Papers by Markus Gschwind
Annals of Clinical and Translational Neurology
Journal of Clinical Anesthesia, 2022
Journal of Clinical Neurology, 2022
Dear Editor, Pharmacoresistant epilepsy with polymorphic behavior remains a great challenge in cl... more Dear Editor, Pharmacoresistant epilepsy with polymorphic behavior remains a great challenge in clinical epileptology. Here we present a 20-year-old female with triple-X syndrome who was admitted because of variable seizures and the suspicion of nonepileptic events. Absences with deep breathing, wagging of the left arm, yawning, nausea, aggressiveness, and amnesia were replaced by turning the head to the left, stretching the left arm, and bending the right arm ("figure-of-4 sign"), followed by confusion. Similar seizures occurred up to seven times per day on up to 20 days per month, resulting in numerous consultations at the emergency department. Tonic-clonic seizures had occurred during her 3rd year of life, and at 8 years old she started to also show focal nonaware cognitive seizures, sometimes with bilateral spread. At that time, several routine electroencephalography (EEG) recordings revealed a right, paracentral epileptic focus. Valproic acid (1,500 mg daily) resulted in a seizure-free period of 6 years, but this had to be discontinued due to weight gain and hirsutism, and was subsequently changed to levetiracetam (2,000 mg daily), lamotrigine (100 mg daily), and lacosamide (200 mg daily), which failed to control the seizures and increased behavioral problems. Brain magnetic resonance imaging (MRI) findings were normal. The patient underwent long-term overnight video-EEG with a 25-channel montage (2017 IFCN guidelines), which revealed several epileptogenic foci with sharp waves in the right inferotemporal (T10-F10) region, in the right central region at C4-P4, and in the left central region (C3-P3) (Fig. 1A-C). We then ran the fully automatic EPILOG ® PreOp algorithm (Epilog NV, Ghent, Belgium) in order to quantify the interictal epileptic discharges and localize their electric source according to the patient's own brain anatomy (Fig. 1D-F). To this end, we used the full 88-hour-long low-density EEG track together with the patient's own 3-T magnetization prepared rapid gradient echo MRI scan, allowing for an anatomical head model with six tissue compartments (gray matter, white matter, CSF, skull, air cavities, and scalp). The electrode positions were estimated by calculating distances over the head after marking specific landmarks such as the inion, nasion, and auricular points. 1,2 EEG source analysis was done using sLORETA as the inverse technique to localize each spike according to its onset, half height, and peak. A patient-specific head model was constructed from the MRI data, and the finite-difference method was used to calculate the lead fields that linked neuronal currents in the brain to the measured scalp potentials. 1,2 After demonstrating the presence of multifocal epilepsy in our patient, we changed the pharmacologic treatment to brivaracetam (100 mg daily), higher-dose lamotrigine (500 mg daily, serum level of 8.7 mg/L; ref. 3-14 mg/L), and low-dose valproic acid (300 mg daily), which subsequently resulted in a remarkable improvement of seizure control. Overnight video-EEG combined with fully automated electric source imaging was successful in confirming the hypothesis of different epileptic foci causing the changing seizure semiologies in our patient. The previously reported triple-X aberration additionally orient
Multiple Sclerosis and Related Disorders, 2019
Swiss Archives of Neurology, Psychiatry and Psychotherapy
Functional neurological disorder (FND) is a fascinating entity defined by neurological symptoms s... more Functional neurological disorder (FND) is a fascinating entity defined by neurological symptoms such as weakness, abnormal movements including psychogenic non-epileptic seizures (PNES), and sensory, swallowing or speech abnormalities that are incompatible with lesions in the central or peripheral nervous systems or recognised medical illness [1]. FND is frequently encountered in neurological clinics [2, 3], yet patients often remain in the interdisciplinary no-man's-land between neurology and psychiatry, being labeled as "difficult to help" [4]. Despite historical interest from the founding fathers of modern neurology [5] and psychiatry [6], functional disorders have long been conceptualised as an exclusion diagnosis. Slater [7] concluded that long-term follow-up of "hysteria" patients showed an organic disorder in 75% of the cases. As a consequence, medical doctors were reluctant to diagnose functional disorders unless an in-depth neurological work-up had been completed to appropriately exclude all possible organic causes. The rate of misdiagnosis in conversion disorder as such (around 4%) [8] is much lower than in other organic movement disorders such as Parkinson's disease (up to 47% when performed in the primary care setting) [9]. Nonetheless, patients with FND often undergo a number of sometimes unnecessary and expensive medical examinations in order to exclude as many organic disorders as possible. Here, we discuss the case of a patient with a rare presentation of FND involving eye movements (functional convergence insufficiency), where this sys tematic exclusion-oriented approach was ended by a mosaic of interdisciplinary anamnestic and clinical elements that finally led to the diagnosis of FND. We use this case to recall the importance of a detailed knowledge about functional neurological disorders, and functional eye movement disorders (FEMDs) in particular, a largely under-investigated subsection of FND. In addition, we emphasise the importance of close collaboration between neurologists, ophthalmologists and psychiatrists.
