Transactive response DNA-binding protein (TDP-43) plays a key pathological role in several neurodegenerative diseases, particularly amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Despite the well-established role of TDP-43 in neurodegenerative disorders, it remains a complex area of study as it is unclear whether nuclear loss-of-function, cytoplasmic gain-of-function, or both drive pathogenesis. TDP-43 overexpression models are advantageous tools when developing drug candidates targeted at TDP-43, however, existing models often lack comprehensive RNA-seq data benchmarked against patient datasets. Given the value of TDP-43 overexpression as a model of ALS-related pathology, we have developed a stable, inducible system in a HEK293-derived cell line, offering a practical and scalable platform to investigate TDP-43 dysregulation. Utilizing this system, we found that TDP-43 overexpression reflected key features associated with ALS pathology, causing cytotoxicity, nucleocytoplasmic mislocalization, and extensive transcriptomic changes. Furthermore, comparative RNA-seq analysis between this model and ALS patient-derived data revealed substantial overlaps, where 64
Alzheimer’s disease (AD) is characterized by cerebral glucose hypome-tabolism, an early hallmark through neuroimaging and neuropathological investigations. Previous researches have established the phenomenon of reduced glucose uptake. Building upon this established knowledge, the field is now increasingly focused on elucidating the underlying molecular mecha-nisms that govern these metabolic changes. In this review, we synthesize current evidence regarding the dysregulation of major glycolytic and pyruvate-metabolizing enzymes, including hexokinase (HK), phosphofructokinase-1 (PFK1), pyruvate kinase (PK), lactate dehydrogenase (LDH), and the pyruvate dehydrogenase complex (PDHc), in both neurons and glial cells. As well as compromising cerebral energy homeostasis, these enzymatic disruptions engage in bidirectional feedback mechanisms with neuroinflammatory pathways and amyloid-β/Tau pathology. By consolidating recent mechanism research, this review offers a potential framework for understanding how metabolic enzyme dysregulation contributes to AD pathogenesis at a molecular level. Emerging therapeutic strategies targeting these metabolic enzymes are also discussed, along with an evaluation of both their preclinical promise and the translational challenges that remain.
Neurotropic viral infections represent an important and increasingly recognised component of the neuro-exposome, functioning as biological environmental exposures that interact with host metabolic systems to influence brain health. While viral neurotropism and immune-mediated mechanisms have been widely studied, the contribution of host lipid metabolism to viral replication, neuroinflammation, and neurodegeneration remains insufficiently integrated across disciplines. This scoping review aimed to synthesise current evidence on the interplay between host lipid metabolism and viral pathogenesis in the central nervous system, and to identify mechanistic pathways and translational opportunities relevant to neuro-exposome research. Following the PRISMA-ScR guidelines, a systematic search was conducted in PubMed, Embase, and Scopus for studies published between 2020 and 2025. Eligible in vitro, in vivo, and multi-omic studies examining lipidomic alterations associated with neurotropic viral infections were included and synthesised thematically. Across diverse viral families, convergent disruptions were identified in cholesterol homeostasis, fatty acid metabolism, sphingolipid signalling, lipid raft organisation, and ferroptosis-related pathways. These lipid alterations were consistently associated with enhanced viral entry and replication, blood–brain barrier dysfunction, chronic neuroinflammation, synaptic impairment, demyelination, and neurodegenerative processes, including Alzheimer’s disease-like pathology, particularly in genetically susceptible populations. The evidence supports dysregulation of host lipid metabolism as a unifying mechanism linking viral environmental exposures to adverse neurological outcomes. Integrating neurolipidomic pathways into neuro-exposome frameworks highlights opportunities for lipid-based biomarkers and metabolically targeted therapeutic strategies, advancing precision approaches to the prevention, diagnosis, and management of virus-associated neurological disorders.
Cold sensation is gaining clinical significance in the diagnosis, prognosis, and treatment of chronic pain. Despite this, mechanisms responsible for normal and abnormal cool/cold detection remain underexplored compared to other sensory modalities. This narrative review presents a synthesis of innocuous cool and noxious cold processing in a standard stepwise framework spanning five stages of transduction, transmission, spinal modulation, projection, and ascending/descending cortical activity. Synthesizing molecular, anatomical, functional, and behavioral evidence, this review suggests that cold sensation relies on highly specialized, though still emerging, molecular and circuit-level frameworks. Specifically, we propose the possibility of P2Y1 role in noxious cold signaling and re-evaluate the potential mechanistic contribution of Nav1.3 to neuropathic cold hypersensitivity. The narrative translates these molecular findings for potential clinical application, advancing the case for cold-specific quantitative sensory testing (QST) as a vital biomarker for assessing descending pain modulation and chronic pain phenotypes.
