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Background: Femoral cannulated extracorporeal membrane oxygenation (ECMO) has been associated with neurologic complications in the lower extremity ipsilateral to the cannulation. There is uncertainty about the prevalence of these complications and their mechanisms of development. Objective: Aim of this systematic review was to investigate the prevalence of neurological complications after ECMO and to describe possible underlying mechanisms. Method: A systematic literature search was performed in Medline-Ovid, Embase, Cochrane Library, CINAHL, and PEDro until April 2021 for clinical trials in English or German language which quantified neurologic complications in the lower extremity ipsilateral to the ECMO cannulation of adults. The complications had to be delimitable to intensive care unit–acquired weakness. Methodological quality was assessed by 2 independent investigators using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies of the National Heart, Lung, and Blood Institute. Results: Eight observational studies were included in the synthesis. Study quality was good to fair in 88% of the papers. Overall, 47 of 202 patients (23.3%; ranging from 3% to 48% across studies) with femoral ECMO cannulation showed neurologic complications of the lower extremity ipsilateral to the cannulation. Peripheral ischemia and compression of nerves by the ECMO cannula are discussed as mechanisms of injury. Conclusion: The occurrence of neurological complications after ECMO was common and can lead to long-term impairment. The mechanisms are largely unknown but currently there is no sufficient evidence for the involvement of ECMO. Standardized assessments are needed to systematically screen for neurological complications early after ECMO, to enable countermeasures and prevent further complications. [ABSTRACT FROM AUTHOR]

Background: Paclitaxel administration causes peripheral neuropathy. Auraptene is a natural bioactive monoterpene with anti-inflammatory and anti-neuropathic effects that is widely used. Objectives: We aimed to study auraptene effects on paclitaxel-induced neuropathy. Materials and Methods: This study was comprised of two steps of evaluation of the preventive and treatment effects of auraptene in mice. In the first step, mice were randomly allocated into three groups of six animals, including the negative control (NEG CTL): animals injected with paclitaxel (PTX) together with normal saline, PTX (paclitaxel 2 mg/kg given on days 1, 3, 5, and 7), and PREVENTION: PTX + auraptene 100 mg/kg on days 1, 3, 5, and 7. In the second step, animals were allocated into six groups of six: NEG CTL (normal saline), PTX (paclitaxel 10 mg/kg given on days 1, 3, 5, and 7), PTX AUR (PTX + auraptene 50, 75, and 100 mg/kg), and a positive control (PTX-treated animals receiving imipramine 10 mg/kg). Intraperitoneal injection of PTX 2 mg/kg on days 1, 3, 5, and 7 was used in order to induce neuropathy. In both steps of the study, a hot plate test was done on day 7 in order to determine the response to heat. After the scarification of animals, the interleukin-6 (IL-6) level in the sciatic nerve was assessed by western blotting. Results: In the preventive group, auraptene could reduce hyperalgesia significantly. In the treatment step, the AUR 100 mg/kg compared to NEG CTL groups had significantly increased heat latency. The expression of IL-6 protein in the sciatic nerve was remarkably decreased in both the preventive and treatment groups compared to NEG CTL. Conclusion: Taken together, our results confirmed that AUR could decrease paclitaxel-induced hyperalgesia in mice and IL-6 protein content in sciatic nerve samples. [ABSTRACT FROM AUTHOR]

Vitamin B12 deficiency can present with a variety of neurological and cognitive symptoms. Especially in elderly patients, vitamin B12 deficiency can be easily overlooked because symptoms may be attributed to comorbid conditions or solely to the aging process. In this case study, we present two patients, a 71-year-old man and a 74-year-old female, with vitamin B12 deficiency. The male patient had a history of (partial) resection of the ileum/jejunum/colon because of intestinal ischemia. The female patient had a history of hypothyroidism, type 2 diabetes with complications (including peripheral neuropathy), mitochondrial myopathy, and chronic lymphocytic leukemia. Both patients presented with severe fatigue, cognitive impairment, and impaired walking. Next to this, the male patient suffered from depressive symptoms and mild disorientation, and the female patient experienced neuropathic pain. She also mentioned a positive family history for B12 deficiency. The first patient had normal to high B12 levels because he was already on B12 injections (once every three weeks) because of an earlier diagnosed B12 deficiency. The female patient had B12 levels within normal range (holotranscobalamin 54 pmol/L) and her diagnosis was confirmed by elevated homocysteine and methylmalonic acid levels. Treatment with frequent hydroxocobalamin injections and other supplements significantly improved their cognitive, emotional, and motor functions. These cases underscore the need for a high level of clinical suspicion in elderly patients, also in cases of normal B12 levels but with clinical signs of deficiency and a positive risk factor, such as stomach or small bowel surgery or positive family history. Plain language title: A case study of two elderly patients with vitamin B12 deficiency and neurological and cognitive complaints Plain language summary: Vitamin B12 deficiency in elderly patients can be easily overlooked as symptoms can also be caused by other age-related diseases or the aging process. In our article we present two elderly patients, a 71-year-old male and a 74-year-old female, with neurological complaints, such as severe fatigue, cognitive decline, and walking impairment. The male patient had a history of small bowel surgery, and the female patient mentioned that she had several siblings with B12 deficiency. Additionally, the male patient suffered from depressive symptoms and mild disorientation, and the female had severe pain in her legs. The male patient already received B12 injections because of an earlier B12 diagnosis, but with a relatively low frequency. The B12 levels of the female patients were within the normal range. However, her diagnoses could be confirmed with additional laboratory measurements, such as homocysteine and methylmalonic acid. Treatment with frequent B12 injections and other supplements significantly improved their cognitive, emotional, and motor functions. Our study shows that clinicians should carefully consider the possibility of B12 deficiency in elderly patients with cognitive and neurological complaints, also in patients with B12 levels within the normal range, but with risk factors such as family members with B12 deficiency or conditions that may impair the vitamin B12 uptake, such as previous stomach or small bowel surgery. [ABSTRACT FROM AUTHOR]

Background: Exertional compartment syndrome (ECS) is an underdiagnosed cause of lower extremity pain among athletes. The condition can be managed operatively by fasciotomy to relieve excess compartment pressure. However, symptom recurrence rates after fasciotomy are considerable, ranging from 3% to 17%. Hypothesis: Leg paresthesia and its distribution during ECS episodes would be a significant predictor of outcomes after fasciotomy. Study Design: Retrospective cohort study. Level of Evidence: Level 4. Methods: We conducted a retrospective chart review of patients who underwent fasciotomy for ECS at our center from 2010 to 2020 (institutional review board no. 21-00107). We measured postoperative outcomes including pain frequency and severity, Tegner activity level, and return to sport. Significant predictors of outcomes were identified using multivariable linear and logistic regression. P values <0.05 were considered significant. Results: A total of 78 legs (from 42 male and 36 female participants) were included in the study with average follow-up of 52 months (range, 3-126 months); 33 participants (42.3%) presented with paresthesia. Paresthesia was an independent predictor of worse outcomes, including more severe pain at rest (P = 0.05) and with daily activity (P = 0.04), reduced postoperative improvement in Tegner scores (P = 0.04), and lower odds of return to sport (P = 0.05). Those with paresthesia symptoms in the tibial nerve distribution had worse outcomes than those without paresthesia in terms of preoperative-to-present improvement in pain frequency (P < 0.01), pain severity at rest (P < 0.01) and with daily activity (P = 0.04), and return to sport (P = 0.04). Conclusion: ECS patients who present with paresthesia have worse pain and activity outcomes after first-time fasciotomy, but prognosis is worst among those with tibial nerve paresthesia. Clinical Relevance: Paresthesia among ECS patients is broadly predictive of more severe recurrent leg pain, reduced activity level, and decreased odds of return to sport after fasciotomy. [ABSTRACT FROM AUTHOR]

