Spatiotemporal Gait Analysis of Patients with Spinocerebellar Ataxia Types 3 and 10 Using Inertial Measurement Units: A Comparative Study.

Given the high morbidity related to the progression of gait deficits in spinocerebellar ataxias (SCA), there is a growing interest in identifying biomarkers that can guide early diagnosis and rehabilitation. Spatiotemporal parameter (STP) gait analysis using inertial measurement units (IMUs) has been increasingly studied in this context. This study evaluated STP profiles in SCA types 3 and 10, compared them to controls, and correlated them with clinical scales. IMU portable sensors were used to measure STPs under four gait conditions: self-selected pace (SSP), fast pace (FP), fast pace checking-boxes (FPCB), and fast pace with serial seven subtractions (FPS7). Compared to healthy subjects, both SCA groups had higher values for step time, variability, and swing time, with lower values for gait speed, cadence, and step length. We also found a reduction in speed gain capacity in both SCA groups compared to controls and an increase in speed dual-task cost in the SCA10 group. However, there were no significant differences between the SCA groups. Swing time, mean speed, and step length were correlated with disease severity, risk of falling and functionality in both clinical groups. In the SCA3 group, fear of falling was correlated with cadence. In the SCA10 group, results of the Montreal cognitive assessment test were correlated with step time, mean speed, and step length. These results show that individuals with SCA3 and SCA10 present a highly variable, short-stepped, slow gait pattern compared to healthy subjects, and their gait quality worsened with a fast pace and dual-task involvement.

Efficacy of subthalamic deep brain stimulation programming strategies for gait disorders in Parkinson's disease: a systematic review and meta-analysis.

Patients with advanced Parkinson's disease often suffer from severe gait and balance problems, impacting quality of live and persisting despite optimization of standard therapies. The aim of this review was to systematically review the efficacy of STN-DBS programming techniques in alleviating gait disturbances in patients with advanced PD. Searches were conducted in PubMed, Embase, and Lilacs databases, covering studies published until May 2024. The review identified 36 articles that explored five distinct STN-DBS techniques aimed at addressing gait and postural instability in Parkinson's patients: low-frequency stimulation, ventral STN stimulation for simultaneous substantia nigra activation, interleaving, asymmetric stimulation and a short pulse width study. Among these, 21 articles were included in the meta-analysis, which revealed significant heterogeneity among studies. Notably, low-frequency STN-DBS demonstrated positive outcomes in total UPDRS-III score and FOG-Q, especially when combined with dopaminergic therapy. The most favorable results were found for low-frequency STN stimulation. The descriptive analysis suggests that unconventional stimulation approaches may be viable for gait problems in patients who do not respond to standard therapies.

Neural Correlates of Optimal Deep Brain Stimulation for Cervical Dystonia.

A total of 15 individuals with cervical dystonia and good outcome after pallidal deep brain stimulation underwent resting-state functional magnetic resonance imaging under three conditions: stimulation using a priori clinically determined optimal settings (ON-Op), non-optimal settings (ON-NOp), and stimulation off (OFF). ON-Op > OFF and ON-Op > ON-NOp were both associated with significant deactivation within sensorimotor cortex (changes not seen with ON-NOp > OFF). Brain responses to stimulation were related to individual long-term clinical improvement (R = 0.73, R2 = 0.53, p = 0.001). The relationship was consistent when this model included four additional patients with generalized or truncal dystonia. These findings highlight the potential for immediate imaging-based biomarkers of clinical efficacy. ANN NEUROL 2022;92:418-424.

Inherited metabolic diseases mimicking hereditary spastic paraplegia (HSP): a chance for treatment.

