BACKGROUND:Diagnosing clinically uncertain parkinsonian syndromes (CUPS) is challenging. Dopamine transporter (DaT) SPECT imaging (DaTscan) aids in differentiation, but its real-world impact on management in Canada, where it is not publicly funded, is unclear. The objective was to determine the impact of DaTscan results on clinical management for patients with CUPS in a Canadian tertiary care movement disorder service. METHODS:We conducted a retrospective chart review of 42 patients with CUPS referred for a DaTscan from a tertiary clinic in London, Ontario. DaTscan result was categorized as "Abnormal" (positive scan) or "Normal" (negative scan). The primary outcome was a change in management (Present/Absent). The association was assessed using Fisher's Exact test. RESULTS:Forty-two patients were included (median age 63 years; 50% female). Twenty-seven scans (64%) were abnormal, and 15 (36%) were normal. Overall, clinical management was changed in 13 patients (31%; 95% CI: 18% to 47%). A change in management was significantly more likely after a normal scan (60%, 9/15 patients) compared to an abnormal scan (15%, 4/27 patients) (p = 0.009). Changes after a normal scan primarily involved discontinuing dopaminergic therapy (7/9, 78%). CONCLUSIONS:In this specialized clinic, DaTscan results informed management in 31% of CUPS patients. A normal scan provides the objective evidence needed to withdraw unnecessary dopaminergic medications confidently.

Oxylipin species are generated from omega-3 and omega-6 fatty acids during inflammation, including fatty acid epoxides by cytochrome P450s (CYP450) and their diol metabolites by soluble epoxide hydrolase (sEH). The CYP450-sEH pathway has been implicated in Alzheimer’s disease (AD) but it remains unclear how plasma oxylipins relate to AD biomarkers and neurodegeneration. Fasting plasma CYP450-sEH total (free + esterified) oxylipins were assayed by ultra-high pressure liquid chromatography-tandem mass spectrometry in participants (NCT04104373) clinically diagnosed with AD or mild cognitive impairment (MCI). Plasma AD biomarkers were assayed by SiMoA. At baseline, 1 and 2 years, regional grey matter and white matter hyperintensity (WMH) volumes were quantified using 3.0 T MRI, and cognitive assessments were performed. At baseline (n = 125), participants with AD vs. MCI had higher CYP450-sEH pathway metabolites, apolipoprotein E (APOE) ε4 carriers vs. non-carriers had higher diol levels, and females vs. males had higher omega-6 vs. omega-3 oxylipins. An oxylipin profile of higher diols and lower epoxides was associated with higher pTau181, temporal lobe and hippocampal atrophy, and declines in cognitive performance in multiple domains over 2 years. Higher CYP450-sEH pathway metabolites were associated with the progression of WMH. Larger oxylipin relationships with atrophy and cognitive decline were seen at the MCI stage, in APOE ε4 carriers, and in females. Elevated sEH metabolites were related to biomarkers of AD pathogenesis, and they predicted atrophy, white matter changes, and cognitive decline over 2 years.

Conventional imaging techniques lack the resolution and sensitivity to adequately characterize cerebral small-vessel abnormalities (CSVA) in vivo. This study aimed to overcome these limitations and evaluate the feasibility of a novel MRI technique called Microvascular In-vivo Contrast Revealed Origins (MICRO), which uses an ultrasmall superparamagnetic iron oxide (USPIO) contrast agent (Ferumoxytol) to resolve the cerebral microvascular architecture with a level of anatomical and physiological detail not previously achievable in vivo. Fifty-nine Parkinson's disease (PD) patients underwent MICRO MRI based on susceptibility-weighted imaging (SWI). Three independent raters identified and categorized CSVAs as large developmental venous anomalies (DVAs), micro DVAs, engorged vessels, and diminished vessels. The location of each CSVA was documented, and its association with white matter hyperintensities (WMHs) was assessed. The MICRO imaging protocol demonstrated excellent inter-rater agreement for identifying these CSVAs. Our findings show a high prevalence of CSVAs in PD patients, with engorged vessels being the most common type (49.06% of subjects). Both engorged vessels (72.41%) and micro DVAs (81.82%) were highly associated with WMHs. CSVAs were most frequently observed in the periventricular white matter (n = 28), deep white matter (n = 32), and putamen (n = 14), suggesting a regional distribution pattern of detectable CSVAs. This work establishes MICRO as a feasible, reliable platform for in vivo microvascular mapping with potential applications in neurovascular research.

