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IntroductionPost-stroke cognitive impairment (PSCI) is common and often under-recognized, particularly in the acute phase. Most cognitive screening tools provide only a global score, overlooking domain-specific deficits that influence functional recovery. The Addenbrooke’s Cognitive Examination-III (ACE-III) is a comprehensive cognitive test whose utility for acute stroke patients remains under-studied. This study evaluated the diagnostic performance of the ACE-III against the stroke-specific Oxford Cognitive Screen (OCS) in detecting PSCI following first-ever stroke in the acute period.MethodsPatients with first-ever stroke and no history of cognitive impairment were prospectively assessed within seven days of onset using both the OCS and ACE-III. PSCI was defined by impairment in one or more cognitive domains on the OCS. The discriminatory capacity of the ACE-III for detecting PSCI was examined, and associations between specific cognitive deficits and functional dependence were analyzed.ResultsThe OCS detected PSCI in 70% of the 30 patients that were recruited. The ACE-III demonstrated good discriminatory capacity (AUC = 0.897); however, it failed to detect PSCI in five patients identified by the OCS, and misclassified two aphasic but cognitively intact patients as impaired. Two patients classified as impaired on ACE-III were deemed cognitively intact by OCS, underscoring its limitations in stroke populations. Standard and stroke-specific ACE-III cut-offs demonstrated suboptimal accuracy for acute screening.ConclusionWhile ACE-III performs well at the group level, it may miss relevant cognitive impairment in the acute stroke setting. Domain-based, stroke-specific tools such as the OCS more reliably detect deficits and may offer greater clinical utility for early cognitive profiling and rehabilitation.

IntroductionAmyotrophic lateral sclerosis (ALS) is an adult-onset, progressive and universally fatal neurodegenerative disorder. In Europe, Australia and Canada, riluzole is the only approved therapeutic agent for the treatment of ALS, while in the USA, riluzole and edaravone have been approved by the Food and Drug Administration (FDA) . Neither riluzole nor edaravone treatment has resulted in substantial disease-modifying effects. There is, therefore, an urgent need for drugs that result in safe and effective treatment. Here, we present the design and rationale for the phase 2 RESCUE-ALS study, investigating the novel nanocatalytic drug, CNM-Au8, as a therapeutic intervention that enhances the metabolic and energetic capacity of motor neurones. CNM-Au8 is an aqueous suspension of clean-surfaced, faceted gold nanocrystals that have extraordinary catalytic capabilities, that enhance efficiencies of key metabolic reactions, while simultaneously reducing levels of reactive oxygen species. This trial utilises a novel design by employing motor unit number index (MUNIX), measured by electromyography, as a quantitative measure of lower motor neurone loss and as an early marker of ALS disease progression.Methods and analysisThis is a multicentre, randomised, double-blind, parallel group, placebo-controlled study of the efficacy, safety, pharmacokinetics and pharmacodynamics of CNM-Au8 in ALS patients. Patients will be randomised 1:1 to either receive 30 mg of CNM-Au8 once daily or matching placebo over a 36-week double-blind treatment period. Efficacy will be assessed as the change in motor neurone loss as measured by electromyography (eg, MUNIX, the primary endpoint; and secondary endpoints including MScanFit, motor unit size index, Split Hand Index, Neurophysiology Index). Exploratory endpoints include standard clinical and quality of life assessments.Ethics and disseminationRESCUE-ALS was approved by the Western Sydney Local Health District Human Research Ethics Committee (Ethics Ref: 2019/ETH12107). Results of the study will be submitted for publication in a peer-reviewed journal.Trial registration number NCT04098406

Spinal and bulbar muscular atrophy (SBMA), or Kennedy’s disease (KD), is a rare hereditary neuromuscular disorder demonstrating commonalities with amyotrophic lateral sclerosis (ALS). The current study aimed to define functional and central nervous system abnormalities associated with SBMA pathology, their interaction, and to identify novel clinical markers for quantifying disease activity. 27 study participants (12 SBMA; 8 ALS; 7 Control) were recruited. SBMA patients underwent comprehensive motor and sensory functional assessments, and neurophysiological testing. All participants underwent whole-brain structural and diffusion MRI. SBMA patients demonstrated marked peripheral motor and sensory abnormalities across clinical assessments. Increased abnormalities on neurological examination were significantly associated with increased disease duration in SBMA patients (R 2  = 0.85, p < 0.01). Widespread juxtacortical axonal degeneration of corticospinal white matter tracts were detected in SBMA patients (premotor; motor; somatosensory; p < 0.05), relative to controls. Increased axial diffusivity was significantly correlated with total neuropathy score in SBMA patients across left premotor (R 2  = 0.59, p < 0.01), motor (R 2  = 0.63, p < 0.01), and somatosensory (R 2  = 0.61, p < 0.01) tracts. The present series has identified involvement of motor and sensory brain regions in SBMA, associated with disease duration and increasing severity of peripheral neuropathy. Quantification of annualized brain MRI together with Total Neuropathy Score may represent a novel approach for clinical monitoring.

