Ultrasensitive assay technology and fluid biomarkers for the evaluation of peripheral nerve disease.

The field of biomarker discovery is rapidly expanding. The introduction of ultrasensitive immunoassays and the growing precision of genetic technologies are poised to revolutionise the assessment and monitoring of many diseases. Given the difficulties in imaging and tissue diagnosis, there is mounting interest in serum and cerebrospinal fluid biomarkers of peripheral neuropathy. Realised and potential fluid biomarkers of peripheral nerve disease include neuronal biomarkers of axonal degeneration, glial biomarkers for peripheral demyelinating disorders, immunopathogenic biomarkers (such as the presence and titre of antibodies or the levels of cytokines) and genetic biomarkers. Several are already starting to inform clinical practice, whereas others remain under evaluation as potential indicators of disease activity and treatment response. As more biomarkers become available for clinical use, it has become increasingly difficult for clinicians and researchers to keep up-to-date with the most recent discovery and interpretation. In this review, we aim to inform practising neurologists, neuroscientists and other clinicians about recent advances in fluid biomarker technology, with a focus on single molecule arrays (Simoa), chemiluminescent enzyme immunoassays (CLEIA), electrochemiluminescence (ECL), proximity extension assays (PEA), and microfluidic technology. We discuss established and emerging fluid biomarkers of peripheral neuropathy, their clinical applications, limitations and potential future developments.

Study protocol: fish oil supplement in prevention of oxaliplatin-induced peripheral neuropathy in adjuvant colorectal cancer patients - a randomized controlled trial. (OxaNeuro).

BACKGROUND: Oxaliplatin-induced peripheral neuropathy (OIPN) in general and painful OIPN in particular is a debilitating late effect that severely affects cancer survivors' quality of life and causes premature cessation of potentially lifesaving treatment. No preventive treatments and no effective treatment for chronic OIPN exist despite many attempts. One of several suggested mechanisms includes neuroinflammation as a contributing factor to OIPN. Fish oil containing long-chain n-3 polyunsaturated fatty acids (n-3 LCPUFAs) are precursors to specialized proresolving mediators that mediate the resolution of inflammation. Our primary hypothesis is that a high supplementation of n-3 LCPUFAs will lower the prevalence and severity of OIPN. METHODS: The OxaNeuro project is an investigator-initiated, multicenter, double-blinded, randomized, placebo-controlled clinical study. We will include 120 patients eligible to receive adjuvant oxaliplatin after colorectal cancer surgery. Patients will receive fish oil capsules containing n-3 LCPUFAs or corn oil daily for 8 months. The primary endpoint is the prevalence of OIPN at 8 months defined as relevant symptoms, including one of the following: abnormal nerve conduction screening, abnormal vibration threshold test, abnormal skin biopsy, or abnormal pinprick test. Additional endpoints include the intensity and severity of OIPN-related neuropathic pain, patient-reported OIPN symptoms, quality of life, mental health symptoms, body composition, and cognitive evaluation. Furthermore, we will evaluate inflammatory biomarkers in blood samples and skin biopsies, including the potential OIPN biomarker neurofilament light protein (NfL) which will be measured before each cycle of chemotherapy. DISCUSSION: If readily available fish oil supplementation alleviates OIPN prevalence and severity, it will significantly improve the lives of both cancer survivors and palliative cancer patients receiving oxaliplatin; it will improve their quality of life, optimize chemotherapeutic treatment plans by lowering the need for dose reduction or premature cessation, and potentially increase survival. TRIAL REGISTRATION: ClinicalTrial.gov identifier: NCT05404230 Protocol version: 1.2, April 25th. 2023.

Acquired hyperexcitable peripheral nerve disorders: Clinical and laboratory features, therapeutic responses, and long-term follow-up.

