Polyneuropathy Type Research Articles

Low serum CTRP3 is related to more severe distal symmetric polyneuropathy in type 2 diabetes patients.

Distal symmetric polyneuropathy (DSPN) is one of the most common chronic complications in patients with type 2 diabetes mellitus (T2DM). Our previous study found that serum C1q tumor necrosis factor-related protein 3 (CTRP3) levels were decreased in type 2 diabetic patients. Thus, this study was designed to reveal the relationship between low serum CTRP3 and the prevalence and severity of DSPN. A total of 178 cases of patients with T2DM were enrolled in the study. The subjects were divided into the DSPN group (n = 89) and the non-DSPN group (n = 89). Both anthropometric parameters and neurologic symptoms were recorded. Furthermore, neurologic signs, the neuropathy symptom score (NSS), and the neuropathy disability score (NDS) were assessed. Biochemical indexes, fasting insulin, and C peptide were measured. Serum CTRP3 concentrations were assayed using the ELISA method. Serum CTRP3 levels decreased significantly in the DSPN group compared with the non-DSPN group (P < 0.05). CTRP3 was negatively associated with the number of positive signs, NSS score, and NDS score in patients with DSPN (all P < 0.05). Interestingly, the higher the NSS score or NDS score, the lower were the levels of serum CTRP3 (all P < 0.05). Moreover, patients with lower CTRP3 levels (< 7.58ng/ml) had a higher rate of neurologic signs (all P < 0.05). Binary logistic regression analysis showed that CTRP3 independently predicted the occurrence of DSPN (β = -0.316, P < 0.001). ROC curve analysis revealed that the best cut-off value of CTRP3 for the prediction of DSPN was 7.55ng/ml (sensitivity 78.7%, specificity 79.8%), the area under the curve (AUC) was 0.763 (95% CI 0.689-0.838, P < 0.001). Low serum CTRP3 could be a predictor for the occurrence and progression of DSPN in Chinese patients with T2DM.

Diagnosis of diabetic polyneuropathy in type 2 diabetes mellitus: focus on changes in peripheral nerves according to ultrasonic research method

Diagnosis of diabetic polyneuropathy in type 2 diabetes mellitus: focus on changes in peripheral nerves according to ultrasonic research method

Modern view on the use of alpha lipoic acid in neurological practice

Modern view on the use of alpha lipoic acid in neurological practice

COVID-19 and Neuromuscular Involvement: A Case Series and Brief Review of Literature

Background: Tough COVID-19 predominantly affects the respiratory tract, and extra-pulmonary manifestations, including neuromuscular complaints have been associated with this disorder. It is vital to monitor COVID-19 cases for the occurrence of Neuromuscular Disorders (NMDs), which could be overshadowed by severe respiratory and cardiovascular symptoms. In this study, we reported electrophysiological findings of a series of COVID-19 patients with complaints of paresthesia and weakness. Methods: In this case series, the Electrodiagnostic studies (EDX) of 36 patients with recent complaints of weakness or paresthesia and a history of COVID-19 before symptoms were reported. Results: 12 cases (33.3%) had abnormal EDX, five males and seven females, with a mean age of 51.42±11.49 years, history of hospitalization in five cases (41.7%), and ICU admission in four (33.3%). Seven cases were concluded as having a predominantly axonal type polyneuropathy (five sensory-motor and two sensory polyneuropathies). Of these seven, one was suggestive of Critical Illness Neuropathy (CIN). Three cases demonstrated a myopathic pattern with a history of ICU admission, hence the impression of Critical Illness Myopathy (CIM). In addition, one of these three, developed both myopathy and neuropathy and thus, is considered as having CIM/N. One case was diagnosed with Chronic Inflammatory Demyelinating Polyneuropathy (CIDP). The last case demonstrated an inflammatory involvement of lumbosacral roots (COVID-19-related radiculitis). Conclusion: COVID-19 could be associated with a wide range of NMDs. In this study, the presence of axonal polyneuropathy, CIDP, and myopathy was demonstrated following SAR-COV-2 infection. Also, CIN/M was observed in COVID-19 patients with a history of ICU admission

Typical CIDP, distal variant CIDP, and anti-MAG antibody neuropathy: An ultra-high frequency ultrasound comparison of nerve structure

