Onset Of Neuropathy Research Articles

Neuroprotective Effect of Vitamin B6 and Vitamin B12 against Vincristine- Induced Peripheral Neuropathy: A Randomized, Double- Blind, Placebo Controlled, Multicenter Trial

Background: Vincristine leads to development of debilitating neuropathy in 40-45% patients with resultant compromised efficacy of chemotherapy, suboptimal treatment and worse prognostic outcome. Vitamin B6 and vitamin B12 improves non- oncological neuropathies. Therefore, this study investigated vitamin B6 and vitamin B12 to prevent vincristine- induced peripheral neuropathy (VIPN) by reducing incidence, absolute risk, relative risk, severity as well as delaying the onset. Methods: Patients with ALL undergoing induction phase were randomly assigned into intervention or placebo arm in a double- blind manner. Vitamin B6 (25 mg Pyridoxine) two tablets were given three times daily for 5 weeks. Vitamin B12 (500 μg/ml Methyl cobalamin) was administered intravenously on day 1, 3 and 5 of every week for 5 weeks during induction period. Placebo arm received oral and intravenous placebo for same duration. Patients were evaluated on the outset of every week by FACT/GOG-NTX questionnaire. Severity was assessed per NCI-CTCAE grading scale. Results: 102 patients were enrolled. Among them 81 completed the study, where 42 received vitamin B6 and B12 and 39 received placebo. There was significant difference in incidence of neuropathy between arms (26.19% intervention arm, 56.41% placebo; P-0.01). Relative risk of neuropathy was significantly (RR-0.46) lower in intervention arm. Besides, absolute risk reduction (ARR) was 30% and relative risk reduction (RRR) was 54%. NNT was 3.33. Significant trend was observed in difference of severity of VIPN between groups (P-0.03). No significant difference observed in between arms for time to onset of neuropathy. Conclusion: Vitamin B6 and vitamin B12 significantly reduced the incidence, relative risk and severity of VIPN. NNT was encouraging too. Henceforth, the status of vitamin B6 and vitamin B12 as neuroprotective agent against VIPN can be recommended as a promising one.

Amyloid neuropathy and autonomic dysfunction

AbstractThe clinical phenotype of amyloid neuropathy is not uniform. Especially in patients with hereditary amyloid neuropathy, the age at onset and severity of autonomic neuropathy are strongly influenced by the patient’s family history and the mutant gene of transthyretin. In the past 30 years, liver transplantation has been actively performed in the hereditary amyloid neuropathy patients with an early onset, resulting in much longer survival with this disease. Furthermore, new information on the pathogeneses of transthyretin‐derived amyloidosis has been accumulating via the analysis of tissue samples biopsied or autopsied from post‐transplanted hereditary amyloid neuropathy patients. The recent introduction of non‐invasive drug therapies has given rise to the possibility of treating amyloid neuropathy. The concept of amyloid neuropathy, including autonomic dysfunction, has changed. This review discusses the clinical picture, pathology, diagnosis, therapy, and post‐treatment changes of amyloid deposition in patients with amyloid neuropathy and autonomic neuropathy.

The PINK1 Activator Niclosamide Mitigates Mitochondrial Dysfunction and Thermal Hypersensitivity in a Paclitaxel-Induced Drosophila Model of Peripheral Neuropathy.

Paclitaxel is a widely used anticancer drug that induces dose-limiting peripheral neuropathy. Mitochondrial dysfunction has been implicated in paclitaxel-induced neuronal damage and in the onset of peripheral neuropathy. We have previously shown that the expression of PINK1, a key mediator of mitochondrial quality control, ameliorated the paclitaxel-induced thermal hyperalgesia phenotype and restored mitochondrial homeostasis in Drosophila larvae. In this study, we show that the small-molecule PINK1 activator niclosamide exhibits therapeutic potential for paclitaxel-induced peripheral neuropathy. Specifically, niclosamide cotreatment significantly ameliorated the paclitaxel-induced thermal hyperalgesia phenotype in Drosophila larvae in a PINK1-dependent manner. Paclitaxel-induced alteration of the dendrite structure of class IV dendritic arborization (C4da) neurons was not reduced upon niclosamide treatment. In contrast, paclitaxel treatment-induced increases in both mitochondrial ROS and aberrant mitophagy levels in C4da neurons were significantly suppressed by niclosamide. In addition, niclosamide suppressed paclitaxel-induced mitochondrial dysfunction in human SH-SY5Y cells in a PINK1-dependent manner. These results suggest that niclosamide alleviates thermal hyperalgesia by attenuating paclitaxel-induced mitochondrial dysfunction. Taken together, our results suggest that niclosamide is a potential candidate for the treatment of paclitaxel-induced peripheral neuropathy with low toxicity in neurons and that targeting mitochondrial dysfunction is a promising strategy for the treatment of chemotherapy-induced peripheral neuropathy.

