Polyneuropathy Research Articles

The Relationship Between Hand Abnormalities and Diabetic Retinopathy in Patients with Type 2 Diabetes Mellitus

Background: The link between diabetes mellitus (DM) and pathological conditions of the hand has been previously investigated. Retinopathy is one of the most common microvascular complications of DM. In this study, we aimed to evaluate the relationship between hand abnormalities and retinopathy in patients with type 2 DM. Methods: Patients with type 2 DM were assessed for hand abnormalities using tactile, functional, and sensory tests. The patients were evaluated electrodiagnostically for carpal tunnel syndrome and polyneuropathy (PNP). A comprehensive ophthalmologic examination was performed to diagnose diabetic retinopathy (DR). Subjective disability and quality of life were evaluated using the Quick DASH questionnaire. The duration of the disease and HbA1c levels were noted. Results: A total of 60 patients with type 2 DM (32 female, 28 male) were recruited for this study. The mean age was 55.1 ± 5.6 years. Among the 60 diabetic patients examined, 15 (25%) were diagnosed with DR. The mean duration of DM was 86.86 ± 51.69 months in patients without DR and 144.75 ± 82.96 months in patients with DR. The mean HbA1c level was 8.86% in the DR group and 8.64% in the non-DR group. PNP was the only hand abnormality that showed a significant association with retinopathy (p = 0.011). Conclusions: PNP might be used as a clue to the presence of retinopathy, especially in long-lasting diabetes. Particular attention should be given to hand abnormalities, especially in patients with PNP, due to their association with DR.

Middle ear cholesteatoma and facial nerve hypertrophy mimicking schwannoma in Charcot-Marie-Tooth disease: A case report

Rationale: Charcot-Marie-Tooth (CMT) disease, a hereditary motor and sensory neuropathy, presents with progressive chronic sensory and distal motor polyneuropathy. While sensorineural hearing loss and vestibular impairment have been documented in CMT patients, concurrent middle ear cholesteatoma and persistent direction-changing positional nystagmus have not. Patient concerns: This study details a 22-year-old man with CMT1 exhibiting these symptoms. Diagnoses: A 22-year-old man with CMT1 (PMP22, c.319+1G>T mutation) presented with rotatory vertigo, left-sided hearing loss, and aural fullness. Examination revealed middle ear effusion and a whitish mass behind the left tympanic membrane. Audiometry showed mixed hearing loss on the left side. Imaging indicated middle ear cholesteatoma and facial nerve hypertrophy. Interventions: Surgical removal of the cholesteatoma revealed a dehiscent hypertrophied facial nerve. Outcomes: Postoperative follow-up showed improved hearing and no recurrence. Lessons: This case highlights 3 key points: facial nerve hypertrophy in CMT requiring differentiation from schwannoma, the first reported instance of middle ear cholesteatoma in a CMT patient, and vertigo due to acute otitis media complicated by serous labyrinthitis, manifesting as direction-changing positional nystagmus. These findings underscore the need for thorough diagnosis and management in such presentations. This is the first report of concomitant middle ear cholesteatoma in a CMT patient, illustrating the complexity of diagnosis and treatment.

Eplontersen (Wainua)

Canada’s Drug Agency (CDA-AMC) recommends that Wainua be reimbursed by public drug plans for the treatment of polyneuropathy (PN) associated with stage I or stage II hereditary transthyretin amyloidosis (hATTR) in adults, if certain conditions are met. Wainua should only be covered to treat adults with stage I or stage II genetically confirmed hATTR with PN (hATTR-PN) who are symptomatic with early-stage neuropathy, do not have severe heart failure symptoms, and have not had a liver transplant. A patient’s response to treatment with Wainua should be assessed at least every 6 months to determine whether they would benefit from continued treatment. Treatment with Wainua should not be continued in patients who are permanently bedridden and dependent on assistance for basic activities of daily living or who are receiving end-of-life care. Wainua should only be reimbursed if the patient is under the care of a specialist with experience in the diagnosis and management of hATTR-PN, and should not be reimbursed if it is used in combination with interfering ribonucleic acid (RNA) drugs or transthyretin stabilizers. The cost of Wainua should be reduced so that it does not cost more than other drugs for hATTR.