Modafinil is a central-acting wakefulness-promoting agent approved for narcolepsy, obstructive sleep apnea, and shift-work sleep disorder and is increasingly prescribed off-label for several neuropsychiatric conditions. Due to its favorable safety profile and lower abuse potential compared with other psychostimulants, modafinil has been increasingly used in treatment for narcolepsy and similar sleep disorders. While its safety profile is generally applauded, there have been an increasing number of case reports detailing rare neuropsychiatric adverse effects associated with modafinil exposure. This systematic review aims to evaluate published case reports of modafinil-associated psychosis in order to characterize patient demographics, clinical presentation, and outcomes. A systematic search of the literature describing psychosis temporally associated with modafinil exposure was conducted using PubMed and Embase on January 24, 2026, identifying case reports published since database inception. Search terms included “modafinil” and “psychosis.” Articles were included if they reported confirmed modafinil exposure with the development of psychiatric symptoms. Non-English articles without translation and reports lacking a clear temporal association were excluded. The articles were screened to ensure the inclusion criteria were met, and the likelihood of a causal relationship between modafinil and the reported psychotic event was assessed using the Naranjo Adverse Drug Reaction Probability Scale. Any discrepancies regarding study eligibility were resolved by the researchers utilizing the Joanna Briggs Institute critical appraisal guidelines. A total of seven articles with nine cases met the inclusion criteria, with the average age being 47.1 years, and a predominance of male patients. Clinical presentation most often included agitation, hallucinations, and delusions, as seen in almost half of the patients. Less frequently, patients expressed manic symptoms, suicide attempts, and disorganized behavior. Psychotic symptoms occurred at doses ranging from 100 to 400 mg and with onset ranging from 48 h to approximately 21 days after initiation, with no clear dose-dependent pattern observed. Patients with a previous psychiatric history appeared to be more vulnerable to developing symptoms. Management universally involved discontinuation of modafinil, with supportive psychiatric treatment when necessary. Complete symptom resolution occurred in 77.8
Erythropoietin (EPO) has emerged as a multifunctional, significant, neuroprotective, and anti-inflammatory agent, extending beyond its traditional hematopoietic role. This review highlights EPO’s therapeutic potential in addressing neurodegenerative and neuropsychiatric disorders, such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), autism, and traumatic brain injury (TBI). By modulating key signaling pathways, including JAK2/STAT5, PI3K/Akt, and MAPK/ERK, EPO reduces oxidative stress, apoptosis, and inflammation while enhancing neurogenesis, synaptic plasticity, and angiogenesis. Preclinical evidence demonstrates EPO’s ability to preserve cognitive function, reduce tau pathology, and mitigate neuroinflammation in AD, as well as to protect dopaminergic neurons in PD models. Additionally, EPO promotes remyelination in MS and spinal cord injury models while improving behavioral and cognitive outcomes in neuropsychiatric disorders. However, clinical translation faces challenges, primarily due to EPO’s limited blood–brain barrier (BBB) penetration, necessitating high systemic doses that lead to hematopoietic side effects such as polycythemia and thromboembolism. Innovations in drug delivery, including intranasal formulations, nanoparticle systems, and receptor-specific analogs like carbamylated EPO (CEPO) and NeuroEPO, aim to enhance CNS targeting and safety. Despite promising preclinical findings, inconsistent clinical trial outcomes underscore the need for optimized dosing strategies, personalized medicine approaches, and rigorous safety evaluations. Moving forward, isoform-selective targeting and combination therapies present exciting avenues for expanding EPO’s applications, positioning it as a transformative agent for neurotherapeutic interventions.
