The importance of pyramidal tract integrity for cortical plasticity and related functionality in patients with multiple sclerosis.

Background: Cortical plasticity induced by quadripulse stimulation (QPS) has been shown to correlate with cognitive functions in patients with relapsing-remitting multiple sclerosis (RRMS) and to not be reduced compared to healthy controls (HCs). Objective: This study aimed to compare the degree of QPS-induced plasticity between different subtypes of multiple sclerosis (MS) and HCs and to investigate the association of the degree of plasticity with motor and cognitive functions. We expected lower levels of plasticity in patients with progressive MS (PMS) but not RRMS compared to HCs. Furthermore, we expected to find positive correlations with cognitive and motor performance in patients with MS. Methods: QPS-induced plasticity was compared between 34 patients with PMS, 30 patients with RRMS, and 30 HCs using linear mixed-effects models. The degree of QPS-induced cortical plasticity was correlated with various motor and cognitive outcomes. Results: There were no differences regarding the degree of QPS-induced cortical plasticity between HCs and patients with RRMS (p = 0.86) and PMS (p = 0.18). However, we only found correlations between the level of induced plasticity and both motor and cognitive functions in patients with intact corticospinal tract integrity. Exploratory analysis revealed significantly reduced QPS-induced plasticity in patients with damage compared to intact corticospinal tract integrity (p < 0.001). Conclusion: Our study supports the notion of pyramidal tract integrity being of more relevance for QPS-induced cortical plasticity in MS and related functional significance than the type of disease.

Long-term potentiation-like plasticity is retained during relapse in patients with Multiple Sclerosis.

OBJECTIVE: To investigate the degree of synaptic plasticity in Multiple Sclerosis (MS) patients during acute relapses compared to stable MS patients and healthy controls (HCs) and to analyze its functional relevance. METHODS: Facilitatory quadripulse stimulation (QPS) was applied to the primary motor cortex in 18 acute relapsing and 18 stable MS patients, as well as 18 HCs. The degree of synaptic plasticity was measured by the change in motor evoked potential amplitude following QPS. Symptom recovery was assessed three months after relapse. RESULTS: Synaptic plasticity was induced in all groups. The degree of induced plasticity did not differ between acute relapsing patients, HCs, and stable MS patients. Plasticity was significantly higher in relapsing patients with motor disability compared to relapsing patients without motor disability. In most patients (n = 9, 50%) symptoms had at least partially recovered three months after the relapse, impeding meaningful analysis of the functional relevance of baseline synaptic plasticity. CONCLUSIONS: QPS-induced synaptic plasticity is retained during acute MS relapses. Subgroup analyses suggest that stabilizing metaplastic mechanisms may be more important to prevent motor disability but its functional relevance needs to be verified in larger, longitudinal studies. SIGNIFICANCE: New insights into synaptic plasticity during MS relapses are provided.

Anesthesia for deep brain stimulation system implantation: adapted protocol for awake and asleep surgery using microelectrode recordings.

PURPOSE: Deep brain stimulation (DBS), an effective treatment for movement disorders, usually involves lead implantation while the patient is awake and sedated. Recently, there has been interest in performing the procedure under general anesthesia (asleep). This report of a consecutive cohort of DBS patients describes anesthesia protocols for both awake and asleep procedures. METHODS: Consecutive patients with Parkinson's disease received subthalamic nucleus (STN) implants either moderately sedated or while intubated, using propofol and remifentanil. Microelectrode recordings were performed with up to five trajectories after discontinuing sedation in the awake group, or reducing sedation in the asleep group. Clinical outcome was compared between groups with the UPDRS III. RESULTS: The awake group (n = 17) received 3.5 mg/kg/h propofol and 11.6 µg/kg/h remifentanil. During recording, all anesthesia was stopped. The asleep group (n = 63) initially received 6.9 mg/kg/h propofol and 31.3 µg/kg/h remifentanil. During recording, this was reduced to 3.1 mg/kg/h propofol and 10.8 µg/kg/h remifentanil. Without parkinsonian medications or stimulation, 3-month UPDRS III ratings (ns = 16 and 52) were 40.8 in the awake group and 41.4 in the asleep group. Without medications but with stimulation turned on, ratings improved to 26.5 in the awake group and 26.3 in the asleep group. With both medications and stimulation, ratings improved further to 17.6 in the awake group and 15.3 in the asleep group. All within-group improvements from the off/off condition were statistically significant (all ps < 0.01). The degree of improvement with stimulation, with or without medications, was not significantly different in the awake vs. asleep groups (ps > 0.05). CONCLUSION: The above anesthesia protocols make possible an asleep implant procedure that can incorporate sufficient microelectrode recording. Together, this may increase patient comfort and improve clinical outcomes.