Clinical Cues for the Early Diagnosis of Transthyretin-Related Polyneuropathy.

The estimated prevalence of hereditary transthyretin-related familial amyloid polyneuropathy (TTR-FAP) and the small number of known patients in Germany indicate that many patients with TTR-FAP remain undiagnosed, and may instead be classified as "idiopathic." The aim of this study was to identify biomarkers for detecting TTR-FAP among a cohort of patients with idiopathic polyneuropathy (PNP). Clinical evaluations (including the Neuropathy Impairment Score and Neuropathy Disability Score), nerve conduction studies (NCSs), quantitative sensory testing, and autonomic function tests were performed on 23 patients with TTR-FAP and 89 with idiopathic PNP. Discriminant analysis was then performed to identify variables useful for predicting TTR-FAP. Patients with TTR-FAP had paresis of the finger and thumb muscles, and reduced vibration perception and increased pressure pain in the upper and lower extremities. The NCSs showed that action potentials were smaller in the median, ulnar (both motor and sensory), and sural nerves in TTR-FAP. The sensory nerve conduction velocity was also reduced in the ulnar nerve. Autonomic neuropathy was confirmed by reduced sympathetic skin responses in the hands and feet in TTR-FAP. Multivariate discriminant analysis revealed that finger abduction strength, sensory ulnar nerve action potential amplitude, and vibration detection and pressure pain thresholds in the upper extremities were sufficient to correctly identify TTR-FAP in 81.3% of cases. Detailed clinical and neurophysiological investigations of standard parameters in the upper limb may help to identify the otherwise-rare TTR-FAP.

Immune Checkpoint Inhibitor (ICI) Associated Atypical Painful Axonal Sensorimotor Polyneuropathy

Immune Checkpoint Inhibitor (ICI) Associated Atypical Painful Axonal Sensorimotor Polyneuropathy

7087 An Unusual Movement Disorder, Case of Diabetic Striatopathy!

Abstract Disclosure: S. Azmat: None. O. Lodhi: None. R. Safi: None. H. harb: None. H. Ashok: None. M.F. Siddiqui: None. J.L. Gilden: None. Background: Non-ketotic Hyperglycemia Hemichorea-Hemiballismus Syndrome (NKH-CB) is rare complication of poorly controlled diabetes mellitus (DM) characterized by continuous, irregular jerky movements localized to one side of the body. It is commonly seen in type 2 DM and is often presented in females of East Asian descent. NKH-CB is often misdiagnosed due to its rarity and radiographic features easily mistaken for intracerebral hemorrhage.Case: A 70-year-old Latino male with type 2 diabetes mellitus, hypertension, bipolar disorder and past history of two cerebrovascular accidents presented to ED with non-radiating, midsternal chest pain. ACS was ruled out with negative serial troponins and normal EKG. Vital signs were significant for elevated blood pressure 151/64 mmHg. Labs showed blood glucose=447 mg/dL. Physical examination revealed large amplitude involuntary movements in left upper and lower extremities and facial region. He also veered to the left when ambulating. The patient reported that these abnormal movements were occurring for last three weeks although sensation was preserved bilaterally. Code stroke was called; non-contrast CT showed unilateral hyper density of the right caudate and putamen with no evidence of acute intracranial hemorrhage or large arterial territory infarction. CT Angiogram did not show any signs of stenosis or occlusion. He received intravenous fluids and 8 units lispro insulin in ED. Was admitted for further evaluation and received basal/bolus insulin therapy with target blood glucose of 140-160 mg%. He also received risperidone for his mental condition. Subsequent testing revealed hemoglobin A1C of 16.9% (reference range: < 5.7%). MRI Brian showed unilateral T1 hyperintensity involving right caudate and putamen corresponding to the hypodensity seen on CT. Neurology service was consulted. Based on clinical signs/symptoms coupled with neuroimaging, he was diagnosed with non-ketotic Hyperglycemia Hemichorea-Hemiballismus Syndrome. On day 2 with resolution of hyperglycemia, amplitude and frequency of involuntary arm movements were minimal. The patient was discharged with Lantus 7 and metformin 1000 mg for DM and risperidone for symptoms management. Conclusion: Diabetic neuropathy is commonly known to result in small and/or large fiber sensorimotor polyneuropathy, proximal motor, and acute mononeuropathies as well as entrapments, radiculopathies, autonomic neuropathies, and even cognitive disorders. This case describes rare case of simultaneous NKH-CB with history of CVA and antipsychotic medication use in a patient with poorly controlled DM which resolved with treatment of hyperglycemia. Thus offers valuable insights into the diagnostic challenges associated with this condition as well as potential links to other neurological complications. One should also remain vigilant of potential onset of seizures commonly seen with NKH. Presentation: 6/3/2024

