Search Results (203)

The myelin sheath has traditionally been viewed as a passive electrical insulator that accelerates nerve impulse propagation. Recent experimental studies, however, indicate that myelin is a dynamic biological material whose structure and hydration state adapt to neuronal activity, metabolic conditions, and environmental perturbations. Building on these observations, we propose a conceptual framework that treats myelin as an adaptive electromechanical multilamellar interface, in which coupled lipid bilayers, hydration layers, and interlayer interactions influence energy dissipation, structural adaptation, and history-dependent behavior. Within this framework, collective excitations and delayed relaxation processes are hypothesized to contribute to transient energy storage and adaptive responses to electrical activity in the integrated axon–glia system. We further argue that testing this framework requires multimodal characterization combining electrophysiology with neutron and X-ray scattering, terahertz spectroscopy, and data-driven analysis to establish quantitative relationships between membrane structure, dynamics, and function. This work outlines experimentally testable predictions and provides a foundation for investigating how electromechanical adaptation of myelin may contribute to normal neural function and the early biophysical changes associated with demyelinating disease. Full article

Myelination, mitochondrial bioenergetics, and oxidative stress are usually discussed as separate problems in optic nerve disease. This review draws them together and reads the published evidence through a single variable, the balance between the energy a retinal ganglion cell (RGC) axon spends and the energy its mitochondria can supply. We review the role of myelin in conduction and axonal support, the mitochondrial cost of building and maintaining it, the vulnerability of oligodendrocytes and myelin to oxidative injury, and the nuclear control of mitochondrial output. We summarize the inherited optic atrophies linked to OPA1, OPA3, AFG3L2, SPG7, and TMEM126A, and set these primary mitochondrial disorders against the immune-mediated demyelinating optic neuropathies. Published studies already support several parts of this picture, including the energetic cost of demyelination, the mitochondrial dependence of RGC axons, and oxidative injury in inflammatory lesions. Drawing on that evidence, we propose, as a testable hypothesis rather than a settled mechanism, that optic nerve degeneration is favored when axonal ATP demand outruns mitochondrial supply, most sharply where the axon crosses from its unmyelinated to its myelinated segment near the lamina cribrosa. We use this framework to separate initiating lesions from disease modifiers and downstream consequences, and to set out therapeutic predictions open to experimental and clinical tests. Full article

Background/Objectives: Ulnar nerve neuropathy at the elbow (UNE) is the second most common focal neuropathy of the upper extremity and often results from entrapment of the ulnar nerve as it traverses the elbow with insidious onset and gradual progression. This study describes the clinical, electrodiagnostic (EDX), and ultrasound (US) findings in a cohort of patients presenting with acute UNE. Methods: This is a review of 103 patients with clinical features of UNE with acute onset who underwent EDX and US studies over a 25-year period (2010–2026) at our Neurodiagnostic Center. Results: Of the 103 patients with acute UNE, all experienced paresthesia in the ulnar nerve distribution. A total of 27 (26.2%) patients had elbow pain, and 99 (96.1%) had decreased pinprick sensation in the ulnar nerve distribution. Weakness of the following muscles was detected: abductor digiti minimi (ADM) (94 [91.3%]), FDI (first dorsal interosseous) (91 [88.3%]), and FDPu (flexor digitorum profundus—ulnar) (76 [73.8%]). Most patients had a clinical grade of 3 (severe: sensory and motor abnormalities as well as atrophy of the FDI and ADM muscles) (93 [90.3%]). Perioperative injuries were the most common etiology of acute UNE, consisting of 65 (63.1%) patients. The perioperative injury was noted after surgical procedures at varied locations, most frequently at the shoulder in 23 (35.4%) followed by coronary artery bypass in 9 (13.8%) and knee joint surgery in 8 (12.3%). Non-iatrogenic injuries affected 11 (10.7%) patients. The US study revealed cysts and tumors such as a Schwannoma in 14/76 (18.4%) patients. Focal demyelination was observed by EDX studies in 95 (92.2%) patients, and a conduction block was detected in 24 (23.3%). Motor and sensory axonal involvement was identified in 81 (78.6%) and 86 (83.5%) patients, respectively. Of the 76 patients who underwent an US study, 68 (90.6%) had an increase in the cross-sectional area of the ulnar nerve and 51 (68.0%) had a hypoechoic ulnar nerve at the elbow. Conclusions: In this study, the most common cause of acute UNE was periprocedural injury, most frequently following shoulder surgery. Acute UNE may also occur without a history of antecedent trauma or a surgical procedure. EDX and US studies provide complementary data to determine the severity and the etiology of acute UNE and guide further management. Full article