INTRODUCTION/AIMS: Hyperexcitable peripheral nerve disorders (HPNDs) are rare. Although their clinical and laboratory features have been well studied, information on treatment and follow-up is limited. The aim of this study is to explore the long-term clinical, investigative, and therapeutic profile of patients with acquired HPNDs. METHODS: This study retrospectively analyzed patients from a single tertiary care center with HPND (January 2012 to January 2022). Patients were recruited according to published inclusion and exclusion criteria. Details of clinical features, diagnostic tests, therapeutic interventions, and follow-up were recorded. This study included patients with follow-up of 2 or more years. RESULTS: A total of 32 patients (M = 26, F = 6) were studied. The common clinical features included myokymia, neuropathic or shock-like pain, cramps, sleep disturbances, encephalopathy, cerebellar ataxia, and seizures. A total of 81.25% of patients responded favorably to corticosteroids and membrane stabilizers. Among the nonresponders, five received intravenous immunoglobulin (IVIG), and one received plasma exchange (PLEX). Two patients required rituximab due to poor responses to the above treatments. The mean duration of response was 6 weeks (4-24 weeks) from the initiation of treatment. All patients had favorable outcomes, reaching clinical remission within 1-5 years from the initiation of treatment. Only two patients had relapses. Immunotherapy could be stopped in 78% of patients within 3 years and 100% by 5 years. DISCUSSION: Chronic immunosuppression starting with corticosteroids is required for satisfactory outcomes of HPNDs. These disorders usually run a monophasic course, and relapses are uncommon.

Electrodiagnostic reporting preferences of referring physicians: An exploratory survey.

INTRODUCTION/AIMS: Electrodiagnostic (EDX) studies play a crucial role in the evaluation of patients with peripheral nervous system disorders. Accurate and succinct communication of test results is critical to patient safety and clinical decision-making. The objective of this study was to explore EDX reporting preferences of referring physicians to improve quality of communication and patient care. METHODS: An online survey was developed, and a purposive sampling strategy was used to recruit physicians in the authors' professional networks. Quantitative and qualitative survey data underwent frequency and thematic analyses, respectively. RESULTS: There were 40 respondents, including: 21 non-surgical specialists, 12 surgical specialists, and 7 family physicians. Sections rated as most critical were diagnostic impression (97%) and summary/interpretation (72%). Only 18% reported numeric data as critical to their needs, preferring this data to be formatted as bullet points or tables without nerve conduction study waveforms. Regarding the format of the data summary and diagnostic impression sections, the majority of respondents preferred bullet points rather than paragraphs. DISCUSSION: The results of this exploratory survey suggest that physicians who refer patients for EDX studies prefer reports that emphasize the interpretation of EDX data and a clear diagnostic impression, particularly in bullet point format. This project highlights important preferences and how they compare to recommended reporting guidelines, which may help improve communication and ultimately patient care. Future efforts should explore larger sample sizes with all key stakeholders in the EDX process to better understand reporting styles and preferences with greater nuance and context.

Initial validation of the Mass. General Neuropathy Exam Tool (MAGNET) for evaluation of distal small-fiber neuropathy.