To date, little is known about the usefulness of ultra-high frequency ultrasound (UHF-US, 50–70 MHz) in clinical practice for the diagnosis of dysimmune neuropathies. We present a prospective study aimed at comparing UHF-US alterations of nerves and fascicles in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), distal CIDP (d-CIDP) and anti-MAG neuropathy and their relationships with clinical and electrodiagnostic (EDX) features. 28 patients were included (twelve CIDP, 6 d-CIDP and 10 anti-MAG) and ten healthy controls. Each patient underwent neurological examination, EDX and UHF-US study of median and ulnar nerves bilaterally. UHF-US was reliable in differentiating immune neuropathies from controls when using mean and/or segmental nerve and/or fascicle cross-sectional area (CSA); furthermore, fascicle ratio (fascicle/nerve CSA) was a reliable factor for differentiating d-CIDP from other types of polyneuropathies. The fascicle CSA appears to be more increased in CIDP and its variant than in anti-MAG neuropathy. UHF-US offers information beyond simple nerve CSA and allows for a better characterization of the different forms of dysimmune neuropathies.

Detection of TTR Amyloid in the Conjunctiva Using a Novel Fluorescent Ocular Tracer.

Transthyretin amyloidosis (ATTR) is a significant cause of cardiomyopathy and other morbidities in the elderly and Black Americans. ATTR can be treated with new disease-modifying therapies, but large shortfalls exist in its diagnosis. The objective of this study was to test whether TTR amyloid can be detected and imaged in the conjunctiva using a novel small-molecule fluorescent ocular tracer, with the implication that ATTR might be diagnosable by a simple eye examination. Three approaches were used in this study. First, AMDX-9101 was incubated with in vitro aggregated TTR protein, and changes in its excitation and emission spectra were quantified. Second, a cadaver eye from a patient with familial amyloid polyneuropathy type II TTR mutation and a vitrectomy sample from an hATTR patient were incubated with AMDX-9101 and counterstained with Congo Red and antibodies to TTR to determine whether AMDX-9101 labels disease-related TTR amyloid deposits in human conjunctiva and eye. Last, imaging of in vitro aggregated TTR amyloid labeled with AMDX-9101 was tested in a porcine ex vivo model, using a widely available clinical ophthalmic imaging device. AMDX-9101 hyper-fluoresced in the presence of TTR amyloid in vitro, labeled TTR amyloid deposits in postmortem human conjunctiva and other ocular tissues and could be detected under the conjunctiva of a porcine eye using commercially available ophthalmic imaging equipment. AMDX-9101 enabled detection of TTR amyloid in the conjunctiva, and the fluorescent binding signal can be visualized using commercially available ophthalmic imaging equipment. AMDX-9101 detection of TTR amyloid may provide a potential new and noninvasive test for ATTR that could lead to earlier ATTR diagnosis, as well as facilitate development of new therapeutics.

MILLER FISHER SYNDROME: A RARE BENIGN VARIANT OF GUILLAIN- BARRE SYNDROME

Abstract&#x0D; Introduction : Guillain-Barré Syndrome (GBS) is a broad category of syndromes that includes several types of acute immune-mediated polyneuropathy. Miller Fisher Syndrome (MFS) is a scarce variant of GBS (1-2:1,000,000) that presents at least 2 of ataxia, areflexia, and ophthalmoplegia.&#x0D; Case Illustration : A 32 years-old-man came to JEC-Candi with ophthalmic discomfort and exhibited a week onset of total ophthalmoplegia, ptosis, diplopia, and lagophthalmos. Two weeks backward, the patient had a respiratory infection then emerged symmetrical sensory abnormalities (glove-and-stocking-type pinprick sensations in distal extremities). Neurological examinations were performed, and the patient got multiple cranial nerve weaknesses (oculomotor, trochlear, abducens, trigeminal, and facial) both in motoric and sensory, ataxia (positive Romberg sign, stepping test, gait, shallow-knee- bend), and negative pathologic reflexes. Hematology showed leukocytosis, MRI and CT-Scan were normal. Pulse therapy was given (Methylprednisolone 1g/day) for three days, neuroprotector and artificial tears added. Ataxia and diplopia improved, then the patient was referred to Kariadi Hospital for five-times plasmapheresis that involved neurologist and internist. Ophthalmoplegia improved slowly, and lagophthalmos disappeared one month after hospital admission.&#x0D; Discussion : GBS subvariant could overlap; this case presents bifacial weakness with paresthesia and MFS. Viral infection precedes neurological symptoms in most cases, with an average of 10 days of the incubation period. Ataxia, diplopia, and ophthalmoplegia may confuse the physician and presume an upper motor neuron sign or central cause. Steroid and plasmapheresis evince meaningful upturn.&#x0D; Conclusion : This rare disease requires a multidisciplinary approach to cure and diagnose. Nonetheless, MFS has a good prognosis. Appropriate treatment selection will enhance patients' quality of life.