Determination of median nerve conduction velocity and F-wave minimal latency to diagnose early onset of diabetic neuropathy

Diabetes mellitus is a metabolic disorder characterized by many abnormalities and leads to long term complications like diabetic neuropathy, nephropathy and retinopathy. Diabetic peripheral neuropathy causes symptoms of peripheral nerve dysfunction. Sensory nerve conduction velocity (SNCV), distal sensory latency and F-waves minimal latency of median nerve are important parameters of electro diagnosis for early detection of diabetic neuropathy. The objective of the study was to determine the specificity and sensitivity of the sensory nerve conduction velocity and F-wave minimal latency of median nerve in diabetic subjects in early detection of diabetic neuropathy. Thirty subjects recruited for the study were divided into group A comprising of healthy subjects (n=10, age: 62.70±10.49 years) and group B consisting of diabetic subjects (n=20, age: 68.05±6.44 years). NICOLET VIKING QUEST instrument was used for the nerve conduction velocity test. SNCV of the median nerve significantly decreased in diabetic subject when compared with control group. However, the F-wave minimal latency was not specific and sensitive over SNCV to diagnose early diabetic neuropathy in clinically asymptomatic patients. We concluded that sensory nerve conduction velocity was much more sensitive and specific than F-wave minimal latency to detect early diabetic neuropathy.

Diabetes Mellitus Is a Possible Risk Factor for Nodo-paranodopathy With Antiparanodal Autoantibodies.

Background and ObjectivesNodo-paranodopathies are peripheral neuropathies with dysfunction of the node of Ranvier. Affected patients who are seropositive for antibodies against adhesion molecules like contactin-1 and neurofascin show distinct clinical features and a disruption of the paranodal complex. An axoglial dysjunction is also a characteristic finding of diabetic neuropathy. Here, we aim to investigate a possible association of antibody-mediated nodo-paranodopathy and diabetes mellitus (DM).MethodsWe retrospectively analyzed clinical data of 227 patients with chronic inflammatory demyelinating polyradiculoneuropathy and Guillain-Barré syndrome from multiple centers in Germany who had undergone diagnostic testing for antiparanodal antibodies targeting neurofascin-155, pan-neurofascin, contactin-1–associated protein 1, and contactin-1. To study possible direct pathogenic effects of antiparanodal antibodies, we performed immunofluorescence binding assays on human pancreatic tissue sections.ResultsThe frequency of DM was 33.3% in seropositive patients and thus higher compared with seronegative patients (14.1%, OR = 3.04, 95% CI = 1.31–6.80). The relative risk of DM in seropositive patients was 3.4-fold higher compared with the general German population. Seropositive patients with DM most frequently harbored anti–contactin-1 antibodies and had higher antibody titers than seropositive patients without DM. The diagnosis of DM preceded the onset of neuropathy in seropositive patients. No immunoreactivity of antiparanodal antibodies against pancreatic tissue was detected.DiscussionWe report an association of nodo-paranodopathy and DM. Our results suggest that DM may be a potential risk factor for predisposing to developing nodo-paranodopathy and argue against DM being induced by the autoantibodies. Our findings set the basis for further research investigating underlying immunopathogenetic connections.

