Accelerated neuropathy among chronic kidney disease patients undergoing hemodialysis: Analysis of an institutional cluster.

BACKGROUND: Accelerated neuropathy is a rare syndrome of rapidly worsening peripheral neuropathy, typically described in end-stage kidney disease (ESKD) patients undergoing dialysis. In our center, we encountered a surge in the occurrence of accelerated neuropathy among ESKD patients undergoing hemodialysis, which prompted systematic research. METHODS: In this case-control study, we present the clinical features, electrophysiologic findings, and outcome of a series of patients who developed accelerated neuropathy after commencing hemodialysis for ESKD. Those who initiated hemodialysis and did not develop accelerated neuropathy were included as controls. We used logistic regression to identify predictors of accelerated neuropathy. RESULTS: Among 436 ESKD patients who initiated hemodialysis over 4 years, 17 were diagnosed with accelerated neuropathy. The median-time (interquartile range) from hemodialysis initiation to presentation with accelerated neuropathy was 3 weeks (2-6). It typically presented as acute onset of unsteadiness of gait necessitating assistance for ambulation. Electrophysiology revealed length-dependent symmetric sensorimotor axonal neuropathy. Diabetes mellitus (odds ratio [OR] 4.1, 95% CI 1.2-13.9, p = 0.02), pre-existing peripheral neuropathy (OR 9.25, 95% CI 2.79-30.6, p < 0.001), and serum alkaline phosphatase (OR 1.2 for every 10 U increase, 95% CI 1.00-1.52, p = 0.04) significantly predicted accelerated neuropathy. With continued dialysis and supportive care, neurologic status improved, total-neuropathy score (summary score of peripheral nerve dysfunction incorporating clinical and electrophysiological parameters) declined from 26.5 to 18.4 (p < 0.001) and most regained unassisted ambulation. CONCLUSION: This study presents the largest series of patients with accelerated neuropathy and has identified predictors. However, in view of the unusually high incidence of accelerated neuropathy we speculate that other unidentified factor(s) could be underlying its pathogenesis.

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

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

Peripheral nervous system manifestations of MOG antibody associated disease.

Recent studies have reported the involvement of peripheral nervous system (PNS) in association with MOG-IgG, including isolated neuropathies. In this retrospective study we characterized the PNS involvement in MOG antibody associated disease (MOGAD). Six out of 215 MOGAD patients had PNS involvement (all polyradiculopathy) that occurred concurrently with a CNS demyelinating episode. We also demonstrated MOG expression in healthy human controls' proximal nerve root. Nine patients with true-positive MOG-IgG1 had PNS involvement temporally unrelated to a CNS demyelinating event. All these patients had an alternate etiology of PNS involvement. Isolated peripheral neuropathy is not a feature of MOGAD, but inflammatory nerve root involvement can occur concurrently with CNS demyelinating events.

Ovarian mass Presenting as Paraneoplastic cerebellar degeneration with peripheral neuropathy and anti-Yo antibody.

Paraneoplastic neurological syndromes (PNS) are a group of disorders with diverse neurological manifestations that are observed in patients with various types of cancer. Any portion of the nervous system can be affected by these syndromes, which are brought on by processes other than metastasis, direct tumour spread or chemotherapy side effects. An immune-mediated attack on the cerebellar Purkinje cells and consequent cerebellar symptoms define paraneoplastic cerebellar degeneration(PCD), a subtype of the PNS. Axonal or demyelinating paraneoplastic peripheral neuropathies are both possible. Here, we describe the case of a middle-aged woman who presented with subacute-onset cerebellar symptoms and peripheral neuropathy, was discovered to have a positive anti-Yo antibody, and was later detected to have an ovarian mass. This case illustrates the significance of considering a paraneoplastic aetiology in patients with otherwise unexplained neurological manifestations and initiating an appropriate workup and early treatment for the primary malignancy.

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

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

Localization and Diagnostic Evaluation of Peripheral Nerve Disorders.