The syndromic group of hereditary spastic paraplegias has a heterogeneous clinical profile and a broad differential diagnosis, including neurometabolic disorders that are potentially treatable. This group includes 5,10-methylenetetrahydrofolate reductase deficiency, cobalamin C deficiency disease, dopamine responsive dystonia, cerebrotendinous xanthomatosis, biotinidase deficiency, GLUT1 deficiency syndrome, delta-e-pyrroline-carboxylase-synthetase deficiency, hyperonithinemia-hyperammonemia-homocitrullinuria syndrome, arginase deficiency, multiple carboxylase deficiency, and X-linked adrenoleukodystrophy. This review describes these diseases in detail, highlighting the importance of early diagnosis and effective treatment aiming at preserving functionality and quality of life in these patients. For the purpose of this study, we carried a non-systematic review on PUBMED, finding an initial sample of 122 papers; upon refining, 41 articles were found relevant to this review. Subsequently, we added review articles and works with historical relevance, totalizing 76 references. An adequate diagnostic workup in patients presenting with spastic paraplegia phenotype should include screening for these rare conditions, followed by parsimonious ancillary investigation.

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.

Lateralized Subthalamic Stimulation for Axial Dysfunction in Parkinson's Disease: A Randomized Trial.

BACKGROUND: Patients with Parkinson's disease might develop treatment-resistant axial dysfunction after bilateral subthalamic stimulation. OBJECTIVES: To study whether lateralized stimulation (unilateral 50% amplitude reduction) for ≥21 days results in ≥0.13 m/s faster gait velocity in the dopaminergic ON state in these patients, and its effects on motor and axial function, quantitative gait and speech measures, quality of life, and selected cognitive tasks. METHODS: Randomized, double-blinded, double-crossover trial. RESULTS: In 22 participants (51-79 years old, 15 women), there were no significant changes in gait velocity, quality of life, cognitive, and speech measures. Reducing left-sided amplitude resulted in a 2.5-point improvement in axial motor Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) (P = 0.005, uncorrected) and a 1.9-point improvement in the Freezing of Gait Questionnaire (P = 0.024, uncorrected). CONCLUSIONS: Lateralized subthalamic stimulation does not result in meaningful improvement in gait velocity in patients with Parkinson's disease who develop treatment-resistant axial dysfunction after bilateral subthalamic stimulation. Left subthalamic overstimulation may contribute to axial deterioration in these patients. © 2022 International Parkinson and Movement Disorder Society.

A Diagnostic Approach to Spastic ataxia Syndromes.

Spastic ataxia is characterized by the combination of cerebellar ataxia with spasticity and other pyramidal features. It is the hallmark of some hereditary ataxias, but it can also occur in some spastic paraplegias and acquired conditions. It often presents with heterogenous clinical features with other neurologic and non-neurological symptoms, resulting in complex phenotypes. In this review, the differential diagnosis of spastic ataxias are discussed and classified in accordance with inheritance. Establishing an organized classification method based on mode inheritance is fundamental for the approach to patients with these syndromes. For each differential, the clinical features, neuroimaging and genetic aspects are reviewed. A diagnostic approach for spastic ataxias is then proposed.

Initiating dopamine agonists rather than levodopa in early Parkinson's disease does not delay the need for deep brain stimulation.

BACKGROUND AND PURPOSE: While levodopa is the most effective symptomatic treatment for Parkinson's disease (PD), its use is associated with an increased risk of motor complications (MCs) in the first 5 years of treatment compared to dopamine agonist (DA) first therapy. It is not known whether this translates into true benefit later in the disease. We aimed to determine whether there is a difference in the time between initial levodopa versus DA treatment and the development of disabling MCs prompting deep brain stimulation (DBS) consideration. METHODS: This was a retrospective cohort study of patients with PD attending the DBS Clinic at Toronto Western Hospital, Canada between March 2004 and February 2022, who underwent globus pallidus interna (GPI) or subthalamic nucleus (STN) DBS in 2005 or later for disabling MCs. RESULTS: Of the 438 patients included in the study, 352 underwent STN DBS and 86 underwent GPi DBS. The median (range) disease duration was 9 (2-30) years. The majority of patients (n = 312) received levodopa first and 126 received a DA. There was no significant difference in disease duration or amantadine use between the two groups. The duration from the first treatment to assesment for DBS (levodopa: median 8 years, interquartile range [IQ] 4 years; DA: median 9, IQR 4 years) or DBS surgery (levodopa: median 10 years, IIQR 5 years; DA: median 10 years, IQR 5 years) did not differ. CONCLUSION: To our knowledge, this is the only study to date to evaluate the duration between levodopa/DA-first treatment and the development of MCs of sufficient severity to warrant consideration of DBS. No association was found. The results suggest that the development of disabling MCs warranting DBS is independent of the type of first dopaminergic treatment.