PURPOSE:The primary purpose of this study was to evaluate the effect of three different types of speech amplification devices on spontaneous speech intelligibility of people with hypophonia secondary to Parkinson's disease or parkinsonism. METHOD:Twenty-one individuals with hypophonia described pictures aloud to their primary communication partner in four device and two noise conditions. Device conditions included no device, a portable wired speech amplifier, a wireless stationary amplifier, and a one-way personal communication system. Noise conditions included quiet and 65-dB multitalker background noise. Speech intelligibility was evaluated from the perspective of two listener groups, familiar communication partners and naive listeners, as a function of device type and noise. RESULTS:Overall, all three devices were associated with improved intelligibility, especially in noise and for longer utterances for both listener groups. Intelligibility was highest for the personal communication system and lowest for the portable wired amplifier. These results for spontaneous speech patterned similarly to those for read sentences reported for these same talkers and listeners in Knowles et al. (2020). CONCLUSIONS:Speech amplification devices demonstrate measurable improvements in intelligibility of spontaneous speech in individuals with hypophonia. Findings add to a growing body of evidence of the potential effectiveness of speech amplification as a management tool for hypophonia. SUPPLEMENTAL MATERIAL:https://doi.org/10.23641/asha.31834960.

BACKGROUND:Foslevodopa-foscarbidopa (LDp/CDp) is a soluble formulation of levodopa/carbidopa delivered as a continuous subcutaneous infusion for the treatment of motor fluctuations in people with Parkinson's disease. No real-world use data exist regarding its efficacy and safety from a high-volume Canadian center. METHODS:This is an ambispective longitudinal study (with the second visit at 1 month of enrollment) in patients with advanced Parkinson's disease from a tertiary care movement disorder center in Canada. OBJECTIVES:The primary objective of the study was to examine the efficacy of LDp/CDp in improving MDS UPDRS III scores, EURO-Q Index, EURO Q VAS score and ON time while reducing OFF time. Secondary objectives focused on safety. RESULTS:The study was conducted from April 2024 to August 2025, with the prospective part comprising 11 patients and the retrospective part 53 patients. There was a significant (p < 0.05) improvement in clinical efficacy parameters like the MDS UPDRS III (-11.37), OFF hours (-2.77), ON time without dyskinesias (+2.07), ON time with troublesome dyskinesias (-0.74 hours) and quality of life-related parameters like EURO Q Index (+0.10) and PDQ-39 (-10.78). One-fourth (26.5%) of the patients discontinued treatment, mostly due to infusion-site reactions or infections. CONCLUSION:LDp/CDp can be an effective treatment option for carefully selected patients with advanced Parkinson's disease and disabling motor complications. Appropriate hygiene measures may reduce the proportion of infusion site reactions, thereby improving patient retention on LDp/CDp infusion.

BACKGROUND:Recognizing cervical dystonia (CD) movement patterns for appropriate botulinum toxin type A (BoNT-A) pattern determination depends on clinical expertise. Kinematic analysis objectively measures dystonic neck movements, and whether BoNT-A patterns determined solely using kinematics can effectively treat CD symptoms was investigated. METHODS:Twenty-two BoNT-A-naïve CD participants were randomized to receive three BoNT-A injections determined clinically ("cb") or by kinematic-based assessment ("kb"). Outcomes included the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and kinematic measures of CD motor symptoms (tonic deviation and dynamic movements) at re-injection (weeks 12, 24) and peak effect (weeks 6, 18, 30) compared to baseline. RESULTS:Mean tonic deviation that returned to neutral was observed in 47% of "kb" and 31% of "cb" participants between weeks 6 and 30. Mean dynamic movements (root mean square amplitude) were significantly reduced in the "kb" group between weeks 12 and 30 compared to baseline. TWSTRS total score and motor severity were significantly reduced in the "cb" group, and disability sub-score was significantly reduced in both groups for all subsequent injections. Treatment-related side effects occurred in two "cb" and four "kb" participants. CONCLUSION:The study indicates that kinematic-based BoNT-A injection patterns can effectively reduce CD symptoms and disability, offering valuable guidance for both novice and experienced injectors.

