Real-life experience with inotersen at CEPARM, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro.

BACKGROUND: Hereditary transthyretin amyloidosis (ATTRv) is an inherited, progressive, and fatal disease still largely underdiagnosed. Mutations in the transthyretin (TTR) gene cause the TTR protein to destabilize, misfold, aggregate, and deposit in body tissues, which makes ATTRv a disease with heterogeneous clinical phenotype. OBJECTIVE: To describe the long-term efficacy and safety of inotersen therapy in patients with ATTRv peripheral neuropathy (ATTRv-PN). METHODS: Patients who completed the NEURO-TTR pivotal study and the NEURO-TTR OLE open-label extension study migrated to the present study and were followed-up for at least 18 more months to an average of 67 months and up to 76 months since day 1 of the inotersen therapy (D1-first dose of inotersen). Disease progression was evaluated by standard measures. RESULTS: Ten ATTRv-PN patients with Val30Met mutation were included. The mean disease duration on D1 was of 3 years, and the mean age of the patients was of 46.8 years. During an additional 18-month follow up, neurological function, based on the Neuropathy Impairment Score and the Polyneuropathy Disability Score, functionality aspects (Karnofsky Performance Status), and nutritional and cardiac aspects were maintained. No new safety signs have been noted. CONCLUSION: The treatment with inotersen was effective and well tolerated for the average of 67 months and up to 76 months. Our results are consistent with those of larger phase-III trials.

ANTECEDENTES: Amiloidose hereditária por transtirretina (ATTRv) é uma doença hereditária, progressiva e fatal ainda largamente subdiagnosticada. Mutações no gene transtirretina (TTR) promovem desestabilização, desdobramento, agregação e depósito da proteína TTR em tecidos do corpo, o que faz da ATTRv uma doença de fenótipo clínico heterogêneo. OBJETIVO: Descrever a eficácia e segurança da terapia com inotersena no longo prazo em pacientes com neuropatia periférica ATTRv (ATTRv-PN). MéTODOS: Pacientes que completaram o estudo pivotal NEURO-TTR e o estudo de extensão aberta NEURO-TTR OLE migraram para este estudo e foram acompanhados por no mínimo 18 meses adicionais, em média por 67 meses, e por até 76 meses, desde o dia 1 da terapia com inotersena (D1­primeira dose de inotersena). A progressão da doença foi avaliada por medidas padronizadas. RESULTADOS: Dez pacientes com ATTRv-PN com mutação Val30Met foram incluídos. A duração média da doença no D1 era de 3 anos, e a média de idade dos pacientes era de 46,8 anos. Durante o período de acompanhamento adicional de 18 meses, a função neurológica, baseada no Neuropathy Impairment Score e no Polyneuropathy Disability Score, os aspectos de funcionalidade (Karnofsky Performance Status), nutricional e cardíacos estavam mantidos. Não se observou nenhum novo sinal de segurança. CONCLUSãO: O tratamento com inotersena foi eficaz e bem tolerado por 67 meses em média, e por até 76 meses. Nossos resultados são consistentes com os de estudos maiores de fase III.

[Role and place of ipidacrine in the therapy of diseases of the peripheral nervous system. The resolution of the expert council]. / Rol' i mesto ipidakrina v terapii zabolevanii perifericheskoi nervnoi sistemy. Rezolyutsiya Soveta ekspertov.

The resolution of the expert council is devoted to discussing aspects of the use of ipidacrine for the treatment of mononeuropathies, polyneuropathies and radiculopathies of various etiologies. Specialists prepared recommendations for ipidacrine's application in treating peripheral nervous system disorders.

Prevalence and characteristics of diabetic symmetric sensorimotor polyneuropathy in Japanese patients with type 2 diabetes: The Japan Diabetes Complication and its Prevention Prospective study (JDCP study 10).