Multicenter Validation of Individual Preoperative Motor Outcome Prediction for Deep Brain Stimulation in Parkinson's Disease.

BACKGROUND: Subthalamic nucleus deep brain stimulation (STN DBS) is an established therapy for Parkinson's disease (PD) patients suffering from motor response fluctuations despite optimal medical treatment, or severe dopaminergic side effects. Despite careful clinical selection and surgical procedures, some patients do not benefit from STN DBS. Preoperative prediction models are suggested to better predict individual motor response after STN DBS. We validate a preregistered model, DBS-PREDICT, in an external multicenter validation cohort. METHODS: DBS-PREDICT considered eleven, solely preoperative, clinical characteristics and applied a logistic regression to differentiate between weak and strong motor responders. Weak motor response was defined as no clinically relevant improvement on the Unified Parkinson's Disease Rating Scale (UPDRS) II, III, or IV, 1 year after surgery, defined as, respectively, 3, 5, and 3 points or more. Lower UPDRS III and IV scores and higher age at disease onset contributed most to weak response predictions. Individual predictions were compared with actual clinical outcomes. RESULTS: 322 PD patients treated with STN DBS from 6 different centers were included. DBS-PREDICT differentiated between weak and strong motor responders with an area under the receiver operator curve of 0.76 and an accuracy up to 77%. CONCLUSION: Proving generalizability and feasibility of preoperative STN DBS outcome prediction in an external multicenter cohort is an important step in creating clinical impact in DBS with data-driven tools. Future prospective studies are required to overcome several inherent practical and statistical limitations of including clinical decision support systems in DBS care.

Clinico-Genetic, Imaging and Molecular Delineation of COQ8A-Ataxia: A Multicenter Study of 59 Patients.

OBJECTIVE: To foster trial-readiness of coenzyme Q8A (COQ8A)-ataxia, we map the clinicogenetic, molecular, and neuroimaging spectrum of COQ8A-ataxia in a large worldwide cohort, and provide first progression data, including treatment response to coenzyme Q10 (CoQ10). METHODS: Cross-modal analysis of a multicenter cohort of 59 COQ8A patients, including genotype-phenotype correlations, 3D-protein modeling, in vitro mutation analyses, magnetic resonance imaging (MRI) markers, disease progression, and CoQ10 response data. RESULTS: Fifty-nine patients (39 novel) with 44 pathogenic COQ8A variants (18 novel) were identified. Missense variants demonstrated a pleiotropic range of detrimental effects upon protein modeling and in vitro analysis of purified variants. COQ8A-ataxia presented as variable multisystemic, early-onset cerebellar ataxia, with complicating features ranging from epilepsy (32%) and cognitive impairment (49%) to exercise intolerance (25%) and hyperkinetic movement disorders (41%), including dystonia and myoclonus as presenting symptoms. Multisystemic involvement was more prevalent in missense than biallelic loss-of-function variants (82-93% vs 53%; p = 0.029). Cerebellar atrophy was universal on MRI (100%), with cerebral atrophy or dentate and pontine T2 hyperintensities observed in 28%. Cross-sectional (n = 34) and longitudinal (n = 7) assessments consistently indicated mild-to-moderate progression of ataxia (SARA: 0.45/year). CoQ10 treatment led to improvement by clinical report in 14 of 30 patients, and by quantitative longitudinal assessments in 8 of 11 patients (SARA: -0.81/year). Explorative sample size calculations indicate that ≥48 patients per arm may suffice to demonstrate efficacy for interventions that reduce progression by 50%. INTERPRETATION: This study provides a deeper understanding of the disease, and paves the way toward large-scale natural history studies and treatment trials in COQ8A-ataxia. ANN NEUROL 2020;88:251-263.

