Probabilistic Mapping of Deep Brain Stimulation: Insights from 15 Years of Therapy.

Deep brain stimulation (DBS) depends on precise delivery of electrical current to target tissues. However, the specific brain structures responsible for best outcome are still debated. We applied probabilistic stimulation mapping to a retrospective, multidisorder DBS dataset assembled over 15 years at our institution (ntotal = 482 patients; nParkinson disease = 303; ndystonia = 64; ntremor = 39; ntreatment-resistant depression/anorexia nervosa = 76) to identify the neuroanatomical substrates of optimal clinical response. Using high-resolution structural magnetic resonance imaging and activation volume modeling, probabilistic stimulation maps (PSMs) that delineated areas of above-mean and below-mean response for each patient cohort were generated and defined in terms of their relationships with surrounding anatomical structures. Our results show that overlap between PSMs and individual patients' activation volumes can serve as a guide to predict clinical outcomes, but that this is not the sole determinant of response. In the future, individualized models that incorporate advancements in mapping techniques with patient-specific clinical variables will likely contribute to the optimization of DBS target selection and improved outcomes for patients. ANN NEUROL 2021;89:426-443.

Efficacy of Caffeine in ADCY5-Related Dyskinesia: A Retrospective Study.

BACKGROUND: ADCY5-related dyskinesia is characterized by early-onset movement disorders. There is currently no validated treatment, but anecdotal clinical reports and biological hypotheses suggest efficacy of caffeine. OBJECTIVE: The aim is to obtain further insight into the efficacy and safety of caffeine in patients with ADCY5-related dyskinesia. METHODS: A retrospective study was conducted worldwide in 30 patients with a proven ADCY5 mutation who had tried or were taking caffeine for dyskinesia. Disease characteristics and treatment responses were assessed through a questionnaire. RESULTS: Caffeine was overall well tolerated, even in children, and 87% of patients reported a clear improvement. Caffeine reduced the frequency and duration of paroxysmal movement disorders but also improved baseline movement disorders and some other motor and nonmotor features, with consistent quality-of-life improvement. Three patients reported worsening. CONCLUSION: Our findings suggest that caffeine should be considered as a first-line therapeutic option in ADCY5-related dyskinesia. © 2022 International Parkinson and Movement Disorder Society.

Functional MRI Safety and Artifacts during Deep Brain Stimulation: Experience in 102 Patients.

BackgroundWith growing numbers of patients receiving deep brain stimulation (DBS), radiologists are encountering these neuromodulation devices at an increasing rate. Current MRI safety guidelines, however, limit MRI access in these patients.PurposeTo describe an MRI (1.5 T and 3 T) experience and safety profile in a large cohort of participants with active DBS systems and characterize the hardware-related artifacts on images from functional MRI.Materials and MethodsIn this prospective study, study participants receiving active DBS underwent 1.5- or 3-T MRI (T1-weighted imaging and gradient-recalled echo [GRE]-echo-planar imaging [EPI]) between June 2017 and October 2018. Short- and long-term adverse events were tracked. The authors quantified DBS hardware-related artifacts on images from GRE-EPI (functional MRI) at the cranial coil wire and electrode contacts. Segmented artifacts were then transformed into standard space to define the brain areas affected by signal loss. Two-sample t tests were used to assess the difference in artifact size between 1.5- and 3-T MRI.ResultsA total of 102 participants (mean age ± standard deviation, 60 years ± 11; 65 men) were evaluated. No MRI-related short- and long-term adverse events or acute changes were observed. DBS artifacts were most prominent near the electrode contacts and over the frontoparietal cortical area where the redundancy of the extension wire is placed subcutaneously. The mean electrode contact artifact diameter was 9.3 mm ± 1.6, and 1.9% ± 0.8 of the brain was obscured by the coil artifact. The coil artifacts were larger at 3 T than at 1.5 T, obscuring 2.1% ± 0.7 and 1.4% ± 0.7 of intracranial volume, respectively (P < .001). The superficial frontoparietal cortex and deep structures neighboring the electrode contacts were most commonly obscured.ConclusionWith a priori local safety testing, patients receiving deep brain stimulation may safely undergo 1.5- and 3-T MRI. Deep brain stimulation hardware-related artifacts only affect a small proportion of the brain.© RSNA, 2019Online supplemental material is available for this article.See also the editorial by Martin in this issue.