OBJECTIVE: This article provides a framework for the initial evaluation of patients with suspected peripheral nerve disease. The key clinical elements of peripheral nerve diseases can help the practicing neurologist differentiate among peripheral neuropathies with similar presentations. LATEST DEVELOPMENTS: The wide range of peripheral nerve diseases with similar clinical presentations can pose a diagnostic challenge. The large array of available testing modalities (including imaging and electrodiagnostic, autonomic, laboratory, biopsy, and genetic testing) further complicates clinical decision making. Recent developments (eg, discovery of new autoantibodies, genetic variations, and histopathologic techniques) across the peripheral neuropathy spectrum have resulted in an increased need to evaluate patients logically and with a tailored diagnostic approach. ESSENTIAL POINTS: A careful approach that focuses on key clinical elements combined with an understanding of purposeful diagnostic testing can lead to a successful diagnosis of peripheral nerve diseases.

Nutritional Neuropathies.

OBJECTIVE: This article reviews the etiologies, presentations, and management of neuropathies related to nutritional deficiencies. LATEST DEVELOPMENTS: Peripheral neuropathy can be the predominant or only manifestation of certain nutrient deficiencies. Cognitive difficulties or involvement of other parts of the central nervous system, such as the optic nerve and spinal cord, may accompany nutritional peripheral neuropathies. In most patients, the nutritional deficiency may have a single predominant cause, but in some cases, multiple causes may coexist. Obesity, for unclear reasons, can be associated with nutrient deficiencies. The rising rates of bariatric surgery and the incidence of nutrient deficiencies following bariatric surgery make this a particularly relevant topic for neurologists. ESSENTIAL POINTS: Neuropathies caused by nutrient deficiencies are preventable with appropriate supplementation in high-risk situations. Early recognition and prompt treatment are essential to ensure an optimal outcome and minimize neurologic morbidity.

Infectious Neuropathies.

OBJECTIVE: This article discusses the clinical manifestations and management of infectious peripheral neuropathies. LATEST DEVELOPMENTS: Several infectious etiologies of peripheral neuropathy are well-recognized and their treatments are firmly established. The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is associated with several central and peripheral nervous system manifestations, including peripheral neuropathies. Additionally, some COVID-19 vaccines have been associated with Guillain-Barré syndrome. These disorders are an active area of surveillance and research. Recent evidence-based guidelines have provided updated recommendations for the diagnosis and treatment of Lyme disease. ESSENTIAL POINTS: Infectious agents of many types (primarily bacteria and viruses) can affect the peripheral nerves, resulting in various clinical syndromes such as mononeuropathy or mononeuropathy multiplex, distal symmetric polyneuropathy, radiculopathy, inflammatory demyelinating polyradiculoneuropathy, and motor neuronopathy. Knowledge of these infections and the spectrum of peripheral nervous system disorders associated with them is essential because many have curative treatments. Furthermore, understanding the neuropathic presentations of these disorders may assist in diagnosing the underlying infection.

Peripheral neuropathy associated with chronic lymphoproliferative disorders of natural killer cells (CLPD-NK): a case report and literature review.

BACKGROUND: Chronic lymphoproliferative disorders of natural killer cells (CLPD-NK) is a rare lymphoproliferative disease. Peripheral neuropathy is an unusual symptom of CLPD-NK. We report a case of peripheral neuropathy associated with CLPD-NK and perform a review of literatures. CASE PRESENTATION: a 62-year-old woman presented with progressive numbness and weakness in both extremities. Electrophysiological examinations indicated a sensorimotor polyneuropathy. Peripheral blood examination revealed that the number of white blood cells (WBC) and lymphocytes were significantly increased. Flow cytometry analysis identified that 84% of the lymphocytes are NK cells that mainly expressed CD56, combined with variable expression of CD16, CD2, CD7, CD94, granzyme B, perforin, and CD158 but negative for CD3. Sural nerve biopsy revealed that a plethora of NK cells infiltrated into nerve fascicles. On treatment with combined cyclophosphamide and corticosteroids, her symptoms rapidly improved. Moreover, the absolute lymphocyte count and its proportion recovered to normal range after 3 months' treatment. CONCLUSION: To the best of our knowledge, this is the first case report of peripheral neuropathy associated with CLPD-NK from Chinese. This rare lymphoproliferative disease should be considered if peripheral neuropathy combines with increased WBC or lymphocytes. Immunosuppressive drugs are the major treatment and most patients can achieve a good prognosis.

