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Purpose: Niemann-Pick disease type C (NPC) is a rare lysosomal storage disease characterized by progressive neurodegeneration and neuropsychiatric symptoms. This study investigated pathophysiological mechanisms underlying motor deficits, particularly speech production, and cognitive impairment., Methods: We prospectively phenotyped 8 adults with NPC and age-sex-matched healthy controls using a comprehensive assessment battery, encompassing clinical presentation, plasma biomarkers, hand-motor skills, speech production, cognitive tasks, and (micro-)structural and functional central nervous system properties through magnetic resonance imaging., Results: Patients with NPC demonstrated deficits in fine-motor skills, speech production timing and coordination, and cognitive performance. Magnetic resonance imaging revealed reduced cortical thickness and volume in cerebellar subdivisions (lobule VI and crus I), cortical (frontal, temporal, and cingulate gyri) and subcortical (thalamus and basal ganglia) regions, and increased choroid plexus volumes in NPC. White matter fractional anisotropy was reduced in specific pathways (intracerebellar input and Purkinje tracts), whereas diffusion tensor imaging graph theory analysis identified altered structural connectivity. Patients with NPC exhibited altered activity in sensorimotor and cognitive processing hubs during resting-state and speech production. Canonical component analysis highlighted the role of cerebellar-cerebral circuitry in NPC and its integration with behavioral performance and disease severity., Conclusion: This deep phenotyping approach offers a comprehensive systems neuroscience understanding of NPC motor and cognitive impairments, identifying potential central nervous system biomarkers., Competing Interests: Conflict of Interest Adam P. Vogel is Chief Science Officer of Redenlab Inc. Jaymin Upadhyay and Walla Al-Hertani receive funding support from SanofiGenzyme. Dr. Bodamer and WallaAl-Hertani are, respectively, site Principal Investigator and Co-Investigator for the Early Access Program with Arimoclomol in US Patients with NPC (NCT04316637, Zevra Therapeutics). Walla Al-Hertani is on the advisory board for Beam Therapeutics and Kriya Therapeutics. All other authors declare that they have no competing interests., (Copyright © 2023 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)

Stereotypical depictions of speech in cannabis users often suggest slow, laboured output, yet objective evidence supporting this assumption is extremely limited. We know that depressants or hallucinogenic drugs such as cannabis can cause acute changes in communication and speech rate, but the long-lasting effects of cannabis use on speech are not well described. The aim of this study was to investigate speech in individuals with a history of recreational cannabis use compared to non-drug-using healthy controls. Speech samples were collected from a carefully described cohort of 31 adults with a history of cannabis use (but not use of illicit stimulant drugs) and 40 non-drug-using controls. Subjects completed simple and complex speech tasks including a monologue, a sustained vowel, saying the days of the week, and reading a phonetically balanced passage. Audio samples were analysed objectively using acoustic analysis for measures of timing, vocal control, and quality. Subtle differences in speech timing, vocal effort, and voice quality may exist between cannabis and control groups, however data remain equivocal. After controlling for lifetime alcohol and tobacco use and applying a false discovery rate, only spectral tilt (vocal effort and intensity) differed between groups and appeared to change in line with duration of abstinence from cannabis use. Differences between groups may reflect longer term changes to the underlying neural control of speech. Our digital analysis of speech shows there may be a signal differentiating individuals with a history of recreational cannabis use from healthy controls, in line with similar findings from gait and hand function studies., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: To systematically describe evidence on the use of instrumental swallowing assessment for residents of aged care homes., Design: Scoping review using the Joanna Briggs Institute methodology for scoping reviews., Setting and Participants: Published peer-reviewed and gray literature written in English between 2000 and 2020 about instrumental swallowing assessment (ISA) in adults in residential aged care homes (RACHs)., Measures: A systematic, 3-tiered search of databases including Medline, CINAHL, Embase, Scopus, and Cochrane Database of Systematic Reviews, and gray literature databases was conducted. Content analysis identified common themes., Results: Forty-two sources, 30 from peer-reviewed journals, 12 gray literature publications, and 66 websites of mobile ISA providers that discussed videofluoroscopic swallowing studies (VFSS) and/or fiberoptic endoscopic evaluation of swallowing (FEES) use in RACHs were included. Most peer-reviewed sources were referenced narratives or surveys of speech pathology practice patterns (53.3%). Researchers in 3 studies used onsite mobile FEES and in 2 studies off-site VFSS, with