Background: The region where the ulnar nerve (UN) is swollen in baseball players with ulnar neuropathy is not apparent. This study investigated the UN's cross-sectional area (CSA) at each entrapment point in baseball players. We also aimed to clarify the relationship between valgus instability and the CSA of the UN. Methods: Forty baseball players were separated into healthy and ulnar neuropathy groups. The CSA and valgus instability were measured using ultrasonography (US). Relative to the medial epicondyle (MEC), the arcade of Struthers (SA) was 5 cm proximal, the cubital tunnel was the posterior part, and Osborne's ligament was defined as 3 cm distal. The ulnohumeral joint space was imaged as a low-echo space between the distal-medial corner of the trochlea and the proximal edge of the sublime tubercle. Results: The UN in the ulnar neuropathy group had significant swelling in the cubital tunnel and Osborne's ligament. We found a weak positive correlation between the CSA and ulnohumeral joint space, and the ulnohumeral joint space at rest and valgus stress. Conclusion: Evaluation and treatment of UN, especially cubital tunnel and Osborne's ligament, are necessary for the rehabilitation of baseball players presenting with ulnar neuropathy and valgus instability. [ABSTRACT FROM AUTHOR]

The aim of this single-centre retrospective study was to evaluate the outcomes of carpal tunnel release surgery in patients with hereditary neuropathy with pressure palsies (HNPP). The secondary aims were to identify prognostic factors for the outcome of carpal tunnel release and to assess the outcome of cubital tunnel release. Our primary hypothesis was postoperative improvement. In total, 18 patients (26 carpal tunnel releases) with at least one symptomatic carpal tunnel syndrome were included. At a median follow-up of 8.5 years, more than 73% of the patients were satisfied with the results. The visual analogue scale (0 to 10) for discomfort decreased by 2.2 points (p < 0.001). The Boston Carpal Tunnel Questionnaire symptom severity scale decreased by 1.3 points (p < 0.001). The decrease in the Functional Status Scale was not significant. No significant prognostic factor for outcome was identified. A total of 12 patients also underwent cubital tunnel release, and three patients underwent just this procedure (23 procedures). Despite the lack of preoperative data, cubital tunnel release provided encouraging results. Level of evidence: III [ABSTRACT FROM AUTHOR]

Background: Platelet-rich plasma (PRP) or corticosteroid injections may be used to conservatively treat mild-to-moderate carpal tunnel syndrome (CTS). We evaluated the cost-effectiveness of PRP injections versus corticosteroid injections for the treatment of mild-to-moderate CTS. Methods: Markov modeling was used to analyze the base-case 45-year-old patient with mild-to-moderate CTS, unresponsive to conservative treatments, never previously treated with an injection or surgery, treated with a single injection of PRP, or methylprednisolone/triamcinolone 40 mg/mL. Transition probabilities were derived from level-I/II studies, utility values from the Tufts University Cost-Effectiveness Analysis Registry reported using visual analog scale (VAS), Boston Carpal Tunnel Questionnaire Symptom severity (BCTQ-S), and Boston Carpal Tunnel Questionnaire Functional status (BCTQ-F), and costs from Medicare, published studies, and industry. Analyses were performed from healthcare/societal perspectives. Outcomes were incremental cost-effectiveness ratios (ICER) and net monetary benefits (NMB). Willingness-to-pay thresholds were $50 000 and $100 000. Deterministic/probabilistic sensitivity analyses were performed. Results: From a healthcare perspective, compared to PRP injections, the ICER for corticosteroid injections measured by VAS: -$13.52/quality-adjusted-life-years (QALY), BCTQ-S: -$11.88/QALY, and BCTQ-F: -$16.04/QALY. PRP versus corticosteroid injections provided a NMB measured by VAS: $428 941.12 versus $375 788.21, BCTQ-S: $417 115.09 versus $356 614.18, and BCTQ-F: $421 706.44 versus $376 908.45. From a societal perspective, compared to PRP injections, the ICER for corticosteroid injections measured by VAS: -$1024.40/QALY, BCTQ-S: -$899.95/QALY, and BCTQ-F: -$1215.51/QALY. PRP versus corticosteroid injections provided a NMB measured by VAS: $428 171.63 versus $373 944.39, BCTQ-S: $416 345.61 versus $354 770.36, and BCTQ-F: $420 936.95 versus $375 064.63. Conclusions: PRP injections were more cost-effective than methylprednisolone/triamcinolone injections from healthcare and societal perspectives for mild-to-moderate CTS. [ABSTRACT FROM AUTHOR]

This document is a letter to the editor discussing the distinction between primary and secondary nerve compression neuropathy. Primary nerve compressions are caused by ligaments or dense structures directly over the nerve, while secondary nerve compressions are caused by identifiable pathologies in structures other than those directly over the nerve. The author raises the question of whether patients with cervical compression should undergo decompression surgery at more distal sites if there is evidence of local nerve compression. The author also discusses lacertus syndrome and the need for further research on the outcomes of surgical release versus nonsurgical treatment for secondary compression. [Extracted from the article]

The Boston Carpal Tunnel Questionnaire is one of the most popular patient-reported outcome measures designed specifically for people with idiopathic median neuropathy at the carpal tunnel. We used electrophysiological and ultrasound measures of median neuropathy from one hand in 185 people to create a single measure of median neuropathy severity as a continuum (through exploratory factor analysis). We assessed if our single measure of median neuropathy severity is independently associated with Boston Carpal Tunnel Questionnaire item groupings. Median neuropathy severity measured as a continuum had modest independent associations with Boston Carpal Tunnel Questionnaire magnitude of capability (adjusted R2 0.063) and paraesthesia intensity (adjusted R2 0.12) items but not with items related to pain intensity. Considering the lack of association of Boston Carpal Tunnel Questionnaire pain items with objective pathophysiology, combined with their notable association with mental health measures in previous studies, it is probably best to omit items related to pain. Level of evidence: III [ABSTRACT FROM AUTHOR]