Role of Vitamin D in Cardiovascular Autonomic Function in Diabetes Mellitus

In India, the most encountered metabolic disorder is Type 2 Diabetes Mellitus (T2DM). T2DM is one of the chronic diseases, and there would be 80 million diabetic individuals in India by 2030.[1] Even though it is usually of adult type, nowadays it is observed frequently in the younger age group. Almost all systems in our body are affected by this disorder. Vitamin D is a fat-soluble vitamin present in sunlight and in certain foods. Vitamin D supports the immune system, cardiovascular system, and it also regulates insulin levels. Vitamin D is a neuroactive substance which stimulates central nervous system to keep the sympathetic and parasympathetic nervous system in balance with each other.[2] Vitamin D Receptors (VDRs) are widely distributed in nerve fibres of the brain and spinal cord to which activated Vitamin D (1,25-dihydroxy vitamin D) binds to build up vagal activity, and this physiological function of Vitamin D is implemented by its potential to traverse the blood-brain barrier to reach the brain. Also, the biogenesis of neurotransmitters regulating cardiovascular autonomic function occurs proportionately with the help of Vitamin D. The basal heart rate and blood pressure regulation by the sympathetic and parasympathetic nervous system are suppressed in case of low serum Vitamin D levels, and thus, Vitamin D deficiency has an adverse effect over cardiac autonomic functions.[2] The onset and severity of cardiac autonomic neuropathy in T2DM is linked to Vitamin D.[3] Autonomic dysfunctions like postural orthostatic tachycardia syndrome and orthostatic hypotension are associated with low Vitamin D levels.[4] Read more . . . 

A Rare Case of Multiple Cranial Nerve Palsies as the First Presentation of Hepatocellular Carcinoma: A Case Report and Review of Literature

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. It mainly occurs in patients with chronic liver diseases such as cirrhosis caused by hepatitis B or C infections, as well as chronic alcoholics. HCC is one of the highly malignant neoplasms. Extrahepatic metastases are seen in 64% of patients with HCC, but metastases to the brain and skull are extremely rare. Here, the case of a 45-year-old male who presented with left III, IV, VI, IX, X, and XII cranial nerve palsies is reported. These were revealed to be caused by a distant metastasis from an unnoticed HCC with a background of previously undiagnosed chronic alcoholic liver disease. Physicians should be aware of the metastatic potential of HCC, in addition to its uncommon presentations, while encountering patients with an underlying liver disease. This case report demonstrates that metastatic HCC can lead to a rare, but possible, new onset of cranial neuropathy.

Genetic variants of ALR (-106C → T /-12C → G) and serum PKC-δ are associated with peripheral neuropathy in Egyptian diabetic patients with impaired handwriting.

Diabetic peripheral neuropathy can injure the hand median nerve and cause extensive nerve damage. PKC and ALR are associated with progression of diabetic complications. We hypothesized a genetic association between the ALR polymorphisms (-106C → T/-12C → G) and elevated serum PKC-δ levels in diabetic neuropathy and its adverse effects on handwriting in Egyptian population. One hundred DPN were compared with 100 DP and 100 healthy volunteers. ALR -106C → T/-12C → G variants were studied using the PCR-RFLP method. A routine set of standard laboratory markers was determined. Serum PKC-δ concentration was determined by ELISA. Logistic regression analysis and areas under the receiver characteristic curves (AUCs) were evaluated to investigate the predictors of diabetic neuropathy. Arabic handwriting was analyzed based on the recognition of functional features, word shape, and ascending/descending parts of letters. Individuals carrying ALR-106C → C and -12G → G had a significantly higher risk of developing diabetic neuropathy than individuals with -106C → T and -12C → G genotypes (P = 0.01, P = 0.02). Carriers of the (-106C → T) CC and (-12C → G) GG genotypes had significantly increased serum levels of PKC-δ, FBG, TC, and LDL-c. PKC- δ serum levels were significantly correlated with glycemic and lipid indicators (P < 0.001). PKC-δ is a significant predictor of diabetes with or without neuropathy at a cutoff value of 16.6, sensitivity was 89%, and specificity 100%. All DPN showed complete deterioration of handwriting after the onset of diabetic neuropathy. The genetic variants ALR-106C → C / -12G → G and PKC-δ in serum may help in the detection and treatment of diabetic neuropathy in Egyptian population before writing performance is affected.