Critical Magnesium and HbA1c Cut-off Values for the Development of Polyneuropathy in Type 2 Diabetes Patients in Ankara City Hospital Between 2021-2023

Critical Magnesium and HbA1c Cut-off Values for the Development of Polyneuropathy in Type 2 Diabetes Patients in Ankara City Hospital Between 2021-2023

Phase Angle of Bioelectrical Impedance Analysis as an Indicator for Diabetic Polyneuropathy in Type 2 Diabetes Mellitus.

Due to the heterogenous clinical symptoms and deficits, the diagnosis of diabetic polyneuropathy (DPN) is still difficult in clinical routines, leading to increased morbidity and mortality. We studied the correlation of phase angle (PhA) of bioelectrical impedance analysis (BIA) with clinical, laboratory, and physical markers of DPN to evaluate PhA as a possible diagnostic method for DPN. In this cross-sectional observational study as part of the Heidelberg Study on Diabetes and Complications, we examined 104 healthy individuals and 205 patients with type 2 diabetes mellitus (T2D), among which 63 had DPN. The PhA was calculated from multifrequency BIA. Nerve conduction studies, quantitative sensory testing (QST) and diffusion-weighted magnetic resonance neurography to determine fractional anisotropy (FA) reflecting peripheral nerve integrity were performed. T2D patients with DPN had lower PhA values (5.71 ± 0.10) compared to T2D patients without DPN (6.07 ± 0.08, P = .007, + 6.1%) and healthy controls (6.18 ± 0.08, P < .001, + 7.9%). Confounder-adjusted analyses showed correlations of the PhA with conduction velocities and amplitudes of the peroneal (β=.28; β=.31, P < .001) and tibial nerves (β=.28; β=.32, P < .001), Z-scores of QST (thermal detection β=.30, P < .05) and the FA (β=.60, P < .001). Receiver-operating characteristic analysis showed similar performance of PhA in comparison to the mentioned diagnostic methods. The study shows that PhA is, in comparison to other test systems used, at least an equally good and much easier to handle investigator-independent marker for detection of DPN.

Sural nerve involvement in patients with acute inflammatory demyelinating polyneuropathy variant of Guillain-Barre syndrome with sural sparing at initial presentation

Introduction: Neurophysiological testing is a valuable tool in the diagnosis of Guillain-Barre syndrome (GBS). Sural sparing is a usual feature of acute inflammatory demyelinating polyneuropathy (AIDP) type GBS. However, sural involvement has been reported in later stages of GBS. It is important to identify patterns of sural nerve involvement to differentiate GBS from its mimickers and to stage the disease. This research aimed to detect the pattern of sural nerve involvement in AIDP-GBS cases with normal electrophysiological responses in the sural nerve at the beginning.Objectives: To determine the location and timing of sural nerve involvement in AIDP-GBS.Methods: This prospective follow up study included diagnosed cases of AIDP-GBS with preserved bilateral sural responses. Nerve conduction and somatosensory evoked potentials (SSEP) were done on admission and weekly thereafter for four consecutive weeks. The last evaluation was done four weeks after the fourth study.Results: All patients (100%) showed normal distal sural responses over the initial four weeks of follow up. They continued to remain normal up to eight weeks in eight patients (53.3%). Two patients had gradual prolongation of their sural SSEP on consecutive studies. One of them had gradual reduction of sural sensory nerve action potential and nerve conduction velocity along with the prolongation of sural SSEP latencies. The difference of SSEP latency increments in the left sural nerve of these two patients was statistically significant (p&lt;0.05). The right sural SSEP latency difference was not significant.Conclusion: Sparing of the distal sural sensory response was demonstrated in 100% of AIDP-GBS cases during the first four weeks of follow up. More than 50% of the cohort demonstrated preserved sural sensory responses for eight weeks from the initial presentation. Two out of fifteen patients showed statistically significant proximal sural sensory pathway involvement with increasing SSEP latencies. This finding suggests that in some patients, the sural sensory pathway may get affected at its proximal segments or at the central nervous system before the distal nerve is affected.