Levodopa Versus Dopamine Agonist after Subthalamic Stimulation in Parkinson's Disease.

BACKGROUND: No clinical trials have been specifically designed to compare medical treatments after surgery in Parkinson's disease (PD). OBJECTIVE: Study's objective was to compare the efficacy and safety of levodopa versus dopamine agonist monotherapy after deep brain stimulation (DBS) in PD. METHODS: Thirty-five surgical candidates were randomly assigned to receive postoperative monotherapy with either levodopa or dopamine agonist in a randomized, single-blind study. All patients were reevaluated in short- (3 months), mid- (6 months), and long-term (2.5 years) follow-up after surgery. The primary outcome measure was the change in the Non-Motor Symptoms Scale (NMSS) 3 months after surgery. Secondary outcome measures were the percentage of patients maintaining monotherapy, change in motor symptoms, and specific non-motor symptoms (NMS). Analysis was performed primarily in the intention-to-treat population. RESULTS: Randomization did not significantly affect the primary outcome (difference in NMSS between treatment groups was 4.88 [95% confidence interval: -11.78-21.53, P = 0.566]). In short- and mid-term follow-up, monotherapy was safe and feasible in more than half of patients (60% in short- and 51.5% in mid-term follow-up), but it was more often possible for patients on levodopa. The ability to maintain dopamine agonist monotherapy was related to optimal contact location. In the long term, levodopa monotherapy was feasible only in a minority of patients (34.2%), whereas dopamine agonist monotherapy was not tolerated due to worsening of motor conditions or occurrence of impulse control disorders. CONCLUSIONS: This trial provides evidence for simplifying pharmacological treatment after functional neurosurgery for PD. The reduction in dopamine receptor agonists should be attempted while monitoring for occurrence of NMSs, such as apathy and sleep disturbances. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Balance and physical functioning in Spinocerebellar ataxias 3 and 10.

OBJECTIVES: Limitations of functional capacity and balance are common features of the natural history of spinocerebellar ataxias (SCA). However, their onset and progression patterns differ according to subtype. The aim of our study was to compare physical functionality and balance parameters in SCA10 and SCA3 patients, correlating with clinical variables. MATERIALS & METHODS: Cross-sectional study evaluating ninety-five SCA patients (60 with SCA3 and 35 with SCA10) with validated scales for functional independence, balance and the severity of signs and symptoms. RESULTS: The groups were similar in terms of age and gender, and results were adjusted for age at symptom onset. The SCA10 patients had better results for balance and functional independence (p < 0.007). They also had lower scores for disease severity (p < 0.0002) and the subitems gait (p < 0.0005), posture (p < 0.0021) and sitting balance (p < 0.0008). Symptom progression in both groups was similar for patients with a disease duration of up to ten years, but there was a more marked decline in SCA3 patients after this period. CONCLUSIONS: We have shown that disease progression as assessed by balance and physical functioning is slower in SCA10 patients than SCA3 patients, particularly after 10 years of disease. These findings are important as they can help to characterize the disease, assisting in the development of new therapies and rehabilitation programs.

Constant Current versus Constant Voltage: Clinical Evidence Supporting a Fundamental Difference in the Modalities.

