Citations

Background Motor disturbances are common in neurologic and neurodegenerative syndromes. A standard motor speed and dexterity measure is the finger tapping test (FTT). The FTT has traditionally been administered in clinic using a mechanical FTT, limiting accessibility and early motor change quantification. This study assessed the validity of a smartphone app-based FTT, which may expand access and enable more frequent testing. Methods The cohort was diagnostically diverse, including participants with frontotemporal dementia (FTD), progressive supranuclear palsy (PSP), corticobasal syndrome, primary progressive aphasia, multiple sclerosis, and clinically unimpaired controls. Participants completed a 20-second ALLFTD Mobile App (mApp)-FTT with each hand. Tapping speed metrics were extracted. Participants completed the gold-standard mechanical FTT, a neurologist-administered finger tapping exam, the PSP Rating Scale (PSPRS) and the Unified Parkinson’s Disease Rating Scale (UPDRS). Correlations assessed mApp-FTT and mechanical FTT relationships; regressions evaluated associations with neurologist-rated finger tapping impairment, PSPRS and UPDRS, adjusting for age and sex. Results The mApp-FTT showed moderate-to-strong correlations with the mechanical FTT (dominant: r=0.63, p<0.001; non-dominant: r=0.55, p<0.001). Taps per second were associated with PSPRS motor severity (dominant hand: std. β=-0.59, 95% CI [-0.91, -0.27], p<0.001) and the UPDRS (dominant hand: std. β=-0.41, 95% CI [-0.82, 0.00], p=0.049). Flight time was modestly associated with neurologist-rated finger tapping impairment (dominant hand: std. β=0.15, 95% CI [0.00, 0.29], p=0.044). Conclusion These findings support mApp-FTT validity as a measure of motor function across neurodegenerative conditions. Validation in longitudinal and unsupervised remote settings is warranted to understand scalability and evaluate change over time.

OBJECTIVE Maximal safe resection of intra-axial brain tumors near the motor cortex is aided by intraoperative motor mapping. Here, the authors compared outcomes in patients undergoing either low-frequency bipolar stimulation (LFBS) or high-frequency monopolar stimulation (HFMS) for cortical and/or subcortical motor mapping during brain tumor resection. METHODS A retrospective analysis of patients undergoing an asleep craniotomy with motor mapping or an awake craniotomy with motor and speech mapping with a single surgeon was performed. Three cohorts were compared: 1) asleep LFBS (AsLFBS), 2) awake LFBS (AwLFBS; motor + speech mapping), and 3) asleep HFMS. HFMS mapping was not used for awake craniotomies. RESULTS A total of 284 patients who underwent 300 craniotomies with motor mapping were identified. No significant differences in permanent neurological deficits (p = 0.377) or extent of resection (EOR) of nonenhancing tumors (p = 0.453) were identified between LFBS or HFMS motor mapping cases. Both EOR (92.7% vs 83.5%, p = 0.035) and permanent neurological deficits (7.6% vs 3.3%) occurred more frequently in enhancing tumors with LFBS, although the latter was not statistically significant. HFMS was associated with higher rates of subcortical motor pathway identification (p = 0.001) and fewer total intraoperative seizures (p = 0.003) compared with LFBS. Previous resection (HR 0.46, p = 0.003) and a higher cortical threshold (HR 0.95, p = 0.023) were significantly associated with longer survival, while preoperative aphasia (HR 2.24, p = 0.022), hospital length of stay (HR 1.1, p = 0.005), an insular-based tumor (HR 3.5, p = 0.021), and a histological diagnosis of glioblastoma (HR 2.9, p = 0.001) were negative predictors. Interestingly, overall FLAIR EOR was significantly associated with a marginally decreased overall survival (HR 1.01, p = 0.011). CONCLUSIONS No significant differences in postoperative neurological deficits were found between LFBS and HFMS paradigms. HFMS may identify subcortical motor fibers more reliably while resulting in significantly fewer intraoperative seizures. Although LFBS was associated with greater EOR of contrast-enhancing tumors, it may also be associated with higher rates of postoperative deficits, perhaps reflecting less reliable identification of subcortical motor fibers.

