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Abstract Background Intragastric botulinum neurotoxin injections (IBNI) are offered off-label in the private medical sector in a few European countries as a safe and effective weight-loss measure. In February and March 2023, an outbreak of iatrogenic botulism occurred in several European countries following IBNI treatment in Turkey. This case series describes the clinical features of severe iatrogenic botulism after IBNI. Methods We retrospectively summarize the clinical course and emergency department and intensive care unit interventions in ten cases of severe iatrogenic botulism that occurred after receiving IBNI in this sudden outbreak in Austria and Germany. Results Seven out of ten cases initially showed characteristic symptoms of botulism with diplopia, dysphagia, dysarthria, dysarthrophonia, and descending paralysis. All patients were hospitalized, six in an intensive care unit and partially requiring mechanical ventilation. All patients recovered and were discharged without relevant permanent deficits. Conclusion Our study highlights ten clinical cases in this iatrogenic botulism outbreak, representing the largest reported outbreak worldwide. Clinicians should be aware of the risks associated with medical procedures involving botulinum neurotoxins and ensure measures to minimize the risk of iatrogenic botulism.

Abstract Background Misfolding and aggregation of amyloid β (Aβ), along with neurofibrillary tangles consisting of aggregated Tau species, are pathological hallmarks of Alzheimer’s disease (AD) onset and progression. In this study, we hypothesized the clearance of Aβ aggregates from the brain and body into the gut. Methods To investigate this, we used surface-based fluorescence intensity distribution analysis (sFIDA) to determine the Aβ aggregate concentrations in feces from 26 AD patients and 31 healthy controls (HC). Results Aβ aggregates were detectable in human feces and their concentrations were elevated in AD patients compared to HC (specificity 90.3%, sensitivity 53.8%). Conclusion Thus, fecal Aβ aggregates constitute a non-invasive biomarker candidate for diagnosing AD. Whether digestion-resistant Aβ aggregates in feces are secreted via the liver and bile or directly from the enteric neuronal system remains to be elucidated.

Background: Subthalamic deep brain stimulation (STN-DBS) is a well-established therapy to treat Parkinson's disease (PD). However, the STN-DBS sub-target remains debated. Recently, a white matter tract termed the hyperdirect pathway (HDP), directly connecting the motor cortex to STN, has gained interest as HDP stimulation is hypothesized to drive DBS therapeutic effects. Previously, we have investigated EEG-based evoked potentials (EPs) to better understand the neuroanatomical origins of the DBS clinical effect. We found a 3-ms peak (P3) relating to clinical benefit, and a 10-ms peak (P10) suggesting nigral side effects. Here, we aimed to investigate the neuroanatomical origins of DBS EPs using probabilistic mapping. Methods: EPs were recorded using EEG whilst low-frequency stimulation was delivered at all DBS-contacts individually. Next, EPs were mapped onto the patients’ individual space and then transformed to MNI standard space. Using voxel-wise and fiber-wise probabilistic mapping, we determined hotspots/hottracts and coldspots/coldtracts for P3 and P10. Topography analysis was also performed to determine the spatial distribution of the DBS EPs. Results: In all 13 patients (18 hemispheres), voxel- and fiber-wise probabilistic mapping resulted in a P3-hotspot/hottract centered on the posterodorsomedial STN border indicative of HDP stimulation, while the P10-hotspot/hottract covered large parts of the substantia nigra. Conclusion: This study investigated EP-based probabilistic mapping in PD patients during STN-DBS, revealing a P3-hotspot/hottract in line with HDP stimulation and P10-hotspot/hottract related to nigral stimulation. Results from this study provide key evidence for an electrophysiological measure of HDP and nigral stimulation.

