Recreational use of nitrous oxide (N2O), commonly known as laughing gas, has increased in the last few years, bringing an increase in the number of reported cases of toxicity due to this gas. Subacute combined degeneration (SCD) of the spinal cord is the most frequently reported neurological disorder due to the use of N2O, as well as polyneuropathy and even psychiatric symptoms. All of these disorders are consequences of a functional deficit of vitamin B12. We are reporting the cases of two patients with a history of N2O abusive use presenting to the emergency department with progressive symptoms of paresthesia, ascending symmetric paraparesis, and gait ataxia, emulating the clinical characteristics of Guillain-Barré Syndrome (GBS). In both cases, magnetic resonance imaging (MRI) showed findings compatible with transverse myelitis of the cervical spinal cord, and electrodiagnosis studies reported the presence of polyneuropathy with a mixed mechanism. All these findings together pointed to the presence of myeloneuropathy due to a vitamin B12 deficit induced by the prolonged use of N2O. Symptoms improved gradually with vitamin B12 supplementation and abstinence from N2O. It is important to acknowledge the clinical characteristics of complications due to neurotoxicity induced by N2O. Such complications are potentially reversible if they are treated appropriately and quickly. Considering the increase in N2O abuse, it should be considered a probable cause when treating patients with myelopathy and/or neuropathy of an unusual etiology.

Creatine kinase (CK) has been associated with neuropathy, but the mechanisms are uncertain. We hypothesized that peripheral nerve function is impaired in subjects with persistent CK elevation (hyperCKemia) compared to age- and sex matched controls in a general population. The participants were recruited from the population based Tromsø study in Norway. Neuropathy impairment score (NIS), nerve conduction studies (NCS) and electromyography (EMG) in subjects with persistent hyperCKemia (n = 113; 51 men, 62 women) and controls (n = 128; 61 men, 67 women) were performed. The hyperCKemia group had higher NIS score than the controls (p = 0.050). NCS of the tibial nerve showed decreased compound motor action potential amplitude (p < 0.001), decreased motor conduction velocity (p < 0.001) and increased F-wave latency (p = 0.044). Also, reduced sensory amplitudes of the median, ulnar, and sural nerves were found. EMG showed significantly increased average motor unit potential amplitude in all examined muscles. CK correlated positively with glycated hemoglobin and non-fasting glucose in the hyperCKemia group, although not when controlled for covariates. The length dependent polyneuropathy demonstrated in the hyperCKemia group is unexplained, but CK leakage and involvement of glucose metabolism are speculated on.

UNASSIGNED: Fabry disease (FD) causes cold-evoked pain and impaired cold perception through small fiber damage, which also occurs in polyneuropathies (PNP) of other origins. The integrity of thinly myelinated fibers and the spinothalamic tract is assessable by cold-evoked potentials (CEPs). In this study, we aimed to assess the clinical value of CEP by investigating its associations with pain, autonomic measures, sensory loss, and neuropathic signs.
UNASSIGNED: CEPs were examined at the hand and foot dorsum of patients with FD (n = 16) and PNP (n = 21) and healthy controls (n = 23). Sensory phenotyping was performed using quantitative sensory testing (QST). The painDETECT questionnaire (PDQ), FabryScan, and measures for the autonomic nervous system were applied. Group comparisons and correlation analyses were performed.
UNASSIGNED: CEPs of 87.5% of the FD and 85.7% of the PNP patients were eligible for statistical analysis. In all patients combined, CEP data correlated significantly with cold detection loss, PDQ items, pain, and autonomic measures. Abnormal CEP latency in FD patients was associated with an abnormal heart frequency variability item (r = -0.684; adjusted p = 0.04). In PNP patients, CEP latency correlated significantly with PDQ items, and CEP amplitude correlated with autonomic measures (r = 0.688, adjusted p = 0.008; r = 0.619, adjusted p = 0.024). Furthermore, mechanical pain thresholds differed significantly between FD (gain range) and PNP patients (loss range) (p = 0.01).
UNASSIGNED: Abnormal CEPs were associated with current pain, neuropathic signs and symptoms, and an abnormal function of the autonomic nervous system. The latter has not been mirrored by QST parameters. Therefore, CEPs appear to deliver a wider spectrum of information on the sensory nervous system than QST alone.