adults living in RACHs, as part of their research design (16.7%). There were 66 mobile instrumental swallowing assessment provider websites, based within the United States. Three countries (Australia, United States, United Kingdom) had professional guidelines that stipulated minimal requirements for the safe and appropriate provision of ISA services across settings. Themes identified across sources included (1) the approach to swallowing management and clinical indicators for ISA, (2) the role of ISA, (3) service and consumer influences on ISA, and (4) mobile FEES., Conclusions and Implications: There is a paucity of quality research on instrumental swallowing assessment in adults living in RACHs. There are broad regional and international variances in the way that videofluoroscopy and FEES are accessed and used. A more robust evidence base is required to guide health professionals to design tailored ISA care pathways for residents of RACHs, to achieve high-quality health, social, and economic outcomes., (Copyright © 2020 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Illicit stimulant use is associated with long-lasting changes in movement and movement-related brain regions. The aim of our study was to investigate the prevalence of movement dysfunction in this population. We hypothesized that prevalence of self-reported movement dysfunction is higher among stimulant users than non-stimulant users., Methods: Three groups of adults completed a survey containing questions about demographics, health, drug use, and movement. The groups consisted of ecstasy users with no history of methamphetamine use (ecstasy group, n = 190, 20 ± 3 yrs.), methamphetamine users (methamphetamine group, n = 331, 23 ± 5 yrs.), and non-stimulant users (control group, n = 228, 25 ± 8 yrs.). Movement data was analyzed with logistic regression., Results: In the unadjusted logistic regression model, group had a significant effect on fine hand control, tremor, and voice/speech questions, but not on other movement domain questions. The prevalence of tremor and abnormal fine hand control was significantly higher in the ecstasy and methamphetamine groups than in the control group (p < 0.018), and changes in voice/speech was more prevalent in the ecstasy group than in the control group (p = 0.015). Age and use of cannabis and hallucinogens were confounding variables. However, inspection of chi-square tables suggests that the effect of these parameters on the movement data is likely to be minor., Conclusions: The prevalence of self-reported tremor and changes in fine hand control and voice/speech is significantly higher in stimulant users than in non-stimulant users. Inclusion of these common and noticeable changes in body function may aid public health campaigns that target prevention or harm minimization., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: The study aim was to determine if use of illicit amphetamines or ecstasy is associated with abnormal excitability of the corticomotoneuronal pathway and manipulation of novel objects with the hand., Methods: Three groups of adults aged 18-50 years were investigated: individuals with a history of illicit amphetamine use, individuals with a history of ecstasy use but minimal use of other stimulants, and non-drug users. Transcranial magnetic stimulation was delivered to the motor cortex and the electromyographic response (motor evoked potential; MEP) was recorded from a contralateral hand muscle. Participants also gripped and lifted a novel experimental object consisting of two strain gauges and an accelerometer., Results: Resting MEP amplitude was larger in the amphetamine group (6M, 6F) than the non-drug and ecstasy groups (p < 0.005) in males but not females. Overestimation of grip force during manipulation of a novel object was observed in the amphetamine group (p = 0.020) but not the ecstasy group., Conclusions: History of illicit amphetamine use, in particular methamphetamine, is associated with abnormal motor cortical and/or corticomotoneuronal excitability in males and abnormal manipulation of novel objects in both males and females., Significance: Abnormal excitability and hand function is evident months to years after cessation of illicit amphetamine use., (Copyright © 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Importance: Multiple sclerosis produces neurological impairments that are variable in duration, severity and quality. Speech is frequently impaired, resulting in decreased communication skills and quality of life. Advancements in technology now makes it possible to use quantitative acoustic assessment of speech as biomarkers of disease progression., Observations: Four domains of speech have been identified: articulation (slow articulation and imprecise consonants), voice (pitch and loudness instability), respiration (decreased phonatory time and expiratory pressure) and prosody (longer and frequent pauses, deficient loudness control). Studies also explored I) predictive models for diagnosis of MS and of ataxia using speech variables, II) the relationship of dysarthria with cognition and III) very few studies correlated neuroimaging with dysarthria. We could not identify longitudinal studies of speech or dysarthria in Multiple Sclerosis., Conclusion and Relevance: Refinement of objective measures of speech has enhanced our understanding of Multiple Sclerosis-related deficits in cross-sectional analysis while both integrative and longitudinal studies are identified as major gaps. This review highlights the potential for using quantitative acoustic assessments as clinical endpoints for diagnosing, monitoring progression and treatment in disease modifying trials., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Despite evidence that cannabinoid receptors are located in movement-related brain regions (e.g., basal ganglia, cerebral cortex, and cerebellum), and that chronic cannabis use is associated with structural and functional brain changes, little is known about the long-term effect of cannabis use on human movement. The aim of the current study was to investigate balance and walking gait in adults with a history of cannabis use. We hypothesised that cannabis use is associated with subtle changes in gait and balance that are insufficient in magnitude for detection in a clinical setting., Methods: Cannabis users (n=22, 24±6years) and non-drug using controls (n=22, 25±8years) completed screening tests, a gait and balance test (with a motion capture system and in-built force platforms), and a clinical neurological examination of movement., Results: Compared to controls, cannabis users exhibited significantly greater peak angular velocity of the knee (396±30 versus 426±50°/second, P=0.039), greater peak elbow flexion (53±12 versus 57±7°, P=0.038) and elbow range of motion (33±13 versus 36±10°, P=0.044), and reduced shoulder flexion (41±19 versus 26±16°, P=0.007) during walking gait. However, balance and neurological parameters did not significantly differ between the groups., Conclusions: The results suggest that history of cannabis use is associated with long-lasting changes in open-chain elements of walking gait, but the magnitude of change is not clinically detectable. Further research is required to investigate if the subtle gait changes observed in this population become more apparent with aging and increased cannabis use., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: Injury is a major public health problem. While the impacts of injury on the injured person are well documented, there is relatively little knowledge about the impacts of injury on those individuals and groups in the community connected to the injured person. This study seeks to describe this breadth of research using a meta-review methodology., Study Design: Systematic meta-review., Methods: To gain a better understanding of the known impacts of injury on family, community and society, a systematic meta-review of injury outcomes research literature was conducted. Seventy-eight peer-reviewed published literature reviews were included in the meta-review., Results: Of these, 70 reported outcomes at the level of the injured person including mortality, body functions, activity and participation limitations. Nine reviews reported impacts at the level of the community including impacts on family members, work colleagues and carers. Six studies reported impacts at the societal level including economic, health system and injury compensation system impacts., Conclusions: In summary, the meta-review identified a substantial body of knowledge at the individual level outcomes of injury, and a relative lack of information regarding the community and societal impacts of injury. An injury outcome framework is proposed on the basis of the findings of the meta-review to guide future research activity, particularly with regard to injury outcome domains where there is currently limited evidence. A comprehensive framework that takes account of all levels of impact is necessary for effective policies, systems and strategies to support recovery following injury., (Copyright © 2014 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Background: Valid, reliable biomarkers of depression severity and treatment response would provide new targets for clinical research. Noticeable differences in speech production between depressed and nondepressed patients have been suggested as a potential biomarker., Methods: One hundred five adults with major depression were recruited into a 4-week, randomized, double-blind, placebo-controlled research methodology study. An exploratory objective of the study was to evaluate the generalizability and repeatability of prior study results indicating vocal acoustic properties in speech may serve as biomarkers for depression severity and response to treatment. Speech samples, collected at baseline and study end point using an automated telephone system, were analyzed as a function of clinician-rated and patient-reported measures of depression severity and treatment response., Results: Regression models of speech pattern changes associated with clinical outcomes in a prior study were found to be reliable and significant predictors of outcome in the current study, despite differences in the methodological design and implementation of the two studies. Results of the current study replicate and support findings from the prior study. Clinical changes in depressive symptoms among patients responding to the treatments provided also reflected significant differences in speech production patterns. Depressed