BACKGROUND: This parallel, randomized controlled trial examined intrinsic motivation, adherence and motor function improvement demonstrated by two groups of subjects that performed a 12-week, home-based upper extremity rehabilitation program. Seventeen subjects played scaffolded games, presenting eight to twelve discrete levels of increasing difficulty. Sixteen subjects performed the same activities controlled by success algorithms that modify game difficulty incrementally.
METHODS: 33 persons 20-80 years of age, at least 6 months post stroke with moderate to mild hemiparesis were randomized using a random number generator into the two groups. They were tested using the Action Research Arm Test, Upper Extremity Fugl Meyer Assessment, Stroke Impact Scale and Intrinsic Motivation Inventory pre and post training. Adherence was measured using timestamps generated by the gaming system. Subjects had the Home Virtual Rehabilitation System (Qiu in J Neuroeng Rehabil 17: 1-10, 2020) placed in their homes and were taught to perform rehabilitation games using it. Subjects were instructed to train twenty minutes per day but were allowed to train as much as they chose. Subjects trained for 12 weeks without appointments and received intermittent support from study staff. Group outcomes were compared using ANOVA. Correlations between subject demographics and adherence, as well as motor outcome, were evaluated using Pearson Correlation Coefficients.
RESULTS: There were 5 dropouts and no adverse events. The main effect of time was statistically significant for four of the five clinical outcome measures. There were no significant training group by time interactions. Measures of adherence did not differ significantly between groups. The combined groups improved their UEFMA scores on average by 5.85 (95% CI 4.73-6.98). 21 subjects from both groups demonstrating improvements in UEFMA scores of at least 5 points, exceeding the minimal clinically important difference of 4.25. IMI scores were stable pre to post training.
CONCLUSIONS: Scaffolding challenges during game based rehabilitation did not elicit higher levels of adherence when compared to algorithm control of game difficulty. Both sparsely supervised programs of game-based treatment in the home were sufficient to elicit statistically significant, clinically meaningful improvements in motor function and activities of daily living.
BACKGROUND: Clinical Trials.gov-NCT03985761, Registered June 14, 2019.

OBJECTIVE: To report a case of delayed death after initial successful treatment of severe bromethalin intoxication in a cat.
METHODS: A 2-year-old neutered male domestic shorthair cat presented as a referral for bromethalin toxicosis and progressive neurological decline. At the time of referral, the cat was nonambulatory tetraparetic with minimal motor function in all 4 limbs and exhibited a dull mentation. Within the first 4 hours of hospitalization, the cat\'s neurological status continued to rapidly decline, and osmotherapy, corticosteroids, and intralipids were administered. The treatment regimen also included levetiracetam, thiamine, cholestyramine, vitamin E, and gingko biloba. Six days after bromethalin ingestion, the cat displayed marked neurological improvement with near normal mentation and mild tetraparesis and was discharged. The cat continued to do well at home with improving neurological status and function. Nine days after discharge, the cat was presented dead on arrival. Postmortem examination revealed transforaminal brain herniation secondary to spongy degeneration of the white matter and increased intracranial pressure as the cause of death.
UNASSIGNED: To the authors\' knowledge, this is the first report of a cat that suffered delayed death despite initial neurological improvement after being treated for severe bromethalin toxicosis.

OBJECTIVE: We aimed to describe clinical and laboratory characteristics and determine the predictors of outcome in patients with cerebral venous sinus thrombosis.
METHODS: This prospective study was conducted over 2 years among hospitalized patients with cerebral venous sinus thrombosis. Patient outcome was assessed using the Modified Rankin Scale (mRS) score at 3 months. Outcome predictors were identified using logistic regression analysis.
RESULTS: Eighty-one patients were included in this study. The median mRS outcome at 3 months was 1 (interquartile range 1-3). Poor outcomes were observed in 27.2% of patients, and the mortality rate was 9.8%. Factors associated with poor outcomes were age >60 years (relative risk [RR] 5.1), hemiparesis (RR 5.4), altered level of consciousness (RR 7.1), and transverse sinus involvement (RR 1.1). In general, mRS scores were not associated with D-dimer levels (RR 2.4). However, older patients with elevated D-dimer levels showed a significant association with poor outcomes (1.6) according to mRS scores.
CONCLUSIONS: Older age, hemiparesis, and altered consciousness levels were independent predictors of poor outcomes in patients with cerebral venous sinus thrombosis. High D-dimer level showed no association with functional disability, except in older patients.