INTRODUCTION/AIMS: Diagnosis of small-fiber neuropathy (SFN) is hampered by its subjective symptoms and signs. Confirmatory testing is insufficiently available and expensive, so predictive examinations have value. However, few support the 2020 SFN consensus-case-definition requirements or were validated for non-diabetes neuropathies. Thus we developed the Massachusetts General Hospital Neuropathy Exam Tool (MAGNET) and measured diagnostic performance in 160 symptomatic patients evaluated for length-dependent SFN from any cause and 37 healthy volunteers. METHODS: We compared prevalences of abnormalities (vital signs, pupil responses, lower-limb appearance, pin, light touch, vibration and position sensitivity, great-toe strength, muscle stretch reflexes), and validated diagnostic performance against objective SFN tests: lower-leg skin-biopsy epidermal neurite densities and autonomic function testing (AFT). Sensitivity/specificity, feasibility, test-retest and inter-rater reliability, and convergence with the Utah Early Neuropathy Scale were calculated. RESULTS: Patients' ages averaged 48.5 ± 14.7 years and 70.6% were female. Causes of neuropathy varied, remaining unknown in 59.5%. Among the 46 with abnormal skin biopsies, the most prevalent abnormality was reduced pin sharpness at the toes (71.7%). Inter-rater reliability, test-retest reliability, and convergent validity excelled (range = 91.3-95.6%). Receiver operating characteristics comparing all symptomatic patients versus healthy controls indicated that a MAGNET threshold score of 14 maximized predictive accuracy for skin biopsies (0.74) and a 30 cut-off maximized accuracy for predicting AFT (0.60). Analyzing patients with any abnormal neuropathy-test results identified areas-under-the-curves of 0.87-0.89 for predicting a diagnostic result, accuracy = 0.80-0.89, and Youden's index = 0.62. Overall, MAGNET was 80%-85% accurate for stratifying patients with abnormal versus normal neuropathy test results. DISCUSSION: MAGNET quickly generates research-quality metrics during clinical examinations.

Electrodiagnostic studies and new diagnostic modalities for evaluation of peripheral nerve disorders.

Electrodiagnostic studies (EDx) are frequently performed in the diagnostic evaluation of peripheral nerve disorders. There is increasing interest in the use of newer, alternative diagnostic modalities, in particular imaging, either to complement or replace established EDx protocols. However, the evidence to support this approach has not been expansively reviewed. In this paper, diagnostic performance data from studies of EDx and other diagnostic modalities in common peripheral nerve disorders have been analyzed and described, with a focus on radiculopathy, plexopathy, compressive neuropathies, and the important neuropathy subtypes of Guillain-Barré syndrome, chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), vasculitic neuropathy and diabetic neuropathy. Overall EDx retains its place as a primary diagnostic modality in the evaluated peripheral nerve disorders. Magnetic resonance imaging and ultrasound have developed important complementary diagnostic roles in compressive and traumatic neuropathies and atypical CIDP, but their value is more limited in other neuropathy subtypes. Identification of hourglass constriction in nerves of patients with neuralgic amyotrophy may have therapeutic implications. Investigation of radiculopathy is confounded by poor correlation between clinical features and imaging findings and the lack of a diagnostic gold standard. There is a need to enhance the literature on the utility of these newer diagnostic modalities.

Impact of Pain on Symptom Burden in Chemotherapy-Induced Peripheral Neurotoxicity.

BACKGROUND: Chemotherapy-induced peripheral neurotoxicity (CIPN) affects the quality of life of cancer survivors. However, the impact of pain on symptom burden remains undefined. This study aimed to define differences in the clinical symptom profile of patients with painful and nonpainful CIPN. PATIENTS AND METHODS: A total of 579 participants (median age, 59 years [IQR, 19 years]; F=66%) were assessed cross-sectionally 6 months posttreatment. CIPN severity was graded using multiple methods, including patient-reported outcome measures, a clinically graded scale (NCI-CTCAE), and a neurologic examination score. Participants were classified into subgroups based on patient symptom report, with painful CIPN characterized by the presence of shooting/burning pain, and nonpainful CIPN characterized by the presence of numbness or tingling without shooting/burning pain. Behavioral changes were assessed via structured patient interview regarding symptom impact on sleep, exercise, and treatment-seeking. RESULTS: Among 579 participants, 24% (n=140) reported painful CIPN, 48% (n=280) reported nonpainful CIPN, and 28% (n=159) had no CIPN. Participants with painful CIPN demonstrated higher CIPN severity than those with nonpainful CIPN across multiple measures, including NCI-CTCAE, neurologic grading, and patient report (all P<.05). Participants with painful CIPN were more likely to report that their symptoms affected their ability to exercise (P=.007), produced sleep impairment, and increased treatment-seeking behavior due to their symptoms (both P<.001) compared with participants with nonpainful CIPN. CONCLUSIONS: Overall, participants with painful CIPN reported higher scores across all CIPN severity measures, including behavioral changes. This study underlines the need for accurate identification of different CIPN subgroups in hopes of informing better treatment and rehabilitation options for cancer survivors with painful CIPN.