Background/Objectives: Optic neuritis is associated with demyelinating diseases such as multiple sclerosis (MS), but atypical presentations, particularly bilateral optic nerve involvement or coexisting systemic symptoms, necessitate broader diagnostic consideration. Case presentation: This case report describes a 50-year-old male with untreated, active hepatitis C virus (HCV) infection who presented with bilateral optic neuritis. Cerebrospinal fluid (CSF) analysis revealed elevated myelin basic protein, positive oligoclonal bands, an elevated immunoglobulin G index, and an HCV viral load of 9.3 million international units/milliliter (IU/mL). Magnetic resonance imaging (MRI) of the orbits showed bilateral optic neuritis with perineuritis. The patient had no history of interferon therapy and lacked markers of cryoglobulinemia, making this a rare case of optic neuritis possibly associated with chronic hepatitis C viral infection. The patient was treated with intravenous immunoglobulin (IVIG) without corticosteroids, with some improvement in vision. Conclusions: This case adds to the expanding spectrum of multiple sclerosis (MS) mimics and underscores diagnostic challenges associated with atypical optic neuritis presentations, particularly in the setting of coexisting systemic viral infections. Full article

Background/Objectives: Autoimmune nodopathies are a distinct subgroup of immune-mediated peripheral neuropathies caused by antibodies targeting nodal and paranodal proteins, including contactin-1 (CNTN1). These disorders are frequently misclassified as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), despite fundamental differences in pathophysiology, clinical course, and treatment response. Growing evidence indicates that systemic manifestations, such as proteinuria, may represent relevant diagnostic red flags. We report a case of anti-CNTN1 autoimmune nodopathy with renal involvement and long-term follow-up after rituximab therapy. Methods: We describe the longitudinal clinical, electrophysiological, laboratory, and therapeutic features of a patient presenting with an acute/subacute sensory ataxic neuropathy evolving into a chronic immune-mediated disorder. Serial nerve conduction studies were performed during multiple hospital admissions and follow-up visits. Autoantibody testing for nodal/paranodal antigens was undertaken, and systemic biomarkers were monitored over time. Results: The patient initially exhibited a robust response to intravenous immunoglobulin (IVIg), consistent with an acute inflammatory neuropathy. Subsequent relapse was characterized by cranial nerve involvement, worsening sensory ataxia, peripheral edema, albuminocytologic dissociation on cerebrospinal fluid analysis, proteinuria, and an inverted albumin/gamma globulin ratio, redirecting the diagnostic hypothesis toward CIDP. The detection of anti-CNTN1 antibodies ultimately established the diagnosis of autoimmune nodopathy. Owing to poor durability of IVIg, rituximab was initiated, resulting in sustained clinical improvement and near-complete recovery of motor and sensory nerve conduction parameters at one-year follow-up (November 2025). Conclusions: This case emphasizes the diagnostic relevance of extraneurological biomarkers, including proteinuria and peripheral edema, in autoimmune nodopathies and supports early nodal/paranodal antibody testing in atypical demyelinating neuropathies. Prompt B-cell-directed therapy may enable functional recovery of nodal integrity and improve long-term outcomes. Further studies are needed to clarify potential immunological triggers, including anti-IL-23 therapies, in the pathogenesis of anti-CNTN1 autoimmune nodopathy. Full article