Movement Disorders in Patients with Subacute Sclerosing Panencephalitis: A Systematic Review.

BACKGROUND: Subacute sclerosing panencephalitis (SSPE) is a complication of measles, occurring after a latency of 4-10 years. It continues to occur in developing countries although resurgence is being reported from developed countries. Characteristic features include progressive neuropsychiatric issues, myoclonus, seizures, movement disorders and visual impairment. Electroencephalography (EEG) typically shows periodic generalized discharges, and elevated CSF anti-measles antibodies are diagnostic. Movement disorders are being increasingly recognized as part of the clinical spectrum, and range from hyperkinetic (chorea, dystonia, tremor, tics) to hypokinetic (parkinsonism) disorders and ataxia. OBJECTIVES: This article aims to comprehensively review the spectrum of movement disorders associated with SSPE. METHODS: A literature search was conducted in PubMed and EMBASE databases in December 2023 and articles were identified for review. RESULTS: Movement disorders reported in SSPE included hyperkinetic (chorea, dystonia, tremor and tics), hypokinetic (parkinsonism), ataxia and extraocular movement disorders. Myoclonus, a core clinical feature, was the most frequent "abnormal movement." Movement disorders were observed in all clinical stages, and could also be a presenting feature, even sans myoclonus. Hyperkinetic movement disorders were more common than hypokinetic movement disorders. An evolution of movement disorders was observed, with ataxia, chorea and dystonia occurring earlier, and parkinsonism later in the disease. Neuroradiological correlates of movement disorders remained unclear. CONCLUSION: A wide spectrum of movement disorders was observed throughout the clinical stages of SSPE. Most data were derived from case reports and small case series. Multicentric longitudinal studies are required to better delineate the spectrum and evolution of movement disorders in SSPE.

Camptocormia in a young man with anti-GAD-seropositive stiff-person syndrome.

Stiff-person syndrome (SPS) usually manifests as an autoimmune neuromuscular disorder characterised by pronounced and advancing rigidity, primarily affecting the trunk and proximal muscles. There are various clinical subtypes like classic SPS (truncal stiffness, generalised rigidity and muscle spasms), partial SPS (stiff-limb syndrome) and uncommon forms including progressive encephalomyelitis with rigidity and myoclonus. Camptocormia, defined as forward flexion of the spine in the upright position that disappears in the supine position, without fixed deformity, has been described only in two cases as an initial presentation of Anti glutamic acid decarboxylase (GAD) autoimmunity. We encountered a young male presenting with a progressive forward-leaning posture and involuntary rhythmic movements in the lower limb. Diagnostic workup included MRI, blood routines, autoimmune screening, genetic testing, lumbar puncture and electromyography. Elevated serum anti-GAD antibody levels, inflammatory CSF and certain other clinical features supported the diagnosis of SPS. Treatment involved benzodiazepines, muscle relaxants and immunotherapy with intravenous immunoglobulin. This case underscores the importance of considering immune-mediated causes, such as SPS, in patients presenting with camptocormia.

C19orf12 mutation causing mitochondrial membrane-protein Associated Neurodegeneration masquerading as spastic paraplegia.

Mitochondrial Membrane-protein Associated Neurodegeneration (MPAN) is a rare disease, caused by C19orf12 mutations and up to 29 different mutations have been described. We report a young woman presented with spastic paraparesis due to C19orf12 gene. MPAN presenting like Hereditary spastic paraplegia-43 is rare and the genetic mutation had been described only once in the literature.

Predicting optimal deep brain stimulation parameters for Parkinson's disease using functional MRI and machine learning.