Single simple question in axonal polyneuropathy.

The single simple question (SSQ), "What percentage of normal (0%-100%) do you feel regarding your disease?" has proven feasible and valid in assessing myasthenia gravis and a heterogeneous spectrum of neuropathies. This study explores the utility of the SSQ in axonal polyneuropathies (PNPs), encompassing diabetic neuropathy, and evaluates its responsiveness to scale changes. A retrospective chart review of 150 patients with axonal PNP responding to the SSQ was performed. Patients underwent clinical and electrophysiological evaluations, and were evaluated by clinical and disability scales, including the Medical Research Council sum score, modified Toronto Clinical Neuropathy score (mTCNS), Overall Neuropathy Limitation Scale, and Rasch-built Overall Disability Scale (RODS). The SSQ total scores correlated moderately with both the RODS score (r = .59, p < .001) and the mTCNS symptom score (r = -.43, p < .001), maintaining significance after adjustment for multiple comparisons. Longitudinally, after adjusting for multiple comparisons, the change in mTCNS symptom score retained statistical significance (adjusted p = .048). The SSQ did not show any association with electrophysiological parameters or sensory symptoms, other than a lower score in those with pain (100% with SSQ <40%, 85% with SSQ 40%-70%, and 34% with SSQ >70%). The SSQ is a feasible, valid scale that may be utilized to assess and follow patients with length-dependent axonal PNPs. Given that the SSQ is not strongly associated with clinical and disability scales or electrophysiological findings, additional investigations are required for a comprehensive assessment of PNP.

Trigeminal neuralgia, demyelinating polyneuropathy, and central nervous system involvement in a patient with an SH3TC2 mutation

Abstract Background Charcot-Marie-Tooth type 4C (CMT4C) is a slowly progressive, autosomal recessive, sensorimotor polyneuropathy characterized by demyelination and distinct clinical features, including cranial nerve involvement. CMT4C is associated with pathogenic mutations in the SH3TC2 gene. Methods A patient presenting with gait instability due to demyelinating polyneuropathy and refractory trigeminal neuralgia underwent comprehensive evaluation. Nerve conduction studies, magnetic resonance imaging (MRI) of the brain, cervical spine, and thoracic spine, lumbar puncture, and genetic test through next generation sequencing were performed. Results The genetic test found an Arg1109Stop mutation in the SH3TC2 gene, associated with demyelinating polyneuropathy and cranial neuropathy. Interestingly, brain MRI showed multiple, nonenhancing white matter hyperintensities. This is the first case of CMT4C associated with white matter lesions. Conclusion Any patient with slowly progressive peripheral nervous system symptoms and disproportionally abnormal nerve conduction study findings should be tested for an inherited polyneuropathy and brain imaging for screening of possible central nervous system involvement should be performed. Further investigation is needed to elucidate the pathogenetic basis of CMT4C and a possible association with white matter lesions.

Obsessive-compulsive disorder as a first manifestation of Ataxia with Oculomotor Apraxia type 2 due to a novel mutation of SETX gene.

Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive disorder presenting with cerebellar ataxia, sensory-motor axonal neuropathy, oculomotor apraxia, cerebellar atrophy and high alpha-fetoprotein (AFP) serum level. AOA2 is due to coding mutations of the SETX gene, mapped to chromosome 9q34. Seldom noncoding mutations affecting RNA processing have been reported too. To date psychiatric symptoms have never been reported in AOA2. A 19 years-old man came to our attention for progressive gait ataxia debuted five years earlier. His past medical history was unremarkable, while his parents were consanguineous. On neurological examination, he had bilateral horizontal gaze-evoked nystagmus with hypometric saccades and saccadic horizontal smooth pursuit, appendicular ataxia, limbs and trunk myoclonic involuntary movements with hands' dystonic postures and dance of the tendons. Psychological evaluation described intrusive and obsessive thoughts experienced by the patient, then diagnosed as obsessive-compulsive disorder. Blood tests detected an elevated AFP level. Brain MRI showed cerebellar atrophy, while electroneuromyography revealed an axonal sensory-motor polyneuropathy. In the suspicion of a pathology belonging to the autosomal recessive cerebellar ataxias (ARCA) spectrum disorder, a direct search of point mutations by whole-exome sequencing was performed revealing a novel biallelic variant in SETX gene (c.6208+2dupT), which was classified as likely pathogenic. The present case expands the genotypic and phenotypic spectrum of AOA2, reporting a novel likely pathogenic SETX mutation (c.6208+2dupT) and highlighting an early psychiatric involvement in AOA2, suggesting the need for psychiatric assessment in these neurologic patients.

Dietary phytochemical index and its relationship with diabetic sensorimotor polyneuropathy: a case-control study

Phytochemicals are compounds found in fruits, vegetables, whole grains, nuts and legumes that are non-nutritive but have bioactive properties. A high intake of these compounds is essential for optimal health and disease prevention. No study has investigated the association between Dietary Phytochemical Index (DPI) and polyneuropathy in patients with diabetes. This study aimed to examine the association between DPI and Diabetic Sensory-motor Polyneuropathy (DSPN) in a case-control study. In this case-control study, a total of 185 diabetic patients with DSPN (case group) and 185 sex- and age-matched diabetic patients without neuropathy (control group) were enrolled in this study. Participants were 30–60 years old. A validated food frequency questionnaire was used to measure the dietary intake of all participants. Daily energy derived from phytochemical-rich foods was used to calculate the DPI score. Toronto clinical neuropathy score was applied to define DSPN. Anthropometric data and fasting blood glucose levels were measured using standard methods. The Binary logistic regression was used to estimate Crude and multivariable-adjusted OR (95% CI) for DSPN across tertiles of DPI for the whole population. In the crude model, there was a significant trend across the tertile of DPI (OR highest vs. lowest tertile of DPI = 0.33; 95%CI 0.18, 0.52; P-trend < 0.001). After controlling for age, sex, and energy, a significant reverse association was observed between DPI and DSPN (OR highest vs. lowest tertile of DPI = 0.27; 95%CI 0.15, 0·48; P-trend < 0.001). Moreover, after adjusting for a wide range of confounding variables such as energy intake, physical activity, education, smoking status, and HbA1c, participants in the third tertile of DPI had 75% reduced odds for DSPN (95%CI 0.14, 0.45; P-trend < 0.001). Finally in the full adjusted model, after further adjustment for BMI, observed significant association was remained (OR highest vs. lowest tertile of DPI: 0.24; 95% CI 0.13, 0.14; P-trend < 0.001). Higher intakes of phytochemical-rich foods are associated with lower odds of DSPN.

Idiopathic Distal Sensory Polyneuropathy and Fibromyalgia Syndrome: A Comparative Phenotyping Study.

Painful idiopathic distal sensory polyneuropathy (IDSP) and fibromyalgia syndrome (FMS) are cryptogenic chronic pain syndromes. The contribution of small fibre pathology (SFP) in FMS remains controversial. This study aims to quantify small nerve pathology in participants with IDSP and FMS and identify relationships of SFP with sensory phenotypes. In this study, 73 individuals (FMS: 25, IDSP: 23, healthy volunteers: 25) underwent comprehensive assessment, including neurological exams, questionnaires, sensory tests, and corneal confocal microscopy. IDSP participants displayed lower wind-up ratio (WUR) relative to FMS (p<0.001), loss of function to thermal and mechanical stimuli and elevated neuropathy disability scores compared to FMS and healthy volunteers (all p<0.001). FMS participants demonstrated gain of function to heat and blunt pressure pain responses relative to IDSP, and healthy volunteers (heat: p=0.002 and p=0.003; pressure: both p<0.001) and WUR (both p<0.001). FMS participants exhibited reduced corneal nerve fibre density (p=0.02), while IDSP participants had lower global corneal nerve measures (density, branch density, and length) relative to healthy volunteers (all p<0.001). Utilising corneal nerve fibre length, SFP was demonstrated in 66.6% of participants (FMS: 13/25; IDSP: 22/23). Participants with SFP,in both FMS and IDSP, reported symptoms indicative of small nerve fibre disease. Although distinctions in pain distributions are evident between individuals with FMS and IDSP, over 50% of participants between the two conditions displayed both a loss and gain of thermal and mechanical function suggestive of shared mechanisms. However, sensory phenotypes were associated with the presence of SFP in IDSP but not in FMS.