IntroductionDysarthria, a motor speech disorder caused by muscle weakness or paralysis, severely impacts speech intelligibility and quality of life. The condition is prevalent in motor speech disorders such as Parkinson's disease (PD), atypical parkinsonism such as progressive supranuclear palsy (PSP), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). Improving intelligibility is not only an outcome that matters to patients but can also play a critical role as an endpoint in clinical research and drug development. This study validates a digital measure for speech intelligibility, the ki: SB-M intelligibility score, across various motor speech disorders and languages following the Digital Medicine Society (DiMe) V3 framework.MethodsThe study used four datasets: healthy controls (HCs) and patients with PD, HD, PSP, and ALS from Czech, Colombian, and German populations. Participants’ speech intelligibility was assessed using the ki: SB-M intelligibility score, which is derived from automatic speech recognition (ASR) systems. Verification with inter-ASR reliability and temporal consistency, analytical validation with correlations to gold standard clinical dysarthria scores in each disease, and clinical validation with group comparisons between HCs and patients were performed.ResultsVerification showed good to excellent inter-rater reliability between ASR systems and fair to good consistency. Analytical validation revealed significant correlations between the SB-M intelligibility score and established clinical measures for speech impairments across all patient groups and languages. Clinical validation demonstrated significant differences in intelligibility scores between pathological groups and healthy controls, indicating the measure's discriminative capability.DiscussionThe ki: SB-M intelligibility score is a reliable, valid, and clinically relevant tool for assessing speech intelligibility in motor speech disorders. It holds promise for improving clinical trials through automated, objective, and scalable assessments. Future studies should explore its utility in monitoring disease progression and therapeutic efficacy as well as add data from further dysarthrias to the validation.

Abstract Background While subthalamic nucleus deep brain stimulation (STN-DBS) improves the quality of life (QoL) of patients with Parkinson’s disease (PD), the clinical parameters that predict this improvement remain debated. This retrospective study explored whether preoperative motor, cognitive, and affective parameters predict QoL or its components at 6 and 12 months after STN-DBS surgery. Methods QoL was assessed with the Parkinson’s Disease Questionnaire-39 (PDQ-39) before (baseline), at 6 months (N = 90) and 12 months (N = 63) after STN-DBS surgery. Changes in the PDQ-39 and its subdomains were analysed with Wilcoxon signed-rank tests. In total, seven motor, cognitive, and affective parameters recorded at baseline were used in multiple linear regressions to predict QoL and its subdomains. Results QoL had improved significantly at six months post STN-DBS surgery. After 12 months, this effect remained significant but was less pronounced. At both time points, significant improvements in mobility, activities of daily living, stigma, and bodily discomfort were present. Correlation and linear regression analyses showed that preoperative QoL status and changes in QoL at 6 and 12 months after surgery were driven by preoperative dopaminergic medication, as well as motor (UPDRS-III medOFF and PIGD-subscore medOFF) and affective (HADS anxiety and depression) symptoms. In contrast, preoperative cognitive performance did not predict QoL at any time point. Conclusion Data show that preoperative motor and affective symptoms drive both QoL baseline status and changes in QoL after STN-DBS surgery. Thus, these clinical parameters need to be assessed appropriately to provide comprehensive presurgical advice to patients suffering from PD.

Abstract Background The effectiveness of Deep Brain Stimulation (DBS) therapy for Parkinson’s disease can be limited by side-effects caused by electrical current spillover into structures adjacent to the target area. The objective of the STEEred versus RING-mode DBS for Parkinson’s disease (STEERING) study is to investigate if directional DBS for Parkinson’s disease results in a better clinical outcome when compared to ring-mode DBS. Methods The STEERING study is a prospective multi-centre double-blind randomised crossover trial. Inclusion criteria are Parkinson’s disease, subthalamic nucleus DBS in a ‘classic’ ring-mode setting for a minimum of six months, and optimal ring-mode settings have been established. Participants are categorised into one of two subgroups according to their clinical response to the ring-mode settings as ‘responders’ (i.e., patient with a satisfactory effect of ring-mode DBS) or ‘non-responder’ (i.e., patient with a non-satisfactory effect of ring-mode DBS). A total of 64 responders and 38 non-responders will be included (total 102 patients). After an optimisation period in which an optimal directional setting is found, participants are randomised to first receive ring-mode DBS for 56 days (range 28–66) followed by directional DBS for 56 days (28–66) or vice-versa. The primary outcome is the difference between ring-mode DBS and directional DBS settings on the Movement Disorders Society Unified Parkinson’s Disease Rating Scale – Motor Evaluation (MDS-UPDRS-ME) in the off-medication state. Secondary outcome measures consist of MDS-UPDRS-ME in the on-medication state, MDS-UPDRS Activities of Daily Living, MDS-UPDRS Motor Complications–Dyskinesia, disease related quality of life measured with the Parkinson’s Disease Questionnaire 39, stimulation-induced side-effects, antiparkinsonian medication use, and DBS-parameters. Participants’ therapy preference is measured at the end of the study. Outcomes will be analysed for both responder and non-responder groups, as well as for both groups pooled together. Discussion The STEERING trial will provide insights into whether or not directional DBS should be standardly used in all Parkinson’s disease DBS patients or if directional DBS should only be used in a case-based approach. Trial registration This trial was registered on the Netherlands Trial Register, as trial NL6508 ( NTR6696 ) on June 23, 2017.