ABSTRACT Introduction Chronic gastroduodenal disorders remain challenging to manage, and new diagnostic approaches are needed to better delineate underlying causes and guide therapeutic decisions. Body Surface Gastric Mapping (BSGM) technologies combine high‐resolution gastric myoelectrical activity measurements with symptom and psychological profiling to provide mechanistic insights into gastric motor and sensory dysfunction. An International Working Group convened to derive the first consensus classification of BSGM phenotypes (the “Auckland Classification”). Methods A Technical Group conducted a systematic literature and clinical database review to identify objective test biomarkers and candidate disease mechanisms. Evidence was synthesized across 50 studies (primarily in gastroparesis, chronic nausea and vomiting, and functional dyspepsia), and BSGM phenotypes were mapped to existing treatment guidelines. Subsequently, iterative review and development of consensus was performed by a Consensus Group composed of international clinical experts familiar with BSGM. Eleven statements underlying the classification were then derived and circulated as a final survey to establish agreement. Results Six BSGM phenotypes were endorsed: three defined by myoelectrical abnormalities (Dysrhythmic, High Frequency, and Low Meal Response) and three by characteristic symptom associations (Sensorimotor, Continuous, and Delayed Onset Symptoms). Published studies plausibly linked these phenotypes to mechanisms including interstitial cell of Cajal depletion, vagal impairment, hypomotility, visceral hypersensitivity, gut‐brain dysregulation, and small bowel dysfunction. Phenotypes were also mapped to existing mechanism‐based treatment guidelines. Ten out of the eleven statements had > 80% agreement. Conclusions The Auckland Classification, derived by international consensus, presents a structured framework for BSGM‐defined patient phenotypes. Evidence and mechanism‐based treatment options are suggested for each phenotype to provide a foundation for research, further validation, and a pathway for integrating BSGM into clinical care.

Abstract INTRODUCTION Similarities between frontotemporal lobar degeneration with transactive response DNA‐binding protein of 43 kDa (TDP‐43) (FTLD‐TDP) and limbic‐predominant age‐related TDP‐43 encephalopathy neuropathologic change (LATE‐NC) raise questions about whether they represent distinct entities or a single disease spectrum. The literature mostly examined series with disproportionate numbers of LATE‐NC over FTLD‐TDP. METHODS Leveraging a clinicopathological collection of FTLD‐TDP ( N = 148) from the University of California, San Francisco, we compared demographic, clinical, genetic, and neuropathological features of FTLD‐TDP, particularly FTLD‐TDP type A ( N = 39), and LATE‐NC ( N = 42). RESULTS FTLD‐TDP type A cases were younger at onset and death, had shorter disease duration, and frequent genetic causes ( GRN , C9ORF72 ) compared to LATE‐NC, which were mostly sporadic and older. Blinded evaluation of middle frontal gyrus (MFG) TDP‐43 immunostaining alone proved insufficient to reliably differentiate FTLD‐TDP type A from LATE‐NC stage 3. However, factoring in all neuropathologic features, FTLD type A and LATE‐NC could be differentiated with >95% confidence. DISCUSSION These overall findings support distinct diagnostic entities for FTLD‐TDP and LATE‐NC.

Premature ventricular contractions (PVCs) are common arrhythmia encountered in patients with and without structural heart disease. Although often benign and asymptomatic, they may also cause palpitations, exercise intolerance, presyncope, and reduced quality of life, and in some patients can contribute to PVC-induced cardiomyopathy or trigger malignant ventricular arrhythmias. Their clinical significance depends on symptom burden, PVC frequency, ventricular function, and the presence of underlying myocardial disease. Diagnostic evaluation includes electrocardiography, ambulatory rhythm monitoring, echocardiography, exercise testing, and cardiac magnetic resonance imaging for tissue characterization and risk stratification. Management ranges from reassurance and lifestyle modification to pharmacologic therapy and catheter ablation. Beta-blockers and nondihydropyridine calcium channel blockers remain common first-line options, whereas antiarrhythmic drugs may be considered in carefully selected patients. Catheter ablation is an effective treatment for symptomatic PVCs, high PVC burden, and PVC-induced cardiomyopathy, with high procedural success rates and favorable effects on arrhythmic burden and ventricular function. Novel approaches, including electrocardiographic imaging-guided planning, pulsed field ablation, stereotactic radioablation, neuromodulation, and renal denervation, may further expand future therapeutic options. This review summarizes the pathophysiology, clinical implications, diagnostic evaluation, and contemporary management of PVCs, with emphasis on medical therapy, catheter ablation, and emerging treatments.