Decompressive nerve surgery associated with low diabetic foot ulcer rate and high-risk bias: A systematic review and meta-analysis.

Diabetic sensorimotor polyneuropathy (DSPN) occurs in 50% of diabetes mellitus (DM) patients. Up to 70% of DM patients incur diabetic foot ulcer(s) (DFU). Of those with DSPN, 20% develop DFU and medical therapy remains challenging. Decompression nerve surgery (DNS) purportedly improves DSPN and DFU. Currently, there is no accurate, pooled DFU incidence post-DNS. Thus, this systematic review meta-analyses DFU incidence post-DNS. Given the 60% global DFU incidence, we hypothesised a lower, pooled DFU incidence following DNS. Two authors searched six databases (MEDLINE/PubMed/Web of Science/Embase/Scopus/Cochrane/Google Scholar) to July 2023 for DNS clinical studies. Primary tracked outcomes were new and recurrent DFU incidence post-DNS. Inclusion criteria: clinical studies, adult DM patients, DNS of tibial nerve(s) at minimum, three-month minimum follow-up, and reported new/recurrent DFU incidence post-DNS. Exclusion criteria: non-clinical, non-human studies. GRADE and MINORS instrument(s) evaluated evidence. With random-effects model, DFU incidence was meta-analysed. For inclusion, 1074 studies were identified and 208 screened. Thirteen studies yielded 2466 and 540 new and recurrent patients with DFU incidence(s) of 1% and 5%, respectively. Primary studies had low-level evidence and high-risk bias, including selection bias using Cochrane Collaboration Bias Risk Tool. A sub-analysis of sample size (new:0% and recurrent:2%) and follow-up length (new:1% and recurrent:7%) produced similar results. Additional analyses based on further co-variables was precluded because of incomplete primary study data. Overall, despite low DFU incidence post-DNS, clinical studies provide too low-level evidence and high-risk bias for any recommendations. Future randomized, control trials may validate DNS for DFU management.

Further insights into anti-IgLON5 disease: a case with complex clinical presentation

BackgroundAnti-IgLON5 disease is an autoimmune encephalitis overlapping with neurodegenerative disorders due to pathological accumulation of hyperphosphorylated tau. It is characterized by several clinical manifestations determined by involvement of different brain areas, and mild response to first-line immunotherapies. We report a case of anti-IgLON5 disease with a multifaceted semiology and an unusually good response to glucocorticoid monotherapy.Case presentationA 68-year-old man with type 2 diabetes was evaluated for an 8-month history of progressive gait disorder causing frequent falls. He also suffered from obstructive sleep apneas and complained of dysphonia, dysarthria, occasional dysphagia, urinary incontinence, and upper limb action tremor. Neurological examination demonstrated bilateral eyelid ptosis, limitation of ocular horizontal smooth pursuit movements, slow horizontal saccades, and lack of inhibition of the vestibulo-ocular reflex during rapid horizontal head torsions. The patient also displayed involuntary, slow, rhythmic movements of the left periorbital and perioral muscles, spreading to the ipsilateral hemipalate and hemitongue, along with bilateral negative upper limb myoclonus. There were proximal muscle wasting in the upper limbs, proximal weakness of the four limbs, and diffuse fasciculations. Ataxia of stance and gait and of the four limbs was noted. MRI of the brain and spine was unremarkable; nerve conduction studies revealed a chronic, predominantly demyelinating, sensory-motor polyneuropathy, probably due to diabetes. Routine CSF examination was unrevealing and serum GFAP level was 89.6 pg/mL; however, the autoimmunity tests revealed a high-titer positivity for anti-IgLON5 autoantibodies in both CSF and serum, leading to the diagnosis of anti-IgLON5 disease. Symptoms improved significantly after intravenous methylprednisolone.ConclusionsHemifacial and hemiorolingual myorhythmia along with peculiar oculomotor abnormalities characterizes the multifaceted clinical picture of our case. The complex semiology of our patient may reflect multifocal targeting of the autoimmune process or sequential spreading of tau inclusions in different brain areas. Our patient’s optimal response to glucocorticoid monotherapy could be underpinned by a slightly different phenotype in which autoimmunity plays a greater pathogenic role than tauopathy, with a lower burden of tau deposition. In such patients, neurodegeneration and tau accumulation could be merely secondary to immune-mediated neuronal dysfunction, supporting the existence of a group of glucocorticoid-responsive patients.