Deep brain stimulation (DBS) for Parkinson’s disease (PD) often necessitates frequent clinic visits for stimulation program optimization, with limited experience in remote patient management. Due to the resource-intensive nature of these procedures, we investigated a way to simplify stimulation optimization for these patients that allows for the continuous monitoring of symptoms while also reducing patient burden and travel distances. To this end, we prospectively recruited ten patients treated with DBS for PD to evaluate the feasibility of telemedicinal optimization in a home-based setting. Patients recorded daily videos of a modified Unified Parkinson’s Disease Rating Scale (UPDRS) III, which experienced DBS physicians located at the clinic assessed to provide instructions on adjusting stimulation settings using a handheld programmer with previously set programs as well as patient amplitude control. This study concluded with significant improvements in participants’ motor status as measured by the UPDRS-III (p = 0.0313) compared to baseline values. These findings suggest that remote video-guided optimization of DBS settings is feasible and may enhance motor outcomes for patients.

Abstract Misfolded and aggregated α-synuclein is a neuropathological hallmark of Parkinson’s disease (PD). Thus, α-synuclein aggregates are regarded as a biomarker for the development of diagnostic assays. Quantification of α-synuclein aggregates in body fluids is challenging, and requires highly sensitive and specific assays. Recent studies suggest that α-synuclein aggregates may be shed into stool. We used surface-based fluorescence intensity distribution analysis (sFIDA) to detect and quantify single particles of α-synuclein aggregates in stool of 94 PD patients, 72 isolated rapid eye movement sleep behavior disorder (iRBD) patients, and 51 healthy controls. We measured significantly elevated concentrations of α-synuclein aggregates in stool of iRBD patients versus those of controls (p = 0.024) or PD patients (p

Abstract Here we report on a patient with Parkinson's Disease and camptocormia due to Myofibrillar Myopathy Type 3. By leading the reader through the clinical reasoning process and highlighting the respective red flags we aim to increase the readers’ awareness for the differential diagnosis of camptocormia.