Zeitschrift für Epileptologie
Epilepsia Open
Electrical source imaging (ESI) is increasingly used to estimate the epileptogenic zone (EZ) in p... more Electrical source imaging (ESI) is increasingly used to estimate the epileptogenic zone (EZ) in patients with epilepsy. Directed functional connectivity (DFC) coupled to ESI helps to better characterise epileptic networks, but studies on interictal activity relied on high density recordings. We investigated the accuracy of ESI and DFC for localising the EZ, based on low-density clinical EEG. Methods: We selected patients with 1) focal epilepsy 2) interictal spikes in the standard EEG 3) either a focal structural lesion concordant with the electroclinical semiology or good postoperative outcome. In 34 patients (20 TLE, 14 ETLE), we marked interictal spikes and estimated the cortical activity during each spike in 82 cortical regions using a patient-specific head model and distributed linear inverse solution. Directed functional connectivity between brain regions was computed using Granger-causal modeling followed by network topological measures. The concordance with the presumed EZ at sublobar level was computed using the epileptogenic lesion or the resected area in post-operative seizure-free patients. Results: ESI, summed outflow and efficiency were concordant with the presumed EZ in 76% of the patients while the clustering coefficient and betweenness centrality were concordant in 70% of patients. There was no significant difference between ESI and connectivity measures. In all measures, TLE patients had a significantly higher (p<0.05) concordance with the presumed EZ than ETLE patients, but the brain volume accepted for concordance was significantly larger in TLE. Significance: ESI and directed functional connectivity derived from low-density EEG can reliably estimate the EZ from interictal spikes. Connectivity measures were not superior to ESI for EZ localisation during interictal spikes, but the current validation of the localisation of connectivity measure is promising for other applications.
Journal of clinical neurology (Seoul, Korea), 2018
Dear Editor, A 40-year-old left-handed carpenter working in an art gallery was admitted for inves... more Dear Editor, A 40-year-old left-handed carpenter working in an art gallery was admitted for investigation of disabling walking difficulties due to imbalance and shaky legs that had insidiously evolved over the previous year. Physical examination found extended hyperkeratotic skin lesions consistent with lichenification (lichen simplex chronicus) on both upper extremities with radial distribution (Fig. 1). Clinical observation uncovered compulsive self-biting of both arms during unobserved moments. Further medical history-taking revealed that the self-injurious behavior (SIB) had started around 7 years previously. Not only did the patient bite his hands and arms, but he also poked his eyes, banged his head, and shouted loudly when he was alone, to such an extent that he was expelled from his apartment due to nocturnal noise. He explicitly denied itching in his arms, and related his behavior to intermittent feelings of loneliness, but denied being depressed. Neurological examination revealed an attentive and friendly man with unremarkable behavior showing cerebellar dysarthria and ataxia and tetrapyramidal signs that caused his unsteady ataxospastic gait, but with no sensory difficulties in the arms, legs, or trunk. Brain and spine MRI showed extensive periventricular white-matter damage in the right temporal lobe (Fig. 2A), as well as multiple demyelinating lesions juxtacortical in the corpus callosum, pons, midbrain, and cerebellum (Fig. 2B), some of which showed also Gd+ contrast enhancement (Fig. 2C). However, there were virtually no lesions in the frontal lobe. An extended infectiological and immunological workup did not find any evidence of acute or chronic infection (including PCRs of the CSF), nor of autoimmune connective-tissue disorder or paraneoplastic disease. The only deficit in vitamin levels was in vitamins B12 and D, for which supplements were administered. Flow cytometry findings were unremarkable. CSF analysis showed a white blood cell count of 15,000/µL (lymphocytes), elevated proteins (0.61 g/L) with a highly elevated albumin quotient at 8.36×10-3 , positivity for oligoclonal bands (IgG index 1.3), and normal interleukin-6. A neuropsychological evaluation revealed memory problems (visuospatial, verbal, short-term, and working memory), and marked executive difficulties (mental inflexibility and psychomotor slowing). Based on the pattern of the brain and spine lesions fulfilling McDonald's revised criteria, we diagnosed primary progressive multiple sclerosis (PPMS) with radiological progression based on the neurological symptoms (notably walking difficulties) for longer than 1 year combined with progressive accumulation of handicap without recovery. An offline treatment with rituximab was introduced. SIB is an intriguing human behavior that is seen in a range of neurological and psychiatric disorders but remains poorly understood. It occurs most frequently in developmental disorders and in psychiatric or neurological conditions involving striatofrontal dysfunction,
Journal of clinical neurology (Seoul, Korea), 2017
Dear Editor, We describe a patient presenting with atypical overlapping Guillain-Barré syndrome (... more Dear Editor, We describe a patient presenting with atypical overlapping Guillain-Barré syndrome (GBS) and Miller Fisher syndrome (MFS), with positivity for anti-GM1, anti-GD1a, and anti-GD1b IgG antigangliosides, whose initial presentation evoked alimentary botulism (AB). A 50-year-old male patient with no medical history presented at the emergency department with blurred vision, dry mouth, and asthenia that had evolved over 24 hours. He reported nausea, vomiting, and diarrhea for 4 days after eating an out-of-date sausage. A neurological examination revealed external ophthalmoplegia with bilateral third cranial nerve and sixth cranial nerve palsy, dysphagia, mild tetraparesis, and preserved deep tendon reflexes. Autonomic dysfunction with urinary retention, constipation, and hypotension were present. This presentation led to suspicion of AB. Stool and blood samples were obtained to screen for Clostridium botulinum. The patient received equine serum trivalent botulism antitoxin of types A, B, and E. He was transferred to our division of neurorehabilitation a few days later, and his clinical symptoms improved rapidly over 3 weeks. Blood and stool tests were negative for Clostridium botulinum. Repetitive nerve stimulation showed no increment in the M-wave amplitude or signs of presynaptic junction disorder. Single-fiber electromyography did not reveal increased jitter. Considering the clinical symptoms, rapid improvement, and findings of ancillary tests, we diagnosed MFS. However, enzyme-linked immunosorbent assay screening (GanglioCombi TM , Bühlmann, Schönenbuch, Switzerland) of anti-GM1, anti-GM2, anti-GD1a, anti-GD1b, and anti-GQ1b IgG antigangliosides revealed high titers for the anti-GM1 (67%), anti-GD1a (78%), and anti-GD1b (91%) antigangliosides. Based on these findings, we concluded that the patient had atypical overlapping GBS-MFS. No relapse was observed during a 3-month follow-up, but the patient still complained about slight fatigue and persistent right sixth cranial nerve palsy. He was able to perform all of the basic activities of daily living without limitation, and resumed his employment as a security guard. MFS is considered as a GBS variant characterized by ophthalmoplegia, ataxia, and areflexia, and is mostly associated with anti-GQ1b serum antibodies. However, Morgan et al. 1 identified a patient with ophthalmoparesis, ptosis, and ataxia presenting anti-GM1 and anti-GD1a antibodies. Fusco et al. 2 described a 6-year-old girl with isolated ophthalmoplegia and normal deep tendon reflexes with the same antibody profile as our patient. The initial presentation of our patient mimicked AB, with multiple cranial nerve palsies, motor impairment, and autonomic dysfunction. However, the clinical course was too favorable for this diagnosis. In addition, bioassays of the toxin in the serum and stool were negative, and electroneuromyography did not reveal any facilitation of compound motor action potential amplitudes during tetanic stimulation or increased jitter. The antiganglioside profile in our patient is unusual for the observed clinical picture-anti-GD1a antibodies are usually associated with acute motor axonal neuropathy (AMAN), facial palsy, and the absence of sen
Brain Stimulation