Choroidal Thickness and Primary Open-Angle Glaucoma—A Narrative Review

The choroid provides the majority of blood flow to the ocular tissues and structures that facilitate the processes of retinal metabolism responsible for vision. Specifically, the choriocapillaris provides a structural network of small blood vessels that supplies the retinal ganglion cells and deep ocular tissues. Similar to retinal nerve fiber layer thickness, choroidal thickness (CT) has been suggested to represent a quantifiable health biomarker for choroidal tissues. Glaucoma is a disease with vascular contributions in its onset and progression. Despite its importance in maintaining ocular structure and vascular functionality, clinical assessments of choroidal tissues have been historically challenged by the inaccessibility of CT biomarker targets. The development of optical coherence tomography angiography and enhanced depth imaging created a framework for assessing CT and investigating its relationship to glaucomatous optic neuropathy onset and progression. Pilot studies on CT in glaucoma are conflicting—with those both in support of, and against, its clinical utility. Complicating the data are highly customized analysis methods, small sample sizes, heterogeneous patient groups, and a lack of properly designed controlled studies with CT as a primary outcome. Herein, we review the available data on CT and critically discuss its potential relevance and limitations in glaucoma disease management.

Skin amyloid deposits and nerve fiber loss as markers of neuropathy onset and progression in hereditary transthyretin amyloidosis.

This study was undertaken to assess skin biopsy as a marker of disease onset and severity in hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN), a treatable disease. In this single center retrospective study, skin Congo red staining and intraepidermal nerve fiber density (IENFD) were evaluated in symptomatic ATTRv-PN patients and asymptomatic TTR gene mutation carriers between 2012 and 2019. Non-ATTRv subjects with suspected small fiber neuropathy who underwent skin biopsy during the same timespan were used as controls. One hundred eighty-three symptomatic ATTRv-PN patients, 36 asymptomatic carriers, and 537 non-ATTRv patients were included. Skin biopsy demonstrated amyloid depositions in 80% of the 183 symptomatic cases. Skin amyloid deposits were found in 75% of early stage ATTRv-PN patients, and in 14% of asymptomatic carriers. All 183 symptomatic and 34 of 36 asymptomatic patients displayed decreased ankle IENFD with a proximal-distal gradient distribution, and reduced IEFND correlated with disease severity and duration. Our study demonstrates skin amyloid deposits are a marker of ATTRv-PN disease onset, and decreased IENFD a marker of disease progression. These results are of major importance for the early identification of ATTRv-PN patients in need of disease-modifying treatments.

Evaluation of Folic Acid in Diabetic Type II Patients with and without Neuropathy

As a result of peripheral neuropathy, diabetes-related mortality and morbidity rates increase. It is possible that a folate deficiency raises the risk of developing diabetic neuropathy since folate is required for the creation and maintenance of neurons. This study evaluated diabetic neuropathy and the role of folic acid in neuropathic and non-neuropathic diabetic individuals. This study was conducted from October 2019 to March 2020 in Peshawar on both from neuropathic (n=105) and non-neuropathic patients (n=100) of having diabetes mellitus type II. Blood samples were collected for estimation of HBA1c, folate and random blood sugar (RBS). Positive family history (87.6%), hypertension (53.3%), and dyslipidemia (54.3%) were more determined in neuropathic patients. HbA1c level was found high among neuropathic patients. Patients with diabetic neuropathy had a considerably greater frequency of folate insufficiency (16 percent ). A significant increase in the number of people with diabetic neuropathy who are folate deficient shows that folate plays a critical role in delaying the onset of diabetic neuropathy. Keywords: Folic Acid, Diabetes, Neuropathy, Diabetic Neuropathy, HBA1c

Increased Pain Symptomatology Among Females vs. Males With Fragile X-Associated Tremor/Ataxia Syndrome.

Individuals with the fragile X premutation report symptoms of chronic pain from multiple systems, have increased incidence of comorbid conditions where pain is a prominent feature, and pathophysiology that supports disrupted pain regulation, inflammation, and energy imbalance. Less is known about how pain manifests for the subpopulation of carriers that develop the motor and cognitive changes of fragile X-associated tremor and ataxia syndrome (FXTAS), and how pain may differ between men and women. We gathered data collected from 104 males and females with FXTAS related to chronic pain, comorbid conditions related to pain, and medications used for pain control to further explore the types of pain experienced and to better characterize how individuals with the fragile X premutation experience pain sensation across genders. We found that women experience significantly more pain symptoms than men, particularly allodynia (20 vs. 2.0%, p = 0.008), peripheral neuropathy pain (43.9 vs. 25.4%, p = 0.0488), migraine (43.9 vs. 14.5%, p = 0.0008), fibromyalgia (26.8 vs. 0%, p = 0.0071) and back pain (48.5 vs. 23.4%, p = 0.008). We found onset of peripheral neuropathy predicts the onset of ataxia (β = 0.63 ± 0.25, p = 0.019) and tremor (β = 0.56 ± 0.17, p = 0.004) across gender. Women also report significantly more anxiety (82.9 vs. 39.7%, p < 0.001), which has implications for ideal pain treatment. These pain symptoms need to be recognized in the medical history and treated appropriately, with consideration for overlapping comorbidities.