DEVELOPMENT OF PATHOLOGICAL CHANGES IN THE ORAL CAVITY ORGANS OF ANIMALS UNDER CONDITIONS OF POLYNEUROPATHIES OF DIFFERENT GENESIS

The aim of our research is to study the effect of polyneuropathy of different genesis on the development of pathological changes in the large salivary glands and periodontal tissues of animals. Methods. The study was conducted on 62 laboratory rats of both sexes. Toxic polyneuropathy was induced by paclitaxel injection, experimental type 1 diabetes mellitus was modeled by streptozocin injection, and alcoholic polyneuropathy was induced by chronic administration of increasing concentrations of ethanol. The development of polyneuropathy was confirmed by a change in the the pain sensitivity threshold (PST) using the Randall-Selitto tensoalgometric method. In the homogenate of oral cavity organs, total proteolytic and total antitryptic activity, catalase activity, content of TBARS, average mass molecules, oxidatively modified proteins, fucose and glycosaminoglycans (GAG), and amylase activity were determined. The level of total, protein-bound and non-protein sulfhydryl groups, activity of superoxide dismutase, glutathione peroxidase, glutathione transferase, glutathione reductase; content of reduced and oxidized glutathione, diene conjugates and Schiff bases were determined in blood serum. Results. We established the increasing of PST in animals that were simulated neuropathies of different genesis. All three types of polyneuropathies are accompanied by the development of carbonyl-oxidative stress in the soft tissues of the periodontium and large salivary glands of rats, which is evidenced by a probable increase in the content of oxidatively modified proteins and the content of TBARS, as well as average mass molecules compared to these indicators in intact animals . Under the conditions of modeling all three polyneuropathies, the protein-synthetic activity in the large salivary glands is suppressed, as evidenced by a decrease in the activity of α-amylase. Under conditions of experimental diabetic and toxic neuropathy in the salivary glands of animals, changes in the proteinase-inhibitor balance of the compensatory type are observed. We found that polyneuropathies of different genesis cause increased catabolism of biopolymers of the extracellular matrix of the periodontal connective tissue of rats, which confirms the increase in the content of GAG and fucose compared to these indicators in control animals. Conclusions. Under conditions of diabetic, toxic and alcoholic neuropathy, the amylolytic activity of the large salivary glands of animals is suppressed, the balance of the pro- and antioxidant system changes. When modeling peripheral polyneuropathy in animals by administration of paclitaxel, streptozocin, and ethanol, the development of periodontal syndrome is observed, the leading pathogenetic mechanisms of which are increased catabolism of connective tissue glycoconjugates and the development of oxidative stress and proteinase-inhibitor imbalance.

Serum neurofilament light chain – A potential biomarker for polyneuropathy in type 2 diabetes?

AimsTo investigate the relationship between neurofilament light chain (NfL) and the presence and severity of diabetic polyneuropathy (DPN). MethodsWe performed cross-sectional analysis of data from 178 participants of the ADDITION-Denmark cohort of people with screen-detected type 2 diabetes and 32 healthy controls. Biobank serum samples were analyzed for NfL using single-molecule array. DPN was defined by Toronto criteria for confirmed DPN. Original and axonal nerve conduction study (NCS) sum z-scores were used as indicators of the severity of DPN and peripheral nerve damage. Results39 (21.9%) participants had DPN. Serum NfL (s-NfL) was significantly higher in participants with DPN (18.8 ng/L [IQR 14.4; 27.9]) than in participants without DPN (15.4 ng/L [IQR 11.7; 20.1]). There were no unadjusted s-NfL differences between controls (17.6 ng/L [IQR 12.7; 19.8]) and participants with or without DPN. Higher original and axonal NCS sum z-scores were associated with 10% higher s-NfL (10.2 and 12.1% [95% CI’s 4.0; 16.8 and 6.6; 17.9] per 1 SD). The AUC of s-NfL for DPN was 0.63 (95% CI 0.52; 0.73). ConclusionsS-NfL is unlikely to be a reliable biomarker for the presence of DPN. S-NfL is however associated tothe severity of the nerve damage underlying DPN.