Brentuximab vedotin plus AVD for Hodgkin lymphoma: incidence and management of peripheral neuropathy in a multisite cohort.

Brentuximab vedotin (BV) in combination with doxorubicin, vinblastine, and dacarbazine (AVD) is increasingly used for frontline treatment of stage III/IV classical Hodgkin lymphoma (cHL). Peripheral neuropathy (PN) was the most common and treatment-limiting side effect seen in clinical trials but has not been studied in a nontrial setting, in which clinicians may have different strategies for managing it. We conducted a multisite retrospective study to characterize PN in patients who received BV + AVD for newly diagnosed cHL. One hundred fifty-three patients from 10 US institutions were eligible. Thirty-four patients (22%) had at least 1 ineligibility criteria for ECHELON-1, including stage, performance status, and comorbidities. PN was reported by 80% of patients during treatment; 39% experienced grade (G) 1, 31% G2, and 10% G3. In total, BV was modified in 44% of patients because of PN leading to BV discontinuation in 23%, dose reduction in 17%, and temporary hold in 4%. With a median follow-up of 24 months, PN resolution was documented in 36% and improvement in 33% at the last follow-up. Two-year progression-free survival (PFS) for the advanced-stage patients was 82.7% (95% confidence interval [CI], 0.76-0.90) and overall survival was 97.4% (95% CI, 0.94-1.00). Patients who discontinued BV because of PN did not have inferior PFS. In the nontrial setting, BV + AVD was associated with a high incidence of PN. In our cohort, which includes patients who would not have been eligible for the pivotal ECHELON-1 trial, BV discontinuation rates were higher than previously reported, but 2-year outcomes remain comparable.

Nutritional peripheral neuropathies.

Nutritional peripheral neuropathies are a global problem, heavily influenced by geopolitical, cultural and socioeconomic factors. Peripheral neuropathy occurs most frequently secondary to B-vitamin deficiencies, which is suspected to increase in years to come due to the popularity of vegan and vegetarian diets and increased use of bariatric surgery.This review will focus on the common B-vitamins for which a causal link to peripheral neuropathy is more established (vitamins B1, B2, B6, B9 and B12). We will review the historical human and animal data on which much of the clinical descriptions of vitamin deficiencies are based and summarise current available tools for accurately diagnosing a nutritional deficiency. We will also review recently described genetic diseases due to pathogenic variants in genes involved in B-vitamin metabolism that have helped to inform the phenotypes and potential causality of certain B-vitamins in peripheral neuropathy (B2 and B9).Endemic outbreaks of peripheral neuropathy over the last two centuries have been linked to food shortages and nutritional deficiency. These include outbreaks in Jamaican sugar plantation workers in the nineteenth century (Strachan's syndrome), World War two prisoners of war, Cuban endemic neuropathy and also Tanzanian endemic optic neuropathy, which remains a significant public health burden today. An improved understanding of lack of which vitamins cause peripheral neuropathy and how to identify specific deficiencies may lead to prevention of significant and irreversible disability in vulnerable populations.

Avian riboflavin deficiency causes reliably reproducible peripheral nerve demyelination and, with vitamin supplementation, rapid remyelination.

Riboflavin deficiency produces severe peripheral neve demyelination in young, rapidly growing chickens. While this naturally-occurring vitamin B2 deficiency can cause a debilitating peripheral neuropathy, and mortality, in poultry flocks, it can also be a useful experimental animal model to study the pathogenesis of reliably reproducible peripheral nerve demyelination. Moreover, restitution of normal riboflavin levels in deficient birds results in brisk remyelination. It is the only acquired, primary, demyelinating tomaculous neuropathy described to date in animals. The only other substance that causes peripheral nerve demyelination similar to avian riboflavin deficiency is tellurium and the pathologic features of the peripheral neuropathy produced by this developmental neurotoxin in weanling rats are also described.