Calcium influx is a fundamental component of neuronal signaling and is markedly altered during neuropathic pain. Voltage-gated calcium channels (VGCCs) play a central role in nociceptive transmission; however, multiple calcium-permeable pathways contribute to calcium-associated neural activity. Because Mn2+ shares similar ionic properties and cellular transport mechanisms with Ca2+, positron-emitting [51Mn]MnCl2 has potential as a molecular imaging probe for visualizing pain-associated calcium activity in vivo. This study evaluated [51Mn]MnCl2 PET/MR for detecting neuropathic pain-associated neural activity in a rat spared nerve injury (SNI) model before and after analgesic intervention. Male Sprague–Dawley rats underwent SNI surgery or sham surgery and were evaluated using von Frey behavioral testing, in vivo [51Mn]MnCl2 PET/MR imaging, before and after sustained-release buprenorphine administration. Ex vivo biodistribution was completed after all imaging studies were completed. Tracer uptake within the spinal cord and peripheral nervous system was compared between SNI and sham animals. SNI animals demonstrated significantly increased mechanical hypersensitivity accompanied by elevated [51Mn]MnCl2 uptake within the spinal cord regions associated with sciatic nerve innervation before analgesic intervention. Following buprenorphine administration, behavioral hypersensitivity and spinal cord tracer uptake were reduced, while ex vivo biodistribution demonstrated significantly greater tracer accumulation within injured sciatic nerves compared to sham controls. These findings provide proof-of-concept evidence that positron-emitting manganese can detect neuropathic pain-associated calcium-related neural activity in the SNI model. While additional studies are needed to establish mechanistic specificity, improve quantitative assessment of peripheral nerves, and validate findings in larger cohorts, [51Mn]MnCl2 PET/MR shows promise as a molecular imaging approach for investigating neuropathic pain.
Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a recently recognized neurodegenerative dementia in the most elderly individuals, characterized by accumulation of TDP-43 protein aggregates in limbic and medial temporal lobe structures. This is clinically important pathology as it often mimics Alzheimer’s disease (AD) and is now understood to be a common contributor to cognitive decline in the “oldest-old”. Pathologically, LATE is distinguished from AD by TDP-43-positive neuronal inclusions (rather than amyloid plaques and neurofibrillary tangles), typically affecting the amygdala, hippocampus, and other limbic regions, often accompanied by hippocampal sclerosis. Clinically, LATE presents with a gradually progressive amnestic dementia syndrome similar to AD which complicates diagnosis. Currently, there are no established antemortem biomarkers for LATE, and definitive diagnosis relies on postmortem confirmation. However, an AD-like dementia with negative amyloid and tau biomarkers in a patient of advanced age is suggestive of LATE. No disease-modifying treatment exists at this time, however multiple therapeutic strategies are under investigation, including immunotherapies targeting pathological TDP-43, small molecules that enhance TDP-43 clearance, and gene or antisense approaches to mitigate TDP-43 toxicity. Continued research is critical to develop effective biomarkers and therapies for this prevalent but under-recognized TDP-43 proteinopathy.
Peripheral neuropathy affects a substantial proportion of the global population and remains incompletely explained by established risk factors. Preclinical studies suggest that gut dysbiosis can modulate neuroimmune pathways and neuropathic phenotypes. However, synthesis of human clinical evidence remains limited. Following PRISMA guidelines, a systematic review was conducted across PubMed and the Cochrane Library to identify human observational/interventional studies evaluating gut dysbiosis in relation to peripheral neuropathic outcomes. Seven eligible clinical studies were identified. Directional concordance of evidence was assessed using a binomial sign test. An albatross plot was constructed to visualize standardized evidence strength and approximate effect size across heterogeneous designs. Mendelian randomization (MR) studies were evaluated as orthogonal evidence of causality. All seven clinical studies demonstrated positive associations between gut dysbiosis and neuropathic symptomatology, yielding a low probability of directional concordance due to chance alone (0.78
Alzheimer’s disease (AD) is characterized by progressive, regionally heterogeneous cortical atrophy. Whether whole-brain cortical thickness homogeneity serves as an informative macro-scale marker of this structural disruption remains unclear. This study evaluated cortical thickness homogeneity across a large, multi-cohort sample and assessed its independent diagnostic utility. Structural MRI data comprising 11,382 scans from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and the Open Access Series of Imaging Studies 3 (OASIS-3) were analyzed. Cortical thickness was extracted across 68 Desikan-Killiany regions. A cortical thickness homogeneity index-defined as the mean pairwise similarity of absolute regional thickness differences-was computed from within-dataset Z-scored values. Linear mixed-effects models with random intercepts for participant ID, adjusted for age and sex, compared diagnostic groups. Logistic regression evaluated added diagnostic value beyond medial temporal lobe (MTL) thickness. Statistical path decomposition evaluated the contribution of MTL atrophy. Dementia patients exhibited significantly lower cortical homogeneity than controls (total effect β = −0.035; LME-adjusted β = −0.029, Cohen’s d = 0.95, p < 0.001), independent of age and sex. The effect was most pronounced in the temporal lobe. The baseline diagnostic model (MTL thickness, age, sex) achieved an area under the curve (AUC) of 0.738 on external validation. Adding cortical homogeneity yielded an AUC of 0.746, a non-significant improvement (DeLong’s test, p = 0.198). Statistical path decomposition showed that MTL atrophy statistically accounted for 31.5