This study aimed to investigate the prevalence and characteristics of diabetic symmetric sensorimotor polyneuropathy (DSPN) in patients with type 2 diabetes registered in the Japan Diabetes Complication and its Prevention Prospective study. In the study, 6,338 patients with diabetes who had been treated by diabetes specialists were registered in 2007-2009. Of these, patients with type 2 diabetes who could be evaluated for DSPN were analyzed using the t-test, χ2 -test and logistic regression analyses. DSPN was diagnosed using the Simple Diagnostic Criteria for Diabetic Polyneuropathy proposed by the Diabetic Neuropathy Study Group in Japan. Of the total participants, 5,451 patients (mean age 61.4 years, duration of diabetes 10.8 years) were analyzed. Based on the criteria, 35.8% of patients were diagnosed with DSPN. The prevalence of sensory symptoms was 25.8%. The following factors increased the risk for DSPN: age (odds ratio [OR] 1.57, 95% confidence interval [CI] 1.42-1.73), duration of diabetes (OR 1.32, 95% CI 1.21-1.43), body mass index (OR 1.19, 95% CI 1.09-1.30), systolic blood pressure (OR 1.06, 95% CI 1.01-1.10), hemoglobin A1c (OR 1.15, 95% CI 1.09-1.22), biguanides (OR 1.22, 95% CI 1.06-1.39) and insulin therapy (OR 1.59, 95% CI 1.36-1.84). The following factors decreased the risk for DSPN: total cholesterol (OR 0.98, 95% CI 0.96-1.00) and exercise therapy (OR 0.85, 95% CI 0.73-0.98). The baseline survey clarified the prevalence and characteristics of DSPN in Japanese patients with type 2 diabetes. The survey also showed the risk factors of DSPN.

Early diagnosis leading to improvement of critical illness polyneuropathy associated with severe Staphylococcus aureus infection in a patient on hemodialysis.

Critical illness polyneuropathy (CIP) is a very rare complication of sepsis and multi-organ failure. Herein, we report the first case of CIP reported in a patient on maintenance hemodialysis, who improved with rehabilitation. A 55-year-old male patient was emergently admitted with fever and altered consciousness and diagnosed with bacterial meningitis based on cerebral spinal fluid and cranial magnetic resonance imaging findings. Methicillin-susceptible Staphylococcus aureus was detected in blood and cerebral spinal fluid cultures. Despite treatment with appropriate antibiotics, blood cultures were positive for 9 days and serum C-reactive protein (CRP) levels were persistently elevated. Magnetic resonance imaging of hands and feet to determine infection origin revealed osteomyelitis in several fingers and toes, which required the amputation of 14 necrotic fingers and toes. Thereafter, blood cultures became negative and CRP levels declined. However, flaccid paralysis was noted in both upper and lower extremities during sepsis treatment. Nerve conduction studies showed peripheral axonal disorder in motor and sensory nerves, and CIP was determined as the cause of paralysis based on the fulfillment of all four CIP diagnostic criteria. The patient's muscle strength improved with early and appropriate medical treatment and physical therapy, and he was discharged home 147 days after admission. Prolonged high-level inflammation is a cause of CIP. Patients on hemodialysis, who are potentially immunosuppressed and vulnerable to infection, are at high risk for CIP. In patients on maintenance hemodialysis who develop flaccid paralysis during treatment for severe infection, CIP should be considered for early diagnosis and intervention.

Sensory Phenotypes Provide Insight Into the Natural Course of Diabetic Polyneuropathy.

We aimed to investigate the characteristics and longitudinal course of sensory phenotypes identified through quantitative sensory testing (QST) in the frame of diabetic sensorimotor polyneuropathy (DSPN). A total of 316 individuals with diabetes were examined (type 2 diabetes 78.8%), 250 of whom were undergoing follow-up visits at 1, 2, and/or 4 (2.88 ± 1.27) years. Allocation into four sensory phenotypes (healthy, thermal hyperalgesia [TH], mechanical hyperalgesia [MH], and sensory loss [SL]) at every time point was based on QST profiles of the right foot. Cross-sectional analysis demonstrated a gradual worsening of clinical and electrophysiological sensory findings and increased DSPN prevalence across the groups, culminating in SL. Motor nerve impairment was observed solely in the SL group. Longitudinal analysis revealed a distinct pattern in the developmental course of the phenotype (from healthy to TH, MH, and finally SL). Those with baseline MH exhibited the highest risk of transition to SL. Reversion to healthy status was uncommon and mostly observed in the TH group. Among those without DSPN initially, presence or future occurrence of SL was associated with a three- to fivefold higher likelihood of DSPN development. Our comprehensive longitudinal study of phenotyped patients with diabetes elucidates the natural course of DSPN. QST-based sensory examination together with other tools for phenotyping may be useful in determining the natural course of diabetic neuropathy to identify patients at high risk of DSPN and guide preventive and therapeutic interventions. ARTICLE HIGHLIGHTS: The course of diabetic sensorimotor polyneuropathy (DSPN) development, from healthy status to overt DSPN, is poorly understood. We studied the characteristics and longitudinal appearance of lower-extremity sensory phenotypes (healthy, thermal hyperalgesia [TH], mechanical hyperalgesia [MH], and sensory loss [SL]) identified through quantitative sensory testing in individuals with diabetes. There was an increasing severity and patterned order of longitudinal appearance across healthy, TH, MH, and SL phenotypes. SL was most strongly associated with formal DSPN. Our findings provide insight into the natural history of DSPN. Sensory phenotyping can be implemented to identify high-risk individuals and those most likely to benefit from therapeutic interventions.