Commonly used for Parkinson's disease (PD), deep brain stimulation (DBS) produces marked clinical benefits when optimized. However, assessing the large number of possible stimulation settings (i.e., programming) requires numerous clinic visits. Here, we examine whether functional magnetic resonance imaging (fMRI) can be used to predict optimal stimulation settings for individual patients. We analyze 3 T fMRI data prospectively acquired as part of an observational trial in 67 PD patients using optimal and non-optimal stimulation settings. Clinically optimal stimulation produces a characteristic fMRI brain response pattern marked by preferential engagement of the motor circuit. Then, we build a machine learning model predicting optimal vs. non-optimal settings using the fMRI patterns of 39 PD patients with a priori clinically optimized DBS (88% accuracy). The model predicts optimal stimulation settings in unseen datasets: a priori clinically optimized and stimulation-naïve PD patients. We propose that fMRI brain responses to DBS stimulation in PD patients could represent an objective biomarker of clinical response. Upon further validation with additional studies, these findings may open the door to functional imaging-assisted DBS programming.

Use of AbobotulinumtoxinA in Adults with Cervical Dystonia: A Systematic Literature Review.

Cervical dystonia (CD) is a neurological movement disorder characterized by sustained involuntary muscle contractions. First-line therapy for CD is intramuscular injections of botulinum neurotoxin (e.g., abobotulinumtoxinA) into the affected muscles. The objective of this systematic literature review is to assess the clinical evidence regarding the effects of abobotulinumtoxinA for treatment of CD in studies of safety, efficacy, patient-reported outcomes, and economic outcomes. Using comprehensive electronic medical literature databases, a search strategy was developed using a combination of Medical Subject Heading terms and keywords. Results were reviewed by two independent reviewers who rated the level of evidence. The search yielded 263 publications, of which 232 were excluded for being duplicate publications, not meeting the selection criteria, or failing to meet predefined eligibility criteria, leaving a total of 31 articles. Clinical efficacy, patient-reported outcomes, and safety data were in 6 placebo-controlled trials (8 articles), 6 active-controlled trials, and 16 observational studies (17 articles). Data on health economic outcomes were provided in one of the clinical trials, in two of the observational studies, and in one specific cost-analysis publication. This review demonstrated that the routine use of abobotulinumtoxinA in CD is well-established, effective, and generally well-tolerated, with a relatively low cost of treatment.

Analysis of the Effect of Dopamine Transporter Scan on the Diagnosis and Management in a Tertiary Neurology Center.

BACKGROUND AND PURPOSE: The dopamine transporter scan or DaT scan is abnormal in presynaptic parkinsonism but normal in nondegenerative or postsynaptic parkinsonism. In this study, we tried to ascertain the impact of DaT scan on the diagnosis and clinical management and if the semiquantitative analysis of the DaT scans has any correlation with the clinical symptoms. METHODS: The electronic and nonelectronic records of patients of Plymouth Hospital NHS Trust, United Kingdom, from 2011 to 2015 were studied to find the indication, outcome, and the impact of the scan on the management of patients. The DaT scan results were assessed visually and semiquantitatively by the Department of Nuclear Medicine. The available data were statistically analyzed with the help of Microsoft XL2010 and GraphPad software. RESULTS: A total of 258 people had DaT scan. The scan results suggested an alternate diagnosis in 50.5% of clinically diagnosed patients with Parkinson disease. Similarly, DaT scan changed the diagnosis of 40% of patients with clinical diagnosis of vascular parkinsonism, 25% of clinically diagnosed drug-induced parkinsonism, and 54% of patients with possible Lewy body dementia. Visual assessment of the DaT scan revealed that more than 60% had grade 2 abnormalities. The distribution volume ratio, a semiquantitative tool for tracer uptake, was significantly less in the patients with akinetic-rigid subtype of Parkinson disease in comparison to a tremor predominant subtype. CONCLUSIONS: Dopamine transporter scan had a significant impact in diagnosis and management.

Unusual gait disorders: a phenomenological approach and classification.