Studying serum neurofilament light chain levels as a potential new biomarker for small fiber neuropathy.

BACKGROUND AND PURPOSE: Diagnosing small fiber neuropathies can be challenging. To address this issue, whether serum neurofilament light chain (sNfL) could serve as a potential biomarker of damage to epidermal Aδ- and C-fibers was tested. METHODS: Serum NfL levels were assessed in 30 patients diagnosed with small fiber neuropathy and were compared to a control group of 19 healthy individuals. Electrophysiological studies, quantitative sensory testing and quantification of intraepidermal nerve fiber density after skin biopsy were performed in both the proximal and distal leg. RESULTS: Serum NfL levels were not increased in patients with small fiber neuropathy compared to healthy controls (9.1 ± 3.9 and 9.4 ± 3.8, p = 0.83) and did not correlate with intraepidermal nerve fiber density at the lateral calf or lateral thigh or with other parameters of small fiber impairment. CONCLUSION: Serum NfL levels cannot serve as a biomarker for small fiber damage.

Physical function as a predictor of chemotherapy-induced peripheral neuropathy in patients with pancreatic cancer.

BACKGROUND: A growing body of research indicates that poor functional status before chemotherapy may be correlated with the severity of chemotherapy-induced peripheral neuropathy (CIPN) after the neurotoxic treatment. However, little is known about the associations between pre-chemotherapy physical function and CIPN in patients with pancreatic cancer. PURPOSE: To identify the predictors of CIPN in relation to pre-chemotherapy physical function in patients with pancreatic cancer. METHODS: This secondary analysis included data from patients with pancreatic cancer who participated in a longitudinal research study at National Cheng Kung University Hospital, Tainan, Taiwan. Four physical function tests (i.e., grip strength, Timed Up and Go (TUG), 2-minute step test (2MST), and Romberg test) and two questionnaires (The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 [EORTC QLQ-C30] and Chemotherapy-Induced Peripheral Neuropathy Module [CIPN20]) were assessed at baseline (i.e., before first chemotherapy session) and 2-, 3-, 4-, and 6-month follow-up. Multiple linear regression with adjustment for confounding factors was used to assess the associations between the four functional tests at baseline and the CIPN20 total score and individual subscale scores (sensory, motor, and autonomic) at 6-month follow-up. RESULTS: Data from a total of 209 pancreatic cancer patients (mean age: 64.4 years, 54.5% male) were analyzed. The findings showed that the severity of CIPN at 6-month follow-up was significantly associated with the baseline TUG completion time (ß = 0.684, p = 0.003). The TUG completion time was also positively correlated with the 6-month CIPN sensory and autonomic subscales. In addition, a baseline positive Romberg test (ß = 0.525, p = 0.009) was a significant predictor of the severity of motor neuropathy at 6-month follow-up. CONCLUSION: The TUG completion time and positive Romberg test before chemotherapy may be predictive factors of the CIPN severity 6 months after the commencement of chemotherapy. Accordingly, the incorporation of TUG and Romberg tests into the clinical assessment protocol emerges as imperative for individuals diagnosed with pancreatic carcinoma undergoing chemotherapy regimens.

Monoclonal gammopathy-associated peripheral neuropathies: Uncovering pearls and challenges.