Abstract Background Acute hypoxemic and hypercapnic respiratory failure are among the most common reasons for ICU admission and need for invasive mechanical ventilation. Noninvasive respiratory support (NIRS) strategies—including high-flow nasal cannula (HFNC), noninvasive ventilation (NIV), and continuous positive airway pressure (CPAP)—may prevent intubation, improve outcomes, and reduce ICU utilization. However, there is uncertainty regarding optimal patient and modality selection, resulting in variable implementation. There are no clinical practice guidelines comprehensively addressing the use of the different noninvasive respiratory support strategies across the spectrum of acute respiratory failure. Objective To update and develop new evidence-based clinical practice recommendations informing noninvasive respiratory support use, including HFNC, NIV and CPAP, in adults with acute respiratory failure. Methods A multidisciplinary panel used the GRADE approach to address four PICO questions related to the use of NIRS for hypoxemic and hypercapnic respiratory failure, preoxygenation for intubation, and post-extubation respiratory support. Recommendations were informed by several systematic reviews and network meta-analyses. Results The panel made a strong recommendation for HFNC and a conditional recommendation for NIV or CPAP for adults with acute hypoxemic respiratory failure with close monitoring for the need for escalation of respiratory support, based primarily on effects on need for intubation. For acute hypercapnic respiratory failure, the panel made a strong recommendation for NIV to reduce mortality and need for invasive mechanical ventilation, and a conditional recommendation for HFNC only in patients with less severe hypercapnia and with mild acidemia (eg, pH &gt; 7.25), provided that close monitoring and prompt escalation to NIV are available. The panel made a strong recommendation for HFNC or NIV for preoxygenation prior to endotracheal intubation to prevent peri-intubation hypoxemia. The panel also issued a risk-based recommendation, suggesting HFNC for low-risk patients and NIV for high-risk patients to reduce the need for re-intubation following extubation after critical illness. Conclusions Noninvasive respiratory support strategies are effective in improving outcomes in a range of clinical scenarios. We provide evidence-based recommendations, which can be further informed by patient risk, institutional capacity, and interface tolerance.

ABSTRACT Background Agrin‐congenital myasthenic syndrome ( AGRN ‐CMS) is a rare, heterogeneous genetic disorder of the neuromuscular transmission that can present from infancy to adulthood. The clinical phenotype includes distal weakness mimicking distal myopathies. Additionally, electromyography and muscle biopsy may demonstrate myopathic features, increasing the diagnostic challenge. Mitochondrial dysfunction has not been reported in the muscle of AGRN ‐CMS patients. Methods We report the clinical, electrophysiological, radiological, myopathological, and genetic findings of a patient with AGRN‐ CMS. Results A 47‐year‐old male presented at age 18 with sudden onset of eyelid ptosis, weakness, and fatigue, followed by dysphagia, dyspnea on exertion, exercise intolerance, and myalgias. Three sisters had similar symptoms. Neurological examination showed lower limb weakness, predominantly affecting the calf muscles with associated atrophy. Tendon reflexes were normal but absent at the ankles. Creatine kinase levels were normal. Electromyography demonstrated myopathic changes in distal muscles with fibrillation potentials in the gastrocnemius. 2 Hz‐Repetitive nerve stimulation of the fibular nerve revealed a 32% decrement in the extensor digitorum brevis without facilitation. Tibialis anterior biopsy showed non‐specific myopathic changes, neurogenic features, and histological evidence of mitochondrial dysfunction, as suggested by the scattered cytochrome c oxidase‐negative fibers. Whole exome sequencing detected a homozygous pathogenic AGRN variant (c.5012G>A, p.Arg1671Gln). No pathogenic or suspected pathogenic variants were detected in muscle mitochondrial DNA or in nuclear genes affecting mitochondrial function. Conclusions This patient expands the pathological spectrum of AGRN ‐CMS to include mitochondrial dysfunction and highlights the importance of low‐frequency repetitive nerve stimulation in the assessment of patients with distal weakness for differentiating myopathies from CMS.