Effects of deep brain stimulation (DBS) depend on millimetric accuracy and are commonly studied across populations by registering patient scans to a stereotactic space. Multiple factors contribute to estimates of electrode position, but the millimetric contributions of these factors remain poorly quantified. We previously validated 32 anatomical fiducials (AFIDs) to measure AFID registration error (AFRE), which can capture focal misregistration not observed using volume-based methods. To this end, we used the AFIDs framework to examine the effects of misregistration on electrode position in stereotactic space, leveraging a retrospective series of patients who underwent subthalamic nucleus (STN) DBS. Raters independently localized DBS electrodes and AFIDs on patient scans, which were non-linearly registered to a common stereotactic (MNI) space. AFIDs provided intuitive measures of registration accuracy, with AFREs ranging from 1.49 mm to 6.85 mm across brain regions. Subcortical AFIDs in proximity to the DBS target (STN) had AFREs that spatially covaried, suggesting consistent spatial patterns of misregistration to stereotactic space. These identified spatial patterns account for 28% of the variance in electrode position along the axis of maximum variance, corresponding to a median of 0.64 mm (range of 0.05 to 2.05 mm). The AFIDs framework provides millimetric estimates of registration accuracy in DBS, while allowing the uncoupling of registration-related factors from other sources of variance in electrode position. Furthermore, they can be employed for estimating registration-related variance in population studies, for quality control, and to provide a basis for comparison as well as optimization of registration parameters and software.

BACKGROUND:Noninvasive stimulation techniques are a promising therapy due to the ease of administration and minimal side effects. We investigated the clinical, electrophysiological and side effects of transcranial pulsed current stimulation (tPCS) in patients with Parkinson's disease (PD). MATERIALS AND METHODS:Ten PD patients were called at monthly intervals in the OFF levodopa state. Patients received active tPCS for 20 minutes in the first visit and sham stimulation for 20 minutes in the second and were assessed for the levodopa response in the third. Clinical and bradykinesia scoring and gait and tremor analysis were done before and after stimulation/sham/levodopa in each visit. Scalp electroencephalography (EEG) was recorded for quantitative analysis during each visit. The interventions were compared between pre- and post-intervention. RESULTS:A significant improvement with levodopa as compared to active and sham tPCS was seen in clinical scores. Upper limb postural tremor severity (z-score = -2.410, p = 0.016) and the stride velocity variability during post active stimulation improved by 20.7% compared to post sham stimulation though the difference was statistically non-significant. KINARM testing showed a statistically significant difference in the reaction time (p = 0.036) when comparing pre- and post-tPCS active stimulation. EEG recording showed a transitory increase of electrical activity after tPCS, with the most significant increase seen in alpha bandpower (p = 7.95*10-07; z score: -4.93). CONCLUSIONS:tPCS was well tolerated in all patients. With minimal side effects, ease of administration and mild improvement in the electrophysiological parameters assessed, tPCS can be an alternative therapeutic option in patients with PD.

Sensorimotor integration (SMI) is a complex process that allows humans to perceive and interact with their environment. Any impairment in SMI may impact the day-to-day functioning of humans, particularly evident in Parkinson's Disease (PD). SMI is critical to accurate perception and modulation of motor outputs. Therefore, understanding the associated neural pathways and mathematical underpinnings is crucial. In this article, a systematic review of the proposed neural and computational models associated with SMI is performed. While the neural models discuss the neural architecture and regions, the computational models explore the mathematical or computational mechanisms involved in SMI. The article then explores how PD may impair SMI, reviewing studies that discuss deficits in the perception of various modalities, pointing to an SMI impairment. This helps in understanding the nature of SMI deficits in PD. Overall, the review offers comprehensive insights into the basis of SMI and the effect of PD on SMI, enabling clinicians to better understand the SMI mechanisms and facilitate the development of targeted therapies to mitigate SMI deficits in PD.

