Till A. Dembek

Individualized current-shaping reduces DBS-induced dysarthria in patients with essential tremor

Objective: To investigate in patients with essential tremor (ET) treated with thalamic/subthalamic deep brain stimulation (DBS) whether stimulation-induced dysarthria (SID) can be diminished by individualized current-shaping with interleaving stimulation (cs-ILS) while maintaining tremor suppression (TS). Methods: Of 26 patients screened, 10 reported SID and were invited for testing. TS was assessed by the Tremor Rating Scale and kinematic analysis of postural and action tremor. SID was assessed by phonetic and logopedic means. Additionally, patients rated their dysarthria on a visual analog scale. Results: In 6 of the 10 patients with ET, DBS-ON (relative to DBS-OFF) led to SID while tremor was successfully reduced. When comparing individualized cs-ILS with a non–current-shaped interleaving stimulation (ILS) in these patients, there was no difference in TS while 4 of the 6 patients showed subjective improvement of speech during cs-ILS. Phonetic analysis (ILS vs cs-ILS) revealed that during cs-ILS there was a reduction of voicing during the production of voiceless stop consonants and also a trend toward an improvement in oral diadochokinetic rate, reflecting less dysarthria. Logopedic rating showed a trend toward deterioration in the diadochokinesis task when comparing ON with OFF but no difference between ILS and cs-ILS. Conclusion: This is a proof-of-principle evaluation of current-shaping in patients with ET treated with thalamic/subthalamic DBS and experiencing SID. Data suggest a benefit on SID from individual shaping of current spread while TS is preserved. Classification of evidence: This study provides Class IV evidence that in patients with ET treated with DBS with SID, individualized cs-ILS reduces dysarthria while maintaining tremor control.

Directional DBS increases side‐effect thresholds—A prospective, double‐blind trial

The objective of this study was to investigate whether directional deep brain stimulation (DBS) of the subthalamic nucleus in Parkinsons disease (PD) offers increased therapeutic windows, side‐effect thresholds, and clinical benefit.

The Effect of Deep Brain Stimulation on the Speech Motor System

PURPOSE Chronic deep brain stimulation of the nucleus ventralis intermedius is an effective treatment for individuals with medication-resistant essential tremor. However, these individuals report that stimulation has a deleterious effect on their speech. The present study investigates one important factor leading to these effects: the coordination of oral and glottal articulation. METHOD Sixteen native-speaking German adults with essential tremor, between 26 and 86 years old, with and without chronic deep brain stimulation of the nucleus ventralis intermedius and 12 healthy, age-matched subjects were recorded performing a fast syllable repetition task (/papapa/, /tatata/, /kakaka/). Syllable duration and voicing-to-syllable ratio as well as parameters related directly to consonant production, voicing during constriction, and frication during constriction were measured. RESULTS Voicing during constriction was greater in subjects with essential tremor than in controls, indicating a perseveration of voicing into the voiceless consonant. Stimulation led to fewer voiceless intervals (voicing-to-syllable ratio), indicating a reduced degree of glottal abduction during the entire syllable cycle. Stimulation also induced incomplete oral closures (frication during constriction), indicating imprecise oral articulation. CONCLUSION The detrimental effect of stimulation on the speech motor system can be quantified using acoustic measures at the subsyllabic level.

Subjective perceived outcome of subthalamic deep brain stimulation in Parkinson's disease one year after surgery