The degree of cortical plasticity correlates with cognitive performance in patients with Multiple Sclerosis.

BACKGROUND: Cortical reorganization and plasticity may compensate for structural damage in Multiple Sclerosis (MS). It is important to establish sensitive methods to measure these compensatory mechanisms, as they may be of prognostic value. OBJECTIVE: To investigate the association between the degree of cortical plasticity and cognitive performance and to compare plasticity between MS patients and healthy controls (HCs). METHODS: The amplitudes of the motor evoked potential (MEP) pre and post quadripulse stimulation (QPS) applied over the contralateral motor cortex served as measure of the degree of cortical plasticity in 63 patients with relapsing-remitting MS (RRMS) and 55 matched HCs. The main outcomes were the correlation coefficients between the difference of MEP amplitudes post and pre QPS and the Symbol Digit Modalities Test (SDMT) and Brief Visuospatial Memory Test-Revised (BVMT-R), and the QPSxgroup interaction in a mixed model predicting the MEP amplitude. RESULTS: SDMT and BVMT-R correlated significantly with QPS-induced cortical plasticity in RRMS patients. Plasticity was significantly reduced in patients with cognitive impairment compared to patients with preserved cognitive function and the degree of plasticity differentiated between both patient groups. Interestingly, the overall RRMS patient cohort did not show reduced plasticity compared to HCs. CONCLUSIONS: We provide first evidence that QPS-induced plasticity may inform about the global synaptic plasticity in RRMS which correlates with cognitive performance as well as clinical disability. Larger longitudinal studies on patients with MS are needed to investigate the relevance and prognostic value of this measure for disease progression and recovery.

Motor Evoked Potentials Improve Targeting in Deep Brain Stimulation Surgery.

OBJECTIVES: One of the main challenges posed by the surgical deep brain stimulation (DBS) procedure is the successful targeting of the structures of interest and avoidance of side effects, especially in asleep surgery. Here, intraoperative motor evoked potentials (MEPs) might serve as tool to identify the pyramidal tract. We hypothesized that intraoperative MEPs are useful to define the distance to the pyramidal tract and reduce the occurrence of postoperative capsular side effects. MATERIALS AND METHODS: Motor potentials were evoked through both microelectrode and DBS-electrode stimulation during stereotactic DBS surgery on 25 subthalamic nuclei and 3 ventral intermediate thalamic nuclei. Internal capsule proximity was calculated for contacts on microelectrode trajectories, as well as for DBS-electrodes, and correlated with the corresponding MEP thresholds. Moreover, the predictivity of intraoperative MEP thresholds on the probability of postoperative capsular side effects was calculated. RESULTS: Intraoperative MEPs thresholds correlated significantly with internal capsule proximity, regardless of the stimulation source. Furthermore, MEPs thresholds were highly accurate to exclude the occurrence of postoperative capsular side effects. CONCLUSIONS: Intraoperative MEPs provide additional targeting guidance, especially in asleep DBS surgery, where clinical value of microelectrode recordings and test stimulation may be limited. As this technique can exclude future capsular side effects, it can directly be translated into clinical practice.

Directional Deep Brain Stimulation for Parkinson's Disease: Results of an International Crossover Study With Randomized, Double-Blind Primary Endpoint.

OBJECTIVE: Published reports on directional deep brain stimulation (DBS) have been limited to small, single-center investigations. Therapeutic window (TW) is used to describe the range of stimulation amplitudes achieving symptom relief without side effects. This crossover study performed a randomized double-blind assessment of TW for directional and omnidirectional DBS in a large cohort of patients implanted with a DBS system in the subthalamic nucleus for Parkinson's disease. MATERIALS AND METHODS: Participants received omnidirectional stimulation for the first three months after initial study programming, followed by directional DBS for the following three months. The primary endpoint was a double-blind, randomized evaluation of TW for directional vs omnidirectional stimulation at three months after initial study programming. Additional data recorded at three- and six-month follow-ups included stimulation preference, therapeutic current strength, Unified Parkinson's Disease Rating Scale (UPDRS) part III motor score, and quality of life. RESULTS: The study enrolled 234 subjects (62 ± 8 years, 33% female). TW was wider using directional stimulation in 183 of 202 subjects (90.6%). The mean increase in TW with directional stimulation was 41% (2.98 ± 1.38 mA, compared to 2.11 ± 1.33 mA for omnidirectional). UPDRS part III motor score on medication improved 42.4% at three months (after three months of omnidirectional stimulation) and 43.3% at six months (after three months of directional stimulation) with stimulation on, compared to stimulation off. After six months, 52.8% of subjects blinded to stimulation type (102/193) preferred the period with directional stimulation, and 25.9% (50/193) preferred the omnidirectional period. The directional period was preferred by 58.5% of clinicians (113/193) vs 21.2% (41/193) who preferred the omnidirectional period. CONCLUSION: Directional stimulation yielded a wider TW compared to omnidirectional stimulation and was preferred by blinded subjects and clinicians.