Neurovascular compression syndromes (NVCS), including trigeminal neuralgia (TN) and hemifacial spasm (HFS), are characterized by disabling symptoms caused by vascular compression of cranial nerves. Although microvascular decompression is an established treatment, mechanisms linking neurovascular compression to abnormal neural activity remain incompletely understood. In this review, we integrate evidence from microanatomical, electrophysiological, and computational studies to provide a mechanistic framework for NVCS. Chronic vascular compression induces focal demyelination, redistribution of voltage-gated ion channels, ectopic impulse generation, and ephaptic transmission, leading to abnormal neuronal excitation. We further summarize emerging evidence that persistent peripheral hyperactivity may contribute to electrophysiological alterations in central neural circuits. Particular attention is given to computational approaches, including cable theory and axonal interaction models, which offer quantitative insights into abnormal synchronization and cross-excitation among nerve fibers. Recent findings regarding ion channel dysfunction, including familial TN associated with gain-of-function calcium channel variants, are also discussed. Collectively, these findings support an integrated model linking neurovascular compression to clinical manifestations, and highlight the value of combining electrophysiology and computational neuroscience to improve mechanistic understanding and to guide future therapeutic strategies for NVCS. Full article

Background and Clinical Significance: Anti–myelin-associated glycoprotein (MAG) antibody polyneuropathy is a rare, chronic IgM-mediated demyelinating peripheral neuropathy predominantly affecting sensory nerves in older adults, commonly in association with monoclonal gammopathy of undetermined significance. Reports describing anesthetic management in patients with this condition remain extremely limited, and no specific guidelines currently exist regarding neuromuscular blocking agent (NMBA) use or neuromuscular monitoring in this population. Case Presentation: A 79-year-old man with anti-MAG antibody polyneuropathy (diagnosed in 2007) and IgM monoclonal gammopathy of undetermined significance developed disproportionate progressive lower-extremity weakness and became wheelchair-dependent following COVID-19 infection in 2020. Preoperative evaluation revealed mildly reduced left ventricular function (ejection fraction 49%), mild chronic kidney disease, and marked intrinsic hand muscle atrophy with absent deep tendon reflexes. He was scheduled for robot-assisted radical cystectomy with ileal conduit diversion under combined general and thoracic epidural anesthesia. Before NMBA administration, neuromuscular monitoring was systematically attempted at the ulnar nerve (electromyography and acceleromyography, up to 60 mA/300 μs) and the corrugator supercilii; despite visible muscle contractions following peripheral nerve stimulation, neither modality produced reliable responses at either site. Given the inability to establish reliable monitoring, the administration of NMBAs was considered to carry an unacceptable risk of a prolonged, undetectable blockade. Anesthesia was maintained with deep sevoflurane (2.0–2.5% end-tidal) and remifentanil infusion without NMBAs, titrated to a bispectral index of 40–60. Tracheal intubation was accomplished via video laryngoscopy without NMBA. The 7 h and 30 min surgery was completed without patient movement or surgical compromise. Postoperatively, the patient developed transient upper airway obstruction attributed to glossoptosis, managed successfully with head elevation and nasopharyngeal airway insertion; supplemental oxygen was required until postoperative day 3, and the patient was discharged from the high-dependency unit on postoperative day 5. Conclusions: No measurable quantitative neuromuscular response could be obtained in this patient with advanced anti-MAG antibody neuropathy, despite appropriate application of electromyography- and acceleromyography-based monitoring and the presence of visible muscle contractions following peripheral nerve stimulation. In such circumstances, avoiding NMBA administration in favor of deep volatile or intravenous anesthesia with opioid supplementation may represent a reasonable, hypothesis-generating approach in carefully selected patients; this observation does not establish the general superiority of an NMBA-free strategy, and caution is warranted before generalizing it to procedures such as robotic surgery, in which profound neuromuscular blockade is often considered desirable. Full article