THU343 Potential Association Among Enteroviruses, Acute Flaccid Myelitis And Type 1 Diabetes

Abstract Disclosure: T.A. Nguyen: None. K. Huynh: None. M. Azad: None. J.P. Perdomo Rodriguez: None. Non-polio enteroviruses, like EV-D68, caused a nationwide outbreak of respiratory illness in the US in 2014, most recently in the fall of 2021. It has been shown that EV-D68 plays a role in causing acute flaccid myelitis (AFM). In addition, the association between enterovirus infections and type 1 diabetes (T1DM) has been widely studied and established. We report a case in which a 19-year-old male consulted for progressively ascending bilateral weakness in the lower extremities. Four weeks prior, he was diagnosed with T1DM and diabetic ketoacidosis (DKA). On exam, he had decreased sensation to light touch, vibration, and temperature below the knees, decreased motor strength 2/5 in bilateral lower extremities, and absence of patellar and Achille reflexes. Thyroid tests, Creatinine Kinase, Aldolase, and vitamin B12 were all normal. Spine MRI showed an enhancement along the L5 and sacral roots. CSF studies were significant for the positive oligoclonal band, the elevated protein level (87gm/dL), and no white blood cell count. CSF gram stain was negative for any organisms. EBV, HSV, and HIV testing were negative. A nonspecific respiratory panel only performed at the time of diagnosis with AFM was negative. The electromyogram did not show any type of acute inflammatory demyelinating polyneuropathy or evidence of myopathy. CT abdomen/pelvis demonstrated mild splenomegaly with small swollen lymph nodes of the periaortic and mesenteric area, which are commonly seen in viral infections. A Digital Subtraction Angiography study did not show any abnormality in spinal vessels. The patient received immunoglobulin and steroid, which was stopped early due to bradycardia and hyperglycemia. Neurology diagnosed the patient with AFM secondary to viral infection, in which the patient may have been infected prior to his diagnosis of DKA. The patient’s weakness resolved, and he was discharged with basal-bolus insulin and is to follow up with neurology and endocrinology outpatient. Enterovirus infection has been associated with T1DM and AFM. While the Respiratory PCR Panel was negative, it was only obtained several weeks after the onset of symptoms. Pathogenesis of extra-respiratory complications of enteroviruses may associate with viremia and systemic dissemination of the virus, which may not be detected by a respiratory PCR panel. Infection by an enterovirus remains the most likely etiology for both immune-mediated disorders, especially during a nationwide outbreak. We recommend providers consider enterovirus infection as a potential cause of AFM, and autoimmune diabetes in order to perform a throughout workup. In a patient with hyperglycemia and flaccid paralysis, T1DM should be suspected. Presentation: Thursday, June 15, 2023

Structural changes in Schwann cells and nerve fibres in type 1 diabetes: relationship with diabetic polyneuropathy

Aims/hypothesisOur aim was to investigate structural changes of cutaneous Schwann cells (SCs), including nociceptive Schwann cells (nSCs) and axons, in individuals with diabetic polyneuropathy. We also aimed to investigate the relationship between these changes and peripheral neuropathic symptoms in type 1 diabetes.MethodsSkin biopsies (3 mm) taken from carefully phenotyped participants with type 1 diabetes without polyneuropathy (T1D, n=25), type 1 diabetes with painless diabetic polyneuropathy (T1DPN, n=30) and type 1 diabetes with painful diabetic polyneuropathy (P-T1DPN, n=27), and from healthy control individuals (n=25) were immunostained with relevant antibodies to visualise SCs and nerve fibres. Stereological methods were used to quantify the expression of cutaneous SCs and nerve fibres.ResultsThere was a difference in the number density of nSCs not abutting to nerve fibres between the groups (p=0.004) but not in the number density of nSCs abutting to nerve fibres, nor in solitary or total subepidermal SC soma number density. The overall dermal SC expression (measured by dermal SC area fraction and subepidermal SC process density) and peripheral nerve fibre expression (measured by intraepidermal nerve fibre density, dermal nerve fibre area fraction and subepidermal nerve fibre density) differed between the groups (all p<0.05): significant differences were seen in participants with T1DPN and P-T1DPN compared with those without diabetic polyneuropathy (healthy control and T1D groups) (all p<0.05). No difference was found between participants in the T1DPN and P-T1DPN group, nor between participants in the T1D and healthy control group (all p>0.05). Correlational analysis showed that cutaneous SC processes and nerve fibres were highly associated, and they were weakly negatively correlated with different neuropathy measures.Conclusions/interpretationCutaneous SC processes and nerves, but not SC soma, are degenerated and interdependent in individuals with diabetic polyneuropathy. However, an increase in structurally damaged nSCs was seen in individuals with diabetic polyneuropathy. Furthermore, dermal SC processes and nerve fibres correlate weakly with clinical measures of neuropathy and may play a partial role in the pathophysiology of diabetic polyneuropathy in type 1 diabetes.Graphical