BACKGROUND: Deep brain stimulation (DBS) is an effective surgical treatment for movement disorders. Early versions of implantable systems delivered stimulation with constant voltage (CV); however, advances in available and newer platforms have permitted programming in constant current (CC). From a treatment management perspective, there are theoretical advantages of CC stimulation. In this case series, we present clinical evidence supporting the maintenance of current regardless of changes to impedance. MATERIALS AND METHODS: This case series included 3 patients with Parkinson's disease status post-bilateral subthalamic nucleus DBS. Patients in this series self-reported intermittent diplopia with pressure applied to the scalp. Patients were subsequently examined and converted from CV to CC and re-examined. Impedances were checked prior to and after conversion from CV to CC as well as while applying pressure to the scalp that induced the adverse effects. RESULTS: Across patients, we observed that compression of the scalp overlying the connector, while patients were maintained in CV, consistently and objectively induced unilateral adduction of an eye. In addition, during scalp compression, while in CV, impedance was reduced, which would increase current delivery. Converting the patients to CC stimulation without changing other stimulation parameters eliminated diplopia and objective findings of eye deviation with compression of the scalp overlying the hardware despite changes in impedance. CONCLUSIONS: In this case series, we provide clinical support for the principal differences between CV and CC stimulation.

Programming Directional Deep Brain Stimulation in Parkinson's Disease: A Randomized Prospective Trial Comparing Early versus Delayed Stimulation Steering.

INTRODUCTION: Programming directional leads poses new challenges as the optimal strategy is yet to be established. We designed a randomized control study to establish an evidence-based programming algorithm for patients with Parkinson's disease undergoing subthalamic nucleus deep brain stimulation with directional leads. METHODS: Fourteen consecutive patients were randomized to programming with either early or delayed (i.e., starting with a "ring mode") steered stimulation. Motor scores, number of programming visits, calls to the clinic, battery consumption, and stimulation adjustments required were recorded and compared between groups, using the Wilcoxon signed-ranks test, after 3 months of open-label programming. RESULTS: Thirteen patients (25 electrodes) were included, of which 23 were steerable. Nine out of 14 electrodes allocated to delayed steered stimulation were changed to steered mode due to side effects during the course of the study. No patients (11 electrodes) initially allocated to early steered stimulation were converted to ring mode. The 2 study arms did not differ in any of the considered measures at 3 months. CONCLUSION: Programming with early or delayed steered stimulation is equally effective in the short term. However, delayed steering is less time consuming and is not always needed.

Multimodal MRI for MRgFUS in essential tremor: post-treatment radiological markers of clinical outcome.

BACKGROUND: MRI-guided focused ultrasound (MRgFUS) thalamotomy is a promising non-invasive treatment option for medication-resistant essential tremor. However, it has been associated with variable efficacy and a relatively high incidence of adverse effects. OBJECTIVES: To assess the evolution of radiological findings after MRgFUS thalamotomy and to evaluate their significance for clinical outcomes. METHODS: Ninety-four patients who underwent MRgFUS between 2012 and 2017 were retrospectively evaluated. Lesion characteristics were assessed on routine MRI sequences, as well as with tractography. Relationships between imaging appearance, extent of white matter tract lesioning (59/94, on a 4-point scale) and clinical outcome were investigated. Recurrence was defined as >33% loss of tremor suppression at 3 months relative to day 7. RESULTS: Acute lesions demonstrated blood products, surrounding oedema and peripheral diffusion restriction. The extent of dentatorubrothalamic tract (DRTT) lesioning was significantly associated with clinical improvement at 1 year (t=4.32, p=0.001). Lesion size decreased over time (180.8±91.5 mm3 at day 1 vs 19.5±19.3 mm3 at 1-year post-treatment). Higher post-treatment oedema (t=3.59, p<0.001) was associated with larger lesions at 3 months. Patients with larger lesions at day 1 demonstrated reduced rates of tremor recurrence (t=2.67, p=0.019); however, lesions over 170 mm3 trended towards greater incidence of adverse effects (sensitivity=0.60, specificity=0.63). Lesion encroachment on the medial lemniscus (Sn=1.00, Sp=0.32) and pyramidal tract (Sn=1.00, Sp=0.12) were also associated with increased adverse effects incidence. CONCLUSION: Lesion size at day 1 predicts symptom recurrence, with fewer recurrences seen with larger lesions. Greater DRTT lesioning is associated with treatment efficacy. These findings may have implications for lesion targeting and extent. TRIAL REGISTRATION NUMBER: NCT02252380.