The importance of medial plantar nerve conduction study in detectıon of polyneuropathy in inflammatory bowel disease

Background &amp; Objective: Peripheral neuropathy is the most frequent neurologic complication of inflammatory bowel disease (IBD). We aimed to evaluate the clinical utility of medial plantar nerve conduction study (NCS) in the detection of distal sensory polyneuropathy in IBD patients. Methods: The study was performed with 21 Crohn’s disease (Group 1) patients, 24 Ulcerative Colitis (Group 2) patients without clinical peripheral neuropathy and 28 healthy participants (Group 3). Each patient group underwent electrophysiological conduction studies. The findings were analyzed statistically. Results: Abnormal medial plantar nerve conduction was present on both sides in 11 (24.4 %) patients with IBD; 5 (11.1 %) patients had low sural nerve amplitude, and 5 (11.1 %) had low superficial peroneal nerve amplitude bilaterally. There were significant differences between the IBD groups (Group 1 and 2) and Group 3 in the mean sensory nerve action potential amplitude of the right medial plantar nerve (p&lt;0.024), and in the mean sensory nerve action potential amplitude of the left medial plantar nerve (p&lt;0.025). The polyneuropathy pattern was mostly of the sensory axonal type in patients with IBD. Conclusions: These electrophysiologic findings indicate that peripheral neuropathy is more prevalent in IBD. In IBD patients the amplitudes of the medial plantar nerve were abnormal more than in the sural and superficial peroneal nerves.

The Association between the Severity of Distal Sensorimotor Polyneuropathy and Increased Carotid Atherosclerosis in Individuals with Type 2 Diabetes.

Diabetes contributes to a spectrum of complications encompassing microvascular and macrovascular disorders. This study aimed to explore the correlation between distal sensorimotor polyneuropathy (DSPN) severity and heightened carotid atherosclerosis among individuals with type 2 diabetes mellitus (T2DM). Method: Participants underwent comprehensive assessments including nerve conduction studies (NCS), Toronto Clinical Neuropathy Score (TCNS) evaluations, assessment of cardiometabolic risk factors, and carotid sonography studies covering dynamic and morphological parameters. The resistance index (RI), pulsatility index (PI), peak systolic velocity (PSV), and end-diastolic velocity (EDV) in both the common carotid artery (CCA) and internal carotid artery (ICA), carotid intima-media thickness (IMT), and carotid plaque score (CPS) were also measured. Peripheral nerve function severity was assessed using composite amplitude scores (CAS) derived from NCS. Individuals with DSPN exhibited lower EDV in the CCA and ICA (p < 0.0001 and p = 0.002), higher PI and RI in both CCA and ICA (all p < 0.0001), and higher CPS (p = 0.002). They also demonstrated a higher prevalence of retinopathy as an underlying condition, higher index HbA1c, and reduced estimated glomerular filtration rate (eGFR) (all p < 0.0001). Multiple linear regression analysis revealed significant associations where eGFR, ICA-PI, index HbA1c, waist circumference, and age were correlated with CAS. Meanwhile, diabetes duration, waist circumference, age, and index HbA1c showed significant associations with TCNS. Our study suggests that individuals with T2DM who exhibit more severe carotid atherosclerosis may not only be at increased risk of developing DSPN but also may experience greater severity of DSPN. PI in both the CCA and ICA, along with the CPS, serve as surrogate biomarkers for DSPN severity.