Distal sensory polyneuropathy (DSP) is a disabling, chronic condition in people with HIV (PWH), even those with viral suppression of antiretroviral therapy (ART), and with a wide range of complications, such as reduced quality of life. Previous studies demonstrated that DSP is associated with inflammatory cytokines in PWH. Adhesion molecules, essential for normal vascular function, are perturbed in HIV and other conditions linked to DSP, but the link between adhesion molecules and DSP in PWH is unknown. This study aimed to determine whether DSP signs and symptoms were associated with a panel of plasma biomarkers of inflammation (d-dimer, sTNFRII, MCP-1, IL-6, IL-8, IP-10, sCD14) and vascular I integrity (ICAM-1, VCAM-1, uPAR, MMP-2, VEGF, uPAR, TIMP-1, TIMP-2) and differed between PWH and people without HIV (PWoH). A cross-sectional study was conducted among 143 participants (69 PWH and 74 PWoH) assessed by studies at the UC San Diego HIV Neurobehavioral Research Program. DSP signs and symptoms were clinically assessed for all participants. DSP was defined as two or more DSP signs: bilateral symmetrically reduced distal vibration, sharp sensation, and ankle reflexes. Participant-reported symptoms were neuropathic pain, paresthesias, and loss of sensation. Factor analyses reduced the dimensionality of the 15 biomarkers among all participants, yielding six factors. Logistic regression was used to assess the associations between biomarkers and DSP signs and symptoms, controlling for relevant demographic and clinical covariates. The 143 participants were 48.3% PWH, 47 (32.9%) women, and 47 (33.6%) Hispanics, with a mean age of 44.3 ± 12.9 years. Among PWH, the median (IQR) nadir and current CD4+ T-cells were 300 (178-448) and 643 (502-839), respectively. Participants with DSP were older but had similar distributions of gender and ethnicity to those without DSP. Multiple logistic regression showed that Factor 2 (sTNFRII and VCAM-1) and Factor 4 (MMP-2) were independently associated with DSP signs in both PWH and PWoH (OR [95% CI]: 5.45 [1.42-21.00], and 15.16 [1.07-215.22]), respectively. These findings suggest that inflammation and vascular integrity alterations may contribute to DSP pathogenesis in PWH, but not PWoH, possibly through endothelial dysfunction and axonal degeneration.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, commonly known as COVID-19, has been associated with various neurological complications. However, the mechanisms underlying these neurological manifestations remain incompletely understood. We present a case of a 63-year-old male who was admitted to the intensive care unit with severe COVID-19 pneumonia. Following recovery from respiratory symptoms, he was found to have weakness in the limbs. Months later, he also developed altered mental status, hallucinations, and behavioral changes. Neurological examination revealed signs consistent with polyneuropathy and autoimmune encephalitis. Further investigations, including nerve conduction studies, cerebrospinal fluid analysis, and response to steroids, supported the diagnosis of COVID-19-related polyneuropathy and autoimmune encephalitis. This is a rare presentation of COVID-19 and has only been described in a few case reports. Further research is warranted to elucidate the pathophysiological mechanisms underlying neurological sequelae of COVID-19 and to develop targeted therapeutic strategies.

Peripheral and autonomic neuropathy are common disease manifestations in systemic amyloidosis. The neurofilament light chain (NfL), a neuron-specific biomarker, is released into the blood and cerebrospinal fluid after neuronal damage. There is a need for an early and sensitive blood biomarker for polyneuropathy, and this systematic review provides an overview on the value of NfL in the early detection of neuropathy, central nervous system involvement, the monitoring of neuropathy progression, and treatment effects in systemic amyloidosis. A literature search in PubMed, Embase, and Web of Science was performed on 14 February 2024 for studies investigating NfL levels in patients with systemic amyloidosis and transthyretin gene-variant (TTRv) carriers. Only studies containing original data were included. Included were thirteen full-text articles and five abstracts describing 1604 participants: 298 controls and 1306 TTRv carriers or patients with or without polyneuropathy. Patients with polyneuropathy demonstrated higher NfL levels compared to healthy controls and asymptomatic carriers. Disease onset was marked by rising NfL levels. Following the initiation of transthyretin gene-silencer treatment, NfL levels decreased and remained stable over an extended period. NfL is not an outcome biomarker, but an early and sensitive disease-process biomarker for neuropathy in systemic amyloidosis. Therefore, NfL has the potential to be used for the early detection of neuropathy, monitoring treatment effects, and monitoring disease progression in patients with systemic amyloidosis.

Widespread contamination of the Amazon basin with mercury has been reported to occur since at least the mid-80s due to heavy gold mining activity. Although initial studies have indicated that this may lead to deleterious neurological consequences to the indigenous populations living in the region, further research is needed to better characterize the neurological burden of such long-term exposure. With this aim, a cross-sectional exploratory study has been conducted with the Yanomami indigenous population residing in a northern Amazon region. All participants underwent a structured interview; detailed neurological examination, including assessment for cognitive, motor, coordination, and sensory functions; and laboratorial testing for serum hemoglobin, blood glucose, and methylmercury levels in hair samples. This study enrolled 154 individuals of 30.9 ± 16.8 years of age, of which 56.1% were female. Mean methylmercury levels in hair were 3.9 ± 1.7 µg/g. Methylmercury levels in hair > 6.0 µg/g were found in 10.3%. Among participants with hair methylmercury levels ≥ 6.0 μg/g, the prevalences of peripheral neuropathy and reduced cognitive performance were, respectively, 78.8% (95%CI 15-177%, p = 0.010) and 95.9% (95%CI 16-230.8%, p = 0.012) higher than those of individuals with lower levels. These results suggest that chronic mercury exposure may lead to significant and potentially irreversible neurotoxicity to Yanomami population living in the northern Amazon basin.

