Aljoscha Thomschewski

High-frequency oscillations in epilepsy and surgical outcome. A meta-analysis

High frequency oscillations (HFOs) are estimated as a potential marker for epileptogenicity. Current research strives for valid evidence that these HFOs could aid the delineation of the to-be resected area in patients with refractory epilepsy and improve surgical outcomes. In the present meta-analysis, we evaluated the relation between resection of regions from which HFOs can be detected and outcome after epilepsy surgery. We conducted a systematic review of all studies that related the resection of HFO-generating areas to postsurgical outcome. We related the outcome (seizure freedom) to resection ratio, that is, the ratio between the number of channels on which HFOs were detected and, among these, the number of channels that were inside the resected area. We compared the resection ratio between seizure free and not seizure free patients. In total, 11 studies were included. In 10 studies, ripples (80–200 Hz) were analyzed, and in 7 studies, fast ripples (>200 Hz) were studied. We found comparable differences (dif) and largely overlapping confidence intervals (CI) in resection ratios between outcome groups for ripples (dif = 0.18; CI: 0.10–0.27) and fast ripples (dif = 0.17; CI: 0.01–0.33). Subgroup analysis showed that automated detection (dif = 0.22; CI: 0.03–0.41) was comparable to visual detection (dif = 0.17; CI: 0.08–0.27). Considering frequency of HFOs (dif = 0.24; CI: 0.09–0.38) was related more strongly to outcome than considering each electrode that was showing HFOs (dif = 0.15; CI = 0.03–0.27). The effect sizes found in the meta-analysis are small but significant. Automated detection and application of a detection threshold in order to detect channels with a frequent occurrence of HFOs is important to yield a marker that could be useful in presurgical evaluation. In order to compare studies with different methodological approaches, detailed and standardized reporting is warranted.

Altered directed functional connectivity in temporal lobe epilepsy in the absence of interictal spikes: A high density EEG study

In patients with epilepsy, seizure relapse and behavioral impairments can be observed despite the absence of interictal epileptiform discharges (IEDs). Therefore, the characterization of pathologic networks when IEDs are not present could have an important clinical value. Using Granger‐causal modeling, we investigated whether directed functional connectivity was altered in electroencephalography (EEG) epochs free of IED in left and right temporal lobe epilepsy (LTLE and RTLE) compared to healthy controls.

Invasive and non-invasive brain stimulation for treatment of neuropathic pain in patients with spinal cord injury: A review

Abstract Context Past evidence has shown that invasive and non-invasive brain stimulation may be effective for relieving central pain. Objective To perform a topical review of the literature on brain neurostimulation techniques in patients with chronic neuropathic pain due to traumatic spinal cord injury (SCI) and to assess the current evidence for their therapeutic efficacy. Methods A MEDLINE search was performed using following terms: “Spinal cord injury”, “Neuropathic pain”, “Brain stimulation”, “Deep brain stimulation” (DBS), “Motor cortex stimulation” (MCS), “Transcranial magnetic stimulation” (TMS), “Transcranial direct current stimulation” (tDCS), “Cranial electrotherapy stimulation” (CES). Results Invasive neurostimulation therapies, in particular DBS and epidural MCS, have shown promise as treatments for neuropathic and phantom limb pain. However, the long-term efficacy of DBS is low, while MCS has a relatively higher potential with lesser complications that DBS. Among the non-invasive techniques, there is accumulating evidence that repetitive TMS can produce analgesic effects in healthy subjects undergoing laboratory-induced pain and in chronic pain conditions of various etiologies, at least partially and transiently. Another very safe technique of non-invasive brain stimulation – tDCS – applied over the sensory-motor cortex has been reported to decrease pain sensation and increase pain threshold in healthy subjects. CES has also proved to be effective in managing some types of pain, including neuropathic pain in subjects with SCI. Conclusion A number of studies have begun to use non-invasive neuromodulatory techniques therapeutically to relieve neuropathic pain and phantom phenomena in patients with SCI. However, further studies are warranted to corroborate the early findings and confirm different targets and stimulation paradigms. The utility of these protocols in combination with pharmacological approaches should also be explored.

Comparison of EEG-features and classification methods for motor imagery in patients with disorders of consciousness.