INTRODUCTION: Gait impairment is a very common problem in clinical practice. Multiple classifications of gait disorders are available based on anatomy, etiology, pathology and phenomenology. These classifications provide a diagnostic guide but do not clearly explain the pathophysiology of some gait disorders, which can sometimes hinder the diagnostic process. In this context, unusual gait disorders become an even more difficult clinical challenge. Areas covered: The scientific and non-scientific literature contains illustrative descriptions of unusual gait disorders based on their predominant signs and/or comparisons with normal and abnormal zoological and folkloric patterns. Unusual gait disorder phenomenology can be carefully deconstructed in order to achieve an integral approach. We present a pragmatic, phenomenological approach to various unusual gait disorders and highlight key features underlying their phenotypes. We also propose unifying terminology to facilitate diagnosis and academic communication. Expert commentary: Advanced gait analysis, neurophysiological and neuroimaging techniques have allowed for us to recognize that locomotion is a complex motor behavior that requires simultaneous integration of multiple neurological and non-neurological systems. A phenomenological approach such as the one proposed in this review could be useful while those objective techniques become more widely available in clinical practice.

A 57-Year-Old Woman With Progressive Left Hand Clumsiness and Falls.

CLINICAL HISTORY: A 57-year old woman presented with left hand pain, periodic leg movement during sleep, gradual onset of stiffness, clumsiness, and falls. Neurological examination showed: generalized rigidity and bradykinesia. There was left hand dystonic posturing and ideomotor apraxia, as well as mirror movements of upper limbs and stimulus-sensitive myoclonus. The patient had a high-pitched voice and hypophonia (Video S1). DISCUSSION: Experts discuss localization and the syndromic diagnosis and predict the underlying pathology. The pathological diagnosis is then provided and clinical learning points are considered.

Patient-adjusted deep-brain stimulation programming is time saving in dystonia patients.

BACKGROUND: Deep-brain stimulation (DBS) programming for dystonia patients is a complex and time-consuming task. OBJECTIVE: To analyze whether programming a programming paradigm based on patient's self-adjustment is practical, effective and time saving in dystonia. METHODS: We retrospectively compared dystonia rating scales as well as the time necessary to optimize programming and the number of in-hospital visits in all patients (n = 102) operated at our center who used simple mode (SM) or advanced mode (AM) programming; the latter uses groups of different stimulation parameters and allows the patient and their caregiver to change stimulation groups at home, using the patient remote control. RESULTS: Both AM- and SM-allocated patients improved clinically to the same extent after DBS, as assessed by the Burke-Fahn-Marsden (BFM) and the Toronto Western Spasmodic Torticollis (TWSTRS) dystonia rating scales. All subscores improved after DBS without statistically significant differences in improvement between AM and SM (BFM: - 43% vs. - 53%, p = 0.569; TWSTRS: - 63% vs. - 72%, p = 0.781). AM and SM patients reached optimization within a similar median time [5.5 months (95% CI 4.6-6.3) for AM vs. 6.2 months (4.2-7.6) for SM, p = 0.674) but patients on advanced programming needed fewer in-hospital visits to achieve the same improvement [median of 5 visits (95% CI 4-7) for AM vs. 8 visits (7-9) for SM, p = 0.008]. CONCLUSIONS: Advanced DBS programming based on patient's self-adjustment under the supervision of the treating physician is feasible, practical and significantly reduces consultation time in dystonia patients.

Dystonia as complication of thalamic neurosurgery.

BACKGROUND: Thalamotomy and deep brain stimulation of the ventralis intermedius nucleus are effective symptomatic treatments for tremor, irrespective of the underlying diagnosis. METHODS AND RESULTS: Herein we describe six tremor patients (2 Parkinson's disease, 1 dystonic tremor, 2 Essential tremor plus dystonia, 1 Essential tremor plus ataxia) who underwent thalamic neurosurgery and acutely or sub-acutely developed dystonia that was permanent in three cases and could not be managed with any adjustments in the stimulation settings. Tremor response was excellent. We argue that thalamic procedures disrupted either or both the cerebello-thalamic and the cortico-striato-pallido-thalamo-cortical loop resulting in an increase of the thalamo-cortical outflow and subsequent change in the clinical picture from tremor to dystonia. CONCLUSION: Thalamic neurosurgery might be rarely complicated by dystonia. Why some patients are more prone to develop this adverse event is still unknown and possibly related to intrinsic factors, which certainly need further studies.