Body composition in Spinocerebellar ataxia type 3 and 10 patients: Comparative study with control group.

Background: Spinocerebellar ataxias (SCAs) are a group of neurodegenerative genetic diseases characterized by movement disorders that can affect nutritional status and body composition. This study sought to assess body composition in SCA3 and SCA10 patients. Methods: Anthropometric assessments and bioelectric impedance analysis were performed in 46 SCA3 and SCA10 patients and 76 controls of both genders. Results: Of the patients, 69.6% had SCA3 and 58.7% were women. SCA3 patients had significantly lower percentages of body fat (%BF) than controls (15.0 ± 6.1 vs. 20.6 ± 7.1; p=0.014) and (22.4 ± 6.9 vs. 30.1 ± 6.0; p<0.001), respectively. Among the women, there was a statistically significant difference in %BF between SCA3 and SCA10 patients (22.4 ± 6.9 vs. 32.4 ± 4.9; p<0.001). Male and female SCA3 patients had significantly lower fat-free mass (FFM) than controls [50.6 kg (46.9-54.7) vs. 58.6 kg (52.6-63.9); p=0.001] and [38.2 kg (35.1-42.6) vs. 42.8 kg (39.7-46.1); p=0.004], respectively. Male SCA10 patients also had lower FFM than controls [51.2 kg (47.1-55.4) vs. (52.6-63.9); p=0.008]. Female SCA10 patients had significantly higher FFM than controls and SCA3 patients [45.0 kg (43.3-45.6) vs. 42.8 kg (39.7-46.1); p=0.004] and [45.0 kg (43.3-45.6) vs. 38.2 kg (35.1-42.6); p=0.004], respectively. There was moderate correlation (-0.42) between disease duration and muscle mass (MM), and weak (-0.38) between SARA (Scale for the Assessment and Rating of Ataxia) and MM in SCA3. In SCA10, there was no significant correlation between these variables. Conclusion: Female SCA3 patients had more body composition changes than female SCA10 patients, mainly in relation to FFM. SCA3 and SCA10 patients need nutritional follow-up to minimize body compartment changes.

The Duels of Pierre Marie and Jules Dejerine.

In no country has the duel prevailed to such a great extent as in France where the matter of dueling and affairs of honor were of frequent occurrence until the 20th century. The term duel has since been established for any contest between 2 persons or parties, be they sporting, intellectual, political, or in other matters. Despite their worldwide recognition and great scientific production, Pierre Marie and Jules Dejerine became rivals at the end of the 19th century. While Marie defended Charcot's neurological school at Salpêtrière Hospital, Dejerine had his own neurology school to contend. The fierce antagonism between them materialized to the verge of a real death duel in 1892 and later to an intellectual duel in the famous debate about aphasias, held in Paris in 1908.

Case Studies in Neuroscience: Lack of inhibitory synaptic plasticity in the substantia nigra pars reticulata of a patient with lithium-induced tremor.

Tremor is a well-known side effect from many psychiatric medications, including lithium and dopamine antagonists. In patients whose psychiatric symptoms are stabilized and only respond to certain medications, deep brain stimulation may offer relief of the consequent motor complications. We report the case of an elderly male with disabling tremor related to lithium therapy for bipolar affective disorder, who was subsequently treated with deep brain stimulation. In this patient, we obtained recordings from the substantia nigra pars reticulata and performed a high-frequency stimulation protocol that robustly elicits long-term potentiation (LTP)-like changes in patients with Parkinson's disease. We hypothesized that in this patient, who did not have Parkinson's disease, the levels of inhibitory plasticity would be much greater. However, we found an unanticipated lack of plasticity in the patient with lithium-induced tremor, compared with two de novo control patients with Parkinson's disease. This patient was successfully treated with deep brain stimulation in the vicinity of the ventral oral posterior nucleus, an area of the thalamus that receives inputs from the basal ganglia. We postulate that the lithium-induced blockade of LTP may bring about motor complications such as tremor while simultaneously contributing to the therapeutic mechanism for treating the symptoms of psychiatric disorders such as bipolar affective disorder.NEW & NOTEWORTHY Use of a dual-microelectrode technique enabled us to compare long-term potentiation (LTP)-like changes in a patient with lithium-induced tremor to that of patients with Parkinson's disease. This study corroborated the findings in rodent brain slices that chronic lithium treatment may block LTP. Whereas a deficit in LTP may underlie the therapeutic mechanism for treating psychiatric disorders such as bipolar affective disorder, it may simultaneously contribute to consequent appearance of tremor.