IntroductionWe report a case of patient presenting with clinical features suggestive of progressive supranuclear palsy (PSP) as well as primary lateral sclerosis (PLS).CaseA 66-year-old left-handed man presented with a 5-year history of progressive gait disorder on a background of a previous ischaemic stroke, punctuated by a more recent 8-month history of functional decline becoming wheelchair bound and with the development of dysarthria and dysphagia. His past medical history included type 2 diabetes mellitus, ischaemic heart disease, hypertension, and prior ischaemic stroke. His father had Parkinson’s disease, one first cousin had amyotrophic lateral sclerosis, and another first cousin with primary lateral sclerosis. All were deceased at the time of assessment of the patient.Neurological examination demonstrated hypomimia, bradykinesia, hypophonia, dysarthria, left upper limb cogwheel rigidity with coactivation, hyperreflexia in the upper and lower limbs, reduced distal power bilaterally in the lower limbs, square wave jerks, saccadic pursuits with restricted upward gaze and a positive palmomental reflex, applause sign and glabella tap.MRI brain demonstrated no specific neurodegenerative pattern. Electrophysiology studies were consistent only with diabetic neuropathy with no active denervation. Lumbar puncture however, was significant for Abeta1–42 and P-Tau 181.Genetic testing was undertaken and identified a pathogenic variant in TBK1 that is associated with autosomal dominant frontotemporal dementia and/or amyotrophic lateral sclerosis but increasingly recognised in also causing atypical Parkinsonism.ConclusionThis unusual presentation highlights the phenotypical overlap of pyramidal and extrapyramidal disorders, further emphasising the vast clinical and genetic heterogeneity in neurodegenerative conditions.

The superconducting quantum interference (SQI) patterns of Josephson junctions fabricated from hybrid structures that interface an s-wave superconductor with a topological insulator can be used to detect signatures of novel quasiparticle states. Here, we compare calculated and experimental SQI patterns obtained from hybrid junctions fabricated on cadmium arsenide, a two-dimensional topological insulator. The calculations account for the effects of Abrikosov (anti-) vortices in the superconducting contacts. They describe the experimentally observed deviations of the SQI from an ideal Fraunhofer pattern, including anomalous phase shifts, node lifting, even/odd modulations of the lobes, irregular lobe spacing, and an asymmetry in the positive/negative magnetic field. We also show that under a current bias, these vortices enter the electrodes even if there is no intentionally applied external magnetic field. The results show that Abrikosov vortices in the electrodes of the junctions can explain many of the observed anomalies in the SQI patterns of topological insulator Josephson junctions.

Two-dimensional topological insulators can feature one-dimensional charge transport via edge modes, which offer a rich ground for studying exotic quasi-particles and for quantum materials applications. In this work, we use lateral junction devices, defined by nanoscale finger gates, to study edge mode transport in the two-dimensional topological insulator Cd3As2. The finger gate can be tuned to transmit an integer number of quantum Hall edge modes and exhibits full equilibration in the bipolar regime. When the Fermi level of the channel crosses a Landau level, reflected modes percolate through the channel, resulting in an anomalous conductance peak. The device does not fully pinch off when the channel is tuned into the topological gap, which is a sign of remnant modes in the channel. These modes are expected from band inversion, while residual bulk conduction associated with the disorder potential may also play a role.