OBJECTIVES Dissatisfaction with subthalamic deep brain stimulation (STN-DBS) despite motor improvements has been observed in Parkinsons disease (PD). Hence, we compared patients subjective perceived outcome 12 months after surgery (12mFU) with clinical measures to identify risk factors of dissatisfaction. METHODS Patients were examined at baseline and 12mFU. Quality of life (QoL), neuropsychiatric, cognitive and neurological functioning was measured. Patients were classified concerning their subjective outcome (negative = dissatisfaction; mixed; positive = satisfaction) at 12mFU using semi-structured interviews. First, the three groups were compared concerning interview statements. Second, repeated measures ANOVAs with group as between-subjects factor were applied to find significant effects of time, group, or interaction. Third, binary logistic regression determined predictors of dissatisfaction. RESULTS Of the 28 enrolled patients, 25% perceived their outcome as negative, 32.1% as mixed, and 42.9% as positive. Concerning interview statements, dissatisfied patients mentioned significantly less often improved QoL and reduced medication, and reported worsening of mental state, and social interaction. For the whole sample, significant improvement over time was found for motor functioning, daily dopamine dosages, and QoL. Apathy significantly worsened over time, but dissatisfied patients were overall more apathetic and depressed than the other groups. Significant interaction of group and time was identified for QoL, which only improved in the mixed and satisfied group. Finally, preoperative apathy and axial symptoms predicted dissatisfaction with STN-DBS. CONCLUSIONS Although motor symptoms and QoL improved in the whole sample, 25% of patients showed disappointment with STN-DBS. Especially apathy predicts dissatisfaction and should be considered preoperatively.

Determining the orientation angle of directional leads for deep brain stimulation using computed tomography and digital x‐ray imaging: A phantom study

Purpose Orientating the angle of directional leads for deep brain stimulation (DBS) in an axial plane introduces a new degree of freedom that is indicated by embedded anisotropic directional markers. Our aim was to develop algorithms to determine lead orientation angles from computed tomography (CT) and stereotactic x‐ray imaging using standard clinical protocols, and subsequently assess the accuracy of both methods. Methods In CT the anisotropic marker artifact was taken as a signature of the lead orientation angle and analyzed using discrete Fourier transform of circular intensity profiles. The orientation angle was determined from phase angles at a frequency 2/360° and corrected for aberrations at oblique leads. In x‐ray imaging, frontal and lateral images were registered to stereotactic space and sub‐images containing directional markers were extracted. These images were compared with projection images of an identically located virtual marker at different orientation angles. A similarity index was calculated and used to determine the lead orientation angle. Both methods were tested using epoxy phantoms containing directional leads (Cartesia™ Boston Scientific, Marlborough, USA) with known orientation. Anthropomorphic phantoms were used to compare both methods for DBS cases. Results Mean deviation between CT and x‐ray was 1.5° ± 3.6° (range: −2.3° to 7.9°) for epoxy phantoms and 3.6° ± 7.1° (range: −5.6° to 14.6°) for anthropomorphic phantoms. After correction for imperfections in the epoxy phantoms, the mean deviation from ground truth was 0.0° ± 5.0° (range: −12° to 14°) for x‐ray. For CT the results depended on the polar angle of the lead in the scanner. Mean deviation was −0.3° ± 1.9° (range: −4.6° to 6.6°) or 1.6° ± 8.9° (range: −23° to 34°) for polar angles ≤ 40° or > 40° Conclusions The results show that both imaging modalities can be used to determine lead orientation angles with high accuracy. CT is superior to x‐ray imaging, but oblique leads (polar angle > 40°) show limited precision due to the current design of the directional marker.

Ageing changes effective connectivity of motor networks during bimanual finger coordination.

