Advancing conventional open‐loop DBS as a therapy for PD is crucial for overcoming important issues such as the delicate balance between beneficial and adverse effects and limited battery longevity that are currently associated with treatment. Closed‐loop or adaptive DBS aims to overcome these limitations by real‐time adjustment of stimulation parameters based on continuous feedback input signals that are representative of the patient's clinical state. The focus of this update is to discuss the most recent developments regarding potential input signals and possible stimulation parameter modulation for adaptive DBS in PD. Potential input signals for adaptive DBS include basal ganglia local field potentials, cortical recordings (electrocorticography), wearable sensors, and eHealth and mHealth devices. Furthermore, adaptive DBS can be applied with different approaches of stimulation parameter modulation, the feasibility of which can be adapted depending on specific PD phenotypes. Implementation of technological developments like machine learning show potential in the design of such approaches; however, energy consumption deserves further attention. Furthermore, we discuss future considerations regarding the clinical implementation of adaptive DBS in PD. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Deep brain stimulation (DBS) for Parkinson’s disease often alleviates the motor symptoms, but causes cognitive and emotional side effects in a substantial number of cases. Identification of the motor part of the subthalamic nucleus (STN) as part of the presurgical workup could minimize these adverse effects. In this study, we assessed the STN’s connectivity to motor, associative, and limbic brain areas, based on structural and functional connectivity analysis of volunteer data. For the structural connectivity, we used streamline counts derived from HARDI fiber tracking. The resulting tracks supported the existence of the so-called “hyperdirect” pathway in humans. Furthermore, we determined the connectivity of each STN voxel with the motor cortical areas. Functional connectivity was calculated based on functional MRI, as the correlation of the signal within a given brain voxel with the signal in the STN. Also, the signal per STN voxel was explained in terms of the correlation with motor or limbic brain seed ROI areas. Both right and left STN ROIs appeared to be structurally and functionally connected to brain areas that are part of the motor, associative, and limbic circuit. Furthermore, this study enabled us to assess the level of segregation of the STN motor part, which is relevant for the planning of STN DBS procedures.

Deep brain stimulation (DBS) is used for the treatment of movement disorders, including Parkinson’s disease, dystonia, and essential tremor, and has shown clinical benefits in other brain disorders. A natural path for the improvement of this technique is to continuously observe the stimulation effects on patient symptoms and neurophysiological markers. This requires the evolution of conventional deep brain stimulators to bidirectional interfaces, able to record, process, store, and wirelessly communicate neural signals in a robust and reliable fashion. Here, we present the architecture, design, and first use of an implantable stimulation and sensing interface (AlphaDBS^R System) characterized by artifact-free recording and distributed data management protocols. Its application in three patients with Parkinson’s disease (clinical trial n. NCT04681534) is shown as a proof of functioning of a clinically viable implanted brain-computer interface (BCI) for adaptive DBS. Reliable artifact free-recordings, and chronic long-term data and neural signal management are in place.

Object: Thoracic disc herniations (TDHs) may occasionally present with an acute myelopathy, defined as a variable degree of motor, sensory, and sphincter disturbances developing in less than 24 hours, and resulting in a Frankel Grade C or worse. Confronted with such a patient, the surgeon has to decide whether to perform an emergency operation and whether to use an anterior or posterior approach. The authors analyze their own experience and the pertinent literature, focusing on clinical presentation, imaging findings, surgical timing, technique, and outcome. Methods: Among 250 patients who underwent surgery for symptomatic TDH, 209 had at least 1 year of follow-up at the time of writing, including 8 patients who presented with an acute myelopathy. They were surgically treated using standard thoracoscopic microdiscectomy, careful blood pressure monitoring, and intravenous methylprednisolone. The authors analyzed pre- and postoperative neuroimaging, and Frankel scores preoperatively, at discharge, and 1 year postoperatively. Results: Although 5 patients had multiple TDHs, the symptomatic TDH was invariably situated between T9–10 and T11–12. Seven TDHs were giant, 6 were calcified, 6 were accompanied by myelomalacia, and 4 were accompanied by segmental stenosis. Although sudden dorsalgia was the initial symptom in 6, a precipitating event was noted in only 1. All patients had severe neurological deficits by the time they underwent surgery. Frankel grades improved from B to D in 2 patients, from C to E in 4, and from C to D and B to E in 1 patient each. All patients regained continence and ambulation. Transient complications were CSF leak (in 2 patients), and intraoperative blood loss greater than 1000 ml, reversible ischemic neurological deficit, and subileus (in 1 patient each). Conclusions: Approximately 4% of TDHs present with an acute myelopathy. They are often situated between T9–10 and T11–12, large or giant, and even calcified. They almost invariably cause important cord compression (sometimes aggravated by an associated segmental stenosis) and myelomalacia. Their clinical presentation may be misleading, and diagnosis may be delayed until other causes (especially vascular) have been excluded and the clinical picture has become more complete. Interestingly, whereas a precipitating event or trauma is rarely present, dorsalgia frequently precedes profound myelopathy and may help to make an early diagnosis. Remarkable recovery is possible even with profound neurological deficit, a delay of several days, in the elderly, and in the presence of myelomalacia, provided the spinal cord is adequately decompressed and intraoperative hypotension is strictly avoided. Although alternative approaches more familiar to most neurosurgeons may be used, the anterior transthoracic approach has the advantage of reaching the TDH in front of the compromised spinal cord, avoiding any manipulation. In experienced hands, thoracoscopic microdiscectomy combines the advantage and versatility of an anterior approach with minimal postoperative discomfort. The authors conclude that TDH-related acute myelopathy may have a favorable outcome when managed correctly, and they strongly recommend that every single patient should undergo surgical treatment.

