Tianxia Wu

Carpal tunnel syndrome (CTS) is the most common peripheral nerve entrapment, and ultrasound provides a fast, cost-efficient method for visualizing the median nerve. Reliable cross-sectional area (CSA) measurement remains challenging across imaging sites and varying scan qualities, and prior studies report segmentation Dice scores ranging from 0.76 to 0.93. Improving the robustness of automated segmentation is critical for achieving consistent, site-independent CSA assessment. This study evaluates a four-layer U-Net for automated segmentation and CSA estimation at two clinically relevant sites: the wrist crease and distal forearm. A primary dataset of 500 images per site was used to establish baseline performance. A second dataset of 35 wrist and 26 forearm still images was used to test generalizability, followed by intensity-based augmentations (CLAHE, gamma correction, speckle noise). Baseline models were tested on these new stills, and an augmented model was trained and evaluated on the combined datasets. The baseline models performed well on the first dataset but showed markedly reduced generalization on new still images (forearm IoU/Dice: 0.185/0.254; wrist IoU/Dice: 0.137/0.188). The augmented models improved within-set performance (forearm: 0.944/0.971; wrist: 0.951/0.974) and significantly enhanced generalization to new images (forearm: 0.408/0.533; wrist: 0.705/0.820). The final combined dataset models achieved Dice/IoU scores of 0.94/0.89 (forearm) and 0.96/0.92 (wrist). CSA measurements showed excellent to moderate correlation with manual tracings across all datasets. These findings demonstrate that targeted intensity-based augmentation substantially improves model generalization and enables robust, reproducible, and site-independent median nerve segmentation, supporting scalable ultrasound-based CTS assessment.

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic, progressive neurological disorder and shares many radiological and clinical features with other more prevalent myelopathies. Here, we quantified spinal cord and brain volumes in adults with HAM/TSP in comparison with healthy volunteers (HVs) and individuals diagnosed with relapsing–remitting or progressive multiple sclerosis (RRMS or P-MS). Clinical disability and MRI were assessed in 24 HVs, 43 HAM/TSP subjects, and 46 MS subjects. Spinal cord cross-sectional area (SCCSA) and brain tissue volumes were measured and compared. HAM/TSP subjects had significantly lower SCCSA corresponding to cervical levels 2 and 3 (C2–3) (54.0 ± 8 mm²), cervical levels 4 and 5 (C4–5) (57.8 ± 8 mm²), and thoracic levels 4 to 9 (T4–9) (22.7 ± 4 mm²) and significantly elevated brain white matter hyperintensity (WMH) fraction (0.004 ± 0.008) compared to the HVs (C2–3: 69.4 ± 8 mm², C4–5: 75.1 ± 9 mm², T4–9: 34.1 ± 4 mm²; all p < 0.0001; and WMH: 0.0005 ± 0.0007; p < 0.001). In the HAM/TSP subjects, SCCSA at all levels but not WMH showed a significant correlation with clinical disability scores. WMH in HAM/TSP subjects, therefore, may not be related to clinical disability. SCCSA in our limited RRMS cohort was higher than the HAM/TSP cohort (C2–3: 67.6 ± 8 mm², C4–5: 72.7 ± 9 mm², T4–9: 33.4 ± 5 mm²; all p < 0.0001) and WMH was lower than in P-MS subjects (p = 0.0067). Principal component analysis suggested that SCCSA and WMH may be used to differentiate HAM/TSP from MS. Understanding these differences msay help establish early diagnostic criteria for HAM/TSP patients.

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic progressive neurological disorder and shares many radiological and clinical features with other more prevalent myelopathies. Here, we quantified spinal cord and brain volumes in adults with HAM/TSP in comparison with healthy volunteers (HVs) and participants diagnosed with multiple sclerosis (MS). Clinical disability and MRI were assessed in 24 HVs, 43 HAM/TSP, and 46 MS participants. Spinal cord cross-sectional area (SCCSA) and brain tissue volumes were measured and compared. HAM/TSP participants had significantly lower SCCSA at C2-3 (54.0±8 mm2), C4-5 (57.8±8 mm2), and T4-9 (22.7±4 mm2) and significantly elevated brain white matter hyperintensity (WMH) fraction (0.004±0.008) was compared to HVs (C2-3: 69.4±8 mm2, C4-5: 75.1±9 mm2, T4-9: 34.1±4 mm2; all p < 0.0001; and WMH: 0.0004±0.0007; p < 0.001). In HAM/TSP, SCCSA at all levels but not WMH showed the significant correlation with clinical disability scores. Brain white matter hyperintensities in HAM/TSP, therefore, may not be related to clinical disability. SCCSA and WMH in our limited MS cohort were higher than the HAM/TSP cohort (67.6±8 mm2, 72.7±9 mm2, 33.4±5 mm2; p < 0.0001). Principal component analysis suggested that SCCSA and WMH may be used to differentiated HAM/TSP from MS. Understanding these differences may help establish early diagnostic criteria for HAM/TSP patients.

