This case of secondary sclerosing cholangitis (SSC‐CIP) emphasizes the need to provide follow‐up care for patients that have recovered from COVID‐19 in order to understand the complexity of SARS‐CoV‐2 associated sequela.

Adaptive deep brain stimulation (aDBS) is a promising concept for feedback-based neurostimulation, with the potential of clinical implementation with the sensing-enabled Percept neurostimulator. We aim to characterize chronic electrophysiological activity during stimulation and to validate beta-band activity as a biomarker for bradykinesia. Subthalamic activity was recorded during stepwise stimulation amplitude increase OFF medication in 10 Parkinson’s patients during rest and finger tapping. Offline analysis of wavelet-transformed beta-band activity and assessment of inter-variable relationships in linear mixed effects models were implemented. There was a stepwise suppression of low-beta activity with increasing stimulation intensity (p = 0.002). Low-beta power was negatively correlated with movement speed and predictive for velocity improvements (p < 0.001), stimulation amplitude for beta suppression (p < 0.001). Here, we characterize beta-band modulation as a chronic biomarker for motor performance. Our investigations support the use of electrophysiology in therapy optimization, providing evidence for the use of biomarker analysis for clinical aDBS.

Bradykinesia is a cardinal hallmark of Parkinson’s disease (PD). Improvement in bradykinesia is an important signature of effective treatment. Finger tapping is commonly used to index bradykinesia, albeit these approaches largely rely on subjective clinical evaluations. Moreover, recently developed automated bradykinesia scoring tools are proprietary and are not suitable for capturing intraday symptom fluctuation. We assessed finger tapping (i.e., Unified Parkinson’s Disease Rating Scale (UPDRS) item 3.4) in 37 people with Parkinson’s disease (PwP) during routine treatment follow ups and analyzed their 350 sessions of 10-s tapping using index finger accelerometry. Herein, we developed and validated ReTap, an open-source tool for the automated prediction of finger tapping scores. ReTap successfully detected tapping blocks in over 94% of cases and extracted clinically relevant kinematic features per tap. Importantly, based on the kinematic features, ReTap predicted expert-rated UPDRS scores significantly better than chance in a hold out validation sample (n = 102). Moreover, ReTap-predicted UPDRS scores correlated positively with expert ratings in over 70% of the individual subjects in the holdout dataset. ReTap has the potential to provide accessible and reliable finger tapping scores, either in the clinic or at home, and may contribute to open-source and detailed analyses of bradykinesia.

Although subthalamic deep brain stimulation (DBS) is a highly-effective treatment for alleviating motor dysfunction in patients with Parkinson’s disease (PD), clinicians currently lack reliable neurophysiological correlates of clinical outcomes for optimizing DBS parameter settings, which may contribute to treatment inefficacies. One parameter that could aid DBS efficacy is the orientation of current administered, albeit the precise mechanisms underlying optimal contact orientations and associated clinical benefits are not well understood. Herein, 24 PD patients received monopolar stimulation of the left STN during magnetoencephalography and standardized movement protocols to interrogate the directional specificity of STN-DBS current administration on accelerometer metrics of fine hand movements. Our findings demonstrate that optimal contact orientations elicit larger DBS-evoked cortical responses in the ipsilateral sensorimotor cortex, and importantly, are differentially predictive of smoother movement profiles in a contact-dependent manner. Moreover, we summarize traditional evaluations of clinical efficacy (e.g., therapeutic windows, side effects) for a comprehensive review of optimal/non-optimal STN-DBS contact settings. Together, these data suggest that DBS-evoked cortical responses and quantitative movement outcomes may provide clinical insight for characterizing the optimal DBS parameters necessary for alleviating motor symptoms in patients with PD in the future.

Deep brain stimulation (DBS) has significant effects on motor symptoms in Parkinson's disease (PD), but existing studies on the effect of DBS on speech are rather inconclusive. It is assumed that deficits in auditory-motor integration strongly contribute to Parkinsonian speech pathology. The aim of the present study was to assess whether subthalamic DBS can modulate these deficits. Twenty PD patients (15 male, 5 female; 62.4 ± 6.7 years) with subthalamic DBS were exposed to pitch-shifted acoustic feedback during vowel vocalization and subsequent listening. Voice and brain activity were measured ON and OFF stimulation using magnetoencephalography (MEG). Vocal responses and auditory evoked responses time locked to the onset of pitch-shifted feedback were examined. A positive correlation between vocal response magnitude and pitch variability was observed for both, stimulation ON and OFF (ON: r = 0.722, p < 0.001, OFF: r = 0.746, p < 0.001). However, no differences of vocal responses to pitch-shifted feedback between the stimulation conditions were found [ t (19) = −0.245, p = 0.809, d = −0.055]. P200m amplitudes of event related fields (ERF) of left and right auditory cortex (AC) and superior temporal gyrus (STG) were significantly larger during listening [left AC P200m: F (1, 19) = 10.241, p = 0.005, f = 0.734; right STG P200m: F (1, 19) = 8.393, p = 0.009, f = 0.664]. Subthalamic DBS appears to have no substantial effect on vocal compensations, although it has been suggested that auditory-motor integration deficits contribute to higher vocal response magnitudes in pitch perturbation experiments with PD patients. Thus, DBS seems to be limited in modulating auditory-motor integration of speech in PD.