The Prevalence of Polyneuropathy in Type 2 Diabetes Subgroups Based on HOMA2 Indices of β-Cell Function and Insulin Sensitivity.

Metabolic syndrome components may cumulatively increase the risk of diabetic polyneuropathy (DPN) in type 2 diabetes mellitus (T2DM) patients, driven by insulin resistance and hyperinsulinemia. We investigated the prevalence of DPN in three T2DM subgroups based on indices of β-cell function and insulin sensitivity. We estimated β-cell function (HOMA2-B) and insulin sensitivity (HOMA2-S) in 4,388 Danish patients with newly diagnosed T2DM. Patients were categorized into subgroups of hyperinsulinemic (high HOMA2-B, low HOMA2-S), classical (low HOMA2-B, low HOMA2-S), and insulinopenic (low HOMA2-B, high HOMA2-S) T2DM. After a median follow-up of 3 years, patients filled the Michigan Neuropathy Screening Instrument questionnaire (MNSIq) to identify DPN (score ≥ 4). We used Poisson regression to calculate adjusted prevalence ratios (PRs) for DPN, and spline models to examine the association with HOMA2-B and HOMA2-S. A total of 3,397 (77%) patients filled in the MNSIq. The prevalence of DPN was 23% among hyperinsulinemic, 16% among classical, and 14% among insulinopenic patients. After adjusting for demographics, diabetes duration and therapy, lifestyle behaviors, and metabolic syndrome components (waist circumference, triglycerides, HDL cholesterol, hypertension, and HbA1c), the PR of DPN was 1.35 (95% CI 1.15-1.57) for the hyperinsulinemic compared with the classical patients. In spline analyses, we observed a linear relation of higher DPN prevalence with increasing HOMA2-B, independent of both metabolic syndrome components and HOMA2-S. Hyperinsulinemia marked by high HOMA2-B is likely an important risk factor for DPN beyond metabolic syndrome components and insulin resistance. This should be considered when developing interventions to prevent DPN.

Nociceptive flexion reflex in small fibers neuropathy and pain assessments†.

The nociceptive flexion reflex (NFR) is a polysynaptic and multisegmental spinal reflex that develops in response to a noxious stimulus and is characterized by the withdrawal of the affected body part. The NFR possesses two excitatory components: early RII and late RIII. Late RIII is derived from high-threshold cutaneous afferent A-delta fibers, which are prone to injury early in the course of diabetes mellitus (DM) and may lead to neuropathic pain. We investigated NFR in patients with DM with different types of polyneuropathies to analyze the role of NFR in small fiber neuropathy (SFN). We included 37 patients with DM and 20 healthy participants of similar age and sex. We performed the Composite Autonomic Neuropathy Scale-31, modified Toronto Neuropathy Scale, and routine nerve conduction studies. We grouped the patients into large fiber neuropathy (LFN), SFN, and no overt neurological symptom/sign groups. In all participants, NFR was recorded on anterior tibial (AT) and biceps femoris (BF) muscles after train stimuli on the sole of the foot, and NFR-RIII findings were compared. We identified 11 patients with LFN, 15 with SFN, and 11 with no overt neurological symptoms or signs. The RIII response on the AT was absent in 22 (60%) patients with DM and 8 (40%) healthy participants. The RIII response on the BF was absent in 31 (73.8%) patients and 7 (35%) healthy participants (P = .001). In DM, the latency of RIII was prolonged, and the magnitude was reduced. Abnormal findings were seen in all subgroups; however, they were more prominent in patients with LFN compared to other groups. The NFR-RIII was abnormal in patients with DM even before the emergence of the neuropathic symptoms. The pattern of involvement before neuropathic symptoms was possibly related to an earlier loss of A-delta fibers.