Background: Diabetic Foot Ulcers (DFUs), a serious complication of diabetes, have limited solutions in conventional therapies. The condition needs holistic management of blood glycemic levels; foot wounds; and possible regeneration of nerves in the soles of patients. Objective: To evaluate the efficacy of Pranic Healing as a complimentary therapy in managing Diabetic Foot Ulcers (DFUs). Methods: Thirty diabetic subjects already on standard therapy for Diabetes, co morbidities and wound care for Diabetic Foot Ulcers were assigned on a 1:1 basis to the trial and control groups. While both groups continued to receive standard therapy, the trial group additionally received Pranic Healing therapy. The Clinician, nursing staff, assessors and patients were blinded. Pranic Healers carried out healing on the trial group remotely, every day for 50 to 60 minute for stress, diabetes, local wound healing, blood cleansing and regeneration of nerves in the soles. The efficacy variables were the mean change from baseline in wound parameters and grade of DFU, overall well-being and HbAlc levels. Results: At the end of the trial, about 83.33% participants in the trial group demonstrated lowering of size and severity of the ulceration and improved to a lower grade of DFU compared to 44.4% in control group. The trial group reported a significant reduction in wound area and HbA1c levels. The trial group showed better readings for improved sensory perception in the soles through changes in the large fibre dysfunction and damaged nerves as compared to the control group. Approximately 76.9% of participants in the trial group reported lower stress levels compared to 22.22% in the control group. Conclusions: Pranic Healing intervention can be a safe and effective adjunct in managing Diabetic Foot Ulcers. Graphical Abstract [ABSTRACT FROM AUTHOR]

Introduction: Bortezomib-induced peripheral neuropathy in patients with multiple myeloma is an undesirable and sometimes severe side effect. Our study aimed to examine whether there was a difference in bortezomib-induced peripheral neuropathy between multiple myeloma patients with normal and abnormal genetic characteristics. Methods: This retrospective analysis is based on the assessment of bortezomib-induced peripheral neuropathy frequency in newly-diagnosed multiple myeloma patients with normal (n = 68) and abnormal (n = 45) genetic profiles. A total of 113 patients diagnosed with multiple myeloma according to the International Myeloma Working Group criteria, between 2016 and 2021, were included in this study. Results: Neuropathy was detected in 42 (37.1%) patients. The most common genetic anomalies were 13q del (in 28.9%), t (4.14) (in 22.2%), and trisomy 7 (in 20.0%). When patients with and without bortezomib-induced peripheral neuropathy were compared, the only significant differences were observed for age (p = 0.032) and genetic grouping (p = 0.001); whereas other characteristics that could be associated with bortezomib-induced peripheral neuropathy were similarly distributed in both groups. Bortezomib-induced peripheral neuropathy was significantly more frequent in multiple myeloma patients with normal genetic characteristics (p = 0.001). Conclusion: As a result of our study, it was observed that the frequency of bortezomib neuropathy was significantly higher in patients with normal genetic features compared to those with abnormal genetic features. This result suggested that factors other than genetic factors should be investigated to clarify the etiology of bortezomib-associated neuropathy in patients with multiple myeloma. [ABSTRACT FROM AUTHOR]

Contactin-associated protein-like 2 (CASPR2) autoantibodies are among those associated with several syndromes with effects on both the central and peripheral nervous systems including neuropathy and encephalitis and is most commonly seen in middle-aged to elderly males. We present a case of autoimmune encephalitis in a 14-month-old female presenting with altered mental status, refusal to bear weight, and hypertension in the setting of mercury exposure. This is the youngest reported case of CASPR2/LGI1/VGKC antibody associated autoimmune encephalitis stimulated by mercury exposure. [ABSTRACT FROM AUTHOR]

Neurosensory disorders such as pain and pruritus remain a major health problem greatly impacting the quality of life, and often increasing the risk of mortality. Current pre-clinical models to investigate dysfunction of sensory neurons have shown a limited clinical translation, in part, by failing to mimic the compartmentalized nociceptor anatomy that exhibits a central compartment containing the soma and a peripheral one harboring the axon endings with distinct molecular and cellular environmental composition. Thus, there is a need to validate compartmentalized preclinical neurosensory models for investigating the pathophysiology of peripheral sensory disorders and to test drug candidates. Here, we have addressed this issue and developed a microfluidic-based preclinical nociceptor model and validated it for investigating inflammatory and neuropathic peripheral disorders. We show that this model reproduces the peripheral sensitization and resolution produced by an inflammatory soup and by the chemotherapeutic drug paclitaxel. Furthermore, compartmentalized nociceptor primary cultures were amenable to co-culture with keratinocytes in the axonal compartment. Interaction of axonal endings with keratinocytes modulated neuronal responses, consistent with a crosstalk between both cell types. These findings pave the way towards translational pre-clinical sensory models for skin pathophysiological research and drug development. [ABSTRACT FROM AUTHOR]

Autoantibodies against contactin-associated protein 2 (CASPR2) are usually associated with autoimmune encephalitis and neuromyotonia. Their association with inflammatory neuropathies has been described in case reports albeit all with distal symmetric manifestation. Here, we report a patient who developed distal arm paresis, dominantly of the right arm, over the course of 1 year. Electroneurography showed a conduction block of motor nerve conduction, nerve ultrasonography a swelling of the right median and ulnar nerve and flow cytometry an increase in natural killer (NK cells) in the blood and natural killer T (NKT) cells in the cerebrospinal fluid (CSF), therefore indicating a multifocal motor neuropathy-like (MMN-like) phenotype. CASPR2 autoantibodies were detected in serum and CSF. Through immunotherapy with intravenous immunoglobulins the patient showed clinical and neurographic improvement. We therefore describe the first association of CASPR2 autoantibodies with a MMN-like clinical manifestation, extending the spectrum of CASPR2-associated diseases. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is one of the most debilitating diseases, diabetic neuropathy happens to be the most common and perhaps the most serious complication of diabetes mellitus, often leading to morbidity and mortality. A 60 year old female presented with disorientation, history of vomiting, shortness of breath, respiratory failure initially. Blood reports revealed that she was positive for ketone bodies with elevated HbA1c and general random blood sugar. Chest radiogram revealed atelectasis of the right lung with prominent involvement of right middle and lower lobes. High-resolution computed tomography of chest confirmed the findings and unilateral diaphragmatic paralysis due to phrenic nerve neuropathy due to undetected type 2 diabetes was diagnosed. Although phrenic nerve paralysis is a rare occurrence with diabetes, the possibility shouldn't be overlooked as a presentation of diabetes mellitus. [ABSTRACT FROM AUTHOR]

The aim of this study was to describe the phenotype of Leber hereditary optic neuropathy occurring in pediatric females. This disease generally affects young adult males, but it can occur also in females, and research data in this population is lacking. The very early onset can challenge the diagnosis and delay treatment. We searched PubMed through February 2021 and identified 226 pediatric females with genetically confirmed Leber hereditary optic neuropathy and added a new case of a 3-year-old female. The male-female ratio was 1.8:1; the mean onset age in females was 11 years with the onset at 3 years of age occurring in 3 females only. Acute onset with mild visual impairment was the most common presentation, associated with optic disc edema in 16%. Differential diagnoses are pseudotumor cerebri, optic nerve drusen and optic neuritis. The outcome is poor with partial recovery in 50%, despite some receiving Idebenone therapy. [ABSTRACT FROM AUTHOR]