Background: Age and comorbidities increase COVID-19 related in-hospital mortality risk, but the extent by which comorbidities mediate the impact of age remains unknown. Methods: In this multicenter retrospective cohort study with data from 45 Dutch hospitals, 4806 proven COVID-19 patients hospitalized in Dutch hospitals (between February and July 2020) from the CAPACITY-COVID registry were included (age 69[58–77]years, 64% men). The primary outcome was defined as a combination of in-hospital mortality or discharge with palliative care. Logistic regression analysis was performed to analyze the associations between sex, age, and comorbidities with the primary outcome. The effect of comorbidities on the relation of age with the primary outcome was evaluated using mediation analysis. Results: In-hospital COVID-19 related mortality occurred in 1108 (23%) patients, 836 (76%) were aged ≥70 years (70+). Both age 70+ and female sex were univariably associated with outcome (odds ratio [OR]4.68, 95%confidence interval [4.02–5.45], OR0.68[0.59–0.79], respectively;both p< 0.001). All comorbidities were univariably associated with outcome (p<0.001), and all but dyslipidemia remained significant after adjustment for age70+ and sex. The impact of comorbidities was attenuated after age-spline adjustment, only leaving female sex, diabetes mellitus (DM), chronic kidney disease (CKD), and chronic pulmonary obstructive disease (COPD) significantly associated (female OR0.65[0.55–0.75], DM OR1.47[1.26–1.72], CKD OR1.61[1.32–1.97], COPD OR1.30[1.07–1.59]). Pre-existing comorbidities in older patients negligibly (<6% in all comorbidities) mediated the association between higher age and outcome. Conclusions: Age is the main determinant of COVID-19 related in-hospital mortality, with negligible mediation effect of pre-existing comorbidities. Trial registration: CAPACITY-COVID (NCT04325412)

Tinnitus is the perception of a ‘ringing’ sound without an acoustic source. It is generally accepted that tinnitus develops after peripheral hearing loss and is associated with altered auditory processing. The thalamus is a crucial relay in the underlying pathways that actively shapes processing of auditory signals before the respective information reaches the cerebral cortex. Here, we review animal and human evidence to define thalamic function in tinnitus. Overall increased spontaneous firing patterns and altered coherence between the thalamic medial geniculate body (MGB) and auditory cortices is observed in animal models of tinnitus. It is likely that the functional connectivity between the MGB and primary and secondary auditory cortices is reduced in humans. Conversely, there are indications for increased connectivity between the MGB and several areas in the cingulate cortex and posterior cerebellar regions, as well as variability in connectivity between the MGB and frontal areas regarding laterality and orientation in the inferior, medial and superior frontal gyrus. We suggest that these changes affect adaptive sensory gating of temporal and spectral sound features along the auditory pathway, reflecting dysfunction in an extensive thalamo-cortical network implicated in predictive temporal adaptation to the auditory environment. Modulation of temporal characteristics of input signals might hence factor into a thalamo-cortical dysrhythmia profile of tinnitus, but could ultimately also establish new directions for treatment options for persons with tinnitus.