Abstract Previous studies have shown less access to deep brain stimulation (DBS) for Parkinson’s disease (PD) in women compared to men raising concerns about a potential gender gap resulting from nonclinical factors or gender differences in clinical efficacy for postoperative quality of life (QoL), motor, and nonmotor symptoms (NMS) outcomes. This was a cross-sectional and a longitudinal, prospective, observational, controlled, quasi-experimental, international multicenter study. A total sample size of 505 consisted of 316 consecutively referred patients for DBS indication evaluation at the University Hospital Cologne (01/2015–09/2020) and 189 consecutively treated patients at DBS centers in the University Hospitals Cologne and Marburg, Salford’s Royal Hospital Manchester, and King’s College Hospital London. In the cross-sectional cohort, we examined gender proportions at referral, indication evaluations, and DBS surgery. In the longitudinal cohort, clinical assessments at preoperative baseline and 6-month follow-up after surgery included the PD Questionnaire-8, NMSScale, Scales for Outcomes in PD-motor scale, and levodopa-equivalent daily dose. Propensity score matching resulted in a pseudo-randomized sub-cohort balancing baseline demographic and clinical characteristics between women with PD and male controls. 316 patients were referred for DBS. 219 indication evaluations were positive (women n = 102, respectively n = 82). Women with PD were disproportionally underrepresented in referrals compared to the general PD population (relative risk [RR], 0.72; 95%CI, 0.56–0.91; P = 0.002), but more likely to be approved for DBS than men (RR, 1.17; 95%CI, 1.03–1.34; P = 0.029). Nonetheless, their total relative risk of undergoing DBS treatment was 0.74 (95%CI, 0.48–1.12) compared to men with PD. At baseline, women had longer disease duration and worse dyskinesia. Exploring QoL domains, women reported worse mobility and bodily discomfort. At follow-up, all main outcomes improved equally in both genders. Our study provides evidence of a gender gap in DBS for PD. Women and men with PD have distinct preoperative nonmotor and motor profiles. We advocate that more focus should be directed toward the implementation of gender equity as both genders benefit from DBS with equal clinical efficacy. This study provides Class II evidence of beneficial effects of DBS in women with PD compared to male controls.

Clinical rating scales for tremors have significant limitations due to low resolution, high rater dependency, and lack of applicability in outpatient settings. Reliable, quantitative approaches for assessing tremor severity are warranted, especially evaluating treatment effects, e.g., of deep brain stimulation (DBS). We aimed to investigate how different accelerometry metrics can objectively classify tremor amplitude of Essential Tremor (ET) and tremor in Parkinson’s Disease (PD). We assessed 860 resting and postural tremor trials in 16 patients with ET and 25 patients with PD under different DBS settings. Clinical ratings were compared to different metrics, based on either spectral components in the tremorband or pure acceleration, derived from simultaneous triaxial accelerometry captured at the index finger and wrist. Nonlinear regression was applied to a training dataset to determine the relationship between accelerometry and clinical ratings, which was then evaluated in a holdout dataset. All of the investigated accelerometry metrics could predict clinical tremor ratings with a high concordance (>70%) and substantial interrater reliability (Cohen’s weighted Kappa > 0.7) in out-of-sample data. Finger-worn accelerometry performed slightly better than wrist-worn accelerometry. We conclude that triaxial accelerometry reliably quantifies resting and postural tremor amplitude in ET and PD patients. A full release of our dataset and software allows for implementation, development, training, and validation of novel methods.

Background: There is still a lack of controlled studies to prove efficacy of thalamic deep brain stimulation for Tourette's Syndrome. Objectives: In this controlled trial, we investigated the course of tic severity, comorbidities and quality of life during thalamic stimulation and whether changes in tic severity can be assigned to ongoing compared to sham stimulation. Methods: We included eight adult patients with medically refractory Tourette's syndrome. Bilateral electrodes were implanted in the centromedian-parafascicular-complex and the nucleus ventro-oralis internus. Tic severity, quality of life and comorbidities were assessed before surgery as well as six and twelve months after. Short randomized, double-blinded sham-controlled crossover sequences with either active or sham stimulation were implemented at both six- and twelve-months’ assessments. The primary outcome measurement was the difference in the Yale Global Tic Severity Scale tic score between active and sham stimulation. Adverse events were systematically surveyed for all patients to evaluate safety. Results: Active stimulation resulted in significantly higher tic reductions than sham stimulation (F = 79.5; p = 0.001). Overall quality of life and comorbidities improved significantly in the open-label-phase. Over the course of the trial two severe adverse events occurred that were resolved without sequelae. Conclusion: Our results provide evidence that thalamic stimulation is effective in improving tic severity and overall quality of life. Crucially, the reduction of tic severity was primarily driven by active stimulation. Further research may focus on improving stimulation protocols and refining patient selection to improve efficacy and safety of deep brain stimulation for Tourette's Syndrome.