[Deep brain stimulation for Parkinson's disease]. / Tiefe Hirnstimulation bei Morbus Parkinson.

Deep brain stimulation is an established and evidence-based therapeutic option for the treatment of advanced Parkinson's disease. Main indication and inclusion criteria are the presence of idiopathic Parkinsonism with motor fluctuations and / or dyskinesias and / or with medication refractory tremor, a significant improvement of akinesia / rigidity in response to dopaminergic medication, the absence of relevant cognitive deficits and other significant comorbidities. DBS neurosurgery has a low risk of complications. The clinical programming should follow an established monopolar review algorithm. Regular follow-up visits are required for stimulation monitoring.

Asleep Surgery May Improve the Therapeutic Window for Deep Brain Stimulation of the Subthalamic Nucleus.

OBJECTIVE: The effect of anesthesia type in terms of asleep vs. awake deep brain stimulation (DBS) surgery on therapeutic window (TW) has not been investigated so far. The objective of the study was to investigate whether asleep DBS surgery of the subthalamic nucleus (STN) improves TW for both directional (dDBS) and omnidirectional (oDBS) stimulation in a large single-center population. MATERIALS AND METHODS: A total of 104 consecutive patients with Parkinson's disease (PD) undergoing STN-DBS surgery (80 asleep and 24 awake) were compared regarding TW, therapeutic threshold, side effect threshold, improvement of Unified PD Rating Scale motor score (UPDRS-III) and degree of levodopa equivalent daily dose (LEDD) reduction. RESULTS: Asleep DBS surgery led to significantly wider TW compared to awake surgery for both dDBS and oDBS. However, dDBS further increased TW compared to oDBS in the asleep group only and not in the awake group. Clinical efficacy in terms of UPDRS-III improvement and LEDD reduction did not differ between groups. CONCLUSIONS: Our study provides first evidence for improvement of therapeutic window by asleep surgery compared to awake surgery, which can be strengthened further by dDBS. These results support the notion of preferring asleep over awake surgery but needs to be confirmed by prospective trials.

Prolonged Neuropsychological Deficits, Central Nervous System Involvement, and Brain Stem Affection After COVID-19-A Case Series.

Objective: The affection of both the peripheral (PNS) and central nervous system (CNS) by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been assumed to play a direct role in the respiratory failure of patients with Corona virus disease 2019 (COVID-19) through affection of medullary cardiorespiratory centers resulting in neurological complications and sequelae. Methods: We used a multimodal electrophysiological approach combined with neuropsychological investigations to study functional alteration of both the PNS and CNS in four patients with severe COVID-19. Results: We found electrophysiological evidence for affection of both the PNS and CNS, and particularly affection of brain stem function. Furthermore, our neuropsychological investigations provide evidence of marked impairment of cognition independent of delirium, and outlasting the duration of acute infection with SARS-CoV-2. Conclusion: This case series provides first direct electrophysiological evidence for functional brain stem involvement in COVID-19 patients without evident morphological changes supporting the notion of the brain stem contributing to respiratory failure and thus promoting severe courses of the disease. Moreover, sustained neuropsychological sequelae in these patients may be of particular psychosocial and possibly also economic relevance for society.

Occipital repetitive transcranial magnetic stimulation does not affect multifocal visual evoked potentials.