The Role of Vitamin B6 in Peripheral Neuropathy: A Systematic Review.

INTRODUCTION: Vitamin B6 is a water-soluble vitamin that is naturally present in many foods and is accessible in many dietary supplements. The three natural forms are pyridoxine, pyridoxal, and pyridoxamine. Both vitamin B6 deficiency and high B6 intake have been described as risk factors for developing peripheral neuropathy (PN). The aim of this systematic review is to characterize and comprehensively describe B6-related PN. METHOD: A systematic, computer-based search was conducted using the PubMed database. Twenty articles were included in this review. RESULTS: Higher vitamin B6 levels, which usually occur following the taking of nutritional supplements, may lead to the development of a predominantly, if not exclusively, sensory neuropathy of the axonal type. After pyridoxine discontinuation, such patients subjectively report improved symptoms. However, although low vitamin B6 levels can be seen in patients suffering from peripheral neuropathy of various etiologies, there is no firm evidence that low B6 levels have a direct causal relationship with PN. Many studies suggest subjective improvement of neuropathy symptoms in patients suffering from PN of various etiologies after receiving B6 supplementation; however, no data about B6 administration as a monotherapy exist, only as part of a combination treatment, usually with other vitamins. Therefore, the potential therapeutic role of B6 cannot be confirmed to date. Supplementation with vitamin B6, even as part of a nutritional multivitamin supplement, has not been proven harmful at permitted daily doses in patients who already suffer from PN. CONCLUSION: Current scientific evidence supports a neurotoxic role of B6 at high levels. Although some studies suggest that low B6 is also a potential risk factor, further studies in this area are needed.

Polyarteritis nodosa initially presenting as concomitant peripheral neuropathy and myositis in unilateral limb: A case report.

RATIONALE: We report the case of a patient who initially presented with peripheral neuropathy and myositis without typical organ involvement, such as the kidneys, skin, or gastrointestinal system, but was ultimately diagnosed with polyarteritis nodosa (PAN). PATIENT CONCERNS: A 62-year-old man presented with radicular pain in his right lower extremity. One week later, he complained of right ankle motor weakness and pain in the right posterior thigh, which led to admission. After 6 weeks of hospitalization, he newly experienced pain in his right testicle and anterior thigh. DIAGNOSIS: The patient was initially diagnosed with polymyositis combined with sciatic neuropathy using magnetic resonance imaging, electrodiagnostic tests, and muscle biopsy. However, with the emergence of other systemic symptoms such as testicular pain, vasculitis was suspected, and the patient was reclassified as PAN using the 2007 European Medicines Agency algorithm and the American College of Rheumatology criteria. INTERVENTIONS: The patient was treated with glucocorticoids for more than 6 months, and antiviral medication was prescribed to prevent hepatitis B virus reactivation. OUTCOMES: The patient's radicular pain and pain in the right anterior and posterior thighs and testicle improved, and there were no signs of recurrence. LESSONS: In patients presenting with radicular and focal muscle pain, it is crucial to consider the potential for PAN, as observed in this case report.

Improving Quality of Life During Chemotherapy: Cannabinoids, Cryotherapy, and Scalp Cooling.

There have been significant advances in the treatment of cancer in the past decade. However, patients continue to suffer from significant side effects of antineoplastic agents that greatly affect their quality of life (QOL), including chemotherapy-induced nausea and vomiting (CINV), chemotherapy-induced peripheral neuropathy (CIPN), and chemotherapy-induced alopecia (CIA). This review aims to provide an updated overview of emerging strategies for the management and prevention of these immediate and long-lasting side effects. The use of integrative medicine including cannabis continues to evolve in the realm of CINV and cancer-related anorexia. Although no pharmaceutical agent has been approved for the prevention of CIPN, cryotherapy, compression therapy and, more recently, cryocompression therapy have shown benefit in small trials, but there are concerns with tolerability especially related to cryotherapy. More data are necessary to determine an effective and tolerable option to prevent CIPN in large, randomized studies. Scalp cooling (SC), which has a similar mechanism to cryotherapy and compression therapy for CIPN prevention, has proven to be an effective and tolerable approach in randomized studies and has significantly limited CIA, an entity that definitively affects the QOL of patients living with cancer. Taken together, cannabis, cryotherapy, compression and cryocompression therapy, and SC all strive to improve the QOL of patients living with cancer by minimizing the side effects of chemotherapeutic agents.