Muscle synergy analysis is a relevant approach to characterize motor control in different contexts, including the use of rehabilitative devices. Pilot studies on healthy individuals allow to derive baseline reference synergies to tailor the interventions and assess their effects in patient populations, but challenging levels of inter-subject variability are often reported. Surface EMG was acquired from 10 upper limb muscles of 40 healthy subjects performing a standardized reaching paradigm with and without the assistance of the Float exoskeleton. We computed “free” (unassisted), ”low” (low assistance), ”high” (high assistance), and “whole” (unassisted+assisted) synergies to characterize the modularity of the experimental paradigm. Synergies from single subjects were grouped according to cosine similarity and averaged to obtain reference sets. We assessed their consistency (i.e. their capability to reliably represent single-subject modules) based on number of excluded single-subject modules, cosine similarity and coefficient of variation. We also explored age as a possible factor influencing the modularity of motor control and contributing to inter-subject variability in our study. Subjects were stratified by age to derive reference synergies from age-homogeneous groups and assess their consistency and the presence of age-related effects on the modularity of the task. Reference synergies obtained from the entire study population showed a consistency level in line with literature. The assistance of Float appeared to not disrupt the synergistic structure of standardized reaching but to modulate it with a reduced effort of the anterior deltoid and an increased involvement of the trapezius muscle. The reference synergies obtained from age groups highlighted some age-specific response to exoskeleton assistance and showed a small but significant improvement in consistency. Statistical analysis indicated that for older subjects the response to exoskeleton assistance appeared more variable. The results of this case study suggest that relying on age-matched reference synergies could improve the robustness of synergy-based assessment in rehabilitative applications. The study also identifies relevant challenges in the development of reliable healthy references that should be further explored in future works. Overall, this study supports the utility of muscle synergy analysis in evaluating rehabilitative devices.
Quantitative assessment of light-touch sensation is essential in the evaluation of peripheral nerve disorders. Although the active von Frey filament test (AvF) provides objective and continuous tactile threshold measurements, the influence of testing conditions on AvF values remains unclear. This study aimed to evaluate whether visual stimulation affects tactile thresholds measured using AvF. Thirty-two healthy adult participants (24 men and 8 women) without comorbid disease were prospectively examined using AvF. The innervation zone of the median and the ulnar nerve (i.e., index and fifth finger volar pad, respectively) was examined using AvF with and without a visual stimulation. Five repeated measurements were obtained at each site, and the mean of the middle three measurements was used for analysis. The primary comparison used participant-level mean AvF thresholds; a mixed-effects model was additionally used to account for repeated finger-level measurements within participants. Participant-level mean AvF values during visual stimulation were significantly higher than those blindfolded (130.4 ± 51.4 mgf vs. 110.5 ± 38.6 mgf, Wilcoxon signed-rank test p = 0.0026). In mixed-effects model accounting for repeated finger-level measurements, visual stimulation increased AvF thresholds by 19.8 mgf (95
Traumatic brain injury (TBI) remains a major cause of mortality and long-term disability worldwide. Computed tomography (CT) is the primary imaging modality for acute TBI assessment, while artificial intelligence (AI) has emerged as a promising tool for improving prognostication through advanced analysis of imaging and clinical data. Given the substantial differences in injury mechanisms, neurophysiological responses, prognostic determinants, and recovery trajectories between paediatric and adult populations, this systematic review was specifically designed to evaluate AI-integrated CT imaging for outcome prediction in adult patients with TBI. To systematically review and evaluate the application of artificial intelligence-integrated computed tomography (CT) imaging for outcome prediction in adult patients with traumatic brain injury (TBI), and to assess the predictive accuracy, clinical utility, and methodological quality of the reported models. A systematic review was conducted according to PRISMA 2020 guidelines and registered in PROSPERO (CRD420251233273). PubMed, Scopus, Web of Science, and IEEE Xplore were searched for studies published between 2015 and 2025. Studies evaluating AI-based models utilizing CT imaging for outcome prediction in adult (≥ 18 years) patients with TBI were included. Data regarding study characteristics, AI methodologies, imaging features, predictive outcomes, and model performance were extracted. Methodological quality was assessed using the Critical Appraisal Skills Programme (CASP) checklist. A random-effects meta-analysis was performed to estimate pooled model performance. Twelve studies comprising 7536 patients were included. Machine-learning models accounted for 66.7