BackgroundMills syndrome is a relatively slowly-progressive, neurodegenerative motor neuron disorder, first described in 1900. A distinctively unilateral disease course remains the hallmark of Mills syndrome.CasesThe present case series describes five patients diagnosed with Mills syndrome.The patient cohort comprises four males and one female, with a mean age at onset of 61 years. Clinical follow up over eleven years established that all patients have disease, most prominently limb weakness, confined to one side of their body. Spasticity was a key feature in all patients, with asymmetric reflexes, brisk on the symptomatic side, and normal sensory examination.Magnetic resonance (MR) tractography established marked asymmetry of the white matter fiber density, corresponding with clinical presentation. Brain imaging with positron emission tomography (PET) scan identified hypometabolism involving the left lateral frontal cortex posteriorly corresponding to the symptomatic side. Transcranial magnetic stimulation (TMS) showed inexcitability of the motor cortex of the affected side, and motor cortex excitability within normal limits on the contralateral side, consistent with disease confined to one hemisphere.DiscussionMills syndrome represents a unique phenotype of ALS. Structural imaging, in particular MR tractography, combined with metabolic (PET imaging) and the assessment of cortical motor function promote an accurate diagnosis. Further understanding the pathophysiology of Mills syndrome will broaden understanding of motor neuron disorders, and perhaps expand knowledge of the ALS-PLS spectrum.

Ambient artificial intelligence (AI) scribes offer promise for reducing documentation burden, yet their effects on surgical practice have not been well defined. We conducted a pilot study of an ambient AI scribe across 79 ambulatory providers (three surgeons) in a multihospital system from December 2024 to February 2025. Surgeon adoption of the AI scribe ranged from 58% to 90% of visits. We evaluated workload via pre- and post-intervention surveys (NASA-TLX mental demand and perceived rush), burnout rates, scheduling capacity, and Epic Signal metrics (note length, time per note) and compared billing data for high utilizers between August and October 2024 and the pilot period. Average \"pajama time\" did not change significantly ( =0.55). NASA-TLX mental demand decreased from 14 to 5 ( =0.08) and perceived rush from 15 to 5 ( =0.06). Burnout declined from 67% to 33%. Two surgeons reported the capacity to add three patients per clinic. The billing metric showed no significant changes. Undivided attention scores improved from 3.5 to 4.1 ( <0.0001). This preliminary data shows promise that ambient AI scribes in surgical clinics may reduce documentation burden and burnout, with potential gains in efficiency and throughput. Larger studies are warranted to further confirm these findings.

Peripheral immunity plays a key role in maintaining homeostasis and conferring crucial neuroprotective effects on the injured nervous system, while at the same time may contribute to increased vulnerability to neuropathic pain. Little is known about the reciprocal relationship between entrapment neuropathy and peripheral immunity. This study investigated immune profile in patients with carpal tunnel syndrome (CTS), the most prevalent entrapment neuropathy. All patients exhibited neurophysiological abnormalities in the median nerve, with the majority reporting neuropathic pain symptoms. We found a significant increase in serum CCL5, CXCL8, CXCL10 and VEGF, and in CD4+ central and effector memory T cells in CTS patients, as compared to healthy controls. CCL5 and VEGF were identified as having the highest power to discriminate between patients and controls. Interestingly, and contrary to the prevailing view of CCL5 as a pro-nociceptive factor, the level of circulating CCL5 was inversely correlated with neuropathic pain intensity and median nerve motor latency. In contrast, the level of central memory T cells was positively associated with abnormal neurophysiological findings. These results suggest that entrapment neuropathy is associated with adaptive changes in the homeostasis of memory T cells and an increase in systemic inflammatory modulating cytokines/chemokines, which potentially regulate neuropathic symptoms.

The provision of written information is a low-cost and readily available intervention that has been found to reduce pain and anxiety in a variety of clinical settings. The current study was undertaken to determine if information provision may improve patients' experience during conventional electrodiagnostic studies. 128 participants were recruited from a tertiary teaching hospital who were referred for electrodiagnostic studies. They were randomized into 2 groups where the intervention group was provided with written information about the electrodiagnostic testing. Patients were invited to complete a questionnaire that included pain and anxiety using a visual analogue scale (VAS) following the testing. All participants underwent nerve conduction studies (NCS) whilst a subset also underwent subsequent needle electromyography (EMG). Those who received information had a statistically significant lower perception of anxiety during NCS, whilst only females who received information had a statistically significant lower perception of pain to both NCS and EMG. The provision of written information can reduce the degree of pain and anxiety experienced during electrodiagnostic testing. Improving patient comfort and tolerability during electrodiagnostic testing may have practical implications towards more reliable and accurate results obtained from such investigations that may in turn improve patient diagnosis and management.