Monoclonal gammopathy-related peripheral neuropathies encompass a spectrum of clinical presentations in which the monoclonal protein directly damages the tissues, including the peripheral nervous system. Given the prevalence of both peripheral neuropathy and monoclonal gammopathy in the general population, these conditions may overlap in clinical practice, posing a challenge for clinicians in determining causality. Therefore, a comprehensive understanding of primary clinical syndromes and their neurophysiological patterns is of great importance for accurate differential diagnoses and effective treatment strategies. In this article, we examine the main forms of monoclonal gammopathies that affect the peripheral nerve. We explore the clinical and electrophysiological aspects and their correlation with each syndrome's corresponding monoclonal protein type. This knowledge is essential for healthcare professionals to diagnose better and manage patients presenting with monoclonal gammopathy-related peripheral nervous system involvement.

Longitudinal follow-up and prognostic factors in nitrous oxide-induced neuropathy.

BACKGROUND AND AIM: Recreational use of nitrous oxide (N2O) has been associated with the development of severe nitrous oxide-induced neuropathy (N2On). Follow-up of these patients poses challenges, and their clinical progression remains largely unknown. The identification of prognostic factors is made difficult by the lack of standardized longitudinal assessments in most studies. The objective was to document the course of neuropathy through systematic follow-up assessments in N2On patients to identify prognostic factors for persistent disability after 6 months. METHODS: We gathered demographic, clinical, biological, and electrophysiological data from N2On patients hospitalized in the Referral center in Marseille, both at baseline and during a standardized follow-up assessment at 6 months. RESULTS: We retrospectively included 26 N2On patients (mean age 22.6 ± 4.4). Significant improvements were observed in all main clinical scores including Rankin, ONLS, and MRC testing (p < .01). Electrophysiological studies (EDX) revealed a predominantly motor neuropathy with marked reduction in CMAP in the lower limbs at baseline, and no significant improvement in motor parameters (p = .543). Rankin score at 6 months correlated with the initial weekly N2O consumption (r = .43, p = .03) and the CMAP sum score in the lower limbs at the first EDX (r = -.47, p = .02). Patients with and without myelitis showed similar Rankin and ONLS score after 6 months. INTERPRETATION: The clinical course generally improved favorably at 6 months with notable amelioration in the primary disability scores, sensory deficits, and ataxia. However, distal motor impairment associated with peripheral neuropathy persisted, with distal axonal loss emerging as the main prognostic factor for long-term disability in these young patients.

Conduction slowing, conduction block and temporal dispersion in demyelinating, dysmyelinating and axonal neuropathies: Electrophysiology meets pathology.

Nerve conduction studies are usually the first diagnostic step in peripheral nerve disorders and their results are the basis for planning further investigations. However, there are some commonplaces in the interpretation of electrodiagnostic findings in peripheral neuropathies that, although useful in the everyday practice, may be misleading: (1) conduction block and abnormal temporal dispersion are distinctive features of acquired demyelinating disorders; (2) hereditary neuropathies are characterized by uniform slowing of conduction velocity; (3) axonal neuropathies are simply diagnosed by reduced amplitude of motor and sensory nerve action potentials with normal or slightly slow conduction velocity. In this review, we reappraise the occurrence of uniform and non-uniform conduction velocity slowing, conduction block and temporal dispersion in demyelinating, dysmyelinating and axonal neuropathies attempting, with a translational approach, a correlation between electrophysiological and pathological features as derived from sensory nerve biopsy in patients and animal models. Additionally, we provide some hints to navigate in this complex field.

Corneal confocal microscopy detects early nerve regeneration after pharmacological and surgical interventions: Systematic review and meta-analysis.

Corneal confocal microscopy (CCM) is an ophthalmic imaging technique that enables the identification of corneal nerve fibre degeneration and regeneration. To undertake a systematic review and meta-analysis of studies utilizing CCM to assess for corneal nerve regeneration after pharmacological and surgical interventions in patients with peripheral neuropathy. Databases (EMBASE [Ovid], PubMed, CENTRAL and Web of Science) were searched to summarize the evidence from randomized and non-randomized studies using CCM to detect corneal nerve regeneration after pharmacological and surgical interventions. Data synthesis was undertaken using RevMan web. Eighteen studies including 958 patients were included. CCM identified an early (1-8 months) and longer term (1-5 years) increase in corneal nerve measures in patients with peripheral neuropathy after pharmacological and surgical interventions. This meta-analysis confirms the utility of CCM to identify nerve regeneration following pharmacological and surgical interventions. It could be utilized to show a benefit in clinical trials of disease modifying therapies for peripheral neuropathy.