Neurodegenerative diseases, which include Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, represent a growing worldwide health burden that can be attributed to the ageing of the population and the lack of effective modalities of early diagnosis. Conventional diagnostic methods rely on clinical assessment and neuroimaging, but they often reveal neuropathology only after it is too late, when neuronal damage has already occurred. Wearable neural biosensors are an emerging approach for continuous, non-invasive monitoring of neurophysiological, neuromuscular, and biochemical biomarkers in real-world applications. This systematic review examines of advancements in wearable biosensor design, the utilization of functional nanomaterials (graphene, CNTs, MXenes, hydrogels), signal detection modalities, and the integration of these sensors with wireless communication systems and artificial intelligence algorithms to extract clinically useful information. This review highlights applications of biosensors in the key neurodegenerative diseases, with a focus on the disease-specific biomarkers in combination with electrophysiological and motion-based signals. Challenges such as biocompatibility, long-term stability in biological fluids, data privacy, multimodal signal fusion, preclinical validation, clinical trials, regulatory systems, and ethical concerns are critically considered. The future opportunities of the multi-omics integration, personalized neuro-monitoring, and privacy-sensitive data systems are described. Overall, wearable neural biosensors show significant potential to enable earlier diagnosis and precision-based treatment of neurodegenerative disorders.
Granulomatosis with polyangiitis (GPA) is an antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis affecting small to medium-sized arteries uncommonly involving the central nervous system (CNS) with cerebral vasculitis, meningitis, and orbital granuloma. Here we report a rare case with GPA with a fourth ventricular mass lesion, choroid plexitis, and hypophysitis. A 46-year-old male presented with subacute headache, fevers, hemoptysis, nausea, vomiting, ataxia, blurred vision, hearing loss, and excessive thirst. He was diagnosed with GPA six years prior and was not on any disease-modifying therapy due to personal preferences. Computed Tomography (CT) of the chest revealed a pulmonary embolism (PE) and multifocal cavitary lung lesions. Cranial Magnetic Resonance Imaging (MRI) revealed a heterogeneously enhancing, enlarged pituitary gland with thickening of the pituitary infundibulum concerning for hypophysitis, in addition to a heterogeneously enhancing mass within the fourth ventricle with signal abnormality in the adjacent brainstem and brachium pontis. Serum and urine studies were consistent with central diabetes insipidus (CDI). The fourth ventricular mass was resected and histopathology showed remnant choroid plexus with vasculitis, necrosis, and mixed inflammatory infiltrate including multinucleated giant cells, consistent with GPA involvement of the fourth ventricular choroid plexus. The patient improved with steroid treatment, desmopressin for CDI, and anticoagulation for PE. After discharge he was treated with rituximab, prednisone, and subsequent addition of mycophenolate mofetil, achieving stable control of his symptoms. GPA can rarely present as a mass-occupying CNS lesion and should be considered with multidisciplinary and histopathologic evaluation for possible immunosuppressive treatment.
Neurological and neuropsychiatric disorders remain among the most complex and often treatment-resistant conditions in modern medicine, largely due to the dynamic, heterogeneous, and context-dependent nature of neural systems. Current therapeutic modalities—including pharmacological agents and neural interface technologies—are predominantly based on static or semi-static intervention paradigms, which may limit their ability to adapt to real-time neural microenvironmental changes. This paper proposes a conceptual framework in which Smart Protein Therapeutics (SPT) function as an adaptive biological control layer with potential to sense neural microenvironmental signals, process contextual biological information, and execute conditional therapeutic responses within a closed-loop architecture. Unlike conventional protein therapeutics or device-centric neuromodulation approaches, SPT are defined functionally rather than structurally, emphasizing adaptive regulation rather than fixed biological activity. By integrating principles from precision medicine, systems biology, protein engineering, and adaptive control theory, this framework outlines a biologically grounded and potentially testable approach for dynamic neural regulation. Potential applications include neuropsychiatric disorders, neurodegenerative diseases, enhancement of neural interface biocompatibility, and personalized neuromodulation strategies. This work does not present experimental data; rather, it establishes a structured, falsifiable foundation intended to guide future translational and experimental research in adaptive neural therapeutics.