Bimanual finger coordination declines with age. However, relatively little is known about the neurophysiological alterations in the motor-system causing this decline. In the present study, we used 128-channel electroencephalography (EEG) to evaluate causal interactions of cortical, motor-related brain areas. Right-handed young and elderly subjects performed complex temporally and spatially coupled as well as temporally coupled and spatially uncoupled finger tappings. Employing dynamic causal modelling (DCM) for induced responses, we inferred task-induced effective connectivity within a core motor network comprising bilateral primary motor cortex (M1), lateral premotor cortex (lPM), supplementary motor area (SMA), and prefrontal cortex (PFC). Behavioural analysis showed significantly increased error rates and performance times for elderly subjects, confirming that motor functions decrease with ageing. Additionally, DCM analysis revealed that this age-related decline can be associated with specific alterations of interhemispheric and prefrontal to premotor connectivity. Young and elderly subjects exhibited inhibitory left to right M1-M1 coupling during performance of temporally and spatially coupled movements. Effects of ageing on interhemispheric connectivity particularly emerged when movements became spatially uncoupled. Here, elderly participants still expressed inhibitory left to right M1-M1 coupling, whereas no such connection was present in the young. Furthermore, ageing affected prefrontal to premotor connectivity. In all conditions, elderly subjects showed significant couplings from left PFC to left lPM. In contrast, young participants exhibited left PFC to SMA connections. These results demonstrate that (i) in spatially uncoupled movements interhemispheric M1-connectivity increases with age and (ii) support the idea that ageing is associated with enhanced lateral prefrontal to premotor coupling (PFC to lPM) and hypoactivation of a medial pathway (PFC to SMA) within the dominant hemisphere.

Quality of life outcome after subthalamic stimulation in Parkinson's disease depends on age: QOL Outcome after STN-DBS in PD Depends on Age

The purpose of this study was to investigate how quality of life outcome after bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinsons disease (PD) depends on age.

Nonmotor symptoms evolution during 24 months of bilateral subthalamic stimulation in Parkinson's disease: 24 months nonmotor effects of STN-DBS in PD

Background: The objective of this study was to investigate 24‐month of effects of bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) on nonmotor symptoms in Parkinsons disease (PD).

Deep brain stimulation of the posterior subthalamic area and the thalamus in patients with essential tremor: study protocol for a randomized controlled pilot trial

BackgroundDeep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of the thalamus is effective in medication refractory essential tremor (ET). In recent years, evidence has accumulated that the region ventral to the VIM, the posterior subthalamic area (PSA), might be an equally or even more effective target for electrode implantation. However, this evidence is primarily based on case series, cross-sectional observations, and retrospective data.Methods/designA prospective crossover pilot study investigating the effects of PSA stimulation in medication refractory ET patients was designed. In this study, bilateral electrodes are implanted such that at least one of the electrode contacts is located in the PSA and VIM, respectively. This implantation approach allows (1) a prospective double-blind investigation of the effects of PSA stimulation compared to baseline, as well as (2) a crossover comparison between VIM and PSA stimulation with respect to tremor suppression and side effect profiles.DiscussionThe results of this double-blinded, prospective study will allow a better understanding of the effects and side effects of PSA compared to VIM-DBS in patients with ET.Trial registrationGerman Clinical Trials Register: DRKS00004235. Registered on 4 July 2012.

Probabilistic mapping of deep brain stimulation effects in essential tremor

Objective To create probabilistic stimulation maps (PSMs) of deep brain stimulation (DBS) effects on tremor suppression and stimulation-induced side-effects in patients with essential tremor (ET). Method Monopolar reviews from 16 ET-patients which consisted of over 600 stimulation settings were used to create PSMs. A spherical model of the volume of neural activation was used to estimate the spatial extent of DBS for each setting. All data was pooled and voxel-wise statistical analysis as well as nonparametric permutation testing was used to confirm the validity of the PSMs. Results PSMs showed tremor suppression to be more pronounced by stimulation in the zona incerta (ZI) than in the ventral intermediate nucleus (VIM). Paresthesias and dizziness were most commonly associated with stimulation in the ZI and surrounding thalamic nuclei. Discussion Our results support the assumption, that the ZI might be a very effective target for tremor suppression. However stimulation inside the ZI and in its close vicinity was also related to the occurrence of stimulation-induced side-effects, so it remains unclear whether the VIM or the ZI is the overall better target. The study demonstrates the use of PSMs for target selection and evaluation. While their accuracy has to be carefully discussed, they can improve the understanding of DBS effects and can be of use for other DBS targets in the therapy of neurological or psychiatric disorders as well. Furthermore they provide a priori information about expected DBS effects in a certain region and might be helpful to clinicians in programming DBS devices in the future.