BACKGROUND: Hereditary transthyretin (ATTRv, v for variant) amyloidosis is a rare, progressive, fatal disease with multisystem manifestations, caused by pathogenic variants in the transthyretin (TTR) gene. Vutrisiran, an RNA interference therapeutic that results in rapid TTR knockdown, improved neuropathy and quality of life (QOL) versus external placebo in patients with ATTRv amyloidosis with polyneuropathy in the phase 3 HELIOS-A study (NCT03759379). This post hoc analysis evaluates the impact of baseline neuropathy severity on response to vutrisiran treatment.
METHODS: Patients were randomized (3:1) to vutrisiran (n = 122; 25 mg subcutaneous injection once every 3 months) or patisiran (n = 42; 0.3 mg/kg intravenous infusion once every 3 weeks), which served as a reference group. In this post hoc analysis, patients were grouped into quartiles of increasing baseline Neuropathy Impairment Score (NIS): Quartile (Q)1 ≥ 5.0 to ≤ 20.5; Q2 > 20.5 to ≤ 44.1; Q3 > 44.1 to ≤ 73.1; Q4 > 73.1 to ≤ 127.0. Mean change from baseline to Month 18 was summarized by quartile for a range of efficacy endpoints.
RESULTS: Across all baseline NIS quartiles, vutrisiran demonstrated benefit versus external placebo in measures of neuropathy severity (modified NIS + 7), QOL (Norfolk Quality of Life-Diabetic Neuropathy), disability (Rasch-built Overall Disability Scale), gait speed (10-m walk test), and nutritional status (modified body mass index). Overall, patients in lower versus higher NIS quartiles (less severe neuropathy) at baseline maintained better scores at Month 18. The external placebo group progressively worsened in all measures at Month 18.
CONCLUSIONS: Vutrisiran demonstrated benefit in neurologic function and other key efficacy measures versus external placebo across all four baseline neuropathy severity quartiles. Patients initiating vutrisiran earlier in their disease course retained the highest neurologic function level after 18 months, highlighting the importance of early diagnosis and treatment.
BACKGROUND: ClinicalTrials.gov: NCT03759379.

UNASSIGNED: It is aimed to investigate the relationship between the asymptomatic individiuals with elevated HbA1c and occurrence of polyneuropathy by way of comparison to normoglycemic condition.
UNASSIGNED: The study includes 30 female patients diagnosed with subclinical elevation of HbA1c and 30 normoglycemic healthy female patients who applied to our hospital polyclinics with symptoms other than neuropathy between January-March 2017. Nerve conduction examination is done in these patients, parameters of both groups are compared.
UNASSIGNED: In regard to amplitude distribution; when compared to control group, tibial motor and ulnar sensory nerve amplitude is lower than the control group (p<0.05). In peroneal, median and ulnar motor nerves, distal latency values are extended compared to control group (p<0.05). Sural, median and ulnar sensory nerve latency is extended compared to control group. In terms of transmission rate distribution; in sural, median and ulnar sensory nerve, transmission speed is lower compared to the control group (p<0.05).
UNASSIGNED: In asymptomatic cases with subclinical elevation of HbA1c, peripheral nervous system involvement is monitored, and early glycemic control should be provided in order to prevent development of neuropathy in patients.

UNASSIGNED: Vincristine, a widely used anticancer chemotherapy drug, may cause polyneuropathy (PNP), potentially resulting in permanent functional impairment. We characterized the occurrence and development of vincristine-induced neuropathy (VIPN) in early treatment of childhood leukemia.
UNASSIGNED: This prospective study of 35 pediatric acute lymphoblastic leukemia (ALL) patients comprised systematic clinical and electrophysiological studies at both the time of diagnosis and at least one time point during the first months of treatment.
UNASSIGNED: After vincristine treatment, all patients had axonal sensorimotor PNP on electroneuromyography (ENMG) In 34/35 patients, the motor and in 24/35 the sensory responses were decreased. Interestingly, in 3 patients PNP was most prominent in the upper limb. However, some children had no PNP symptoms despite moderate ENMG findings, and not all clinical symptoms were correlated with abnormal ENMG.
UNASSIGNED: Pediatric VIPN is a sensorimotor, predominantly motor axonal neuropathy. VIPN can be detected even in its early phase by ENMG, but it is difficult to detect by symptoms and clinical examination only.
UNASSIGNED: Pediatric ALL patients treated with vincristine are at risk of developing VIPN. Since the clinical signs of PNP in acutely ill children are difficult to identify, VIPN can easily be overlooked if ENMG is not performed.