Abstract To identify predictors of 36-month follow-up quality of life (QoL) outcome after bilateral subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson’s disease (PD). In this ongoing, prospective, multicenter international study (Cologne, Manchester, London) including 73 patients undergoing STN-DBS, we assessed the following scales preoperatively and at 6-month and 36-month follow-up: PD Questionnaire-8 (PDQ-8), NMSScale (NMSS), Scales for Outcomes in PD (SCOPA)-motor examination, -activities of daily living, and -complications, and levodopa equivalent daily dose (LEDD). We analyzed factors associated with QoL improvement at 36-month follow-up based on (1) correlations between baseline test scores and QoL improvement, (2) step-wise linear regressions with baseline test scores as independent and QoL improvement as dependent variables, (3) logistic regressions and receiver operating characteristic curves using a dichotomized variable “QoL responders”/“non-responders”. At both follow-ups, NMSS total score, SCOPA-motor examination, and -complications improved and LEDD was reduced significantly. PDQ-8 improved at 6-month follow-up with subsequent decrements in gains at 36-month follow-up when 61.6% of patients were categorized as “QoL non-responders”. Correlations, linear, and logistic regression analyses found greater PDQ-8 improvements in patients with younger age, worse PDQ-8, and worse specific NMS at baseline, such as ‘difficulties experiencing pleasure’ and ‘problems sustaining concentration’. Baseline SCOPA scores were not associated with PDQ-8 changes. Our results provide evidence that 36-month QoL changes depend on baseline neuropsychological and neuropsychiatric non-motor symptoms burden. These findings highlight the need for an assessment of a wide range of non-motor and motor symptoms when advising and selecting individuals for DBS therapy.

Background: Subthalamic (STN) and pallidal (GPi) deep brain stimulation (DBS) improve quality of life, motor, and nonmotor symptoms (NMS) in advanced Parkinson’s disease (PD). However, few studies have compared their nonmotor effects. Objective: To compare nonmotor effects of STN-DBS and GPi-DBS. Methods: In this prospective, observational, multicenter study including 60 PD patients undergoing bilateral STN-DBS (n = 40) or GPi-DBS (n = 20), we examined PDQuestionnaire (PDQ), NMSScale (NMSS), Unified PD Rating Scale-activities of daily living, -motor impairment, -complications (UPDRS-II, –III, -IV), Hoehn&Yahr, Schwab&England Scale, and levodopa-equivalent daily dose (LEDD) preoperatively and at 6-month follow-up. Intra-group changes at follow-up were analyzed with Wilcoxon signed-rank or paired t-test, if parametric tests were applicable, and corrected for multiple comparisons. Inter-group differences were explored with Mann-Whitney-U/unpaired t-tests. Analyses were performed before and after propensity score matching which balanced out demographic and preoperative clinical characteristics. Strength of clinical changes was assessed with effect size. Results: In both groups, PDQ, UPDRS-II, -IV, Schwab&England Scale, and NMSS improved significantly at follow-up. STN-DBS was significantly better for LEDD reduction, GPi-DBS for UPDRS-IV. While NMSS total score outcomes were similar, explorative NMSS domain analyses revealed distinct profiles: Both targets improved sleep/fatigue and mood/cognition, but only STN-DBS the miscellaneous (pain/olfaction) and attention/memory and only GPi-DBS cardiovascular and sexual function domains. Conclusions: To our knowledge, this is the first study to report distinct patterns of beneficial nonmotor effects of STN-DBS and GPi-DBS in PD. This study highlights the importance of NMS assessments to tailor DBS target choices to patients’ individual motor and nonmotor profiles.

Intra- and perioperatively recorded local field potential (LFP) activity of the nucleus subthalamicus (STN) has been suggested to guide contact selection in patients undergoing deep brain stimulation (DBS) for Parkinson’s disease (PD). Despite the invention of sensing capacities in chronically implanted devices, a comprehensible algorithm that enables contact selection using such recordings is still lacking. We evaluated a fully automated algorithm that uses the weighted average of bipolar recordings to determine effective monopolar contacts based on elevated activity in the beta band. LFPs from 14 hemispheres in seven PD patients with newly implanted directional DBS leads of the STN were recorded. First, the algorithm determined the stimulation level with the highest beta activity. Based on the prior determined level, the directional contact with the highest beta activity was chosen in the second step. The mean clinical efficacy of the contacts chosen using the algorithm did not statistically differ from the mean clinical efficacy of standard contact selection as performed in clinical routine. All recording sites were projected into MNI standard space to investigate the feasibility of the algorithm with respect to the anatomical boundaries of the STN. We conclude that the proposed algorithm is a first step towards LFP-based contact selection in STN-DBS for PD using chronically implanted devices.