Background/Objectives: With the biphasic of cataract onset age, presenile cataract (40–55 years) and age-related cataract (≥70 years) demonstrate notable differences in perioperative dry eye manifestations. This review aims to systematically compare their differential characteristics, mechanisms, and management strategies. Methods: An indirect evidence synthesis was conducted, encompassing 71 clinical and mechanistic studies evaluating perioperative dry eye in these two patient populations. Results: Presenile patients predominantly present with evaporative dry eye secondary to meibomian gland dysfunction (55–70%), persisting for 3–6 months postoperatively, especially in subgroups with metabolic disorders, female sex, diabetes with rosacea, or preoperative anxiety. In contrast, age-related patients primarily exhibit mixed-type dry eye, with a shorter recovery period (1–3 months), characterized by corneal nerve demyelination and meibomian gland fibrosis. Mechanistically, the presenile group is associated with glandular functional overload, acute inflammation, and exogenous oxidative stress, while the age-related group shows degenerative degenerative atrophy, chronic low-grade inflammation (senescence-associated secretory phenotype, SASP), and impaired nerve regeneration. Conclusions: Perioperative dry eye exhibits inherent differences between presenile and age-related cataract patients, requiring age-stratified and subgroup-targeted management strategies for precise ocular surface care. However, due to the absence of direct head-to-head studies, these findings are derived from indirect evidence and should be considered hypothesis-generating. Full article

In peripheral nervous system (PNS), immature Schwann cells differentiate into two functionally distinct types of mature Schwann cells: myelinating Schwann cells, which establish a one-to-one relationship with large-diameter axons and initiate the complex myelination program that enables the rapid saltatory conduction of nerve impulses, and non-myelinating Schwann cells, which envelop multiple small-diameter axons without forming myelin, but support axon survival and maintain microenvironment homeostasis. Here, we demonstrate that discoidin domain receptor 1 (DDR1) signaling plays a pivotal role in Schwann cell maturation and peripheral nerve myelination. Ddr1^−/− mice of both sexes exhibited fewer myelinating Schwann cells and profound hypomyelination, reduced nerve conduction velocity, and apparent motor dysfunction. Expression of myelin markers was markedly reduced in the mutants accompanied by the formation of abnormal myelin ultrastructure resembling “onion bulbs”. Mechanistically, Ddr1 deficiency impaired Schwann cell myelination through the marked hyperactivation of the MAPK/ERK signaling pathway. These findings establish DDR1 as a novel regulator of Schwann cell myelination and highlight its potential as a therapeutic target for demyelinating neuropathies. Full article

Background: Neurovascular compression syndromes (NVCS) represent a spectrum of disabling neurologic disorders caused by vascular or structural compression of cranial nerves, most commonly at the root entry zone. Conditions such as trigeminal neuralgia (TN), hemifacial spasm (HFS), and glossopharyngeal neuralgia (GN) are associated with significant pain, functional impairment, and reduced quality of life. This review provides a multidisciplinary, anatomically grounded overview of the pathophysiology, diagnosis, imaging, and contemporary management strategies for NVCS. Methods: A narrative review of the literature was conducted, synthesizing historical perspectives, neuroanatomy of the cerebellopontine angle, mechanisms of neurovascular conflict, advances in imaging and neuromonitoring, and current treatment modalities. Medical, percutaneous, surgical, radiosurgical, and neuromodulatory approaches were evaluated, with emphasis on patient selection and outcome considerations. Results: Neurovascular compression, most frequently arterial compression at the root entry zone, leads to focal demyelination, ephaptic transmission, and neuronal hyperexcitability. High-resolution Magnetic resonance imagin (MRI) remains the diagnostic gold standard. First-line management for TN and related syndromes typically includes pharmacotherapy, particularly sodium channel blockers. Refractory cases may benefit from percutaneous rhizotomy, balloon compression, stereotactic radiosurgery, or microvascular decompression (MVD), which offers the most durable relief in appropriately selected patients. Emerging technologies, including endoscopic visualization, advanced neuromodulation, and virtual reality-assisted surgical planning, continue to refine treatment precision and safety. Conclusions: Effective management of NVCS requires a comprehensive understanding of neuroanatomy, pathogenesis, and individualized risk–benefit profiles. A multidisciplinary, stepwise approach optimizes outcomes and improves quality of life in patients with these complex disorders. Full article