BACKGROUND. In Lewy body diseases (LBDs) Parkinson disease (PD), and dementia with Lewy bodies (DLB), by the time parkinsonism or cognitive dysfunction manifests clinically, substantial neurodegeneration has already occurred. Biomarkers are needed to identify central LBDs in a preclinical phase, when neurorescue strategies might forestall symptomatic disease. This phase may involve catecholamine deficiency in the autonomic nervous system. We analyzed data from the prospective, observational, long-term PDRisk study to assess the predictive value of low versus normal cardiac ¹⁸F-dopamine positron emission tomography (PET), an index of myocardial content of the sympathetic neurotransmitter norepinephrine, in at-risk individuals. METHODS. Participants self-reported risk factor information (genetics, olfactory dysfunction, dream enactment behavior, and orthostatic intolerance or hypotension) at a protocol-specific website. Thirty-four with 3 or more confirmed risk factors underwent serial cardiac ¹⁸F-dopamine PET at 1.5-year intervals for up to 7.5 years or until PD was diagnosed. RESULTS. Nine participants had low initial myocardial ¹⁸F-dopamine–derived radioactivity (P = 0.0009 by Fisher’s exact test). Conversely, all 9 LBD+ participants had low ¹⁸F-dopamine–derived radioactivity before or at the time of diagnosis of a central LBD, whereas among 25 participants without a central LBD only 1 (4%) had persistently low radioactivity (P < 0.0001 by Fisher’s exact test). CONCLUSION. Cardiac ¹⁸F-dopamine PET highly efficiently distinguishes at-risk individuals who are diagnosed subsequently with a central LBD from those who are not. TRIAL REGISTRATION. ClinicalTrials.gov NCT00775853. FUNDING. Division of Intramural Research, NIH, NINDS.

Background: Xeroderma pigmentosum (XP) is a rare autosomal recessive genetic disorder with defective DNA nucleotide excision repair and associated with a high frequency of skin cancer. Approximately 25% of patients develop progressive neurological degeneration. Complementation groups XP-A and XP-D are most frequently associated with neurological disorders. Design/methods: This is a retrospective review of patients with XP who were evaluated at NIH from 1986 to 2015 and had nerve conduction studies (NCS). In the complementation groups with peripheral neuropathy, further comparisons of the NCS were made with audiological, brain imaging, neuropsychological assessments that were also performed on most of the patients. Limited neuropathology of XP-A and XP-D patients were examined.. Results: The 33 patients had NCS: XP-A (9 patients), XP-C (7 patients), XP-D (10 patients), XP-E (1 patient), XP-V (4 patients), and XP-unknown (2 patients). Peripheral neuropathy based on nerve conduction studies was documented only in two complementation groups: 78% (7/9) of XP-A patients had a sensorimotor neuropathy while 50% (5/10) of XP-D patients had a sensory neuropathy only. Analysis of sural sensory nerve amplitude in both complementation groups XP-A and XP-D correlated with sensorineural hearing loss (SNHL), MRI/CT severity, and Full-scale Intelligence Quotient (IQ). Analysis of fibular motor nerve amplitude in complementation XP-A correlated with SNHL and MRI/CT severity. Limited follow-up studies showed gradual loss of NCS responses compared to an earlier and more rapid progression of the hearing loss. Conclusions: Despite similar brain imaging and audiological findings patients, XP-A and XP-D complementation groups differ in the type of neuropathy, sensorimotor versus sensory alone. A few cases suggest that sensorineural hearing loss may precede abnormal NCS in XP and therefore serve as valuable clinical indicators of XP patients that will later develop peripheral neuropathy.

Introduction: Discrepancies between diffusion tensor imaging (DTI) findings and functional rating scales in amyotrophic lateral sclerosis (ALS) may be due to symptom heterogeneity, particularly coexisting cognitive-behavioural dysfunction affecting non-motor regions of the brain. Carriers of expansion mutations in the C9orf72 gene, whose motor and cognitive-behavioural symptoms span a range from ALS to frontotemporal dementia, present an opportunity to evaluate the relationship between symptom heterogeneity and DTI changes.Methods: Twenty-eight C9orf72 mutation carriers with varied cognitive and motor symptoms underwent clinical evaluation and DTI imaging. Twenty returned for two or more follow-up evaluations. Each evaluation included motor, executive and behavioural scales and disease staging using the King’s college staging system.Results: Widespread reduction of white matter integrity occurred in C9orf72 mutation carriers compared with 28 controls. The ALS Functional Rating Scale (ALSFRS-R) and King’s stage correlated with DTI measures of the corticospinal tract and mid-callosum. Cognitive and behavioural scores correlated with diffusion measures of frontal white matter. King’s stage, but not ALSFRS-R, correlated with anterior callosum DTI measures. Over a 6-month follow-up, DTI changes spread from anterior to posterior, and from deep to superficial subcortical white matter. In C9orf72 carriers with ALS or ALS-FTD, changes in corticospinal tractography measures correlated with changes in ALSFRS-R.Conclusion: Discrepancies between DTI findings and clinical measures of disease severity in ALS may partly be accounted for by cognitive-behavioural deficits affecting extramotor white matter tracts. Both ALSFRS-R and King’s stage correlated with corticospinal DTI measures. Group-level DTI changes could be detected over 6 months.