No abstract

Deep brain stimulation (DBS) of single-target nuclei has produced remarkable functional outcomes in a number of movement disorders such as Parkinson’s disease, essential tremor, and dystonia. While these benefits are well established, DBS efficacy and strategy for unusual, unclassified movement disorder syndromes is less clear. A strategy of dual pallidal and thalamic electrode placement is a rational approach in such cases where there is profound, medically refractory functional impairment. The authors report a series of such cases: midbrain cavernoma hemorrhage with olivary hypertrophy, spinocerebellar ataxia-like disorder of probable genetic origin, Holmes tremor secondary to brainstem stroke, and hemiballismus due to traumatic thalamic hemorrhage, all treated by dual pallidal and thalamic DBS. All patients demonstrated robust benefit from DBS, maintained in long-term follow-up. This series demonstrates the flexibility and efficacy, but also the limitations, of dual thalamo-pallidal stimulation for managing axial and limb symptoms of tremors, dystonia, chorea, and hemiballismus in patients with complex movement disorders.

No abstract

Objectives Neuromodulation is a treatment option for people suffering from painful diabetic neuropathy (PDN) unresponsive to conventional pharmacotherapy. We systematically examined the pain outcomes of patients with PDN receiving any type of invasive neuromodulation for treatment of neuropathic pain. Materials and Methods MEDLINE and Embase were searched through 10 January 2020, without language restriction. All study types were included. Two reviewers independently screened publications and extracted data. Quantitative meta‐analysis was performed with pain scores converted to a standard 100‐point scale. Randomized controlled trial (RCT) scores were pooled using the inverse variance method and expressed as mean differences. Results RCTs of tonic spinal cord stimulation (t‐SCS) showed greater pain improvement than best medical therapy at six months (intention‐to‐treat: 38/100, 95% CI: 29–47). By per‐protocol analysis, case series of t‐SCS and dorsal root ganglion stimulation (DRGS) showed improvement by 56 (95% CI: 39–73) and 55 (22–87), respectively, at 12 months. For t‐SCS, the rate of failing a therapeutic stimulation trial was 16%, the risk of infection was 4%, and the rate of lead problems requiring surgery to resolve was 4% per year of follow‐up. High‐frequency SCS and burst SCS both showed efficacy, with few patients studied. Conclusion Efficacious, lasting and safe surgical pain management options are available to diabetic patients suffering from PDN. Tonic‐SCS is the established standard of treatment; however, other SCS paradigms and DRGS are emerging as promising treatments offering comparable pain benefits, but with few cases published to date. Randomized controlled trials are ongoing to assess their relative merits.

A cognitive task, the n-back task, was used to interrogate the cognitive dimension of pain in patients with implanted dorsal root ganglion stimulators (DRGS). Magnetoencephalography (MEG) signals from thirteen patients with implanted DRGS were recorded at rest and while performing the n-back task at three increasing working memory loads with DRGS-OFF and the task repeated with DRGS-ON. MEG recordings were pre-processed, then power spectral analysis and source localization were conducted. DRGS resulted in a significant reduction in reported pain scores (mean 23%, p = 0.001) and gamma oscillatory activity (p = 0.036) during task performance. DRGS-induced pain relief also resulted in a significantly reduced reaction time during high working memory load (p = 0.011). A significant increase in average gamma power was observed during task performance compared to the resting state. However, patients who reported exacerbations of pain demonstrated a significantly elevated gamma power (F(3,80) = 65.011612, p < 0.001, adjusted p-value = 0.01), compared to those who reported pain relief during the task. Our findings demonstrate that gamma oscillatory activity is differentially modulated by cognitive load in the presence of pain, and this activity is predominantly localized to the prefrontal and anterior cingulate cortices in a chronic pain cohort.

Deep brain stimulation of the pedunculopontine nucleus is a promising surgical procedure for the treatment of Parkinsonian gait and balance dysfunction. It has, however, produced mixed clinical results that are poorly understood. We used tractography with the aim to rationalise this heterogeneity. A cohort of eight patients with postural instability and gait disturbance (Parkinson’s disease subtype) underwent pre-operative structural and diffusion MRI, then progressed to deep brain stimulation targeting the pedunculopontine nucleus. Pre-operative and follow-up assessments were carried out using the Gait and Falls Questionnaire, and Freezing of Gait Questionnaire. Probabilistic diffusion tensor tractography was carried out between the stimulating electrodes and both cortical and cerebellar regions of a priori interest. Cortical surface reconstructions were carried out to measure cortical thickness in relevant areas. Structural connectivity between stimulating electrode and precentral gyrus (r = 0.81, p = 0.01), Brodmann areas 1 (r = 0.78, p = 0.02) and 2 (r = 0.76, p = 0.03) were correlated with clinical improvement. A negative correlation was also observed for the superior cerebellar peduncle (r = −0.76, p = 0.03). Lower cortical thickness of the left parietal lobe and bilateral premotor cortices were associated with greater pre-operative severity of symptoms. Both motor and sensory structural connectivity of the stimulated surgical target characterises the clinical benefit, or lack thereof, from surgery. In what is a challenging region of brainstem to effectively target, these results provide insights into how this can be better achieved. The mechanisms of action are likely to have both motor and sensory components, commensurate with the probable nature of the underlying dysfunction.

Cervical dystonia is a non-degenerative movement disorder characterised by dysfunction of both motor and sensory cortico-basal ganglia networks. Deep brain stimulation targeted to the internal pallidum (GPi) is an established treatment, but its specific mechanisms remain elusive, and response to therapy is highly variable. Modulation of key dysfunctional networks via axonal connections is likely important. Fifteen patients underwent pre-operative diffusion-MRI acquisitions and then progressed to bilateral DBS targeting the posterior GPi. Severity of disease was assessed pre-operatively and later at follow-up. Scans were used to generate tractography-derived connectivity estimates between the bilateral regions of stimulation and relevant structures. Connectivity to the putamen correlated with clinical improvement, and a series of cortical connectivity-based putaminal parcellations identified the primary motor (M1) putamen as the key node (r = 0.70, p = 0.004). A regression model with this connectivity and electrode coordinates explained 68% of variance in outcomes (r = 0.83, p = 0.001), with both as significant explanatory variables. We conclude that modulation of the M1 putamen—posterior GPi limb of the cortico-basal ganglia loop is characteristic of successful DBS treatment of cervical dystonia. Pre-operative diffusion imaging contains additional information that predicts outcomes, implying utility for patient selection and/or individualised targeting.

Infarction of the insula is a common scenario with large tissue-volume strokes in the middle cerebral artery territory. Considered to be part of the central autonomic network, infarction of this region is associated with autonomic disturbances, in particular cardiovascular dysregulation. Risk of aspiration following stroke is also associated with involvement of the insula, consistent with its purported participation in complex functions of the mouth and pharynx. Strokes restricted to the insula are rare and present with a broad range of symptoms that offer a window of insight into the diverse functionality of the insular cortex. Chemosensory, autonomic, vestibular, auditory, somatosensory, language and oropharyngeal functional deficits are all recognised, among others. Long-term sequelae are unknown but profound symptoms, such as hemiparesis, are usually transient. Understanding the patterns of dysfunction highlighted provides the basis for future strategies to optimise stroke management on the discovery of insula involvement.