BACKGROUND General paresis of the insane (GPI) is characterized by cognitive impairment, neuropsychiatric symptoms, and brain structural abnormalities, mimicking many neuropsychiatric diseases. Olfactory dysfunction has been linked to cognitive decline and neuropsychiatric symptoms in numerous neuropsychiatric diseases. Nevertheless, it remains unclear whether patients with GPI experience olfactory dysfunction and whether olfactory dysfunction is associated with their clinical manifestations. MATERIAL AND METHODS Forty patients with GPI and 37 healthy controls (HCs) underwent the \"Sniffin Sticks\" test battery, Mini-Mental State Examination, and Neuropsychiatric Inventory to measure olfactory function, cognitive function, and neuropsychiatric symptoms, respectively. Brain structural abnormalities were evaluated using visual assessment scales including the medial temporal lobe atrophy (MTA) visual rating scale and Fazekas scale. RESULTS Compared with HCs, patients with GPI exhibited significant olfactory dysfunction, as indicated by deficits in the odor threshold (OT) (P=0.001), odor discrimination (OD) (P<0.001), and odor identification (OI) (P<0.001). In patients with GPI, the OI was positively correlated with cognitive function (r=0.57, P<0.001), but no significant correlation was found between olfactory function and neuropsychiatric symptoms, blood, or cerebrospinal fluid biomarkers (rapid plasma reagin circle card test and Treponema pallidum particle agglutination test), or brain structural abnormalities (MTA and Fazekas scale scores). Mediation analysis indicated that the impaired OI in patients with GPI was mediated by cognitive impairment and impaired OT respectively. CONCLUSIONS Patients with GPI exhibited overall olfactory dysfunction. OI is correlated with cognitive function and the impaired OI is mediated by cognitive impairment in patients with GPI. Thus, OI may serve as a marker for reflecting cognitive function in patients with GPI.

We identified a rustrela virus variant in a wild mountain lion (Puma concolor) in Colorado, USA. The animal had clinical signs and histologic lesions compatible with staggering disease. Considering its wide host range in Europe, rustrela virus should be considered as a cause for neurologic diseases among mammal species in North America.

BACKGROUND: During inpatient rehabilitation, physical therapists (PTs) often need to manually advance patients\' limbs, adding physical burden to PTs and impacting gait retraining quality. Different electromechanical devices alleviate this burden by assisting a patient\'s limb advancement and supporting their body weight. However, they are less ideal for neuromuscular engagement when patients no longer need body weight support but continue to require assistance with limb advancement as they recover. The objective of this study was to determine the feasibility of using a hip flexion exosuit to aid paretic limb advancement during inpatient rehabilitation post-stroke.
METHODS: Fourteen individuals post-stroke received three to seven 1-hour walking sessions with the exosuit over one to two weeks in addition to standard care of inpatient rehabilitation. The exosuit assistance was either triggered by PTs or based on gait events detected by body-worn sensors. We evaluated clinical (distance, speed) and spatiotemporal (cadence, stride length, swing time symmetry) gait measures with and without exosuit assistance during 2-minute and 10-meter walk tests. Sessions were grouped by the assistance required from the PTs (limb advancement and balance support, balance support only, or none) without exosuit assistance.
RESULTS: PTs successfully operated the exosuit in 97% of sessions, of which 70% assistance timing was PT-triggered to accommodate atypical gait. Exosuit assistance eliminated the need for manual limb advancement from PTs. In sessions with participants requiring limb advancement and balance support, the average distance and cadence during 2-minute walk test increased with exosuit assistance by 2.2 ± 3.1 m and 3.4 ± 1.9 steps/min, respectively (p < 0.017). In sessions with participants requiring balance support only, the average speed during 10-meter walk test increased with exosuit by 0.07 ± 0.12 m/s (p = 0.042). Clinical and spatiotemporal measures of independent ambulators were similar with and without exosuit (p > 0.339).
CONCLUSIONS: We incorporated a unilateral hip flexion exosuit into inpatient stroke rehabilitation in individuals with varying levels of impairments. The exosuit assistance removed the burden of manual limb advancement from the PTs and resulted in improved gait measures in some conditions. Future work will understand how to optimize controller and assistance profiles for this population.