Temporal Trends in Distal Symmetric Polyneuropathy in Type 2 Diabetes: The Fremantle Diabetes Study.

CONTEXT: Macrovascular outcomes in type 2 diabetes have improved over recent decades. There are scant equivalent distal symmetric polyneuropathy (DSPN) data. OBJECTIVE: This work aimed to characterize temporal changes in DSPN prevalence and incidence rates (IRs) in community-based Australians. METHODS: An observational study was conducted among an urban population. Participants included individuals with type 2 diabetes from the Fremantle Diabetes Study phases I (FDS1; n = 1296 recruited 1993-1996) and II (FDS2; n = 1509 recruited 2008-2011). Main outcome measures included Michigan Neuropathy Screening Instrument (MNSI) clinical grading. RESULTS: DSPN prevalence by 8-point MNSI was 30.8% (FDS1) and 58.9% (FDS2; P < .001), and by 6-point (excluding foot appearance) and 2-point (biothesiometry alone) MNSI was 37.5% and 35.7% (P = .336), and 33.8% and 38.7% (P = .011), respectively. Given between-phase changes in appearance assessment, 8-point MNSI data were not analyzed further. In multivariable analysis, FDS2 vs FDS1 participation was associated with 6-point (odds ratio (95% CI) 0.68 (0.56-0.83); P < .001) but not 2-point (0.90 (0.74-1.11); P = .326) MNSI DSPN prevalence. Four-year DSPN IRs (95% CI) for 6-point MNSI were 13.6 (12.0-15.4) and 17.6 (15.9-19.4)/100 person-years in FDS1 and FDS2, respectively (IR ratio [IRR] 1.31 [1.12-1.55]; P < .001), and for 2-point MNSI were 13.9 (12.3-15.8) and 7.4 (16.3-8.6/100 person-years; IRR 0.53 [0.43-0.64]; P < .001). FDS2 vs FDS1 independently predicted incident DSPN for 6-point (hazard ratio [95% CI] 1.25 [1.06-1.48]; P = .009) and 2-point (0.42 [0.33-0.55]; P < .001) MNSI. CONCLUSION: DSPN prevalence was lower or equivalent in FDS2 vs FDS1, and its incidence was greater or lower, in multivariable models depending on the MNSI features used.

Lower serum cholesterol levels as a risk factor for critical illness polyneuropathy: a matched case-control study.

Critical illness polyneuropathy (CIP) is a frequent and underdiagnosed phenomenon among intensive care unit patients. The lipophilic nature of neuronal synapses may result in the association of low serum cholesterol levels with a higher rate of CIP development. We aimed to investigate this issue in critically ill patients. All cases diagnosed with CIP in our tertiary care hospital between 2013 and 2017 were 1:1 matched with controls without the condition by age, sex, and ICD diagnoses. The main risk factors examined were the differences in change between initial and minimum serum total cholesterol levels, and minimum serum total cholesterol levels between matched pairs. Other predictors were serum markers of acute inflammation. We included 67 cases and 67 controls (134 critically ill patients, 49% female, 46% medical). Serum total cholesterol levels decreased more profoundly in cases than controls (median: -74 (IQR -115 to -24) vs. -39 (IQR -82 to -4), median difference: -28, 95% CI [-51, -5]), mg/dl). Minimum serum total cholesterol levels were lower in the cases (median difference: -24, 95% CI [-39, -9], mg/dl). We found significant median differences across matched pairs in maximum serum C-reactive protein (8.9, 95% CI [4.6, 13.2], mg/dl), minimum albumin (-4.2, 95% CI [-6.7, -1.7], g/l), decrease in albumin (-3.9, 95% CI [-7.6, -0.2], g/l), and lowest cholinesterase levels (-0.72, 95% CI [-1.05, -0.39], U/l). Subsequently, more pronounced decreases in serum total cholesterol levels and lower minimum total cholesterol levels during critical care unit hospitalizations may be a risk factor for CIP.