Current research aims at identifying voluntary brain activation in patients who are behaviorally diagnosed as being unconscious, but are able to perform commands by modulating their brain activity patterns. This involves machine learning techniques and feature extraction methods such as applied in brain computer interfaces. In this study, we try to answer the question if features/classification methods which show advantages in healthy participants are also accurate when applied to data of patients with disorders of consciousness. A sample of healthy participants (N = 22), patients in a minimally conscious state (MCS; N = 5), and with unresponsive wakefulness syndrome (UWS; N = 9) was examined with a motor imagery task which involved imagery of moving both hands and an instruction to hold both hands firm. We extracted a set of 20 features from the electroencephalogram and used linear discriminant analysis, k-nearest neighbor classification, and support vector machines (SVM) as classification methods. In healthy participants, the best classification accuracies were seen with coherences (mean = .79; range = .53−.94) and power spectra (mean = .69; range = .40−.85). The coherence patterns in healthy participants did not match the expectation of central modulated -rhythm. Instead, coherence involved mainly frontal regions. In healthy participants, the best classification tool was SVM. Five patients had at least one feature-classifier outcome with p0.05 (none of which were coherence or power spectra), though none remained significant after false-discovery rate correction for multiple comparisons. The present work suggests the use of coherences in patients with disorders of consciousness because they show high reliability among healthy subjects and patient groups. However, feature extraction and classification is a challenging task in unresponsive patients because there is no ground truth to validate the results.

Connectivity biomarkers can differentiate patients with different levels of consciousness

OBJECTIVE In the present study, we searched for resting-EEG biomarkers that distinguish different levels of consciousness on a single subject level with an accuracy that is significantly above chance. METHODS We assessed 44 biomarkers extracted from the resting EEG with respect to their discriminative value between groups of minimally conscious (MCS, N=22) patients, vegetative state patients (VS, N=27), and - for a proof of concept - healthy participants (N=23). We applied classification with support vector machines. RESULTS Partial coherence, directed transfer function, and generalized partial directed coherence yielded accuracies that were significantly above chance for the group distinction of MCS vs. VS (.88, .80, and .78, respectively), as well as healthy participants vs. MCS (.96, .87, and .93, respectively) and VS (.98, .84, and .96, respectively) patients. CONCLUSIONS The concept of connectivity is crucial for determining the level of consciousness, supporting the view that assessing brain networks in the resting state is the golden way to examine brain functions such as consciousness. SIGNIFICANCE The present results directly show that it is possible to distinguish patients with different levels of consciousness on the basis of resting-state EEG.

Noninvasive Spinal Cord Stimulation: Technical Aspects and Therapeutic Applications.

Electrical and magnetic trans‐spinal stimulation can be used to increase the motor output of multiple spinal segments and modulate cortico‐spinal excitability. The application of direct current through the scalp as well as repetitive transcranial magnetic stimulation are known to influence brain excitability, and hence can also modulate other central nervous system structures, including spinal cord.

Real movement vs. motor imagery in healthy subjects

Motor imagery tasks are well established procedures in brain computer interfaces, but are also used in the assessment of patients with disorders of consciousness. For testing awareness in unresponsive patients it is necessary to know the natural variance of brain responses to motor imagery in healthy subjects. We examined 22 healthy subjects using EEG in three conditions: movement of both hands, imagery of the same movement, and an instruction to hold both hands still. Single-subject non-parametric statistics were applied to the fast-Fourier transformed data. Most effects were found in the α- and β-frequency ranges over central electrodes, that is, in the μ-rhythm. We found significant power changes in 18 subjects during movement and in 11 subjects during motor imagery. In 8 subjects these changes were consistent over both conditions. The significant power changes during movement were a decrease of μ-rhythm. There were 2 subjects with an increase and 9 subjects with a decrease of μ-rhythm during imagery. α and β are the most responsive frequency ranges, but there is a minor number of subjects who show a synchronization instead of the more common desynchronization during motor imagery. A (de)synchronization of μ-rhythm can be considered to be a normal response.