Deep brain stimulation for pantothenate kinase-associated neurodegeneration: A meta-analysis.

BACKGROUND: Pantothenate kinase-associated neurodegeneration is a rare autosomal-recessive disorder, characterized by progressive neurodegeneration associated with brain iron accumulation. DBS has been trialed to treat related movement disorders, particularly dystonia. The objective of this study was to determine the outcome and safety of DBS for pantothenate kinase-associated neurodegeneration. METHODS: We performed a meta-analysis using independent participant data (n = 99) from 38 articles. Primary outcome was change in movement and disability scores of the Burke-Fahn-Marsden Dystonia Rating Scale 1 year postoperatively. Secondary outcomes were response rate and complications. RESULTS: Patients with classic-type (n = 58) and atypical-type (n = 15) pantothenate kinase-associated neurodegeneration were operated on at a median age of 11 and 31 years, respectively (P < 0.001). GPi was primarily targeted (n = 87). Mean dystonia movement score improved 1 year following GPi-DBS (-26%; 95% confidence interval, -37% to -15%), particularly in atypical versus classic cases (-45% vs -16%; P < 0.001). At least 30% improvement was observed in 34% of classic versus 73% of atypical cases (P = 0.04). Higher preoperative score and atypical type predicted larger improvement. GPi-DBS improved dystonia disability score in atypical (-31%; 95% confidence interval, -49% to -13%) but not classic (-5%; 95% confidence interval, -17% to 8%) cases. Prevalence of surgical infections (6%) and hardware failure (7%) was similar to other dystonia etiologies. Two patients died within 3 months. There was insufficient data to describe outcome > 1 year following GPi-DBS or with other DBS targets. Overall, small sample sizes limited generalizability. CONCLUSIONS: This meta-analysis provides level 4 evidence that GPi-DBS for pantothenate kinase-associated neurodegeneration may improve dystonia movement scores in classic type and atypical type and disability scores in atypical type 1 year postoperatively. © 2019 International Parkinson and Movement Disorder Society.

Olfactory Function in SCA10.

Although the main clinical manifestations of spinocerebellar ataxias (SCAs) result from damage of the cerebellum, other systems may also be involved. Olfactory deficits have been reported in other types of ataxias, especially in SCA3; however, there are no studies on olfactory deficits in SCA type 10 (SCA10). To analyze olfactory function of SCA10 patients compared with that of SCA3, Parkinson's, and healthy controls. Olfactory identification was tested in three groups of 30 patients (SCA10, SCA3, and Parkinson's disease (PD)) and 44 healthy controls using the Sniffin' Sticks (SS16) test. Mean SS16 score was 11.9 ± 2.9 for the SCA10 group, 12.3 ± 1.9 for the SCA3 group, 6.6 ± 2.8 for the PD group, and 12.1 ± 2.0 for the control group. Mean SS16 score for the SCA10 group was not significantly different from the scores for the SCA3 and control groups but was significantly higher than the score for the PD group (p < 0.001) when adjusted for age, gender, and history of smoking. There was no association between SS16 scores and disease duration in the SCA10 or SCA3 groups or number of repeat expansions. SS16 and Mini Mental State Examination scores were correlated in the three groups: SCA10 group (r = 0.59, p = 0.001), SCA3 group (r = 0.50, p = 0.005), and control group (r = 0.40, p = 0.007). We found no significant olfactory deficits in SCA10 in this large series.