Identification of blood metabolic biomarkers associated with diabetic distal symmetric sensorimotor polyneuropathy in patients with type 2 diabetes mellitus.

BACKGROUND: Distal symmetric sensorimotor polyneuropathy (DSPN) is a common neurologic complication of type 2 diabetes mellitus (T2DM), but the underlying mechanisms and changes in serum metabolites remain largely undefined. This study aimed to characterize the plasma metabolite profiles of participants with T2DM using targeted metabolomics analysis and identify potential biomarkers for DSPN. METHODS: A combined liquid chromatography MS/MS and direct flow injection were used to quantify plasma metabolite obtained from 63 participants with T2DM, 81 with DSPN, and 33 nondiabetic control participants. A total of 130 metabolites, including amino acids, biogenic amines, sphingomyelins (SM), phosphatidylcholines, carnitines, and hexose, were analyzed. RESULTS: A total of 16 plasma metabolites and 3 cholesterol-related laboratory parameters were found to have variable importance in the projection score >1.0 and false discovery rate <5.0% between control, T2DM, and DSPN. Among these variables, five serum metabolites, including phenylalanine (AUC = 0.653), alanine (AUC = 0.630), lysine (AUC = 0.622) tryptophan (AUC = 0.620), and SM C16:0 (AUC = 0.630), are potential biomarkers (all p < .05) in distinguishing T2DM with DSPN from those without (AUC = 0.720). CONCLUSIONS: In this cross-sectional study, derangement of several metabolites in the plasma was observed in T2DM with and without DSPN, and these metabolites may be potential biomarkers for predicting DSPN. Longitudinal studies are warranted.

Diphtheritic Polyneuropathy: A Case Report.

Diphtheria is showing a resurgence in recent years. A fall in the immunity of adults to diphtheria due to multiple reasons is showing a rise in diphtheria cases in the adult population. Diphtheritic polyneuropathy shows a prevalence of 20-27% of infections. It affects the axial muscle and the palatine muscle fastHere we report a case of diphtheritic polyneuropathy in a 27-year-old COVID-19-infected man.

Polyneuropathy Associated with Age of Starting the Transfusion and Serum Ferritin Level in Iranian Patients with Thalassemia Major and Intermedia.

Considering the importance of managing patients with ß-thalassemia and the importance of early detection of disease complications, we examined the rate of sensorimotor neuropathy in patients with ß-thalassemia and the risk factors related to it. This cross-sectional study included 44 blood transfusion-dependent ß-thalassemia patients aged 5 years and older. Nerve conduction studies (NCSs) were performed via standard procedures for both motor and sensory nerves. Neuropathy was observed in 14 patients (31.8%). NCS results for sensorimotor nerves in patients were within normal range. In motor NCS results, increased ulnar nerve amplitude was observed in patients with increasing age, and peroneal nerve delay in patients with an increase in serum ferritin level (p < 0.05). In sensory NCS results, delayed ulnar and sural nerves latencies were found in patients with an increase in serum ferritin level (p < 0.05). We provide data that sensorimotor neuropathy exists in thalassemia patients. It seems that with the increase of serum ferritin level and the age of patients, neuropathy becomes more obvious, while other factors such as gender, body mass index, and the number of transfusions may not be associated with neuropathy.

Prevalence of polyneuropathies among systemic sclerosis patients and impact on health-related quality of life.