Neurodegeneration is essentially a large-scale dynamical instability of brain networks. It has been shown that pathological oscillations, bioenergetic failure, hub degradation, and progressive structural disconnection are manifestations of regulatory control failure rather than isolated cellular pathology. Traditional therapeutic interventions focus on downstream medical or symptomatic outcomes and conventional markers of persistent neural activity, but do not essentially touch the structures and architecture necessitating the arrangement of the system(s). We propose synthetic resilience as a facilitating engineering perspective and address resilience as a controllable dynamical variable, in relation to network topology, oscillatory regulation, and metabolic sufficiency. Based on systems neuroscience, synthetic biology, biohybrid engineering, and control theory, we generalize degeneration changes in neural circuits to leave a bounded stability regime and offer strategies for crossing instability thresholds and restoring contractive dynamics. We discuss underlying malfunctions of the network onset, such as loss of criticality, excitatory-inhibitory imbalance, mitochondrial impairment, and breakdown of antagonizing motifs, and trace by network, these malfunctions onto strategies of network regulation. New components, like synthetic neurotransmission systems, programmable gene circuits, CRISPR-based genomic regulation, neuromorphic biohybrid interfaces, chemogenetic modulation, and adaptive deep brain stimulation, provide mechanistic avenues to stabilize pathological behavior through closed-loop mechanisms. Integration of synaptic reconstruction with principles of adaptive control reframes neurodegeneration as a controllable system-level instability, and it provides a framework for constructing precision neural networks with heterogeneous disease trajectories while acknowledging the practical and ethical limitations of long-term neural regulation.
To develop a visual nomogram integrating white matter hyperintensity (WMH) and brain atrophy from routine MRI for risk stratification of cognitive impairment in high vascular-risk patients. This retrospective study included 143 patients (93 impaired, 50 normal). Cognitive impairment was defined by MMSE (< 27). WMH was assessed via Fazekas scale on T2-FLAIR, and brain atrophy via Global Cortical Atrophy scale on T1-weighted images. A multivariable logistic model was built and evaluated by AUC, calibration (Hosmer-Lemeshow), 5-fold cross-validation, and decision curve analysis. Brain WMH (aOR = 1.35, 95
Localization of clinically relevant pain generators remains a major diagnostic challenge. MRI frequently demonstrates structural abnormalities that may lack symptomatic correlation, limiting identification of true nociceptive targets. ¹⁸F-FDG PET/MRI enables simultaneous metabolic and anatomic assessment and may help identify clinically actionable pain generators. A 68-year-old man with chronic refractory neck pain underwent ¹⁸F-FDG PET/MRI, which demonstrated focal hypermetabolism within the right obliquus capitis inferior and right longus colli muscles without corresponding structural MRI abnormalities. In conjunction with clinical findings, imaging results supported a presumptive diagnosis of cervical dystonia. Targeted CT- and US-guided lidocaine/triamcinolone injection, followed by botulinum toxin type A injection, was temporally associated with marked symptomatic improvement. ¹⁸F-FDG PET/MRI may help localize metabolically active pain generators not identified on conventional imaging and support hypothesis-driven image-guided procedural targeting in selected patients with unexplained persistent pain.
We present a challenging case that serves as a cautionary tale pertaining to the appropriate incorporation of electrophysiological assessment of the acute neuromuscular patient. This 64 year-old man presented with acute arm pain and weakness, with electrophysiological assessment suggestive of a brachial plexopathy. Subsequent investigation, however, led to a diagnostic shift to one of a radiculoplexus neuropathy, leading to a revised diagnosis of Lyme Polyradiculoneuritis. This new diagnosis had implications for management. Knowledge of the limitations of electrophysiological assessment is important for both the neuromuscular specialist and general neurologist. The case also bears educational import for the modern practice of neurology in the Appalachian region of the United States, as Lyme disease has become endemic to Appalachia as well.