BackgroundMotor signs, such as rigidity, bradykinesia, tremor, gait and balance impairment, are hallmark features of idiopathic Parkinson's disease (PD). The basal ganglia, involved in voluntary and automatic movements, are affected by reduced dopaminergic activity, contributing to motor signs in PD. Motor signs may be exacerbated by cortical white matter hyperintensities (WMH), but the relationship between basal ganglia WMH and motor signs remains unclear.ObjectiveTo investigate the association between subcortical WMH burden and motor severity in PD participants.MethodThis cross-sectional study included 140 PD participants from the Ontario Neurodegenerative Disease Research Initiative (ONDRI). The relative WMH (i.e, percentage) in the whole brain, frontal, temporal, parietal, occipital lobes, and basal ganglia+thalamus (BGT) were calculated. Adjusted regression models were used to test the associations between WMH and motor signs. WMH burden was stratified by quartiles, and Analysis of Covariance was applied to determine which WMH quartile most affected motor signs.ResultsIncreased WMH burden in BGT was associated with better motor function. In contrast, WMH burden in cortical brain regions, i.e., frontal, parietal, temporal, and occipital lobes, was not associated with worse motor signs. Participants with larger BGT WMH volumes exhibited better motor function compared to those in lower quartilesConclusionHyperintense lesions in the basal ganglia+thalamus were significantly associated with better motor function, suggesting that disruption of inhibitory basal ganglia circuitry may recalibrate motor output. These findings raise novel hypotheses about circuit-level modulation in Parkinson's disease and may guide future mechanistic and therapeutic investigations. However, as the results are correlational, they do not imply causality.

Patients with Parkinson’s disease (PD) present with speech difficulties including abnormal speech intensity regulation. It is possible that the neural circuitry in speech may be unique and more complex compared to the other major motor symptoms. The current study aimed to provide a better understanding of the sensorimotor integration and loudness perception deficits in PD using an altered intensity feedback (AIF) paradigm. Twenty-six participants with PD and 26 neurologically healthy control participants completed a magnitude production task (normal loudness, 2× louder, 4× louder, and max loudness) while being presented with AIF and background noise. The task was repeated in complete masking noise and loudness perception ratings were obtained in all conditions (no noise and background noise). Results suggest that unlike previous studies in other sensorimotor domains, individuals with PD display a reduced reliance on auditory sensory feedback such that during a speech magnitude production task, their perception of those productions may rely less on the auditory sensory feedback being received. Loudness perception results in the absence of auditory feedback suggest a modulating effect of sensory feedback on somatosensation or sense of effort in PD.

PURPOSE:This exploratory study evaluated the test-retest stability of three participation-based patient-reported outcome measures (PROMs) rated by individuals with Parkinson's disease (IWPD), primary communication partners (PCPs) serving as proxy raters, and control participants over three study visits spanning approximately 1 month. METHOD:Twenty-three IWPD and hypophonia, 23 PCPs, and 30 control participants attended three non-intervention experimental visits. During each visit, all participants completed three participation-based PROMs: Communicative Participation Item Bank (CPIB), Voice Activity and Participation Profile (VAPP), and Levels of Speech Usage Scale (LSUS). Proxy ratings for each PROM were completed by PCPs. RESULTS:Results indicated significant differences between IWPD and control participants on all PROMs. IWPD exhibited lower scores on the CPIB and LSUS and higher scores on the VAPP compared to control participants. There was relative agreement in ratings between IWPD and their PCPs on all PROMs. Finally, there were relatively stable test-retest scores on all three PROMs over the three study visits, both within and between IWPD and PCPs. An exception was a statistically, but not clinically significant, decrease in CPIB scores between Visit 1 and Visit 3 for IWPD. CONCLUSIONS:This study has contributed to our understanding of the measurement properties of the CPIB, VAPP, and LSUS related to the test-retest stability of these measures over three time points in IWPD, proxy raters, and control participants. These findings provide additional context in the interpretation of participation-based PROMs in this clinical population and may prove to be useful in interpreting changes to participation-based PROM scores.