BACKGROUND: To identify mechanisms of cortical plasticity of the visual cortex and to quantify their significance, sensitive parameters are warranted. In this context, multifocal visual evoked potentials (mfVEPs) can make a valuable contribution as they are not associated with cancellation artifacts and include also the peripheral visual field. OBJECTIVE: To investigate if occipital repetitive transcranial magnetic stimulation (rTMS) can induce mfVEP changes. METHODS: 18 healthy participants were included in a single-blind crossover-study receiving sessions of excitatory, occipital 10 Hz rTMS and sham stimulation. MfVEP was performed before and after each rTMS session and changes in amplitude and latency between both sessions were compared using generalized estimation equation models. RESULTS: There was no significant difference in amplitude or latency between verum and sham group. CONCLUSION: We conclude that occipital 10 Hz rTMS has no effect on mfVEP measures, which is in line with previous studies using full field VEP.

Effect of conditioning and test stimulus intensity on cortical excitability using triad-conditioning transcranial magnetic stimulation.

Cortical facilitation assessed with triad conditioning transcranial magnetic stimulation has been termed triad-conditioned facilitation (TCF). TCF has been supposed to reflect increased intracortical facilitation (ICF) at short interstimulus intervals (ISI) around 10 ms and an intrinsic rhythm of the motor cortex at longer ISI around 25 ms. To gain further insight into the pathophysiological mechanism of TCF, we systematically studied the effect of suprathreshold conditioning stimulus (CS) and test stimulus (TS) intensity on TCF. Various CS intensities and TS intensities were used in a triad-conditioning paradigm that was applied to 11 healthy subjects. ISI between pulses were studied between 5 and 200 ms. TCF at 10 ms ISI enhanced with increasing CS intensity but decreased with increasing TS intensity. The duration of facilitation was longer with higher CS intensity. However, TCF at 25 ms ISI could not be elicited with none of the CS and TS intensities addressed here. Our results are consistent with the notion of TCF at short ISI reflecting ICF. The enhanced and prolonged facilitation with increase of CS without additional isolated facilitation at longer ISI suggest a prolongation of ICF.

Cerebellar Involvement in DYT-THAP1 Dystonia.

DYT-THAP1 dystonia is known to present a variety of clinical symptoms. To the best of our knowledge, this is the first case with DYT-THAP 1 dystonia and clinical signs of cerebellar involvement studied with transcranial magnetic stimulation in vivo. We report a case of a 51-year-old male DYT-THAP1 mutation carrier with dystonia, who additionally developed ataxia 1.5 years ago. To study cerebellar involvement in our patient, we used a TMS protocol called cerebellar inhibition (CBI). The lack of CBI in our patient strongly suggests cerebellar involvement. According to our findings, cerebellar syndrome may be part of the phenotypical spectrum of DYT-THAP1 mutations.

Cerebellar inhibition in hepatic encephalopathy.

OBJECTIVE: Previous animal work reported that hyperammonemia leads to opposing changes of GABAergic neurotransmission in terms of increase in the cerebellum and decrease in the cerebral cortex. In this study, we investigate GABAergic tone in the cerebellum in patients with hepatic encephalopathy (HE) at different stages of the disease and its relation to critical flicker frequency (CFF) and ataxia. METHODS: Cerebellar inhibition using transcranial magnetic stimulation was investigated in 15 patients with different stages of HE and 15 healthy controls. All patients were assessed using CFF and the score for assessment and rating of ataxia (SARA). RESULTS: Decreased cerebellar inhibition (CBI) was observed in manifest HE at interstimulus interval from 5 to 7 ms. However, the degree of CBI at 7 ms correlated significantly with disease severity measured with SARA and with CFF by trend. CONCLUSION: Reduced CBI in HE patients indicates affection of the cerebellar efferent pathway. The disease severity dependent increase of CBI magnitude supports the notion of disease stage dependent increase of GABAergic neurotransmission in Purkinje cells. SIGNIFICANCE: The results support previous animal experiments showing increase of GABA-ergic neurotransmission in the cerebellum and decrease in the motor cortex in HE.

GABA-ergic tone hypothesis in hepatic encephalopathy - Revisited.