1008 Excessive daytime sleepiness in myotonic dystrophy treated with modafinil

Abstract Introduction Physiology of excessive daytime sleepiness (EDS) in myotonic dystrophy type 1 (DM1) remains incompletely understood and best practice treatment approaches are unclear. Report of case(s) We present a 73-year-old man with atrial fibrillation, implantable cardioverter defibrillator for inducible ventricular tachycardia, hypertension, and severe obstructive sleep apnea (OSA) was referred after a recent diagnosis of myotonic dystrophy type 1 (DM1) for EDS. He presented with foot pain, balance issues, and falls. A subdural hemorrhage from a fall prompted thorough evaluation including electromyography. This showed length-dependent polyneuropathy type pattern with features of subacute and chronic denervation change and myotonic discharges in right vastus medialis and bilateral tibialis anterior and gastrocnemius muscles. Myotonic Syndrome Advanced Evaluation revealed with a repeat expansion mutation in DMPK gene (85 and 13 CTG repeats). He was previously diagnosed severe OSA with an AHI of 64 and titrated onto bilevel. He recalled no improvement in symptoms with bilevel. He noted sleeping 10-12 hours per night and feeling rested. However, he takes multiple times per day for hours at a time. When actively working on tasks he feels alert and focused. Epworth sleepiness scale (ESS) was 12. Polysomnogram on bilevel followed by MSLT demonstrated control of OSA and mean sleep onset latency of 8 minutes and 5 sleep onset REM periods. With relatively little impairment and a desire for intermittent improved wakefulness, he was started on modafinil 200mg daily as needed. He reported a robust response to modafinil without the need for additional naps or cardiac complications thus far. Repeat ESS only improved to 10. Conclusion This case highlights the need for a precision medicine approach as subpopulations exist even within the specific diagnosis excessive daytime sleepiness in myotonic dystrophy. People with DM1 have been similarly reported with little improvement in ESS but dramatic subjective improvement in symptoms with modafinil. A Cochrane Review and a European Medicines Agency recommendations on modafinil are not supportive of its use in DM1 despite a subpopulation with a clear response. Interestingly, clinical measures do not seem to predict response to modafinil, suggesting unmeasured and, potentially, varied pathologies of excessive daytime sleepiness in DM1. Support (if any)

Abstract #1408228: Potential Association Among Enteroviruses, Acute Flaccid Myelitis and Type 1 Diabetes

Non-polio enteroviruses, like EV-D68, caused a nationwide outbreak of respiratory illness in the US in the fall of 2021. It has been shown that EV-D68 plays a role in causing acute flaccid myelitis (AFM). In addition, the association between enterovirus infections and type 1 diabetes (T1DM) has been widely studied and established. We report a case in which a 19-year-old male consulted for progressively ascending bilateral weakness in the lower extremities. Four weeks prior, he was diagnosed with T1DM and diabetic ketoacidosis (DKA). On exam, he had decreased sensation to light touch, vibration, and temperature below the knees, decreased motor strength 2/5 in bilateral lower extremities, and absence of patellar and Achille reflexes. Thyroid tests, Creatinine Kinase, Aldolase, and vitamin B12 were all normal. Spine MRI showed an enhancement along the L5 and sacral roots. CSF studies were significant for the positive oligoclonal band, the elevated protein level (87gm/dL), and no white blood cell count. CSF gram stain was negative for any organisms. EBV, HSV, and HIV testing were negative. A nonspecific respiratory panel only performed at the time of diagnosis with AFM was negative. The electromyogram did not show any type of acute inflammatory demyelinating polyneuropathy or evidence of myopathy. CT abdomen/pelvis demonstrated mild splenomegaly with small swollen lymph nodes of the periaortic and mesenteric area, which are commonly seen in viral infections. A Digital Subtraction Angiography study did not show any abnormality in spinal vessels. The patient received immunoglobulin and steroid, which was stopped early due to bradycardia and hyperglycemia. Neurology diagnosed the patient with AFM secondary to viral infection, in which the patient may have been infected prior to his diagnosis of DKA. The patient’s weakness resolved, and he was discharged with basal-bolus insulin and is to follow up with neurology and endocrinology outpatient. Enterovirus infection has been associated with T1DM and AFM. While the Respiratory PCR Panel was negative, it was only obtained several weeks after the onset of symptoms. Pathogenesis of extra-respiratory complications of enteroviruses may associate with viremia and systemic dissemination of the virus, which may not be detected by a respiratory PCR panel. Infection by an enterovirus remains the most likely etiology for both immune-mediated disorders, especially during a nationwide outbreak. We recommend providers consider enterovirus infection as a potential cause of AFM, and autoimmune diabetes in order to perform a throughout workup. In a patient with hyperglycemia and flaccid paralysis, T1DM should be suspected.