Background: It is difficult to detect optic nerve changes in patients with thyroid-associated ophthalmopathy (TAO) before the development of optic neuropathy. Purpose: To detect changes in the intraorbital segment of the optic nerve in patients with TAO using diffusion tensor imaging (DTI) and determine any correlations with disease severity. Material and Methods: A total of 74 participants (17 normal, 22 mild, and 35 moderate-severe TAO) were organized to be given 3-T DTI to measure fractional anisotropy (FA) and mean diffusivity (MD) for the orbital segments of their optic nerves. All underwent ophthalmological examinations for visual acuity, intraocular pressure, exophthalmos, and fundoscopy, and were assessed based on the Clinical Activity Score (CAS). Univariate analysis of variance and Pearson's correlation coefficients were carried out. Results: Patients with moderate-to-severe TAO had significantly lower FA values and higher MD values (P < 0.05). FA values were negatively correlated with CAS but had no obvious correlations with the degree of exophthalmos. MD values had no obvious correlations with CAS or the degree of exophthalmos. Conclusion: DTI parameters of the intraorbital optic nerves were significantly altered in moderate-to-severe patients before onset of clinical optic nerve dysfunction and may, therefore, be used as an imaging biomarker for assessing the disease. [ABSTRACT FROM AUTHOR]

Introduction: Recurrent Painful Ophthalmoplegic Neuropathy, previously known as Ophthalmoplegic Migraine, is a poorly characterized disorder mainly because there are few cases described. We report a new case of Recurrent Painful Ophthalmoplegic Neuropathy and a review of the literature to contribute to increasing the knowledge of the clinical features of this disorder. Case report and review of literature: A 45-year-old woman presented with adult-onset recurrent attacks of abducens and oculomotor palsy associated with diplopia followed by headache. Most notably, pain always presented many days after oculomotor impairment, a feature never described in the literature. A diagnosis of possible Recurrent Painful Ophthalmoplegic Neuropathy was made after excluding other possible mimicking disorders. Symptoms usually resolved gradually with corticosteroid therapy, albeit without a clear-cut benefit. Clinical data collected from 1989 to 2022 showed that adult onset in Recurrent Painful Ophthalmoplegic Neuropathy is not uncommon. While III cranial nerve palsy is typical, VI and IV nerve palsy have also been described. Pathophysiology and diagnosis: Several hypotheses have been proposed, including nerve compression, ischemia or inflammation/demyelination, but none has been completely accepted. Diagnosis remains of exclusion; magnetic resonance imaging and blood exams are key in differential diagnosis. Conclusions: Our case gives us the possibility to expand the clinical features of Recurrent Painful Ophthalmoplegic Neuropathy, also contributing to updating the pathophysiological hypotheses. [ABSTRACT FROM AUTHOR]

Background: Sensitive imaging modalities in the diagnosis of microcircular complications of the lower extremities induced by metabolic diseases are becoming a focus of interest. Purpose: To investigate the [99mTc]HMPAO uptake of the legs in type 2 diabetes mellitus (T2DM) and obesity, and to search for associations with clinical parameters and nerve conducting studies. Material and Methods: A total of 57 patients with controlled T2DM and 46 obese participants without DM were enrolled in the study. [99mTc]HMPAO SPECT/CT examinations were performed to evaluate the radiopharmaceutical accumulation of the legs. For the quantitative assessment of tracer uptake, standardized uptake value (SUVpeak) was measured in fixed spheric volumes of interest placed on both sural muscles on the attenuation-corrected images. Measurement of current perception threshold applying Neurometer (NM-01/CPT) was used to evaluate peripheral nerve dysfunction. Laboratory parameters assessing the glucose homeostasis of the study participants were also measured. Results: In the diabetic group, significantly lower leg SUV values were detected compared to the non-DM obese group (median: 0.517 vs. 0.607; P < 0.001). Body mass index (BMI) (P < 0.0001), age (P = 0.0283), HbA1c (P = 0.0068), and glucose level (P = 0.0044) proved to be significant predictors of muscle tracer uptake. Neurometer studies showed positive correlation with HbA1c levels in the T2DM group (P = 0.0002). Conclusion: We assume that [99mTc]HMPAO uptake of leg muscles is associated with microcirculation, so quantitative [99mTc]HMPAO SPECT/CT might be a sensitive method for evaluating lower limb microvascular alterations. BMI, age, HbA1c, and glucose level may be significant predictors of peripheral vascular abnormalities triggered by metabolic disturbances. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic has had an enormous impact on practically every aspect of daily life, and those with neuromuscular disorders have certainly not been spared. The effects of COVID-19 infection are far-reaching, going well beyond respiratory symptoms alone. From simple myalgias to debilitating critical illness neuromyopathies, we continue to learn and catalog the diverse pathologies presented by the severe acute respiratory syndrome coronavirus 2 (SARS - CoV-2) as it relates to the neuromuscular system. Complications have been documented both as a direct result of primary infection but also in those with pre-existing neuromuscular disorders from myasthenia gravis to devastating critical illness neuromyopathies. In this review, we will discuss the relationship between COVID-19 infection and critical illness neuromyopathy, peripheral nerve palsies, myalgias, positional compressive neuropathy, myasthenia gravis, and Guillain-Barré syndrome. [ABSTRACT FROM AUTHOR]

Objective: Since there is a lack of effective pharmacological therapies for chemotherapy-induced neuropathy and many patients ask for integrative cancer therapies such as acupuncture, the objective of this pilot study was to describe patients' experiences, and to study the feasibility and short-term effects of genuine acupuncture for chemotherapyinduced neuropathic pain and unpleasant sensations compared to sham acupuncture. Methods: The pilot study used mixed methods, collecting quantitative and qualitative data. Patients (n = 12) with chemotherapy-induced neuropathy after colorectal cancer were blindly randomized to genuine acupuncture or telescopic sham acupuncture. Individual interviews were conducted, and were analyzed using qualitative content analysis. The patients registered pain and unpleasant sensations (100 mm Visual Analog Scales) before and after n = 120 sessions, n = 60 genuine and n = 60 sham acupuncture sessions. Results: Five categories of patient experiences were described. The neuropathy negatively affected life. Physical activity was perceived to be important for health, but neuropathy was a barrier. The neuropathy required symptom-managing strategies. Acupuncture was pleasant and valuable, but some patients presented doubts regarding its effect mechanisms. After the genuine acupuncture sessions, pain (mean -2.0 steps relief during each session) and unpleasant sensations (-2.4) in the face was reduced more than after sham acupuncture (+0.1 steps worse pain, P = .018, +0.1 steps worse unpleasant sensations, P = .036). After genuine acupuncture, unpleasant sensations in the hands were reduced less (-0.23) compared to after sham acupuncture (-5.5, P = .002). Pain or unpleasant sensations in the feet did not change. Conclusions: Patients experienced that the neuropathy negatively changed their life and that acupuncture was pleasant and valuable. Patients receiving genuine acupuncture had short-term effects regarding pain and unpleasant sensations in the face compared to patients receiving sham acupuncture, while hands and feet did not improve. The patients were successfully blinded and complied with the acupuncture. We welcome future full-scaled randomized sham-controlled acupuncture studies. [ABSTRACT FROM AUTHOR]