INTRODUCTION: Systemic sclerosis (SSc) is a chronic rheumatic disease that affects multiple organ systems, including the peripheral nervous system. However, studies into the involvement of polyneuropathies (PNP) have shown inconsistent results. The aim of this study was to determine the prevalence of small (SFN) and large (LFN) fibre neuropathy among SSc patients and the impact on health-related quality of life (HRQoL). MATERIAL AND METHODS: The study enrolled 67 patients with diagnosed SSc. The severity of neuropathic symptoms was evaluated using shortened and revised total neuropathy scoring criteria. Nerve conduction studies were used for LFN, and quantitative sensory testing was used to evaluate SFN. Neuropathic pain was evaluated using a Douleur Neuropathique en 4 questionnaire, and the severity of anxiety symptoms was assessed using a Generalised Anxiety Disorder-7 scale. The Health Assessment Questionnaire-Disability Index was used to assess HRQoL. Previous data on antinuclear autoantibodies (ANA) test results was obtained. Statistical analysis was performed using SPSS software. RESULTS: LFN was diagnosed in 47.8% (n = 32/67) and SFN in 40.3% (n = 27/67) of the subjects. ANA positivity was not associated with the presence of LFN/SFN. The severity of neuropathic pain had a significant correlation with anxiety symptoms (r = 0.61, p < 0.001), the severity of neuropathy symptoms (r = 0.51, p < 0.001) and HRQoL (r = 0.45, p < 0.001). The severity of neuropathy symptoms correlated with HRQoL (r = 0.39, p = 0.001). CONCLUSIONS: We demonstrated that PNP are found in almost all SSc patients. Also, SFN is as common as LFN. Additionally, we found that the severity of neuropathy symptoms and neuropathic pain are both associated with a worse HRQoL.

[Clinical features of 8 patients with multifocal motor neuropathy in the long-term follow-up].

OBJECTIVE: To clarify the clinical and long-term characteristics of multifocal motor neuropathy (MMN). METHODS: We retrospectively evaluated data from 8 consecutive MMN patients in Yamaguchi University Hospital from 2005 to 2020. Clinical information including dominant hand, occupations, hobbies, nerve conduction data, protein level in cerebrospinal fluid (CSF), responsiveness to intravenous immunoglobulin (IVIg) therapy as initial therapy as well as maintenance therapy were collected. RESULTS: Unilateral upper limb was initially affected in all patients and a dominant upper extremity was affected in six of them. Seven patients had occupations or hobbies which were associated with overuse of their dominant upper extremity. CSF protein level was normal or slightly elevated. Nerve conduction studies showed conduction blocks in 4 cases. Effectiveness of IVIg treatment as initial therapy was observed in all patients. Maintenance therapy was not needed in 2 patients because of mild symptoms with stable clinical course. Long-term maintenance therapy with immunoglobulin was effective in 5 patients during the follow-up period. CONCLUSION: Dominant upper extremity was frequently affected and most patients had job or habit associated with its overuse, suggesting that physical overload induces inflammation or demyelination in MMN. IVIg was commonly effective as both introduction and long-term maintenance therapies. Complete remission was achieved after several IVIg treatments in some patients.

A retrospective survey of patients with hereditary transthyretin-mediated (hATTR) amyloidosis treated with patisiran in real-world clinical practice in Belgium.

INTRODUCTION: Hereditary transthyretin-mediated (hATTR) amyloidosis, a genetic disease caused by mutations in the transthyretin gene, leads to progressive sensory and autonomic neuropathy and/or cardiomyopathy and is associated with renal and ophthalmologic manifestations and a poor prognosis. METHODS: This is a retrospective study based on data collected from the medical records of patients with hATTR amyloidosis treated with patisiran between 01 July 2018 and 01 February 2021. Six Belgian neuromuscular reference centers participated, covering all patisiran-treated hATTR amyloidosis patients at the study time. This study was conducted to collect data requested in the context of the reimbursement of patisiran in Belgium. RESULTS: Thirty-one patients were diagnosed with hATTR amyloidosis with polyneuropathy, Coutinho stage 1 or 2, and eligible for active treatment during the data collection period. Of the hATTR amyloidosis patients treated with patisiran (n = 12), seven and five had polyneuropathy stages 1 and 2, respectively. Six patients had cardiac symptoms (New York Heart Association class 2 or above). Follow-up information was available for nine patients. Following patisiran treatment, eight patients showed stable or improved assessments for most neurological or cardiological parameters. Only one patient presented with worsening statuses at the end of the data collection period. CONCLUSIONS: The patients with hATTR amyloidosis in Belgium have similar baseline demographics and disease characteristics to those studied in the patisiran APOLLO study and show a similar therapeutic response in the real-world, altering the expected disease progression in most patients.