Objective: To investigate the relation between deep brain stimulation (DBS) of the posterior-subthalamic-area (PSA) and the ventral-intermediate-nucleus (VIM) and the distance to the dentatorubrothalamic tract (DRTT) in essential tremor (ET). Methods: Tremor rating scale (TRS) hemi-scores were analyzed in 13 ET patients, stimulated in both the VIM and the PSA in a randomized, crossover trial. Distances of PSA and VIM contacts to population-based DRTTs were calculated. The relationships between distance to DRTT and stimulation amplitude, as well as DBS efficiency (TRS improvement per amplitude) were investigated. Results: PSA contacts were closer to the DRTT (p = 0.019) and led to a greater improvement in TRS hemi-scores (p = 0.005) than VIM contacts. Proximity to the DRTT was related to lower amplitudes (p

The glioblastoma, a malignant human brain tumor, is known for its devastating intracranial progress and its dismal prognosis. Whereas treatment and research are most prominently focused on the primary tumor lesion, in recent years evidence has accumulated that points to the rare occurrence of extracranial glioblastoma metastases. We here present a case of a female patient with a known glioblastoma who was detected to harbor multiple metastases in the bones, lung, pleura, liver, mesentery, and the subcutaneous soft tissue. Pathogenetically, these metastatic lesions developed most probably after a local progression of the left temporal glioblastoma through the skull base, thus getting access to the systemic lymphatics. Similar cases of extensive glioblastoma metastization, their putative underlying mechanisms, and implications for clinical care are discussed.

The authors wish to make the following correction to [...]

Directional deep brain stimulation (DBS) leads are now widely used, but the orientation of directional leads needs to be taken into account when relating DBS to neuroanatomy. Methods that can reliably and unambiguously determine the orientation of directional DBS leads are needed. In this study, we provide an enhanced algorithm that determines the orientation of directional DBS leads from postoperative CT scans. To resolve the ambiguity of symmetric CT artifacts, which in the past, limited the orientation detection to two possible solutions, we retrospectively evaluated four different methods in 150 Cartesia™ directional leads, for which the true solution was known from additional X-ray images. The method based on shifts of the center of mass (COM) of the directional marker compared to its expected geometric center correctly resolved the ambiguity in 100% of cases. In conclusion, the DiODe v2 algorithm provides an open-source, fully automated solution for determining the orientation of directional DBS leads.

This study investigated syllable coordination patterns in Essential Tremor (ET) patients treated with Deep Brain Stimulation (DBS) by using electromagnetic articulography. We analyzed articulatory timing patterns for nine ET patients with activated and inactivated DBS and compared them to a group of healthy age-matched controls. We focused on timing patterns among gestures in syllables with low and high complexity in natural sentence production (simple CV versus complex CCV syllables). These articulatory patterns were interpreted in the framework of a coupled oscillator planning model of speech timing. In simple CV syllables, ET patients did show a similar coordination pattern to healthy control speakers. However, when complexity increased, the patients showed deviant coordination patterns for complex CCV syllables. These deviant patterns even aggravated under activated stimulation. We were able to show that the behavior of the speech system changes when the stimulation was activated, inducing a change in the dynamical system the ET patients have to adapt to. We conclude that coordination problems are not categorical but gradient in nature, pointing to the fact that there are dynamic mechanisms of regulation behind phonetic realization of phonological syllable parses.