OBJECTIVE: The GABA hypothesis of hepatic encephalopathy (HE) proposes an increased cerebral GABA-ergic tone in HE but has not been investigated in vivo in HE-patients yet. Cortical GABA-ergic and glutamatergic neurotransmission in HE-patients were evaluated using transcranial magnetic stimulation. METHODS: Twenty-one patients with HE grade 1 and 2 and age matched controls participated in the study. GABA-ergic (short- and long-interval intracortical inhibition (SICI and LICI)) and glutamatergic (intracortical and short-interval intracortical facilitation (ICF and SICF)) excitability of the primary motor cortex (M1) and global corticospinal excitability (motor threshold, motor evoked potential recruitment curve (MEP-RC) were compared between the groups. SICI and ICF were correlated to the critical flicker frequency (CFF) as measure for disease severity. RESULTS: In HE-patients, the slope of MEP-RC was significantly shallower compared to healthy controls. SICI was significantly reduced in patients with HE grade 2 compared to healthy controls. In HE-patients, SICI and ICF was significantly correlated to CFF. CONCLUSION: Although global corticospinal excitability was reduced in HE-patients, GABA-ergic inhibition was reduced in M1 depending on HE severity. Moreover CFF related alteration of GABAergic and glutamatergic neurotransmission in patients with HE could support the notion of a severity dependent alteration of cortical excitability. SIGNIFICANCE: The decrease of cortical GABA-ergic tone challenges the classical GABA hypothesis in HE.

Less is more - Pulse width dependent therapeutic window in deep brain stimulation for essential tremor.

BACKGROUND: Shorter pulse widths than conventional pulse width settings may lead to reduction of side effects and therefore be a valuable therapeutic option for deep brain stimulation (DBS) in patients with essential tremor (ET). OBJECTIVE: To compare the DBS effect of shorter pulse width at 40 µs (DBS-40 µs) to conventional pulse width at 60 µs (DBS-60 µs) on the therapeutic window in ET patients. METHODS: For this prospective, randomized, double-blind, crossover study 9 ET patients with chronic DBS of the ventral intermediate nucleus (VIM)/posterior subthalamic area (PSA) were recruited. Therapeutic window was calculated by determining efficacy and side effect thresholds for DBS-40 µs and DBS-60 µs. Tremor Rating Scales and Kinesia tremor analyses were used to compare clinical efficacy between the considered settings and deactivated DBS (DBS-OFF). Volume of neural activation (VNA) was calculated for both efficacy and side effect thresholds at each pulse width. RESULTS: DBS-40 µs showed a significantly larger therapeutic window than DBS-60 µs mainly due to higher side-effect thresholds. Both conditions significantly improved tremor compared to DBS-OFF, while efficacy was comparable between DBS-40 µs and DBS-60 µs. Moreover, VNA at efficacy threshold was smaller and less energy was required for tremor suppression with DBS-40 µs compared to DBS-60 µs. CONCLUSIONS: VIM/PSA-DBS with short pulse width represents a promising programming option for DBS in ET as it reduces side effects while maintaining efficient tremor suppression. Furthermore, our data support the notion of pulse width dependent selective modulation of distinct fiber tracts leading to widening of the therapeutic window.

Comparison of Awake vs. Asleep Surgery for Subthalamic Deep Brain Stimulation in Parkinson's Disease.

BACKGROUND: Deep brain stimulation (DBS) surgery for Parkinson's disease (PD) is usually performed as awake surgery allowing sufficient intraoperative testing. Recently, outcomes after asleep surgery have been assumed comparable. However, direct comparisons between awake and asleep surgery are scarce. OBJECTIVE: To investigate the difference between awake and asleep surgery comparing motor and nonmotor outcome after subthalamic nucleus (STN)-DBS in a large single center PD population. METHODS: Ninety-six patients were retrospectively matched pairwise (48 asleep and 48 awake) and compared regarding improvement of Unified PD Rating Scale Motor Score (UPDRS-III), cognitive function, Levodopa-equivalent-daily-dose (LEDD), stimulation amplitudes, side effects, surgery duration, and complication rates. Routine testing took place at three months and one year postoperatively. RESULTS: Chronic DBS effects (UPDRS-III without medication and with stimulation on [OFF/ON]) significantly improved UPDRS-III only after awake surgery at three months and in both groups one year postoperatively. Acute effects (percentage UPDRS-III reduction after activation of stimulation) were also significantly better after awake surgery at three months but not at one year compared to asleep surgery. UPDRS-III subitems "freezing" and "speech" were significantly worse after asleep surgery at three months and one year, respectively. LEDD was significantly lower after awake surgery only one week postoperatively. The other measures did not differ between groups. CONCLUSIONS: Overall motor function improved faster in the awake surgery group, but the difference ceased after one year. However, axial subitems were worse in the asleep surgery group suggesting that worsening of axial symptoms was risked improving overall motor function. Awake surgery still seems advantageous for STN-DBS in PD, although asleep surgery may be considered with lower threshold in patients not suitable for awake surgery.

Occurrence of thalamic high frequency oscillations in patients with different tremor syndromes.