Peripheral neuropathy secondary to a 'domino' liver transplant: a case report.

BACKGROUND: Peripheral neuropathy caused by amyloidosis is one of the well-recognised sequelae of mutations in the transthyretin gene (TTR). CASE PRESENTATION: We describe a case of peripheral neuropathy in a White British 74 year old man with wild-type TTR, 8 years following receipt of a 'domino' liver transplant (from a donor with a TTR mutation). The clinical phenotype and neurophysiology, coupled with presence of ATTR amyloid deposits on fat biopsy, established the diagnosis of ATTR amyloid neuropathy, as a consequence of receipt of a variant-TTR secreting liver. A nerve biopsy was not clinically appropriate for this patient. Such cases are rare since recipients of such livers are typically restricted to people whose natural lifespan is unlikely to stretch into the anticipated symptomatic period of ATTR amyloidosis. However, novel "gene silencing" therapeutics are now available which can dramatically alter the course of this disorder, by reducing the proportion of abnormal proteins. CONCLUSIONS: This represents a rare but predictable iatrogenic side effect, and doctors should be aware of this eventuality occurring in a shorter time span than previously anticipated.

Investigation and Management of Immunoglobulin M- and Waldenström-Associated Peripheral Neuropathies.

The immunoglobulin M (IgM)-associated peripheral neuropathies (PN) are a heterogeneous group of disorders representing most paraproteinemic neuropathy cases. They are associated with IgM monoclonal gammopathy of undetermined significance (MGUS) or Waldenström macroglobulinemia. Establishing a causal link between a paraprotein and neuropathy can be challenging but is necessary to adopt an appropriate therapeutic approach. The most common type of IgM-PN is Antimyelin-Associated-Glycoprotein neuropathy, but half of the cases are of other causes. Progressive functional impairment is an indication for treatment, even when the underlying disorder is IgM MGUS, involving either rituximab monotherapy or combination chemotherapy to achieve clinical stabilization.

Dysmetabolism-related Early Sensory Deficits and Their Relationship With Peripheral Neuropathy Development.

AIM: To investigate the association of early peripheral sensory dysfunction (EPSD) identified through quantitative sensory testing (QST) with factors related to a dysmetabolic status in individuals with and without type 2 diabetes (T2DM) without peripheral neuropathy (PN), and the impact of those factors on PN development. METHODS: A total of 225 individuals (117 and 108 without and with T2DM, respectively) without PN based on clinical and electrophysiological criteria were analyzed. Comparative analysis was conducted between those identified as "healthy" and those with EPSD based on a standardized QST protocol. A total of 196 were followed-up over a mean of 2.64 years for PN occurrence. RESULTS: Among those without T2DM, apart from male sex, height, and higher fat and lower lean mass, only higher insulin resistance (IR; homeostatic model assessment for IR: odds ratio [OR], 1.70; P = .009; McAuley index OR, 0.62, P = .008), was independently associated with EPSD. In T2DM, metabolic syndrome (OR, 18.32; P < .001) and skin advanced glycation end-products (AGEs; OR, 5.66; P = .003) were independent predictors of EPSD. In longitudinal analysis, T2DM (hazard ratio [HR], 3.32 vs no diabetes mellitus; P < .001), EPSD (adjusted HR, 1.88 vs healthy; P = .049 adjusted for diabetes mellitus and sex), higher IR and AGEs predicted PN development. Among the 3 EPSD-associated sensory phenotypes, "sensory loss" was most strongly associated with PN development (adjusted HR, 4.35; P = .011). CONCLUSION: We demonstrate for the first time the utility of a standardized QST-based approach in identifying early sensory deficits in individuals with and without T2DM. These are associated with a dysmetabolic status signified by IR markers, metabolic syndrome, and higher AGEs, which in turn are shown to influence PN development.