BACKGROUND: Hereditary transthyretin amyloidosis, caused by transthyretin gene mutations, progresses with systemic impact and often presents peripheral neuropathy. Recent research reveals central nervous system involvement, marked by leptomeningeal amyloid accumulation and transient focal neurological episodes displaying cortical dysfunction.
METHODS: A 47-year-old Caucasian man with hereditary transthyretin amyloidosis presented with motor aphasia, right hemiparesis, fever, and an altered state of consciousness. Tests ruled out stroke or infection. While improving, the patient reported an ongoing auditory repetition phenomenon for 48 hours despite efforts to shift focus or introduce new stimuli.
CONCLUSIONS: This represents the first known case report documenting palinacousis in hereditary transthyretin amyloidosis attributed to central nervous system involvement. This case highlights the complexities in assessment and management of patients when neurological and psychiatric symptoms overlap.

Locomotor and balance disorders are major limitations for subjects with hemiparesis. The Timed Up and Go (TUG) test is a complex navigational task involving oriented walking and obstacle circumvention. We hypothesized that subjects with hemiparesis adopt a cautious gait during complex locomotor tasks. The primary aim was to compare spatio-temporal gait parameters, indicators of cautious gait, between the locomotor subtasks of the TUG (Go, Turn, Return) and a Straight-line walk in people with hemiparesis. Our secondary aim was to analyze the relationships between TUG performance and balance measures, compare spatio-temporal gait parameters between fallers and non-fallers, and identify the biomechanical determinants of TUG performance. Biomechanical parameters during the TUG and Straight-line walk were analyzed using a motion capture system. A repeated measures ANOVA and two stepwise ascending multiple regressions (with performance variables and biomechanical variables) were conducted. Gait speed, step length, and % single support phase (SSP) of the 29 participants were reduced during Turn compared to Go and Return and the Straight-line walk, and step width and % double support phase were increased. TUG performance was related to several balance measures. Turn performance (R2 = 63%) and Turn trajectory deviation followed by % SSP on the paretic side and the vertical center of mass velocity during Go (R2 = 71%) determined TUG performance time. People with hemiparesis adopt a cautious gait during complex navigation at the expense of performance.