ABSTRACT Background Disparities in management of atrial fibrillation in rural and urban hospitals across the U.S. have been reported. However, studies investigating disparities regarding outcomes and complications after left atrial appendage occlusion (LAAO) based on hospital location are lacking. Objective To evaluate differences in outcomes and complications related to LAAO among rural and urban hospitals. Methods The National Inpatient Sample was used to identify patients who underwent LAAO implantations in the U.S. from 2016−2020. Study endpoints assessed included inpatient complications, outcomes, and resource utilization after LAAO procedures among rural and urban hospitals. Results From 2016−2020, there were a total of 87 315 and 1985 LAAO device placements in urban and rural hospitals, respectively. Baseline characteristics were similar among both groups, with a few exceptions. After multivariable adjustment for confounders, odds of inpatient complications and mortality were similar among both groups. However, rural LAAO recipients experienced greater rates of discharge to an acute care facility (3.3% vs 2.4%, p = 0.01), as well as lower costs (aOR: 0.58, 95% CI: 0.49–0.69) and length of stay (aOR: 0.89, 95% CI: 0.81–0.98). Conclusions A majority of LAAO implantations occurred in urban hospitals in the U.S. Baseline characteristics and adjusted odds of inpatient complications and mortality were similar in rural and urban recipients. However, important differences were described regarding resource utilization and disposition. Further investigation into the specific factors driving these inequities is encouraged to promote improved access to and outcomes of cardiovascular care for rural residents.

Abstract Objective The upper frequency limit of human brain activity remains unknown. Using ultrahigh sampling rate (≥20 kHz) intracranial microelectroencephalography, this study aimed to systematically explore and quantitatively characterize brain field oscillations beyond the established high‐frequency oscillation range (>2 kHz), and to determine their relationship to epileptogenic tissue. Methods We analyzed intracranial electroencephalographic recordings from 15 patients with drug‐resistant epilepsy, comprising 466 microcontacts and 434 macrocontacts implanted in mesiotemporal structures across four international epilepsy centers. A custom spectrogram‐based detector optimized for ultrahigh frequencies was developed to identify ultrafast oscillations (UFOs; >2 kHz). UFO rates were assessed in epileptic (successfully resected) and nonepileptic hippocampi and compared with established electrophysiological biomarkers, including interictal epileptiform discharges, ripples, and fast ripples. Statistical comparisons were performed using mixed‐effects models to account for intersubject and interelectrode variability. Results We identified a previously undescribed class of short‐duration oscillatory events spanning 2–8 kHz. UFOs occurred at significantly higher rates in epileptic compared with nonepileptic mesiotemporal regions, with the strongest differentiation observed in the 2–3‐kHz band. Two distinct UFO phenotypes were consistently observed: (1) spindlelike, narrow‐band oscillations and (2) sharp‐onset, rapidly decaying bursts. Both forms were prevalent within epileptic hippocampi but were exceedingly rare in nonepileptic structures. UFOs exhibited pronounced temporal intermittency and spatial focality and frequently arose independently of ripples, fast ripples, and very high‐frequency oscillations, indicating that they represent a distinct electrophysiological phenomenon. Macrocontacts detected UFOs only exceptionally, highlighting the necessity of microelectrode recordings to capture activity in this ultrahigh‐frequency regime. Significance These findings substantially extend the known frequency range of human brain field activity and identify ultrafast oscillations as a novel biomarker of neuronal hyperexcitability. UFOs likely reflect pathological microcircuit dynamics inaccessible to conventional clinical recordings and provide new insights into the organization and pathophysiology of epileptogenic networks.