Normal and pathogenic variation of RFC1 repeat expansions: implications for clinical diagnosis.

Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is an autosomal recessive neurodegenerative disease, usually caused by biallelic AAGGG repeat expansions in RFC1. In this study, we leveraged whole genome sequencing data from nearly 10 000 individuals recruited within the Genomics England sequencing project to investigate the normal and pathogenic variation of the RFC1 repeat. We identified three novel repeat motifs, AGGGC (n = 6 from five families), AAGGC (n = 2 from one family) and AGAGG (n = 1), associated with CANVAS in the homozygous or compound heterozygous state with the common pathogenic AAGGG expansion. While AAAAG, AAAGGG and AAGAG expansions appear to be benign, we revealed a pathogenic role for large AAAGG repeat configuration expansions (n = 5). Long-read sequencing was used to characterize the entire repeat sequence, and six patients exhibited a pure AGGGC expansion, while the other patients presented complex motifs with AAGGG or AAAGG interruptions. All pathogenic motifs appeared to have arisen from a common haplotype and were predicted to form highly stable G quadruplexes, which have previously been demonstrated to affect gene transcription in other conditions. The assessment of these novel configurations is warranted in CANVAS patients with negative or inconclusive genetic testing. Particular attention should be paid to carriers of compound AAGGG/AAAGG expansions when the AAAGG motif is very large (>500 repeats) or the AAGGG motif is interrupted. Accurate sizing and full sequencing of the satellite repeat with long-read sequencing is recommended in clinically selected cases to enable accurate molecular diagnosis and counsel patients and their families.

Elevated liver enzymes and fasting glucose levels correlate with neuropathy in patients diagnosed with alcohol use disorder independently of the blood thiamine levels.

AIMS: Chronic alcohol consumption is well known to cause peripheral neuropathy, affecting both small and large nerve fibers. The aim of this study was to correlate biochemical and neurophysiological findings and investigate possible biomarkers and risk factors for pathogenetic mechanisms of neuropathy in patients diagnosed with alcohol use disorder (AUD). METHODS: Ninety patients diagnosed with AUD were enrolled in this prospective study over a period of 3 years. Serum biochemical parameters, as well as thiamine blood levels, were determined upon admission. Every subject was assessed by clinical neurological examination, followed by Nerve Conduction Studies, Quantitative Sensory Testing, and Sympathetic Skin Response. Fifty age and gender-matched patients without a diagnosis of AUD were used as the control group. RESULTS: Peripheral neuropathy was diagnosed in 54 patients (60%). Among them, pure large fiber neuropathy was found in 18 patients, pure small fiber neuropathy in 12 patients, and both large and small fiber neuropathy was diagnosed in 24 patients. Elevated liver enzymes and fasting glucose levels upon admission were significantly correlated with neuropathy. Lower blood thiamine levels (than reference) were found in seven patients and were not correlated with neuropathy. CONCLUSIONS: Our study suggests that alcohol-related liver dysfunction and hyperglycemia may contribute as risk factors of peripheral neuropathy in patients diagnosed with AUD, while blood thiamine levels do not correlate with neuropathy. Moreover, we suggest that liver enzymes and the De Ritis ratio could be potentially used as biomarkers for the incidence and severity of alcohol-related neuropathy.

Sensory disturbances in Creutzfeldt-Jakob disease.