Multiparametric Quantitative MRI of Peripheral Nerves to Differentiate Axonal from Demyelinating Neuropathies (P11-8.002)

<h3>Objective:</h3> To develop a multiparametric quantitative MRI (qMRI) method to track pathological changes of peripheral nerves in patients with peripheral neuropathies. <h3>Background:</h3> Irrespective of the causes or types of polyneuropathies, peripheral nerves are mainly afflicted by two kinds of pathologies – axonal loss and demyelination. It is critical to differentiate the two as treatments are different for the two conditions. While nerve conduction studies (NCS) have been used to differentiate the two pathologies in the distal nerves, there are no tools to probe the pathologies in the proximal peripheral nerves. This is particularly needed when distal nerves become non-responsive in NCS. <h3>Design/Methods:</h3> We have developed a multiparametric qMRI method that quantifies the sciatic and tibial nerves with 10 parameters that are sensitive to different aspects of myelin and axonal pathologies: magnetization transfer ratio (MTR), magnetization transfer saturation index (MTsat), longitudinal relaxation time (T1), proton density (PD), effective transverse relaxation time (T2*), fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), and nerve fascicular volume (fVol). In this pilot study, we studied 4 patients with Charcot-Marie-Tooth type-1A (CMT1A), 2 patients with CMT type-2S (CMT2S), and 17 healthy controls. <h3>Results:</h3> Compared with healthy controls, patients with CMT2S (reportedly as axonal type) had comparable MTR, MTsat, T1, PD and fVol, but reduced T2*. While patients with CMT1A (dysmyelinating type) had reduced MTR and MTsat, increased fVol, T1 and PD, and comparable T2*. All the 6 patients shared changes of reduced FA which was driven by a reduced AD and an increased RD. <h3>Conclusions:</h3> The data show different qMRI patterns between axonal and demyelinating neuropathies. The differential changes will be further verified in a larger cohort of patients with peripheral neuropathies. <b>Disclosure:</b> Dr. Chen has nothing to disclose. Mr. Baraz has nothing to disclose. Ms. Xuan has nothing to disclose. Sadaf Saba has nothing to disclose. Dr. Yang has nothing to disclose. Dr. Castoro has nothing to disclose. Yang Xuan has nothing to disclose. Dr. Roth has nothing to disclose. The institution of Dr. Dortch has received research support from NIH. The institution of Dr. Dortch has received research support from DOD. Dr. Li has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Guidepoint. The institution of Dr. Li has received research support from NIH. Dr. Li has a non-compensated relationship as a Board of Directors with ANA that is relevant to AAN interests or activities.

Local Inflammatory Mediators Involved in Neuropathic Pain.

Polyneuropathy (PNP) is a term to describe diseases of the peripheral nervous system, 50% of which present with neuropathic pain. In some types of PNP, pain is restricted to the skin distally in the leg, suggesting a local regulatory process leading to pain. In this study, we proposed a pro-inflammatory pathway mediated by NF-κB that might be involved in the development of pain in patients with painful PNP. To test this hypothesis, we have collected nerve and skin samples from patients with different etiologies and levels of pain. We performed RT-qPCR to analyze the gene expression of the proposed inflammatory pathway components in sural nerve and in distal and proximal skin samples. In sural nerve, we showed a correlation of TLR4 and TNFα to neuropathic pain, and an upregulation of TNFα in patients with severe pain. Patients with an inflammatory PNP also presented a lower expression of TRPV1 and SIRT1. In distal skin, we found a reduced expression of TLR4 and miR-146-5p, in comparison to proximal skin. Our findings thus support our hypothesis of local inflammatory processes involved in pain in PNP, and further show disturbed anti-inflammatory pathways involving TRPV1 and SIRT1 in inflammatory PNP.