position of TPM and the treatment latency of more than 8 days. Based on these results and in line with the findings of other case series, TPM can be considered an alternative option for treating RSE and SRSE

DTI and VBM reveal white matter changes without associated gray matter changes in patients with idiopathic restless legs syndrome

BACKGROUND AND PURPOSE: We evaluated cerebral white and gray matter changes in patients with iRLS in order to shed light on the pathophysiology of this disease. METHODS: Twelve patients with iRLS were compared to 12 age- and sex-matched controls using whole-head diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) techniques. Evaluation of the DTI scans included the voxelwise analysis of the fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD). RESULTS: Diffusion tensor imaging revealed areas of altered FA in subcortical white matter bilaterally, mainly in temporal regions as well as in the right internal capsule, the pons, and the right cerebellum. These changes overlapped with changes in RD. Voxel-based morphometry did not reveal any gray matter alterations. CONCLUSIONS: We showed altered diffusion properties in several white matter regions in patients with iRLS. White matter changes could mainly be attributed to changes in RD, a parameter thought to reflect altered myelination. Areas with altered white matter microstructure included areas in the internal capsule which include the corticospinal tract to the lower limbs, thereby supporting studies that suggest changes in sensorimotor pathways associated with RLS

Diffusion tensor imaging in episodic cluster headache

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

Drug-resistant juvenile myoclonic epilepsy: Misdiagnosis of progressive myoclonus epilepsy

Juvenile myoclonic epilepsy (JME) is a common epilepsy syndrome characterized by bilateral myoclonic and tonic-clonic seizures typically starting in adolescence and responding well to medication. Misdiagnosis of a more severe progressive myoclonus epilepsy (PME) as JME has been suggested as a cause of drug-resistance. Medical records of the Epilepsy Center Hessen-Marburg between 2005 and 2014 were automatically selected using keywords and manually reviewed regarding the presence of a JME diagnosis at any timepoint. The identified patients were evaluated regarding seizure outcome and drug resistance according to ILAE criteria. 87/168 identified JME patients were seizure-free at last follow-up including 61 drug-responsive patients (group NDR). Seventy-eight patients were not seizure-free including 26 drug-resistant patients (group DR). Valproate was the most efficacious AED. The JME diagnosis was revised in 7 patients of group DR including 6 in whom the diagnosis had already been questioned or revised during clinical follow-up. One of these was finally diagnosed with PME (genetically confirmed Lafora disease) based on genetic testing. She was initially reviewed at age 29 yrs and considered to be inconsistent with PME. Intellectual disability (p = 0.025), cognitive impairment (p < 0.001), febrile seizures in first-degree relatives (p = 0.023) and prominent dialeptic seizures (p = 0.009) where significantly more frequent in group DR. Individuals with PME are rarely found among drug-resistant alleged JME patients in a tertiary epilepsy center. Even a very detailed review by experienced epileptologists may not identify the presence of PME before the typical features evolve underpinning the need for early genetic testing in drug-resistant JME patients

Brivaracetam in the Treatment of Patients with Epilepsy—First Clinical Experiences

ObjectivesTo assess first clinical experiences with brivaracetam (BRV) in the treatment of epilepsies.MethodsData on patients treated with BRV from February to December 2016 and with at least one clinical follow-up were collected from electronic patient records. Data on safety and efficacy were evaluated retrospectively.ResultsIn total, 93 patients were analyzed; 12 (12.9%) received BRV in monotherapy. The mean duration to follow-up was 4.85 months (MD = 4 months; SD = 3.63). Fifty-seven patients had more than one seizure per month at baseline and had a follow-up of more than 4 weeks; the rate of ≥50% responders was 35.1% (n = 20) in this group, of which five (8.8%) patients were newly seizure-free. In 50.5% (47/93), patients were switched from levetiracetam (LEV) to BRV, of which 43 (46.2%) were switched immediately. Adverse events (AE) occurred in 39.8%, with 22.6% experiencing behavioral and 25.8% experiencing non-behavioral AE. LEV-related AE (LEV-AE) were significantly reduced by switching to BRV. The discontinuation of BRV was reported in 26/93 patients (28%); 10 of those were switched back to LEV with an observed reduction of AE in 70%. For clinical reasons, 12 patients received BRV in monotherapy, 75% were seizure–free, and previous LEV-AE improved in 6/9 patients. BRV-related AE occurred in 5/12 cases, and five patients discontinued BRV.ConclusionBRV seems to be a safe, easy, and effective option in the treatment of patients with epilepsy, especially in the treatment of patients who have psychiatric comorbidities and might not be good candidates for LEV treatment. BRV broadens the therapeutic spectrum and facilitates personalized treatment

Temporal encephaloceles in epilepsy patients and asymptomatic cases: size may indicate epileptogenicity

Objective: This study was undertaken to identify temporal encephaloceles (TEs) and examine their characteristics in patients with temporal lobe epilepsy (TLE) and ex- tratemporal lobe epilepsy (ETLE), as well as in asymptomatic cases. Methods: Four hundred fifty-eight magnetic resonance imaging scans were exam- ined retrospectively to identify TE in 157 patients with TLE, 150 patients with ETLE, and 151 healthy controls (HCs). Results: At least one TE was identified in 9.6% of the TLE patients (n = 15, 95% confidence interval [CI] = 5.3%–15.3%), in 3.3% of patients with ETLE (n = 5, 95% CI = 1.1%–7.6%), and in 2.0% of the HCs (n = 3, 95% CI = .4%–5.7%), indicating a significantly higher frequency in patients with TLE compared to ETLE and HC sub- jects (p = .027, p = .005). Examining the characteristics of TEs in both asymptomatic and epilepsy patients, we found that TEs with a diameter of less than 6.25 mm were more likely to be asymptomatic, with a sensitivity of 91.7% and a specificity of 73.3% (area under the curve = .867, 95% CI = .723–1.00, p = .001). Significance: Temporal encephaloceles may occur without presenting any clinical symp- toms. Patients with TLE show a higher frequency of TEs compared to the ETLE and HC groups. According to our study, TE size could be used to suggest potential epileptogenicity