Advancing the Diagnosis of Diabetic Neuropathies: Electrodiagnostic and Skin Autofluorescence Methods.

Diabetic neuropathy (DN) is a generic term for various neuropathies coexisting in a single patient. Clinical diagnosis alone can be misleading, yet routine electrodiagnostic studies in diabetes care are rare. Skin autofluorescence (SAF) is a recognized DN risk factor with potential screening value. This article highlights the diagnostic challenges and raises awareness of the often underdiagnosed neuropathic conditions in diabetes patients. We present common entrapment neuropathy cases from our diabetes clinic's electrodiagnosis laboratory in Iași, Romania. We selected seven type 2 diabetes patients with sensory or sensory-motor distal polyneuropathy and atypical DN presentations investigated through electroneurography (ENG) and electromyography (EMG) with the Neurosoft® EMG instrument and SAF measured by standard procedures. Subsequently, a narrative literature review was conducted. Entrapment neuropathies were diagnosed in all the patients: three carpal tunnel syndromes, two ulnar neuropathies (one proximal, one distal), one peroneal neuropathy, and one case of meralgia paresthetica. The lower-limb cases showed radiculoplexopathy, and there was one case of superficial radial nerve neuropathy. The SAF values ranged from 2.5 AU to 3.4 AU. Electrodiagnosis is essential for detecting focal neuropathies in patients with sensory-motor distal polyneuropathy. Elevated SAF levels may correlate with symptom severity, although further research, including large cohorts, is needed.

Blood-based biomarkers of neuronal and glial injury in active major neuropsychiatric systemic lupus erythematosus.

Neuropsychiatric systemic lupus erythematosus (NPSLE) is a poorly understood and heterogeneous manifestation of SLE. Common major NPSLE syndromes include strokes, seizures, myelitis, and aseptic meningitis. Easily obtainable biomarkers are needed to assist in early diagnosis and improve outcomes for NPSLE. A frequent end-result of major syndromes is neuronal or glial injury. Blood-based neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) have been utilized as markers for monitoring disease activity and/or severity in other neurodegenerative and neuroinflammatory diseases; however, they have not been evaluated in active major NPSLE. This was a case-control study. We enrolled patients aged 12-60 years with active major NPSLE, SLE without active major NPSLE, and healthy controls. Active NPSLE was defined as being <6months from last new or worsening neuropsychiatric symptom. Demographics, clinical data, and serum or plasma biosamples were collected. Thirteen patients with active major NPSLE, 13age/sex/kidney function matched SLE controls without active major NPSLE, and 13age/sex matched healthy controls (mean ages 26.8, 27.3, 26.6years) were included. 92% of each group were female. Major syndromes included stroke (5), autonomic disorder (3), demyelinating disease (2), aseptic meningitis (2), sensorimotor polyneuropathy (2), cranial neuropathy (1), seizures (1), and myelopathy (2). Mean (standard deviation) blood NfL and GFAP were 3.6 pg/ml (2.0) and 50.4 pg/ml (15.0), respectively, for the healthy controls. Compared to healthy controls, SLE without active major NPSLE had mean blood NfL and GFAP levels 1.3pg/ml (p = .42) and 1.2pg/ml higher (p = .53), respectively. Blood NfL was on average 17.9 pg/ml higher (95% CI: 9.2, 34.5; p < .001) and blood GFAP was on average 3.2pg/ml higher (95% CI: 1.9, 5.5; p < .001) for cases of active major NPSLE compared to SLE without active major NPSLE. In a subset of 6 patients sampled at multiple time points, blood NfL and GFAP decreased after immunotherapy. Blood NfL and GFAP levels are elevated in persons with SLE with active major NPSLE compared to disease matched controls and may lower after immunotherapy initiation. Larger and longitudinal studies are needed to ascertain their utility in a clinical setting.

Schwann cell JUN expression worsens motor performance in an amyotrophic lateral sclerosis mouse model.