IMPACT OF CHEMOTHERAPY-INDUCED PERIPHERAL NEUROPATHY ON THE QUALITY OF LIFE IN CANCER PATIENTS.

The aim of the study was to investigate the correlation between chemotherapy-induced peripheral neuropathy (CIPN) and quality of life, as well as to establish whether there was a difference in peripheral neuropathy symptoms and their effect on the quality of life depending on the type of agents applied. The study encompassed 156 patients treated at the Department of Oncology from March to May 2017. Data were collected through self-reported questionnaires issued by the European Organization for Research and Treatment of Cancer (EORTC QLQ-C30) and by Chemotherapy-Induced Peripheral Neuropathy module (CIPN20). The results showed sensory and motor neuropathy to be statistically significantly correlated with the general quality of life variables of pain, tiredness, diarrhea, insomnia and breathing difficulty. Oxaliplatin had a significantly greater effect on the onset of motor and sensory neuropathy than taxane and cisplatin/carboplatin. Nursing interventions based on specific characteristics of certain chemotherapeutic agents should be developed for CIPN alleviation.

Taurine Ameliorates Oxidative Stress in Spinal Cords of Diabetic Rats via Keap1-Nrf2 Signaling.

Hyperglycemia associated with diabetes mellitus (DM) causes oxidative stress, which is involved in the onset and development of diabetic neuropathy. Taurine, a powerful antioxidant, is an effective inhibitor of oxidative stress. The present experiment was conducted to explore the effect of taurine treatment on alterations in body weight, blood glucose, oxidative stress, and Keap1-Nrf2 signaling in the spinal cords of DM rats. The DM rat model was established by STZ injection, and taurine was administered in the drinking water. Body weight and blood glucose were recorded during the experiment. The expression of Gap-43 and MBP proteins was examined by Western blot. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were examined as indicators of oxidative stress. The expression of Keap1, Nrf2, and HO-1 gene was examined by real-time PCR. The results showed that compared with the control group, the body weight was decreased, blood glucose was increased, and both Gap-43 and MBP expression were decreased in DM rats, which were all remarkably reversed by taurine treatment. Oxidative stress, as reflected by lower SOD activity and higher MDA concentration, was inhibited in taurine-treated DM rats. Supplemental taurine also downregulated the mRNA level of Keap1, while upregulating Nrf2 and HO-1 mRNA levels. These results showed that taurine inhibits oxidative stress in the spinal cords of DM rats, an effect that might involve the regulation of Keap1-Nrf2 signaling.

A Clinical Retrospective Study of Recurrent Painful Ophthalmoplegic Neuropathy in Adults.

Introduction Recurrent painful ophthalmoplegic neuropathy (RPON) is quite rare and usually occurs in children. In this report, we describe the clinical features, diagnosis, and treatment of RPON in adults. Methods A retrospective review was conducted of all RPON cases seen and treated at the Zhongshan Ophthalmic Center of Sun Yat-sen University and the Department of Neurology of the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China, over the period from January 2016 to May 2020. Results A total of 8 patients (3 males and 5 females) with a mean age of 42.9 years (range: 23–64 years) met the diagnostic criteria of RPON. Headaches were present prior to the onset of ophthalmoplegic neuropathy in 50% of these patients, while in the remaining 50%, headaches occurred simultaneously with eye symptoms. The degree of these headaches was described as being mild or moderate. Abnormalities involving cranial nerve III were the most frequently reported pathologies (6 cases, 75%), followed by nerve VI (4 cases, 50%) and then nerve IV (1 case, 12.5%) (more than one nerve was affected in some cases). Following either with glucocorticoid treatment or with observation only, symptoms and signs within all 8 patients completely dissipated within 3–28 days. Conclusions All adult cases of RPON along with their clinical features as reported here were similar to those of children.