Two-year real-world experience with perampanel in patients with refractory focal epilepsy: Austrian data

Background: The aim of this study was to analyse registry data of seizure outcome and adverse events (AEs) for perampanel as add-on therapy in patients with focal epilepsy since its approval in 2012 for adjunctive treatment of focal epilepsy in patients ⩾12 years. Method: A retrospective 2-year chart review of all patients receiving perampanel was carried out. Results: A total of 122 patients received perampanel [median treatment length: 20.1 (range: 3.4–26.8) months]; 71 (58%) remained on treatment at last follow up. Overall, 33 patients (27%) were seizure-free for ⩾3 months at last follow up; of these, eight were seizure free for ⩾3 times the longest interictal interval before perampanel therapy; 18 (15%) had reduced seizure frequency ⩾50%. A total of 58 (47%) had an AE and 34 (28%) withdrew from treatment because of AEs. AEs included dizziness (33%), fatigue (12%), psychiatric symptoms (8%), cognitive deficits (7%), speech problems (5%), nausea (4%) and gait problems (4%). AEs subsided in 17/18 patients (94%) following a 2 mg dose reduction. A total of 43 (35%) took a concomitant enzyme inducer. Patients not taking enzyme inducers were more likely to be seizure free (p = 0.002); there were no other between-group differences. Conclusions: Perampanel was well tolerated and improved seizure control in 42% of patients (50– 100% reduction), with higher rates in those not receiving a concomitant enzyme inducer. AEs, particularly dizziness, were common but often disappeared with a slight dose reduction. The results are consistent with those from randomized controlled trials.

Central motor conduction studies in patients with spinal cord disorders: a review.

Study design:Topical review of the literature.Objectives:The evaluation of patients with myelopathies requires radiological investigations; however, for the correct interpretation of the neuroimaging findings, the functional assessment of corticospinal conduction is helpful or even mandatory in many conditions. The objective of this review article was to assess the utility of the motor evoked potentials (MEPs) in diagnosis and management of the most frequent spinal cord disorders.Setting:Salzburg (Austria) and Merano (Italy).Methods:A MEDLINE search was performed using following terms: ‘motor evoked potentials’, ‘transcranial magnetic stimulation’, ‘central motor conduction’, ‘compressive myelopathy’, ‘spinal cord infarction’, ‘spinal cord injury’, ‘syringomyelia’, ‘myelitis’, ‘hereditary spastic paraparesis’, ‘subacute combined degeneration’ and ‘hepatic myelopathy’.Results:Central motor conduction abnormalities can be detected also in the absence of neuroradiological abnormalities—for example, in patients with subacute combined degeneration or hepatic myelopathy. In the most frequent patients with compressive myelopathies, MEPs were found to be very helpful in determining the functional significance of neuroimaging findings. MEP recording can supplement clinical examination and neuroimaging findings also in the assessment of the spinal cord injury level. In patients with spinal cord infarction, the MEP study can demonstrate spinal involvement even when radiological evidence for spinal cord damage is absent or equivocal, thus allowing an important early diagnosis.Conclusion:MEPs represent a highly sensitive and accurate diagnostic tool in many different spinal cord disorders. MEPs can also be useful in follow-up evaluation of motor function during treatment and rehabilitation.

Serotonergic transmission after spinal cord injury

Changes in descending serotonergic innervation of spinal neural activity have been implicated in symptoms of paralysis, spasticity, sensory disturbances and pain following spinal cord injury (SCI). Serotonergic neurons possess an enhanced ability to regenerate or sprout after many types of injury, including SCI. Current research suggests that serotonine (5-HT) release within the ventral horn of the spinal cord plays a critical role in motor function, and activation of 5-HT receptors mediates locomotor control. 5-HT originating from the brain stem inhibits sensory afferent transmission and associated spinal reflexes; by abolishing 5-HT innervation SCI leads to a disinhibition of sensory transmission. 5-HT denervation supersensitivity is one of the key mechanisms underlying the increased motoneuron excitability that occurs after SCI, and this hyperexcitability has been demonstrated to underlie the pathogenesis of spasticity after SCI. Moreover, emerging evidence implicates serotonergic descending facilitatory pathways from the brainstem to the spinal cord in the maintenance of pathologic pain. There are functional relevant connections between the descending serotonergic system from the rostral ventromedial medulla in the brainstem, the 5-HT receptors in the spinal dorsal horn, and the descending pain facilitation after tissue and nerve injury. This narrative review focussed on the most important studies that have investigated the above-mentioned effects of impaired 5-HT-transmission in humans after SCI. We also briefly discussed the promising therapeutical approaches with serotonergic drugs, monoclonal antibodies and intraspinal cell transplantation.