OBJECTIVE: To assess whether high frequency oscillations (HFOs, >150 Hz), known to occur in basal ganglia nuclei, can be observed in the thalamus. METHODS: We recorded intraoperative local field potentials from the ventral intermediate nucleus (VIM) of the thalamus in patients with Essential Tremor (N = 16), Parkinsonian Tremor (3), Holmes Tremor (2) and Dystonic Tremor (1) during implantation of electrodes for deep brain stimulation. Recordings were performed with up to five micro/macro-electrodes that were simultaneously advanced to the stereotactic target. RESULTS: Thalamic HFOs occurred in all investigated tremor syndromes. A detailed analysis of the Essential Tremor subgroup revealed that medial channels recorded HFOs more frequently than other channels. The highest peaks were observed 4 mm above target. Macro- but not microelectrode recordings were dominated by peaks in the slow HFO band (150-300 Hz), which were stable across several depths and channels. CONCLUSION: HFOs occur in the thalamus and are not specific to any of the tremors investigated. Their spatial distribution is not homogeneous, and their appearance depends on the type of electrode used for recording. SIGNIFICANCE: The occurrence of HFOs in the thalamus of tremor patients indicates that HFOs are not part of basal ganglia pathophysiology.

Pulse duration settings in subthalamic stimulation for Parkinson's disease.

BACKGROUND: Stimulation parameters in deep brain stimulation (DBS) of the subthalamic nucleus for Parkinson's disease (PD) are rarely tested in double-blind conditions. Evidence-based recommendations on optimal stimulator settings are needed. Results from the CUSTOM-DBS study are reported, comparing 2 pulse durations. METHODS: A total of 15 patients were programmed using a pulse width of 30 µs (test) or 60 µs (control). Efficacy and side-effect thresholds and unified PD rating scale (UPDRS) III were measured in meds-off (primary outcome). The therapeutic window was the difference between patients' efficacy and side effect thresholds. RESULTS: The therapeutic window was significantly larger at 30 µs than 60 µs (P = ·0009) and the efficacy (UPDRS III score) was noninferior (P = .00008). INTERPRETATION: Subthalamic neurostimulation at 30 µs versus 60 µs pulse width is equally effective on PD motor signs, is more energy efficient, and has less likelihood of stimulation-related side effects. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Intraoperative Localization of the Subthalamic Nucleus Using Long-Latency Somatosensory Evoked Potentials.

BACKGROUND: Target localization for deep brain stimulation (DBS) is a challenging step that determines not only the correct placement of stimulation electrodes, but also influences the success of the DBS procedure as reflected in the desired clinical outcome of a patient. OBJECTIVE: We report on the feasibility of DBS target localization in the subthalamic nucleus (STN) by long-latency somatosensory evoked potentials (LL-SSEPs) (>40 msec) in Parkinson's disease (PD) patients. METHODS: Micro-macroelectrode recordings were performed intraoperatively on seven PD patients (eight STN hemispheres) who underwent DBS treatment. LL-SSEPs were elicited by ipsi- and contralateral median nerve stimulation to the wrist. RESULTS: Four distinctive LL-SSEP components were elicited ("LL-complex" consisting of P80, N100, P140, and N200). The P80 appeared as the most visible and reliable intraoperative component. Localization of the "LL-complex" within the target was approved with typical microelectrode firing activity patterns, atlas visualization of recording electrodes, and postoperative CT-based visualization of final DBS electrodes. CONCLUSIONS: LL-SSEPs represent a promising approach for DBS target localization in the STN, provided deeper understanding on their anesthesia effect is obtained. This approach is advantageous in that it does not require the patient's participation in an intraoperative setting.

Alteration of cortical excitability and its modulation by Miglustat in Niemann-Pick disease type C.

Niemann-Pick type C (NP-C) is a rare, neurodegenerative, lysosomal storage disease. Cortical excitability using different transcranial magnetic stimulation (TMS) protocols together with clinical and neuropsychological testing was longitudinally assessed in a patient with NP-C. Cerebellar inhibition, a measure for the integrity of the cerebello-thalamo-cortical network, was impaired. Short-latency afferent inhibition, a measure for cholinergic transmission, and cognitive functions were also impaired and improved under Miglustat treatment. Short interval intracortical facilitation, a marker for glutamatergic neurotransmission, was absent initially but increased after treatment with Miglustat. Our results provide new insights into pathophysiological mechanisms of NP-C and the response to Miglustat treatment.