We read with pleasure the paper of San-Juan and coworkers [1] published recently in Brain Stimula... more We read with pleasure the paper of San-Juan and coworkers [1] published recently in Brain Stimulation. This review has provided a step forward in the direction of the use of this promising technique also in a therapeutic setting with patients suffering from epilepsy. At present, the technical approaches of transcranial direct current stimulation (tDCS) are still very heterogeneous. Nearly every study uses different patient categories, different stimulation protocols, different electrode sizes, stimulation sites and different stimulation current strength, so that comparison between the different studies is limited. It is therefore highly useful to compare all studies, and to provide standardizable measures in order to judge stimulation effects across them. San-Juan and coworkers have calculated for every study the applied current density and the total electrical charge during stimulation. However, their calculation of the electrical charge is based on an incorrect formula. In the paragraph Data extraction (p.456), they define electrical charge as "Q = I / t", and in both Table 1, Table 2, they report values of some hundred nanoCoulombs (nC). For example, for the study of Fregni et al. (2006), they report I = 1 mA and Q = 833 nC during a total of 20 min. stimulation. So they effectively calculated 0.001 A / (20 × 60 s) = 8.333e-7 = 833.333e-9 Coulomb. They did the like for every reported value of electrical charge Q.
Brain Topography
Epilepsy surgery is the most efficient treatment option for patients with refractory epilepsy. Be... more Epilepsy surgery is the most efficient treatment option for patients with refractory epilepsy. Before surgery, it is of utmost importance to accurately delineate the seizure onset zone (SOZ). Non-invasive EEG is the most used neuroimaging technique to diagnose epilepsy, but it is hard to localize the SOZ from EEG due to its low spatial resolution and because epilepsy is a network disease, with several brain regions becoming active during a seizure. In this work, we propose and validate an approach based on EEG source imaging (ESI) combined with functional connectivity analysis to overcome these problems. We considered both simulations and real data of patients. Ictal epochs of 204-channel EEG and subsets down to 32 channels were analyzed. ESI was done using realistic head models and LORETA was used as inverse technique. The connectivity pattern between the reconstructed sources was calculated, and the source with the highest number of outgoing connections was selected as SOZ. We compared this algorithm with a more straightforward approach, i.e. selecting the source with the highest power after ESI as the SOZ. We found that functional connectivity
Epilepsia Open
Objective: We investigated the performance of automatic spike detection and subsequent electroenc... more Objective: We investigated the performance of automatic spike detection and subsequent electroencephalogram (EEG) source imaging to localize the epileptogenic zone (EZ) from long-term EEG recorded during video-EEG monitoring. Methods: In 32 patients, spikes were automatically detected in the EEG and clustered according to their morphology. The two spike clusters with most single events in each patient were averaged and localized in the brain at the half-rising time and peak of the spike using EEG source imaging. On the basis of the distance from the sources to the resection and the known patient outcome after surgery, the performance of the automated EEG analysis to localize the EZ was quantified. Results: In 28 out of the 32 patients, the automatically detected spike clusters corresponded with the reported interictal findings. The median distance to the resection in patients with Engel class I outcome was 6.5 and 15 mm for spike cluster 1 and 27 and 26 mm for cluster 2, at the peak and the half-rising time of the spike, respectively. Spike occurrence (cluster 1 vs. cluster 2) and spike timing (peak vs. half-rising) significantly influenced the distance to the resection (p < 0.05). For patients with Engel class II, III, and IV outcomes, the median distance increased to 36 and 36 mm for cluster 1. Localizing spike cluster 1 at the peak resulted in a sensitivity of 70% and specificity of 100%, positive prediction value (PPV) of 100%, and negative predictive value (NPV) of 53%. Including the results of spike cluster 2 led to an increased sensitivity of 79% NPV of 55% and diagnostic OR of 11.4, while the specificity dropped to 75% and the PPV to 90%. Significance: We showed that automated analysis of long-term EEG recordings results in a high sensitivity and specificity to localize the epileptogenic focus.