Cranial Neuropathies in Advanced Nasopharyngeal Carcinoma: Neurological Recovery and Prognosis After Modern Radiotherapy and Systemic Chemotherapy

Cranial neuropathy is a common presenting symptom of advanced T4 nasopharyngeal carcinoma (NPC). Data on neurological outcomes after modern intensity-modulated radiotherapy (IMRT) and chemotherapy are scarce. This study sets to evaluate the prognostic factors and recovery pattern of cranial neuropathies, using longitudinal clinical data from two tertiary oncology centers in endemic areas.Case records of consecutive T4 NPC patients who received definitive IMRT in 2004-2019 were reviewed. Distribution of cranial neuropathies at disease presentation were recorded. Time to partial and full neurological recovery, time from neurological recovery to re-palsy, relapse-free survival (RFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Predictors for neurological recovery were analyzed using multivariable Cox regression.During the study period, 257 T4 NPC patients presented with 504 individual cranial neuropathies. The median time from neuropathy onset to NPC diagnosis was 2 months (IQR, 1-4 months). All patients completed definitive IMRT, and 94% of patients received chemotherapy. The 5-year RFS and OS of the combined cohort were 50.8% and 60.1% respectively. Median RFS of patients with single versus multiple neuropathies were 5.8 years and 4.2 years (P = 0.62). Cranial nerves (CN) VI (56.4%), V2 (47.9%) and V3 (29.2%) were most frequently involved. Over a median follow-up of 6.4 years, 111 (22%) and 289 (57.3%) neuropathies attained partial and full recovery respectively, and 86% of the recoveries occurred within the first year after definitive radiotherapy. CN III, IV, VI had the highest 5-year full recovery rate (72.7%), followed by CN V1-3 (60.3%), CN XII (48.6%), and CN II (18.2%) (P < 0.001). Positive smoking history, optic nerve involvement, and long duration of neuropathy were independent negative predictors for neurological recovery. After full recovery, re-palsy was observed in 6.9% (20/289) of the nerves, 60% of which co-occurred with local NPC recurrences at the base of skull.Rate and durability of cranial neuropathy recovery in this contemporary NPC cohort compared favorably with data from the 2D radiotherapy era. Both patient and disease factors affected the chance of nerve recovery. Re-palsy of recovered nerves should prompt careful evaluation for local recurrence.

The Genotype and Phenotype Features in a Large Chinese MFN2 Mutation Cohort.

Introduction: Charcot–Marie–Tooth disease type 2A (CMT2A) is a group of clinically and genetically heterogeneous disorders, which is mostly caused by mutations of the mitofusin2 (MFN2) gene. As the genotype–phenotype characteristics of CMT2A were still incompletely understood, we further explored the spectrum of CMT2A variants in China and demonstrated their phenotypic diversities.Methods: A total of 402 index patients/families with CMT throughout Mainland China were enrolled in this study. Among them, we analyzed 20 unrelated index cases with CMT2A by Sanger sequencing, next-generation sequencing, or whole-exome sequencing. Detailed clinical and genetic features of CMT2A patients were collected and analyzed. Of note, de novo mutations were not rare in MFN2 gene; we compared the clinical features of patients from the de novo group with those from the non-de novo group.Results: We identified 20 MFN2 variants, occupying 5.0% of CMT. Most patients presented with early onset and moderate phenotype with abnormal gait and foot drop as the main complaints at onset. Pyramidal signs accounts for 31.6% (6/19) in all patients, which is not uncommon. Four novel variants (p.Tyr752*, c.475-2A>G, p.Val99Met, and p.Arg275_Gln276insArg) were identified in the cohort. Besides, de novo variants occupied 35.0% (7/20) in our study with a much earlier age at onset compared with those in the non-de novo group (p = 0.021).Conclusion: Chinese CMT2A is a predominant typical pure CMT2A, with early onset and mild to moderate phenotype. Given the high frequency of de novo MFN2 mutations, genetic study should be considered for patients with early onset and severe idiopathic axonal neuropathy.