Background/Objectives: Hyperventilation-induced nystagmus (HVIN) has been described as a sensitive clinical sign in vestibular schwannoma (VS), potentially reflecting a reversible conduction block in partially demyelinated vestibular nerve fibers. However, its relationship with tumor size and instrumental vestibular deficits remains controversial. This study aimed to investigate the association between HVIN, tumor size, clinical presentation, and vestibular function assessed by the video Head Impulse Test (vHIT) and functional Head Impulse Test (fHIT). Methods: Eighty consecutive patients with unilateral VS were retrospectively evaluated. All underwent bedside vestibular examination, the vHIT, the fHIT, and the Hyperventilation Test (HVT). Tumors were classified according to the modified Koos–Sanna grading system. Associations between HVIN (presence and direction), demographic and clinical variables, vestibular deficits, and tumor size were analyzed using binary logistic regression, Fisher’s exact test, Welch’s independent samples t-test, and the Mann–Whitney U test. Results: HVIN was observed in 73% of patients. Among the patients with HVIN, ipsilesional horizontal nystagmus occurred in 57% of cases, 41% of the subjects showed contralesional nystagmus and one patient had downbeat nystagmus. vHIT abnormalities were identified in 54% of patients, while 30% of these also demonstrated fHIT deficits. No patient presented isolated fHIT abnormality. HVIN was detected even in patients with intracanalicular or small tumors and in some asymptomatic individuals. No statistically significant correlations were found between tumor size and HVIN presence, HVIN direction, or vestibular deficits in the vHIT/fHIT (all p > 0.05). Conclusions: HVIN is frequently observed in patients with VS, including those with small or asymptomatic lesions. However, neither its presence nor direction correlates with tumor size or objective vestibular deficit. The Hyperventilation Test should not be considered a prognostic tool but may serve as a simple and valuable adjunctive bedside examination in the early diagnostic suspicion of vestibular schwannoma. Full article

Diabetic peripheral neuropathy (DPN) is a common and debilitating complication of diabetes mellitus which affects individuals with both type 1 and type 2 diabetes mellitus (T2DM), presenting with sensory loss, pain, and progressive nerve dysfunction. DPN pathogenesis is multifactorial: chronic hyperglycemia activates the polyol, hexosamine, and protein kinase C (PKC) pathways, increases advanced glycation end-products, and drives oxidative stress, mitochondrial dysfunction, inflammation, and impaired neurotrophic signaling. In addition to hyperglycemia-driven mechanisms, dyslipidemia and microvascular insufficiency exacerbate neural ischemia and metabolic stress. Recent mechanistic, animal, and associative human studies further implicate amyloidogenic toxicity, particularly from human islet amyloid polypeptide (hIAPP), as a plausible contributory factor in peripheral nerve degeneration in T2DM, linking protein misfolding and aggregation to axonal damage and demyelination in DPN. Despite increased understanding of these mechanisms, current treatments remain mainly symptomatic. Emerging therapeutic strategies, including antioxidants, anti-inflammatory agents, modulators of mitochondrial function, amyloid oligomer modulators, neurotrophic enhancers, and regenerative approaches such as stem cells and gene-based therapies, offer potential to modify disease progression. The strength of evidence across these methods varies, ranging from mechanistic and animal studies to early human research and, in some cases, randomized clinical trials. Therefore, although several candidates show potential to alter the disease, few have demonstrated consistent benefits on objective measures of nerve structure or function in large clinical trials. This review summarizes the key mechanisms driving DPN in T2DM and highlights promising therapeutic innovations poised for clinical translation. Full article