Cerebral Cortex
As a functional homolog for left-hemispheric syntax processing in language, neuroimaging studies ... more As a functional homolog for left-hemispheric syntax processing in language, neuroimaging studies evidenced involvement of right prefrontal regions in musical syntax processing, of which underlying white matter connectivity remains unexplored so far. In the current experiment, we investigated the underlying pathway architecture in subjects with 3 levels of musical expertise. Employing diffusion tensor imaging tractography, departing from seeds from our previous functional magnetic resonance imaging study on music syntax processing in the same participants, we identified a pathway in the right ventral stream that connects the middle temporal lobe with the inferior frontal cortex via the extreme capsule, and corresponds to the left hemisphere ventral stream, classically attributed to syntax processing in language comprehension. Additional morphometric consistency analyses allowed dissociating tract core from more dispersed fiber portions. Musical expertise related to higher tract consistency of the right ventral stream pathway. Specifically, tract consistency in this pathway predicted the sensitivity for musical syntax violations. We conclude that enduring musical practice sculpts ventral stream architecture. Our results suggest that training-related pathway plasticity facilitates the right hemisphere ventral stream information transfer, supporting an improved sound-to-meaning mapping in music.
Swiss Medical Weekly, 2016
Alcohol Benzodiazepine Barbiturate Rarely vitamin B12, Vitamin B 6 (young children) Other Posteri... more Alcohol Benzodiazepine Barbiturate Rarely vitamin B12, Vitamin B 6 (young children) Other Posterior reversible encephalopathy syndrome Cerebral anoxia Eclampsia Multiple sclerosis within 7 d of relapse Adapted from [1, 2].
Frontiers in Behavioral Neuroscience, 2016
Ecstatic epileptic seizures are a rare but compelling epileptic entity. During the first seconds ... more Ecstatic epileptic seizures are a rare but compelling epileptic entity. During the first seconds of these seizures, ecstatic auras provoke feelings of well-being, intense serenity, bliss, and "enhanced self-awareness." They are associated with the impression of time dilation, and can be described as a mystic experience by some patients. The functional neuroanatomy of ecstatic seizures is still debated. During recent years several patients presenting with ecstatic auras have been reported by others and us (in total n = 52); a few of them in the setting of presurgical evaluation including electrical brain stimulation. According to the recently recognized functions of the insula, and the results of nuclear brain imaging and electrical stimulation, the ecstatic symptoms in these patients seem to localize to a functional network centered around the anterior insular cortex, where we thus propose to locate this rare ictal phenomenon. Here we summarize the role of the multiple sensory, autonomic, affective, and cognitive functions of the insular cortex, which are integrated into the creation of self-awareness, and we suggest how this system may become dysfunctional on several levels during ecstatic aura.
NeuroImage: Clinical, 2016
Spontaneous fluctuations of neuronal activity in large-scale distributed networks are a hallmark ... more Spontaneous fluctuations of neuronal activity in large-scale distributed networks are a hallmark of the resting brain. In relapsing-remitting multiple sclerosis (RRMS) several fMRI studies have suggested altered restingstate connectivity patterns. Topographical EEG analysis reveals much faster temporal fluctuations in the tens of milliseconds time range (termed "microstates"), which showed altered properties in a number of neuropsychiatric conditions. We investigated whether these microstates were altered in patients with RRMS, and if the microstates' temporal properties reflected a link to the patients' clinical features. We acquired 256-channel EEG in 53 patients (mean age 37.6 years, 45 females, mean disease duration 9.99 years, Expanded Disability Status Scale ≤4, mean 2.2) and 49 healthy controls (mean age 36.4 years, 33 females). We analyzed segments of a total of 5 min of EEG during resting wakefulness and determined for both groups the four predominant microstates using established clustering methods. We found significant differences in the temporal dynamics of two of the four microstates between healthy controls and patients with RRMS in terms of increased appearance and prolonged duration. Using stepwise multiple linear regression models with 8-fold cross-validation, we found evidence that these electrophysiological measures predicted a patient's total disease duration, annual relapse rate, disability score, as well as depression score, and cognitive fatigue measure. In RRMS patients, microstate analysis captured altered fluctuations of EEG topographies in the sub-second range. This measure of high temporal resolution provided potentially powerful markers of disease activity and neuropsychiatric co-morbidities in RRMS.
Uploads
Papers by Markus Gschwind