An 8-y-old Labrador Retriever dog had mild ataxia of the hindlimbs 4 mo after lumbosacral dorsal laminectomy for intervertebral disk disease. Ataxia of the hindlimbs gradually worsened over the next 6 y. On autopsy, gross lesions were not recognized in the spinal cord. Histopathology revealed an intradural extraparenchymal cholesterol granuloma in the cauda equina associated with remnant nerve roots. Nerves associated with the cholesterol granuloma had axonal degeneration, myelin vacuolation, and edema. In those foci, macrophages were increased in number between nerve fibers. Immunohistochemistry for neurofilament protein and Luxol fast blue staining highlighted the presence of remnant axons and myelin sheaths within the granuloma. Inflammatory cell infiltrates in the granuloma were mainly macrophages and CD3- or CD20-immunopositive T or B lymphocytes, respectively. We conclude that the cholesterol granuloma likely formed subsequent to degenerative neuropathy in the cauda equina. [ABSTRACT FROM AUTHOR]

Breast cancer, the most prevalent cancer among women, often requires chemotherapy with docetaxel being a key agent. However, docetaxel-inducted peripheral neuropathy (DIPN) can adversely impact patients’ quality of life. This case discusses an unusual instance of severe DIPN leading to wheelchair dependence in a 35-years old woman undergoing neoadjuvant treatment for locally advanced breast cancer.Following anthracycline and cyclophosphamide cycles without neurological symptoms, docetaxel administration resulted in progressive neuropathy. Despite dose reduction, the patient developed severe paraesthesias, foot weakness, and eventually wheelchair dependence.Docetaxel's microtubule-stabilizing mechanism, vital for cell division, may disrupt axonal structures, causing sensory and motor neuropathy. While rare, severe motor neuropathy, leading to wheelchair dependence, poses a significant challenge. The frequency of DIPN varies, with docetaxel exhibiting lower neuropathy rates than other taxanes. Risk factors include age, diabetes mellitus, cumulative dose, and genetic polymorphisms in GSTP1 and ABCB1. In our case, despite the patient being young, fit and without diabetes, severe DIPN occured, suggesting a potential genetic predisposition. Genetic variations, such as GSTP1 polymorphisms have been associated with DIPN. Our patient carried GSTP1 (I1e105Val) mutations, emphasizing the need for further research to establish their role as risk factors.This case underscores the importance of recognizing severe DIPN, even in atypical patient profiles. Genetic factors, like GSTP1 polymorphisms, may contribute to DIPN risk. Large-scale studies are crucial to establishing the significance of these genetic variations in DIPN susceptibility. [ABSTRACT FROM AUTHOR]

Objective: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, can result in persistent loss of taste and smell. This study was performed to assess acoustic reflex threshold (ART) in patients with taste disorders caused by SARS-CoV-2. Material and Methods: This retrospective study enrolled 11 patients (9 men, 2 women; average age = 22.3 years) with a history of COVID-19 and had complaints of taste disorder and sensitivity to loud sounds. The control group consisted of 13 healthy participants (10 men, 3 women; average age = 23.4 years). Anamnesis, neuro-otological, ear, nose and throat, and eye examinations, as well as a taste test, pure tone audiometry, speech discrimination test, and impedance audiometry were performed in all participants. Results: All participants in the study group had a negative taste test result. In addition, ART values were significantly higher in the study group than the control group at all frequencies. Conclusions: SARS-CoV-2 could be a neurotropic virus that can cause facial nerve neuropathy. [ABSTRACT FROM AUTHOR]

Patients with rheumatoid arthritis (RA) experience pain from inflammation, joint destruction, and neuropathy. Antidepressants may play a role among patients with RA and depression, fibromyalgia, or neuropathy to achieve desired outcomes. This commentary evaluated evidence for medications individually and identified important variables for future research. While we await the results of well-designed studies, a trial of duloxetine or milnacipran may be considered for patients with remnant pain and RA remission. Research is needed to evaluate the efficacy and safety of serotonin–norepinephrine reuptake inhibitors and tricyclic antidepressants in patients with RA and associated comorbid conditions. [ABSTRACT FROM AUTHOR]

The interchange of information from one cell to another relies on the release of hundreds of different molecules including small peptides, amino acids, nucleotides, RNA, steroids, retinoids, or fatty acid metabolites. Many of them are released to the extracellular matrix as free molecules and others can be part of the cargo of cellular vesicles. Small extracellular vesicles (30–150 nm), also known as exosomes, are a known mechanism of cell-to-cell communication in the nervous system. Exosomes participate in the pathogenesis of several neurological conditions including Alzheimer’s and Parkinson’s disease. However, exciting emerging evidence demonstrates that exosomes also regulate mechanisms of the sensory process including nociception. The goal of this review is to summarize the literature on exosome biogenesis, methods of small vesicle isolation and purification, and their role in nociception. We also provide insights on the potential applications of exosomes as pain biomarkers or as novel therapeutics. [ABSTRACT FROM AUTHOR]

Background: Wireless percutaneous nerve stimulation (PNS) for chronic pain is rapidly evolving in the ever expanding neuromodulation paradigm. Safety and lower risks with a potential of long-term analgesia cannot be over emphasised especially with the ongoing opioid pandemic. PNS with an implanted pulse generator (IPG) has also been shown to provide good benefit, without often unpleasant widespread paraesthesia from conventional spinal cord stimulators. Aim and Methods: We retrospectively extracted data on all wireless PNS implants in our highly specialised pain neuromodulation centre since initiation of wireless PNS service in August 2019. Patient demographics, pain history, analgesic intake and details on implant follow-up data within 1 year post-implant including pain relief, EuroQol-5 Dimension (EQ-5D) and Patients' Global Impression of Change (PGIC) scores were extracted. The cases are presented in a narrative format. Result: A total of five patients were implanted with wireless (Stimwave®) PNS from August 2019 to February 2020. Neuropathic pain was the most common presenting diagnosis. All patients showed >50% pain relief at 3 months. EQ-5D and PGIC did not show any improvement in the subjects. Two of the patients managed to decrease their analgesics after implantation. Similar sustained benefits could not be demonstrated after 1 year. Discussion: PNS can provide analgesia in appropriately selected cases. Naivety of the technique and procedure might cause some degree of uncertainty. External pulse generator with wireless transmission avoids IPG and tunnelling related side effects, but requires individualised special wearable technology to power the lead. Minimally invasive nature of the technique might be attractive and preferable for patients with complex medical issues, nickel allergy and poor general health who may otherwise be unsuitable for Spinal Cord Stimulation (SCS) with conventional hardware. Robust prospective controlled studies and RCTs in future might provide further insights on utility in other neuropathic pain diagnosis, long-term outcomes and acceptability compared to conventional SCS. [ABSTRACT FROM AUTHOR]

Opium addiction can cause symptoms in the central or peripheral neurological systems, as well as gastrointestinal disorders and anemia; in such situations, lead poisoning should be considered and chelation therapy should be started as soon as possible. In adults, lead poisoning is an unusual cause of abdominal pain. A common form of lead neuropathy includes weakness of the wrist and finger extensors. We describe a 24-year-old female who developed severe lead poisoning after 3 years of opium consumption, leading to gastrointestinal complaints and bilateral wrist drops. [ABSTRACT FROM AUTHOR]