BACKGROUND: Creutzfeldt-Jakob disease (CJD) is a fatal neurodegenerative disease characterized by rapidly progressive dementia, motor impairments, and psychiatric symptoms. Sensory disturbances were occasionally reported as well. The study aims to describe the sensory symptoms of the disease. METHODS: The CJD Israeli National Database was screened for patients who presented sensory symptoms throughout the disease course. Symptoms, characteristics, and distribution were reviewed and the demographic and clinical data (sex, etiologies of the disease, age of onset, disease duration, neurological exam finding, tau protein level, EEG and MRI findings) were compared with the demographics and clinical data of CJD without sensory symptoms. Then, the patients with sensory symptoms were divided into patients with symptom distribution consistent with peripheral nervous system (PNS) involvement and central nervous system (CNS) involvement. The demographics and clinical data of the 2 groups were compared. RESULTS: Eighty-four CJD patients with sensory symptoms and 645 CJD patients without sensory symptoms were included in the study. Sensory symptoms were more common in genetic E200K CJD patients (14.6% vs. 5.6% respectively, p = 0.0005) (chi-squared test). Numbness and neuropathic pain were the most common symptoms and distribution of symptoms of "stocking gloves" with decreased deep tendon reflexes suggesting peripheral neuropathy in 44% of the patients. In these patients, the classical EEG findings of Periodic Sharp Wave Complexes were less often found (58% vs. 22%, p = 0.02) (chi-squared test). CONCLUSIONS: Sensory symptoms are more common in E200K patients and often follow peripheral neuropathy distribution that suggests PNS involvement.

Epidemiology and Functional Impact of Early Peripheral Neuropathy Signs in Older Adults from a General Population.

INTRODUCTION: Peripheral neuropathy (PN) becomes more common with increasing life expectancy, but general population prevalence estimates are lacking. We investigated an epidemiological distribution of signs of PN among 2,996 community-dwelling participants in Good Aging in Skåne Study, age 60-97, and their impact on physical and autonomic function. METHODS: Signs of PN were measured with Utah Early Neuropathy Scale (UENS). Associations between UENS and physical tests, pain, and dysautonomic phenomena were calculated for each sex, adjusted for age, with estimated marginal means (EMM) and odds ratios (ORs) in four UENS quantiles (Q1-Q4). RESULTS: Participants in Q4 had worse EMM for: time to complete Timed Up and Go test (Q4-Q1: male 10.8-9.6 s; female 11.7-10.2 s), 15 m Walk test (Q4-Q1: male 11.1-9.9 s; female 11.2-10.4 s), and fewer repetitions in Step test (Q4-Q1: male 15.2-17.0 steps; female 14.5-15.8 steps). Higher OR of failing one-leg balance 60 s test {male 2.5 (confidence interval [CI] 95%: 1.7-3.8); female 2.1 (1.1-3.2)}, Foam Pad Balance test (male 4.6 [CI 95%: 3.2-6.7]; female 1.8 [1.3-2.6]), and lower physical quality of life were seen in Q4 compared to Q1. Participants in Q4 had higher OR for walking aid usage, falls, fear of falling, pain, and urinary incontinence, while in males, higher OR for orthostatic intolerance, fecal incontinence, and constipation. CONCLUSIONS: In a general population, 20-25% of older adults who have highest UENS scores, a sensitive measure of early PN, express slower gait, worse balance, lower quality of life, pain, falls and fear of falling, and autonomic symptoms.

Neuropathy Screening for Patients with Peripheral Vascular Disease Helps to Identify Those at an Increased Risk of Amputation, Revascularization, and Death.