patients who did not improve clinically showed smaller vocal acoustic changes and/or changes that were directionally opposite to treatment responders., Conclusions: This study supports the feasibility and validity of obtaining clinically important, biologically based vocal acoustic measures of depression severity and treatment response using an automated telephone system., (Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Transport injuries are a substantial cause of disability and death internationally. There is little published information regarding patterns of healthcare utilisation following transport injury., Aims: To investigate patterns of in-hospital and post-discharge healthcare use following transport injury., Methods: Analysis of all accepted adult claims from the database of the transport accident compensation regulator in Victoria, Australia between 1995 and 2008. The analyses focused on injuries resulting in hospitalisation. Indicators of in-hospital and post-discharge healthcare utilisation (e.g. number of services per practitioner group) within the first 12-months were summarised., Results: More than a third (33.6%, n = 68,639) of all accepted compensable transport injuries resulted in admission to an acute care facility within 28 days of injury. In this group, the compensation authority paid for a total of 4.5 million healthcare services in the 12 months post-discharge (median of 19 services per claim). Services provided by medical practitioners were accessed by nearly all claimants (95.7%) at a median of 11 (5-26) per claimant. Less than half of claimants (46.7%) accessed paramedical or allied health services but the median number of services accessed was higher at 29 (9-82) per claimant., Conclusion: Transport-related injury cases require a substantial interaction with multiple components of the healthcare system in the year following hospital discharge. Compensation system data may provide a detailed understanding of healthcare utilisation, a key element of injury burden., (Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.)

Dysarthria following surgical resection of childhood posterior fossa tumour (PFT) is most commonly documented in a select group of participants with mutism in the acute recovery phase, thus limiting knowledge of post-operative prognosis for this population of children as a whole. Here we report on the speech characteristics of 13 cases seen long-term after surgical treatment for childhood PFT, unselected for the presence of post-operative mutism (mean time post-surgery=6y10m, range 1;4-12;6 years, two had post-operative mutism), and examine factors affecting outcome. Twenty-six age- and sex- matched healthy controls were recruited for comparison. Participants in both groups had speech assessments using detailed perceptual and acoustic methods. Over two-thirds of the group (69%) with removal of PFT had a profile of typically mild dysarthria. Prominent speech deficits included consonant imprecision, reduced rate, monopitch and monoloudness. We conclude that speech deficits may persist even up to 10 years post-surgery in participants who have not shown mutism in the acute phase. Of cases with unilateral lesions, poorer outcomes were associated with right cerebellar tumours compared to left, consistent with the notion based on adult data that speech is controlled by reciprocal right cerebellar/left frontal interactions. These results confirm the important role of the cerebellum in the control of fine speech movements in children., (2011. Published by Elsevier Inc. All rights reserved.)

Hemispherectomy (disconnection or removal of an entire cerebral hemisphere) is a rare surgical procedure used for the relief of drug-resistant epilepsy in children. After hemispherectomy, contralateral hemiplegia persists whereas gross expressive and receptive language functions can be remarkably spared. Motor speech deficits have rarely been examined systematically, thus limiting the accuracy of postoperative prognosis. We describe the speech profiles of hemispherectomized participants characterizing their intelligibility, articulation, phonological speech errors, dysarthric features, and execution and sequencing of orofacial speech and non-speech movements. Thirteen participants who had undergone hemispherectomy (six left, seven right; nine with congenital, four with acquired hemiplegia; operated between four months and 13 years) were investigated. Results showed that all participants were intelligible but showed a mild dysarthric profile characterized by neuromuscular asymmetry and reduced quality and coordination of movements, features that are characteristic of adult-onset unilateral upper motor neuron dysarthria, flaccid-ataxic variant. In addition, one left and four right hemispherectomy cases presented with impaired production of speech and non-speech sequences. No participant showed evidence of verbal or oral dyspraxia. It is concluded that mild dysarthria is persistent after left or right hemispherectomy, irrespective of age at onset of hemiplegia. These results indicate incomplete functional re-organization for the control of fine speech motor movements throughout childhood, and provide no evidence of hemispheric differences., (2010 Elsevier Inc. All rights reserved.)