Autoimmune encephalitis often causes acute psychiatric symptoms and epileptic seizures. However, it is becoming increasingly clear that depending on the target antigen both symptoms and disease severity may vary. Furthermore, the identification and characterization of antibody subtypes are highly relevant for personalizing the treatment and to prevent relapses. Here we present an atypical case of encephalitis with cerebellar and temporal dysfunction but without seizures associated with high levels of cerebrospinal fluid neuropil antibodies against a yet unknown epitope on the neuronal surface in the cerebellum, hippocampus, thalamus, and the olfactory bulb. We treated the patient successfully with corticosteroids, plasmapheresis, and rituximab.

The present study investigates speech changes in Parkinson’s disease on the acoustic and articulatory level with respect to prosodic prominence marking. To display movements of the underlying articulators, speech data from 16 patients with Parkinson’s disease were recorded using electromagnetic articulography. Speech tasks focused on strategies of prominence marking. Patients’ ability to encode prominence in the laryngeal and supra-laryngeal domain is tested in two conditions to examine the influence of motor performance on speech production further: without dopaminergic medication and with dopaminergic medication. The data reveal that patients with Parkinson’s disease are able to highlight important information in both conditions. They maintain prominence relations across- and within-accentuation by adjusting prosodic markers, such as vowel duration and pitch modulation, while the acoustic vowel space remains the same. For differentiating across-accentuation, not only intensity but also all temporal and spatial parameters related to the articulatory tongue body movements during the production of vowels are modulated to signal prominence. In response to the levodopa intake, gross motor performance improved significantly by 42%. The improvement in gross motor performance was accompanied by an improvement in speech motor performance in terms of louder speech and shorter, larger and faster tongue body movements. The tongue body is more agile under levodopa increase, a fact that is not necessarily detectable on the acoustic level but important for speech therapy.

The new essential tremor (ET) classification defined ET-plus (ET-p) as an ET subgroup with additional neurological signs besides action tremor. While deep brain stimulation (DBS) is effective in ET, there are no studies specifically addressing DBS effects in ET-p. 44 patients with medication-refractory ET and thalamic/subthalamic DBS implanted at our center were postoperatively classified into ET and ET-p according to preoperative documentation. Tremor suppression with DBS (stimulation ON vs. preoperative baseline and vs. stimulation OFF), measured via the Fahn–Tolosa–Marin tremor rating scale (TRS), stimulation parameters, and the location of active contacts were compared between patients classified as ET and ET-p. TRS scores at baseline were higher in ET-p. ET-p patients showed comparable tremor reduction as patients with ET, albeit higher stimulation parameters were needed in ET-p. Active electrode contacts were located more dorsally in ET-p of uncertain reason. Our data show that DBS is similarly effective in ET-p compared to ET. TRS scores were higher in ET-p preoperatively, and higher stimulation parameters were needed for tremor reduction compared to ET. The latter may be related to a more dorsal location of active electrode contacts in the ET-p group of this cohort. Prospective studies are warranted to investigate DBS in ET-p further.

Postoperative choice of the most effective deep brain stimulation (DBS) contact in patients with essential tremor (ET) so far relies on lengthy clinical testing. Previous studies showed that the postoperative effectiveness of DBS contacts depends on the distance to the dentatorubrothalamic tract (DRTT). Here, we investigated whether the most effective DBS contact could be determined from calculating stimulation overlap with the individual DRTT. Seven ET patients with bilateral thalamic deep brain stimulation were included retrospectively. Tremor control was assessed for each contact during test stimulation with 2mA. Individual DRTTs were identified from diffusion tensor imaging and contacts were ranked by their stimulation overlap with the respective DRTT in relation to their clinical effectiveness. A linear mixed-effects model was calculated to determine the influence of the DRTT overlap on tremor control. In all investigated DBS leads, the contact with the best clinical effect was the contact with the highest or second-highest DRTT overlap. At the group level, the DRTT-overlap explained 26.7% of the variance in the clinical outcomes (p < 0.001). Our data suggest that the overlap with the DRTT based on individual tractography may serve as a marker to determine the most effective DBS contact in ET patients and reduce burdensome clinical testing in the future.