Introduction: Oxaliplatin is a third-generation platinum compound that used extensively for the treatment of various types of cancer especially gastrointestinal neoplasms. The main dose-limiting toxicities of oxaliplatin are hematological toxicity and peripheral sensory neuropathy. Case report: A 42-year-old man with refractory peripheral T-cell lymphoma (PTCL) was admitted to receive GEMOX chemotherapy regimen (gemcitabine, oxaliplatin). Three days after receiving his third cycle of chemotherapy regimen, he was re-admitted to the emergency department with complaint of severe generalized weakness, and paraplegia in the lower extremities. According to clinical and para-clinical findings, chronic sensorimotor polyneuropathy with ongoing axonal loss was confirmed. Management & Outcome: Intravenous dexamethasone 8 mg three times daily was started at the time of admission for the patient. Muscle weakness and sensory impairment improved dramatically within 10 days and the patient was able to walk with assistance. Discussion: Several cases of neuropathy following oxaliplatin and only one case with gemcitabine-based chemotherapy regimen have been previously reported. However, motor symptoms are rare unless in the setting of acute neuropathy due to oxaliplatin. The most striking finding of our study was the incidence of a chronic sensorimotor axonaldemyelinating polyneuropathy in a patient who were subjected to oxaliplatin therapy. In conclusion, we report a case of severe generalized weakness and paraplegia following administration of Oxaliplatin. [ABSTRACT FROM AUTHOR]

Background: Neuropathic pain is a condition caused by a lesion or disease of the somatosensory nervous system. It may present as debilitating pain with a sensation of burning and electric-like symptoms and is often difficult to manage effectively. Although pharmacological medications are the first line of treatment, multidisciplinary teams are sometimes required to provide appropriate treatment to improve quality of life and overall wellbeing. Aim: The aim of this study is to present a case of post herpetic neuralgia relieved successfully by the compound palmitoylethanolamide (PEA) – a natural alternative to pharmacological pain relief. Methods: We present the case of a 67 year-old male with ongoing post-herpetic neuralgia, over a 3-year period, as a result of complications from shingles (herpes zoster). Previous studies on the relationship between PEA and neuropathy were reviewed, with an attempt to discuss the possible underlying mechanism of PEA on neuropathic pain. Results: PEA demonstrated effective pain relief within 48 hours at an administered daily dose of 900 mg (10 mg/kg). Conclusions: PEA may offer a valid nutraceutical treatment for practitioners. [ABSTRACT FROM AUTHOR]

Background: Treating critically sized defects (CSDs) of bone remains a significant challenge in foot and ankle surgery. Custom 3D-printed implants are being offered to a small but growing subset of patients as a salvage procedure in lieu of traditional alternates such as structural allografts after the patient has failed prior procedures. The long-term outcomes of 3D-printed implants are still unknown and understudied because of the limited number of cases and short follow-up durations. The purpose of this study was to evaluate the outcomes of patients who received custom 3D-printed implants to treat CSDs of the foot and ankle in an attempt to aid surgeons in selecting appropriate surgical candidates. Methods: This was a retrospective study to assess surgical outcomes of patients who underwent implantation of a custom 3D-printed implant made with medical-grade titanium alloy powder (Ti-6Al-4V) to treat CSDs of the foot and ankle between June 1, 2014, and September 30, 2019. All patients had failed previous nonoperative or operative management before proceeding with treatment with a custom 3D-printed implant. Univariate and multivariate odds ratios (ORs) of a secondary surgery and implant removal were calculated for perioperative variables. Results: There were 39 cases of patients who received a custom 3D-printed implant with at least 1 year of follow-up. The mean follow-up time was 27.0 (12-74) months. Thirteen of 39 cases (33.3%) required a secondary surgery and 10 of 39 (25.6%) required removal of the implant because of septic nonunion (6/10) or aseptic nonunion (4/10). The mean time to secondary surgery was 10 months (1-22). Multivariate logistic regression revealed that patients with neuropathy were more likely to require a secondary surgery with an OR of 5.76 (P =.03). Conclusion: This study demonstrated that 74% of patients who received a custom 3D-printed implant for CSDs did not require as subsequent surgery (minimum of 1-year follow-up). Neuropathy was significantly associated with the need for a secondary surgery. This is the largest series to date demonstrating the efficacy of 3D-printed custom titanium implants. As the number of cases using patient-specific 3D-printed titanium implant increases, larger cohorts of patients should be studied to identify other high-risk groups and possible interventions to improve surgical outcomes. Level of Evidence: Level IV, case series. [ABSTRACT FROM AUTHOR]

Both sepsis and treatment of cancer with chemotherapy are known to cause neurologic dysfunction. The primary defects seen in both groups of patients are neuropathy and encephalopathy; the underlying mechanisms are poorly understood. Analysis of preclinical models of these disparate conditions reveal similar defects in ion channel function contributing to peripheral neuropathy. The defects in ion channel function extend to the central nervous system where lower motoneurons are affected. In motoneurons the defect involves ion channels responsible for subthreshold currents that convert steady depolarization into repetitive firing. The inability to correctly translate depolarization into steady, repetitive firing has profound effects on motor function, and could be an important contributor to weakness and fatigue experienced by both groups of patients. The possibility that disruption of function, either instead of, or in addition to neurodegeneration, may underlie weakness and fatigue leads to a novel approach to therapy. Activation of serotonin (5HT) receptors in a rat model of sepsis restores the normal balance of subthreshold currents and normal motoneuron firing. If an imbalance of subthreshold currents also occurs in other central nervous system neurons, it could contribute to encephalopathy. We hypothesize that pharmacologically restoring the proper balance of subthreshold currents might provide effective therapy for both neuropathy and encephalopathy in patients recovering from sepsis or treatment with chemotherapy. [ABSTRACT FROM AUTHOR]

Following implantation of patient-derived xenograft (PDX) breast carcinomas from three separate individuals, 33/51 female NOD. Cg-Prkdc scid Il2rg tm1Wjl /SzJ (NSG) mice presented with progressive, unilateral to bilateral, ascending hindlimb paresis to paralysis. Mice were mildly dehydrated, in thin to poor body condition, with reduced to absent hindlimb withdrawal reflex and deep pain sensation. Microscopically, there was variable axonal swelling, vacuolation, and dilation of myelin sheaths within the ventral spinal cord and spinal nerve roots of the thoracolumbar and sacral spinal cord, as well as within corresponding sciatic nerves. Results of PCR screening of PDX samples obtained at necropsy and pooled environmental swabs from the racks housing affected animals were positive for lactate dehydrogenase–elevating virus (LDV). LDV is transmitted through animal-animal contact or commonly as a contaminant of biologic materials of mouse origin. Infection is associated with progressive degenerative myelopathy and neuropathy in strains of mice harboring endogenous retrovirus (AKR, C58), or in immunosuppressed strains (NOD-SCID, Foxn1nu), and can interfere with normal immune responses and alter engraftment and growth of xenograft tumors in immunosuppressed mice. This is the first reported series of LDV-induced poliomyelitis in NSG mice and should be recognized as a potentially significant confounder to biomedical studies utilizing immunodeficient xenograft models. [ABSTRACT FROM AUTHOR]