Higher Levels of Cerebrospinal Fluid and Plasma Neurofilament Light in Human Immunodeficiency Virus-Associated Distal Sensory Polyneuropathy.

BACKGROUND: Neurofilament light (NFL) chain concentrations, reflecting axonal damage, are seen in several polyneuropathies but have not been studied in human immunodeficiency virus (HIV) distal sensory polyneuropathy (DSP). We evaluated NFL in cerebrospinal fluid (CSF) and plasma in relation to DSP in people with HIV (PWH) from 2 independent cohorts and in people without HIV (PWoH). METHODS: Cohort 1 consisted of PWH from the CHARTER Study. Cohort 2 consisted of PWH and PWoH from the HIV Neurobehavioral Research Center (HNRC). We evaluated DSP signs and symptoms in both cohorts. Immunoassays measured NFL in CSF for all and for plasma as well in Cohort 2. RESULTS: Cohort 1 consisted of 111 PWH, mean ± SD age 56.8 ± 8.32 years, 15.3% female, 38.7% Black, 49.6% White, current CD4+ T-cells (median, interquartile range [IQR]) 532/µL (295, 785), 83.5% with plasma HIV RNA ≤50 copies/mL. Cohort 2 consisted of 233 PWH of similar demographics to PWH in Cohort 1 but also 51 PWoH, together age 58.4 ± 6.68 years, 41.2% female, 18.0% Black, Hispanic, non-Hispanic White 52.0%, 6.00% White. In both cohorts of PWH, CSF and plasma NFL were significantly higher in both PWH with DSP signs. Findings were similar, albeit not significant, for PWoH. The observed relationships were not explained by confounds. CONCLUSIONS: Both plasma and CSF NFL were elevated in PWH and PWoH with DSP. The convergence of our findings with others demonstrates that NFL is a reliable biomarker reflecting peripheral nerve injury. Biomarkers such as NFL might provide, validate, and optimize clinical trials of neuroregenerative strategies in HIV DSP.

Muscle quantitative MRI as a novel biomarker in hereditary transthyretin amyloidosis with polyneuropathy: a cross-sectional study.

BACKGROUND: The development of reproducible and sensitive outcome measures has been challenging in hereditary transthyretin (ATTRv) amyloidosis. Recently, quantification of intramuscular fat by magnetic resonance imaging (MRI) has proven as a sensitive marker in patients with other genetic neuropathies. The aim of this study was to investigate the role of muscle quantitative MRI (qMRI) as an outcome measure in ATTRv. METHODS: Calf- and thigh-centered multi-echo T2-weighted spin-echo and gradient-echo sequences were obtained in patients with ATTRv amyloidosis with polyneuropathy (n = 24) and healthy controls (n = 12). Water T2 (wT2) and fat fraction (FF) were calculated. Neurological assessment was performed in all ATTRv subjects. Quantitative MRI parameters were correlated with clinical and neurophysiological measures of disease severity. RESULTS: Quantitative imaging revealed significantly higher FF in lower limb muscles in patients with ATTRv amyloidosis compared to controls. In addition, wT2 was significantly higher in ATTRv patients. There was prominent involvement of the posterior compartment of the thighs. Noticeably, FF and wT2 did not exhibit a length-dependent pattern in ATTRv patients. MRI biomarkers correlated with previously validated clinical outcome measures, Polyneuropathy Disability scoring system, Neuropathy Impairment Score (NIS) and NIS-lower limb, and neurophysiological parameters of axonal damage regardless of age, sex, treatment and TTR mutation. CONCLUSIONS: Muscle qMRI revealed significant difference between ATTRv and healthy controls. MRI biomarkers showed high correlation with clinical and neurophysiological measures of disease severity making qMRI as a promising tool to be further investigated in longitudinal studies to assess its role at monitoring onset, progression, and therapy efficacy for future clinical trials on this treatable condition.

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

AIMS: To investigate the relationship between neurofilament light chain (NfL) and the presence and severity of diabetic polyneuropathy (DPN). METHODS: We 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. RESULTS: 39 (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). CONCLUSIONS: S-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.