Background: This study aims to systematically review the current literature on the application of radiomic features and artificial intelligence (AI) in the diagnosis and prognosis of common peripheral nerve-related conditions, including carpal tunnel syndrome (CTS), chronic inflammatory demyelinating polyneuropathy (CIDP), polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin abnormalities (POEMS) syndrome, and in distinguishing between benign and malignant tumors. Methods: A comprehensive literature search was conducted in PubMed and Google Scholar for studies published between January 2019 and September 2025. Inclusion criteria comprised studies that used radiomics or AI-based radiomics approaches with diagnostic or prognostic purposes in peripheral nerve disorders. Results: A total of 40 studies were identified, of which 17 met the inclusion criteria. Among these, 9 studies employed magnetic resonance imaging (MRI), including one combined with PET/CT, while 8 used ultrasound (US). Most studies were retrospective and limited by small sample sizes, lack of external validation, and predominance of single-center designs. Conclusions: Since a seminal study published in 2019, there has been increasing evidence supporting the role of radiomics and AI in improving the diagnosis and prognosis of peripheral nerve disorders, particularly using MRI and US. However, significant challenges remain, including variability in imaging data, segmentation complexity, and limited availability of validated datasets. Future advancements in imaging technologies and multidisciplinary collaboration are essential to enhance clinical applicability. Full article

Background: Connexins (Cx) are a family of transmembrane proteins that form gap junctions and connexin hemichannels (HCs), enabling direct intercellular communication within the nervous system. Connexin 43 (Cx43), the principal astrocytic connexin, exhibits a context-dependent dual role: under physiological conditions it maintains tissue homeostasis and metabolic support, whereas under pathological conditions excessive activation of Cx43 hemichannels promotes neuroinflammation, excitotoxicity, blood–brain barrier disruption, and secondary neural tissue damage. Other connexin isoforms also contribute to the pathogenesis of neurological and psychiatric disorders through alterations in neuronal synchronization, glial signaling, and myelin integrity. Objective: To systematize current evidence on the role of key connexin isoforms in acute nervous system injuries—including stroke, traumatic brain injury, spinal cord injury, and peripheral nerve injury—as well as chronic disorders such as neurodegenerative diseases, epilepsy, and psychiatric disorders, with particular emphasis on the functional duality of connexin channels and the therapeutic potential of their selective modulation. Methods: A systematic literature search was conducted in the PubMed, Scopus, and Web of Science databases in accordance with the PRISMA framework and the PRISMA Extension for Scoping Reviews guidelines. The review included data from experimental models, postmortem brain studies, genetic association analyses, and pharmacological intervention studies. The retrieved studies were screened, assessed for eligibility, and integrated using a qualitative narrative synthesis approach. Results: In acute neural injuries, hyperactivation of Cx43 hemichannels amplifies inflammatory signaling, edema formation, and neuronal death, whereas selective HCs inhibitors reduce lesion volume and improve functional outcomes in experimental models. Connexin 36 (Cx36) contributes to cortical spreading depolarization and seizure propagation, while Connexin 32 (Cx32) and Connexin 47 (Cx47) are critically involved in oligodendrocyte function and white-matter demyelination. In PNI, Cx43 upregulation contributes to neuropathic pain, whereas mutations in Cx32 cause hereditary demyelinating neuropathies. In neurodegenerative diseases—including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis—Cx43 hemichannel activity promotes neuroinflammation and pathological protein accumulation, while reduced Cx32/Cx47 expression disrupts metabolic support of axons. In psychiatric disorders such as major depressive disorder, bipolar disorder, and schizophrenia, decreased astrocytic connexin expression (Cx43 and Cx30) has been associated with impaired glial–neuronal communication and cognitive–emotional dysfunction. In epilepsy, increased Cx43/Cx30 expression contributes to neuronal hypersynchronization and blood–brain barrier dysfunction, whereas selective hemichannel blockade suppresses seizure activity. Conclusions: Cx—particularly Cx43—occupies a central position in the molecular mechanisms of secondary neural injury and network dysfunction. The dual functional properties of gap junctions and hemichannels determine their context-dependent effects across neurological and psychiatric diseases. Selective inhibition of pathological HCs activity shows significant neuroprotective and anticonvulsant potential and represents a promising direction for the development of targeted therapeutic strategies. Further studies are required to determine optimal therapeutic time windows, tissue-specific effects, and the long-term safety of Cx modulation. Full article