BACKGROUND: Peripheral neuropathy is associated with amputation risk among patients with diabetes mellitus and chronic limb-threatening ischemia (CLTI). Detection of peripheral neuropathy may help identify those who are at an increased risk, but the predictive ability of the screening tool used in patients with peripheral arterial disease (PAD) needs to be more clearly defined. METHODS: Patients referred to vascular surgery clinic for PAD were recruited from a single center. Exclusion criteria were a documented history of neuropathy or prior lower limb amputation. Screening utilized the Michigan Neuropathy Screening Instrument (MNSI). Scores >2.5 were considered abnormal and scores >4 were considered positive for peripheral neuropathy. Limb-specific outcomes of amputation and revascularization as well as a composite outcome including death were modeled using time to event analysis. RESULTS: 86 patients were recruited. Mean age was 67 ± 10.2 years, 30% were women, 24% were black. Mean ankle-brachial index was 0.74 ± 0.3. PAD symptoms at initial evaluation were claudication in 52% of patients and CLTI in 38% of patients. Neuropathy was present in 20% of the cohort with a significantly higher proportion in diabetics (34% vs. 3%; P = 0.0009). Neuropathy was more common in patients with CLTI compared to claudicants (36% vs. 9%; P = 0.011). Forty patients (47%) reached the composite outcome of amputation, revascularization, or death with a median time to event of 16 months. Abnormal MNSI examination was significantly associated with the increased risk of the composite outcome (hazard ratio = 3.19; P 0.0005). CONCLUSIONS: A significant proportion of patients presenting to vascular specialists for PAD have undiagnosed neuropathy. Patients with PAD and neuropathy have an increased risk of amputation, revascularization, and death. Expanding neuropathy screening in vascular surgery clinic visits may help to identify patients at higher risk.

[Electrophysiological diagnostics in choosing treatment strategy for neuropathies in children with transcondylar fractures]. / Rol' elektrofiziologicheskoi diagnostiki v vybore taktiki lecheniya neiropatii u detei s chrezmyshchelkovymi perelomami.

BACKGROUND: A common complication of transcondylar fractures (TCF) in children is neuropathy requiring not only therapeutic but also surgical treatment. Despite numerous reports, clear criteria for selecting patients for surgical treatment have not been defined. OBJECTIVE: To clarify the role of clinical and electrophysiological diagnostics in choosing treatment tactics for neuropathies in children with TCF. MATERIAL AND METHODS: There were 20 patients with neuropathies after TCF between 2020 and 2022. Of these, 10 ones were selected for surgical treatment according to electrophysiological diagnostic data. Inclusion criteria: age 6-12 years, closed TCF within previous 3-12 months, symptoms of neuropathy confirmed by electroneuromyography (ENMG), no nerve disruption according to ultrasound data. Exclusion criteria: elbow joint contracture and post-traumatic ulnar nerve dislocation. All patients underwent needle myography with functional assessment of motor and sensory fibers, spontaneous activity in muscles, recruitment pattern and motor unit potentials. Intraoperative electrophysiological diagnostics included stimulation of motor fascicles with registration of M-responses from the target muscles. The follow-up period was 3-6 months. RESULTS: The study included 20 patients aged 6-12 years without peripheral nerve disruption. A group of 10 patients who required surgical treatment was identified. The control group consisted of 10 patients who did not require surgical treatment. To choose treatment tactics, we considered ENMG data. Surgical procedure was determined according to intraoperative neuromonitoring (IONM) data. CONCLUSION: When choosing treatment strategy, surgeons should consider objective ENMG and IONM criteria, as well as fascicular anatomy.

A patient with neuropathy and ataxia: what do I have to consider?

PURPOSE OF REVIEW: An increasing number of peripheral neuro(no)pathies are identified as involving other components of the neurological system, particularly those that further impair balance. Here we aim to outline an evidence-based approach to the diagnosis of patients who present with a somatosensory disorder which also involves at least one other area of neurological impairment such as the vestibular, auditory, or cerebellar systems. RECENT FINDINGS: Detailed objective investigation of patients who present with sensory impairment, particularly where the degree of imbalance is greater than would be expected, aids the accurate diagnosis of genetic, autoimmune, metabolic, and toxic neurological disease. SUMMARY: Diagnosis and management of complex somatosensory disorders benefit from investigation which extends beyond the presenting sensory impairment.