Postoperative peripheral neuropathy considered to be induced by surgical stress

BackgroundMost surgeons are unaware that idiopathic neuropathy, which occurs independently of mechanical injury, can present as postoperative peripheral neuropathy. The aim of this study was to reveal the presence of postoperative neuropathy considered to be induced by surgical stress and to make surgeons aware that idiopathic neuropathy can occur postoperatively. MethodsWe conducted a survey among orthopedic surgeons regarding patients with postoperative neuropathies of unknown cause. For each case, the type of neuropathy, preceding surgery and anesthesia, patient background, clinical findings, and clinical course were investigated. ResultsSeven patients were identified. The mean time from surgery to the onset of neuropathy was 9.3 days (range 1–15 days). Five of the patients fully recovered spontaneously within 1 year, while the remaining two underwent neurolysis. One patient presented with hourglass-like constrictions in the radial nerve. No inflammatory cells were found in the epineurium of the affected nerve. ConclusionsAlthough it is rare, postoperative idiopathic neuropathy occurs in clinical practice, and it is crucial that surgeons recognize the existence of this neuropathy to elucidate its pathogenesis as well as to reduce the risk of litigation.

AUTOIMMUNE & INFLAMMATORY NMD: EP.15 Severe Guillain-Barre syndrome associated with nelarabine with good prognosis

Nelarabine is a purine nucleoside analogue which has T-cell specificity and is highly active in relapsed and refractory T-cell lymphoma. Neurotoxicity occurs in approximately 20% of patients treated with nelarabine and is predominantly peripheral neuropathy. Reports of recovery are variable. We report a severe nelarabine related neuropathy with quadriparesis and respiratory failure and excellent recovery. Diagnosis of stage III biphenotypic lymphoblastic lymphoma was made at 11 years of age in a previously healthy male who presented with supraclavicular lymphadenopathy. He was treated according to UKALL 2011 schedule B. Two months later, as there had been no response to treatment, he received nelarabine. Within two weeks he developed limb weakness and sensory symptoms, weakness progressed rapidly to quadriparesis and respiratory failure. MRI scan of spine showed diffusely thickened nerve roots with contrast enhancement, CSF was acellular with protein 3.27 g/L, initial nerve conduction study showed attenuated motor responses and absent F-waves. He had five cycles of plasmapheresis and IVIG. He required ventilation for 50 days. Muscle weakness slowly improved. He received a matched unrelated donor stem cell transplant (SCT) 6 months after his neuropathy onset. At review, 21 months post-SCT, he remains in remission from his lymphoma, has only mild residual ankle dorsiflexion weakness and no functional impairment. This case of neuropathy temporally associated with nelarabine administration fulfills diagnostic criteria for GBS and raises the possibility that the neuropathy was immune-mediated rather than due to direct neurotoxicity. GBS like presentation of neuropathy following nelarabine administration may have a better prognosis with implications for continuation of life-sustaining treatment and treatment of the malignancy.

Cranial neuropathies in advanced nasopharyngeal carcinoma: Neurological recovery after modern radiotherapy and systemic chemotherapy

ObjectivesCranial neuropathy is a common presenting symptom of advanced T4 nasopharyngeal carcinoma (NPC). Data on neurological outcomes after modern intensity-modulated radiotherapy (IMRT) and chemotherapy are scarce. Materials and methodsCase records of consecutive T4 NPC patients who received definitive IMRT in two tertiary oncology centers in 2004–2019 were reviewed. Patterns of cranial neuropathies at disease presentation were recorded. Time to neurological recovery and the rate of subsequent re-palsy were estimated by the Kaplan-Meier method. Clinical predictors were analyzed using multivariable Cox regression. ResultsDuring the study period, 257 T4 NPC patients presented with 504 individual cranial neuropathies. The median time from neuropathy onset to NPC diagnosis was two months (IQR, 1–4 months). Cranial nerves (CN) VI (56.4%), V2 (47.9%), and V3 (29.2%) were most frequently involved. At a median follow-up of 6.4 years, the crude partial and full recovery rates of neuropathies were 111 (22%) and 289 (57.3%), respectively. CN III, IV, and VI had the highest 5-year full recovery rate (72.7%), followed by CN V1-3 (60.3%), XII (48.6%), and II (18.2%) (p < 0.001). Positive smoking history, optic nerve involvement, and longer duration of neuropathy were independent negative predictors for neurological recovery. After full recovery, re-palsy was observed in 6.9% (20/289) of the nerves, 60% of which co-occurred with local NPC recurrences. ConclusionDurable recovery of most cranial neuropathies in advanced T4 NPC was observed in the era of modern IMRT and effective systemic chemotherapy. Both patient and disease factors affected the chance of neurological recovery. Re-palsy of recovered nerves should prompt careful evaluation for local recurrence.