Background: Skin disorders and neuropathy often occur as side effects of chemotherapy. We encountered a patient who was treated for drug-induced skin symptoms, but the symptoms did not improve, and he was eventually diagnosed as having dermatomyositis. Case presentation: A 71-year-old man underwent chemotherapy with regorafenib in February 2020 for the postoperative recurrence of sigmoid colon cancer, but treatment was discontinued after about 2 months owing to the appearance of skin symptoms, which were thought to be side effects of regorafenib. Subsequently, his symptoms further worsened, and he was hospitalized 3 weeks after the appearance of the initial skin symptoms, and a palliative care team was asked to relieve his back pain caused by the drug-induced skin symptoms. Erythema was widely observed on the lower back and limbs, and he experienced needle stick-like pain. Furthermore, the patient demonstrated difficulty in lifting both upper limbs. As acetaminophen was effective for his pain, the dose was slowly increased with careful observation. The cause of the patient's muscle weakness was unclear, and after careful discussion of the possible causes among specialists in dermatology, neurology, and rheumatoid arthritis, a diagnosis of dermatomyositis associated with the malignant tumor was made about 10 days after his admission. The patient's symptoms gradually improved with steroid pulse treatment (methylprednisolone 1 g/day for 3 days) followed by high-dose gamma globulin treatment (2.5 g/day for 5 days), and the patient was discharged 48 days after admission. Discussion: Because this patient was referred to a palliative care team for the purpose of relieving pain caused by skin symptoms associated with chemotherapy, a crucial point is the symptoms were treated as side effects of the chemotherapy from the beginning. As neuropathy can occur as a result of chemotherapy, the pain and muscle weakness could be explained at the time; however, the symptoms continued to worsen even after the chemotherapy was stopped. Because the symptoms were not typical of polymyositis/dermatomyositis, diagnosis of the patient was delayed, even though he was treated in each specialized department. Our present case indicates that paraneoplastic syndrome should always be kept in mind when treating cancer patients. [ABSTRACT FROM AUTHOR]

Objective: To describe a case of idiopathic bilateral cochlear nerve atrophy acquired in adulthood. Patient: A 75-year-old male with acquired bilateral cochlear nerve atrophy. Intervention(s): Unilateral cochlear implantation. Main Outcome and Results: Description of a patient with acquired bilateral cochlear nerve atrophy diagnosed at the age of 75. The patient had normal hearing and no communication deficits until the age of 66. At this point, the patient demonstrated a slight asymmetric hearing loss, which progressed to severe sensorineural hearing loss. Due to the resulting communication deficit, cochlear device implantation candidacy was pursued. Pre-operative magnetic resonance imaging (MRI) showed severe atrophy versus absence of the cochlear nerves bilaterally. After careful counseling regarding the expected communication outcomes given the MRI findings, the patient underwent left-sided cochlear implantation. The patient gained sound awareness, but no additional communication benefit compared to pre-operative baseline abilities. Conclusion: Cochlear nerve deficiency is a known finding in certain cases of congenital and acquired hearing loss, but no cases of idiopathic adult-onset bilateral nerve atrophy have been reported. Without MR imaging, the clinically significant finding would not have been identified. Thus, MRI is advantageous when compared with other imaging modalities in patients with progressive sensorineural hearing loss and enables improved patient counseling regarding expected auditory and communication outcomes. [ABSTRACT FROM AUTHOR]

Active duty military members have significant service-related risks for developing pain from injury. Although estimates for neuropathic pain (NP) are available for civilian populations, the incidence and prevalence for NP in military members is less clear. Understanding correlates of pain in military members is vital to improving their physical, mental, and social health. Using a comparative design, a secondary analysis was conducted on longitudinal PASTOR data from 190 pain management center patients. The objectives were to compare trends in patient-reported outcomes over time between those screening positive and negative for NP (NP+, NP−, respectively) based on PROMIS Neuropathic Pain Scale T-scores. Findings showed improvements in fatigue, sleep-related impairment, and anger over time. There was a difference between those screening NP+ and NP− for sleep-related impairment, and the cross-level interaction effect showed sleep-related impairment worsening over time. These results emphasize the need to identify NP and implement and evaluate targeted therapies. [ABSTRACT FROM AUTHOR]

Inorganic arsenic (iAs) exposure is a serious health problem that affects more than 140 million individuals worldwide, mainly, through contaminated drinking water. Acute iAs poisoning produces several symptoms such as nausea, vomiting, abdominal pain, and severe diarrhea, whereas prolonged iAs exposure increased the risk of several malignant disorders such as lung, urinary tract, and skin tumors. Another sensitive endpoint less described of chronic iAs exposure are the non-malignant health effects in hepatic, endocrine, renal, neurological, hematological, immune, and cardiovascular systems. The present review outlines epidemiology evidence and possible molecular mechanisms associated with iAs-toxicity in several non-carcinogenic disorders. [ABSTRACT FROM AUTHOR]

Purpose: Intensive care unit-acquired weakness (ICUAW) can manifest as muscle weakness or neuropathy-like symptoms, with diagnosis remaining a challenge. Uncertainties surround the long-term cause and sequelae. Therefore, the purpose was to assess incidence, time course and long-term influence on quality of life (QoL) of symptoms in ICU survivors. Methods: After ethical approval and registration (www.drks.de: DRKS00011593), in a single-center cohort study all patients admitted to the ICU in 2007-2017 in a German university hospital were screened. Out of 1,860 patients (≥7d ICU care including ventilation support for ≥72 h, at least 6mo-10y after ICU) 636 were deceased, 912 survivors were contacted. Results: 149 former patients (age: 63.5 ± 13.1y; males: 73%; duration in ICU: 20.8 ± 15.7d; duration of ventilation: 16.5 ± 13.7 h; time post-ICU: 4.4 ± 2.7y, 5-10y: 43%) consented to be interviewed concerning occurrence, duration, recovery and consequences of ICUAW-associated muscle weakness or neuropathy-like symptoms after ICU. In 75% at least 1 persistent or previous symmetrical symptom was reported (myopathy-like muscle weakness: 43%; neuropathy-like symptoms: 13%; both: 44%) and rated as incidence of ICUAW. However, only 18% of participants had received an ICUAW diagnosis by their physicians, although 62% had persistent symptoms up to 10y after ICU (5-10y: 46%). Only 37% of participants reported a complete recovery of symptoms, significantly associated with an initially low number of symptoms after ICU (p < 0.0001), myopathy-like symptoms (p = 0.024), and younger age at the time of ICU admission (55.7 ± 13.1 vs. 62.6 ± 10.6y, p < 0.001). ICUAW still impaired the QoL at the time of the interview in 74% of affected survivors, with 30% reporting severe impairment. Conclusion: ICUAW symptoms were disturbingly common in the majority of long-term survivors, indicating that symptoms persist up to 10y and frequently impair QoL. However, only a small number of patients had been diagnosed with ICUAW. Trial registry: Deutsches Register Klinischer Studien (DRKS), https://www.drks.de/drks&lowbar;web/navigate.do?navigationId=trial.HTMLID=DRKS00011593, registration number: DRKS00011593. [ABSTRACT FROM AUTHOR]