Freezing of gait (FOG) affects up to 80

INTRODUCTION:Cerebellar ataxias are a heterogeneous group of disorders clinically manifest as impaired coordination during a voluntary motor task resulting from cortico-cerebellar brain network dysfunction, resulting in multiple motor systems including speech, upper limb dexterous movement and gait. Objective assessment of these dysfunctional motor domains provides vital clues in assessing the underlying pathophysiology. METHODS:In this study, speech, upper limb kinematics and gait were studied using acoustic software (Praat), upper limb robot (KINARM) and gait carpet (Zeno Walkway with PKMAS). Clinical assessment was conducted using the Scale for the Assessment and Rating of Ataxia (SARA). RESULTS:In speech analysis, ataxia patients had slower and variable 'tuh' syllable repetition performance than healthy controls. In KINARM reaching tasks, ataxia patients displayed less accuracy and efficacy as measured by endpoint error (EE) and mean perpendicular error, along with slower mean and peak velocity of arm movements, prolonged reaction time and increased inter-trial variability. Moreover, there were more EEs while applying load during arm movement. Gait analysis revealed reduced cadence, reduced stride velocity, reduced step length, longer time in the double support phase and increased variability of step length, stride velocity, double support percentage and gait cycle time. CONCLUSION:The study highlights the critical role played by the cerebellum during movement execution and has paved the way for more comprehensive future studies on degenerative cerebellar ataxia, incorporating kinematic measurements in multiple motor domains.

Background: The primary effect of Botulinum toxin (BoNT) is to cause weakness in the injected muscles by inhibiting the release of acetyl choline from presynaptic nerve terminals. Its effect on sensorimotor integration (SMI) has largely been confined to small studies. The aim of this review is to highlight effect of BoNT on SMI in the context of Parkinson’s disease (PD), Cervical dystonia (CD), and Writer’s cramp (WC). Methods: Using keywords “Botulinum toxin” and “sensorimotor integration” or “Freezing of gait (FOG)” or ‘Tremor”or “Cervical dystonia” or “Parkinson’s disease”, or “Writer’s cramp”, PubMed database was searched for relevant articles supporting our view. The abstracts of all resultant articles (case reports, case series, randomized trials, observational studies) were reviewed to look for evidence of effects of botulinum toxin on SMI. The relevant articles were charted in excel sheet for further full text review. Results: In FOG, chronic BoNT injections may alter central motor patterns with inclusion of alternative striatal systems, cerebellum, and its connections. In tremor, the afferent proprioceptive input may be modified with reduction of intracortical facilitation and increment of intracortical inhibition. In CD, BoNT can restore disorganized cortical somatotrophy, the key pathophysiology behind cervical dystonia. Similarly, in WC, both the deficient sensory system and abnormal reorganization of the sensorimotor cortex may be altered following chronic BoNT injections. Conclusions: There is preliminary evidence that BoNT may modulate SMI in PD, CD, and WC by altering inputs from the muscle spindles in short term and modifying circuits/particular anatomic cerebral cortices in the long term. Properly conducted randomized trials comparing BoNT with placebo or prospective large-scale studies to look for effect on various surrogate markers reflective of changes in SMI should be the next step to confirm these findings. Targeting the system of afferents like spindles and golgi tendon organs in muscles may be a better way of injecting BoNT, with lower amounts of toxin needed and potential for lesser side-effects like weakness and atrophy. However, this needs to be proven in controlled trials.

Loss of dopaminergic neurons in the substantia nigra (SN) pars compacta (SNc) is a pathological hallmark of Parkinson's disease (PD). This is accompanied by a reduction of the dopamine synthesis byproduct neuromelanin (NM), which can be detected in vivo with NM-sensitive MRI, showing potential as a biomarker of PD. This relies on delineating the NM-rich region, which is achieved by applying manual or automated methods. Currently, there is a lack of publicly available tools for this task, so we trained a deep neural network intended for publishing, while exploring the effects of incorporating multiparametric MRI for segmenting the NM hyperintensity of the SN. We obtained multiple MRI contrasts, including NM-sensitive magnetization transfer contrast from 109 individuals (87 PD, 22 healthy controls) comprising a Norwegian and a Canadian cohort. The method was further evaluated on 209 MRIs from the Parkinson's Progressive Markers Initiative (PPMI). We observed that models trained naively on images from a single site tended to perform very poorly when exposed to similar data from different sites, emphasizing the importance of validating on out-of-distribution data. By applying aggressive data augmentation, we could largely attenuate the problem. We also observed a small additional regularizing effect from training the neural network on multiparametric MRIs. Volume and contrast-to-noise ratio (CNR) of the SN hyperintensity to the crus cerebri were used to distinguish patients from controls, with an area under the receiver operating characteristic (AUROC) of 0.863. CNR was found to be a better marker of disease status than volume, and we discuss a potential confusion in discerning the two measures. No contralateral association was observed between the severity of motor symptoms and volume or CNR.