Amyotrophic lateral sclerosis is a devastating neurodegenerative disease characterized by motor neuron death and distal axonopathy. Despite its clinical severity and profound impact in the patients and their families, many questions about its pathogenesis remain still unclear, including the role of Schwann cells and axon-glial signaling in disease progression. Upon axonal injury, upregulation of JUN transcription factor promotes Schwann cell reprogramming into a repair phenotype that favors axon regrowth and neuronal survival. To study the potential role of repair Schwann cells on motoneuron survival in amyotrophic lateral sclerosis, we generated a mouse line that over-expresses JUN in the Schwann cells of the SOD1G93A mutant, a mouse model of this disease. Then, we explored disease progression by evaluating survival, motor performance and histology of peripheral nerves and spinal cord of these mice. We found that Schwann cell JUN overexpression does not prevent axon degeneration neither motor neuron death in the SOD1G93A mice. Instead, it induces a partial demyelination of medium and large size axons, worsening motor performance and resulting in more aggressive disease phenotype.

Comparative Analysis of Diabetic Neuropathy Examination Scores and Nerve Conduction Velocity in Patients with Diabetic Neuropathy

Background: Diabetic neuropathy is a prevalent consequence of diabetes, resulting in substantial morbidity. Precise evaluation is essential for prompt intervention and control. The study assessed the correlation and effectiveness of the Diabetic Neuropathy Examination (DNE) scores and Nerve Conduction Velocity (NCV) as diagnostic tools in individuals with diabetic neuropathy. Methods: An observational research was done, comprising 200 diabetic patients who were diagnosed with diabetic sensory-motor polyneuropathy. Participants completed Dynamic Neuromuscular Examination (DNE) grading and Nerve Conduction Velocity (NCV) testing. The data were analysed using SPSS version 20.0. Results: The study found a considerable negative correlation (r = -0.68, p &lt; 0.001) between DNE scores and NCV results. Higher DNE scores were associated with lower NCV values. Specifically, 20% of participants had mild neuropathy, 40% had moderate neuropathy, and 40% had severe neuropathy according to DNE scores. NCV testing revealed that 65% of participants had abnormal nerve conduction, with 25% showing mild reduction, 25% moderate reduction, and 15% severe reduction. Multivariate regression confirmed that DNE scores are significant predictors of NCV outcomes (Beta = -0.52, p &lt; 0.001), even after adjusting for confounding variables such as gender, age, diabetes duration, and HbA1C levels. Conclusion: DNE scoring is a reliable tool for assessing neuropathy severity in diabetic patients, correlating well with NCV results. Integrating DNE scoring in routine clinical practice can enhance the early detection and management of diabetic neuropathy. Recommendations: Routine use of DNE scoring along with NCV testing is recommended for comprehensive evaluation of diabetic neuropathy. Further research should explore additional diagnostic tools to improve early detection and intervention. Keywords: Diabetic Neuropathy, Diabetic Neuropathy Examination Score, Nerve Conduction Velocity Testing, Diabetic Polyneuropathy, Neuropathy Assessment..

Muscle Network Connectivity Study in Diabetic Peripheral Neuropathy Patients.

Diabetic peripheral neuropathy (DPN) is a prevalent complication of chronic diabetes mellitus and has a significant impact on quality of life. DPN typically manifests itself as a symmetrical, length-dependent sensorimotor polyneuropathy with severe effects on gait. Surface electromyography (sEMG) is a valuable low-cost tool for assessing muscle activation patterns and precise identification of abnormalities. For the present study, we used information theory methods, such as cross-correlation (CC), normalized mutual information (NMI), conditional granger causality (CG-Causality), and transfer entropy (TE), to evaluate muscle network connectivity in three population groups: 33 controls (healthy volunteers, CT), 10 diabetic patients with a low risk of DPN (LW), and 17 moderate/high risk patients (MH). The results obtained indicated significant alterations in the intermuscular coupling mechanisms due to diabetes and DPN, with the TE group showing the best performance in detecting differences. The data revealed a significant increase in information transfer and muscle connectivity in the LW group over the CT group, while the MH group obtained significantly lower values for these metrics than the other two groups. These findings highlight the sEMG coupling metrics' potential to reveal neuromuscular mechanisms that could aid the development of targeted rehabilitation strategies and help monitor DPN patients.