UNASSIGNED: Genetic association studies can reveal biology and treatment targets but have received limited attention for stroke recovery. STRONG (Stroke, Stress, Rehabilitation, and Genetics) was a prospective, longitudinal (1-year), genetic study in adults with stroke at 28 US stroke centers. The primary aim was to examine the association that candidate genetic variants have with (1) motor/functional outcomes and (2) stress-related outcomes.
UNASSIGNED: For motor/functional end points, 3 candidate gene variants (ApoE ε4, BDNF [brain-derived neurotrophic factor], and a dopamine polygenic score) were analyzed for associations with change in grip strength (3 months-baseline), function (3-month Stroke Impact Scale-Activities of Daily Living), mood (3-month Patient Health Questionnaire-8), and cognition (12-month telephone-Montreal Cognitive Assessment). For stress-related outcomes, 7 variants (serotonin transporter gene-linked promoter region, ACE [angiotensin-converting enzyme], oxytocin receptor, FKBP5 [FKBP prolyl isomerase 5], FAAH [fatty acid amide hydrolase], BDNF, and COMT [catechol-O-methyltransferase]) were assessed for associations with posttraumatic stress disorder ([PTSD]; PTSD Primary Care Scale) and depression (Patient Health Questionnaire-8) at 6 and 12 months; stress-related genes were examined as a function of poststroke stress level. Statistical models (linear, negative binomial, or Poisson regression) were based on response variable distribution; all included stroke severity, age, sex, and ancestry as covariates. Stroke subtype was explored secondarily. Data were Holm-Bonferroni corrected. A secondary replication analysis tested whether the rs1842681 polymorphism (identified in the GISCOME study [Genetics of Ischaemic Stroke Functional Outcome]) was related to 3-month modified Rankin Scale score in STRONG.
UNASSIGNED: The 763 enrollees were 63.1±14.9 (mean±SD) years of age, with a median initial National Institutes of Health Stroke Scale score of 4 (interquartile range, 2-9); outcome data were available in n=515 at 3 months, n=500 at 6 months, and n=489 at 12 months. At 1 year poststroke, the rs6265 (BDNF) variant was associated with poorer cognition (0.9-point lower telephone-Montreal Cognitive Assessment score, P=1×10-5). For stress-related outcomes, rs4291 (ACE) and rs324420 (FAAH) were risk factors linking increased poststroke stress with higher 1-year depression and PTSD symptoms (P<0.05), while rs4680 (COMT) linked poststroke stress with lower 1-year depression and PTSD. Findings were unchanged when considering stroke subtype. STRONG replicated GISCOME: rs1842681 was associated with lower 3-month modified Rankin Scale score (P=3.2×10-5).
UNASSIGNED: This study identified genetic associations with cognitive function, depression, and PTSD 1 year poststroke. Genetic susceptibility to PTSD and depressive symptoms varied according to the amount of poststroke stress, underscoring the critical role of lived experiences in recovery. Together, the results suggest that genetic association studies provide insights into the biology of stroke recovery in humans.

BACKGROUND: Spinal cord compression is a rare presentation of non-Hodgkin lymphoma (NHL) in children. We aimed to describe the prevalence, histological subtypes, clinical presentation, therapy, and outcome of those children in a population-based cohort. The chemotherapy regimen remained comparable over time.
METHODS: We retrospectively identified all children and adolescents with paresis as initial manifestations of the NHL between January 1990 and December 2020 from the NHL-BFM database. Characteristics, therapy, and outcome data were gathered from the database and patient files.
RESULTS: Fifty-seven of 4779 children (1.2%) presented with initial paresis due to spinal cord compression. The median age was 10.3 years (range, 3.1-18.0 years), and 33% were female. Initial symptoms were paresis/weakness (n = 50, 88%), back pain (n = 33, 58%), paresthesia (n = 23, 40%), and bladder dysfunction and/or constipation (n = 22, 39%), persisting for a median of 14 days before diagnosis. Subtype distribution was mature B-NHL (n = 41, 72%), precursor B-lymphoblastic lymphoma (LBL) (n = 12, 21%), anaplastic large cell lymphoma (ALCL) (n = 3, 5%), and T-LBL (n = 1, 2%). Initial emergency therapy included surgery (70%) and/or chemotherapy/steroids (63%). Five-year event-free survival and overall survival (80% ± 5% and 82% ± 5%, respectively) were comparable with all other NHL patients. Neurological symptoms persisted in approximately one-third of surviving patients at the last follow-up.
CONCLUSIONS: 1.2% of pediatric NHL patients presented with paresis from spinal cord compression mainly due to B-cell lymphomas. Neurological sequelae were observed in one-third of surviving patients.