Introduction Deep brain stimulation (DBS) has become the standard of care in patients with Parkinson's Disease (PD) experiencing motor fluctuations. The existing literature suggests that deep-brain stimulation (DBS) of the subthalamic nucleus (STN) alleviates levodopa-induced dyskinesias (LID), particularly those associated with high plasma levels of levodopa (peak dose), through medication reduction. Case presentation We report a case of early-onset PD with motor fluctuations and levodopa-induced peak-dose dyskinesias, who developed an interesting phenomenon of diphasic dyskinesias during the monopolar review of DBS. These dyskinesias resolved when the stimulation amplitude was increased to achieve a more stable 'ON' phase. Conclusion This rare phenomenon suggests that when predominantly lower-limb dyskinesias occur at low current stimulation, increasing stimulation amplitude might improve the excessive movements. Diphasic dyskinesias are often misdiagnosed and under-reported. Future studies should clarify the frequency.

Speech rate reduction is a global speech therapy approach for speech deficits in Parkinson’s disease (PD) that has the potential to result in changes across multiple speech subsystems. While the overall goal of rate reduction is usually improvements in speech intelligibility, not all people with PD benefit from this approach. Speech rate is often targeted as a means of improving articulatory precision, though less is known about rate-induced changes in other speech subsystems that could help or hinder communication. The purpose of this study was to quantify phonatory changes associated with speech rate modification across a broad range of speech rates from very slow to very fast in talkers with and without PD. Four speaker groups participated: younger and older healthy controls, and people with PD with and without deep brain stimulation of the subthalamic nucleus (STN-DBS). Talkers read aloud standardized sentences at 7 speech rates elicited using magnitude production: habitual, three slower rates, and three faster rates. Acoustic measures of speech intensity, cepstral peak prominence, and fundamental frequency were measured as a function of speech rate and group. Overall, slower rates of speech were associated with differential effects on phonation across the four groups. While all talkers spoke at a lower pitch in slow speech, younger talkers showed increases in speech intensity and cepstral peak prominence, while talkers with PD and STN-DBS showed the reverse pattern. Talkers with PD without STN-DBS and older healthy controls behaved in between these two extremes. At faster rates, all groups uniformly demonstrated increases in cepstral peak prominence. While speech rate reductions are intended to promote positive changes in articulation to compensate for speech deficits in dysarthria, the present results highlight that undesirable changes may be invoked across other subsystems, such as at the laryngeal level. In particular, talkers with STN-DBS, who often demonstrate speech deterioration following DBS surgery, demonstrated more phonatory detriments at slowed speech rates. Findings have implications for speech rate candidacy considerations and speech motor control processes in PD.

The obliquus capitis inferioris (OCI) muscle is a significant driver of cervical dystonia with torticaput movements and a no–no head tremor. Limited data are available on the efficacy of OCI injections on patient outcomes. Our study aims to determine whether the botulinum toxin injection into OCI improves subjective patient quality of life in those with dystonic head tremors. A retrospective chart review was performed for 25 patients receiving injections into the OCI for a dystonic head tremor at the London Movement Disorders Clinic between January 2020 and January 2022. Toronto Western Spasmodic Torticollis Scale-2 (TWSTRS-2) subscale scores for disability and pain, TWSTRS-PSYCH scores, and the global impression of severity were extracted. The average TWSTRS-2 disability subscale change was −2.8 points (p < 0.003). The average TWSTRS-2 pain subscale change was −4.6 points (p < 0.003). The average TWSTRS-PSYCH score prior to injection was 5.6. After injection, the average score was 3.7 (p < 0.004). The patient self-reported average global impression of severity before injection was 7.0; after this, it was 4.2 (p < 0.0003). The OCI injection showed significant improvement in retrospective patient self-reported outcomes; it should be considered early in the treatment plan for cervical dystonia with a no–no head tremor.