Background: Suprascapular neuropathy has been observed in the setting of rotator cuff tears (RCTs), but its association with these tears and their treatment are unclear. Hypothesis: Arthroscopic suprascapular nerve release during rotator cuff repair will not alter the outcomes of neuropathy. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 42 patients with large/massive reparable RCTs and suprascapular neuropathy were recruited and followed up at 6 and 12 months. Electrophysiological results as well as Disabilities of the Arm, Shoulder and Hand (DASH), American Shoulder and Elbow Surgeons (ASES), and Constant scores were evaluated at selected time periods. Patients were randomly assigned to 2 groups. Patients in the control group underwent arthroscopic repair of the rotator cuff without combined arthroscopic release of the superior transverse scapular ligament; in the second group, the superior transverse ligament was released. The primary outcome was to examine full suprascapular nerve recovery through electrophysiological changes between groups. The secondary/tertiary outcomes were analysis of clinical outcomes and assessment of the relation between RCT size and the degree of suprascapular nerve recovery. Patients, clinical staff members, and the neurologist were blinded to the type of surgical procedure. Results: Of 42 patients, 37 completed the follow-up at 12 months (median age, 64 years [range, 50-75 years]). Overall, 17 of 19 (89.5%) patients in the control group and 15 of 18 (83.3%) patients in the nerve release group had full nerve recovery, with no significant difference between the 2 groups. Clinically, all patients in both groups showed a significant improvement (P <.001), but no significant difference was observed between the 2 groups in terms of 12-month postoperative scores (control group: DASH: median, 5 [range, 0-21]; ASES: median, 88 [range, 83-98]; Constant: median, 86 [range, 70-98]) (nerve release group: DASH: median, 6 [range, 0-25]; ASES: median, 90 [range, 83-98]; Constant: median, 88 [range, 75-98]). Also, no significant difference was found between the 2 groups regarding other secondary and tertiary outcomes. Conclusion: Combined arthroscopic release of the superior transverse scapular ligament and rotator cuff repair in patients with large/massive RCTs and suprascapular neuropathy did not produce statistically significant improved outcomes compared with repair of the rotator cuff alone. Registration: NCT02318381 (ClinicalTrials.gov identifier). [ABSTRACT FROM AUTHOR]

This review discusses the evidence on diabetic retinopathy (DR) in patients with diabetic foot ulceration (DFU). A systematic literature review was performed on PubMed, Medline, Springer Nature, and Scopus, following the PRISMA guidelines, using the following terms, individually or in combination: "diabetic foot ulcer" OR "diabetic foot syndrome" OR "DFU" and "diabetic retinopathy." The initial search yielded 648 articles published between 1975 and 2020. After applying exclusion and inclusion criteria, a total of 9 articles were analyzed, assessing the correlations between DR and DFU. In all cases, DR and especially proliferative diabetic retinopathy were significantly higher in the presence of DFU, though the frequency of DR showed large variability (22.5% to 95.6%). There was a significant correlation between advanced stages of DFU and increased frequency of DR and proliferative diabetic retinopathy. On the other hand, there is a risk of accelerated progression of DR in nonhealing DFUs, possibly related to chronic inflammation and associated infection. Hence, patients with DFUs should be monitored by an ophthalmologist, and those with DR should be promptly referred to a specialized diabetic foot clinic. [ABSTRACT FROM AUTHOR]

Abetalipoproteinemia (ABL) is a rare recessive condition caused by biallelic loss-of-function mutations in the MTTP gene encoding the microsomal triglyceride transfer protein large subunit. ABL is characterized by absence of apolipoprotein B–containing lipoproteins and deficiencies in fat-soluble vitamins leading to multisystem involvement of which neurological complications are the most serious. We present 3 siblings with ABL who were born to non-consanguineous parents of Filipino and Chinese background. Identical twin boys with long-standing failure to thrive and malabsorption were diagnosed at age 2 years. ABL therapy with vitamins and a specialized diet was initiated, replacing total parenteral nutrition at age 3 years. Their younger sister was diagnosed from a blood sample taken at birth; treatment was instituted shortly thereafter. We observed in the twins reversal and in their sister prevention of ABL systemic features following early implementation of fat restriction and high doses of oral fat-soluble vitamins. A targeted sequencing panel found that each affected sibling is homozygous for a novel MTTP intron 13 -2A>G splice acceptor site mutation, predicted to abolish splicing of intron 13. This variant brings to more than 60 the number of reported pathogenic mutations, which are summarized in this article. The twin boys and their sister are now doing well at 11 and 4 years of age, respectively. This experience underscores the importance of early initiation of targeted specialized dietary and fat-soluble vitamin replacements in ABL. [ABSTRACT FROM AUTHOR]

Gastrointestinal inflammatory neuropathy, namely, eosinophilic myenteric ganglioneuronitis (EMG) and lymphocytic ganglioneuronitis (LG), is a form of chronic intestinal pseudo-obstruction and results from the infiltration of the myenteric plexus by eosinophils and lymphocytes, respectively. The literature related to the clinicopathological features of adult inflammatory neuropathy is scarce. We aim to elucidate the clinical and histological details of 7 cases of inflammatory neuropathy (EMG, n = 4, and LG, n = 3) and compare the features of EMG and LG retrospectively. There was no difference between these two entities in terms of clinical, hematological, or biochemical parameters. Histologically, almost all cases (n = 6/7) showed accompanying elements of ganglion cell vacuolization, mesenchymopathy, and partial/complete desmosis in addition to the disease-defining pathology. Besides, all cases of EMG showed infiltration of the inner circular muscle of muscularis propria by eosinophils. Two cases of LG showed additional muscular pathology pertaining to the muscularis propria. Inflammatory infiltration of the myenteric plexus is pathognomonic for the diagnosis of gastrointestinal inflammatory neuropathy although additional features in the form of ganglion cell vacuolization, reduction in the number of ganglia, desmosis, mesenchymopathy, and inflammation of the muscularis propria (eosinophils in EMG) can be seen. The pathologists need proper awareness along with judicious use of special and immunostains for clinching the diagnosis. [ABSTRACT FROM AUTHOR]

Objectives: Ruptured popliteal artery aneurysm is a rare entity, which can cause severe nerve neuropathy. Open surgical repair is the preferred treatment for ruptured popliteal artery aneurysm but may aggravate nerve injuries or lead to postoperative aneurysm enlargement. The current surgical techniques for ruptured popliteal artery aneurysm have some deficiencies.Methods: We present the case of a 78-year-old woman with sudden swelling of left knee joint and left foot drop, which was caused by the ruptured popliteal artery aneurysm and its compression. A modified open surgical repair was applied in our case, and glucocorticoid therapy was given perioperatively.Results: The motor function of left lower limb had rapidly recovered after operation, and six-month follow-up showed patency of prosthetic vessel and significant shrinkage of aneurysm sac.Conclusions: Our modified open surgical repair can relieve the compression and prevent possible "type II endoleak" without dissecting in popliteal fossa. Acute common peroneal nerve neuropathy and foot drop are reversible with immediate removal of compression and glucocorticoid therapy for patients with ruptured popliteal artery aneurysm. [ABSTRACT FROM AUTHOR]

Background: Tissue inhibitor of metalloproteinase-1 (TIMP-1) has been suggested as a marker for abnormal regulation of tissue remodelling in type 1 diabetes. Metalloproteinase-9 (MMP-9) has been associated with matrix turnover, and Neutrophil gelatinase associated lipocalin (NGAL) is a marker of tubular injury in diabetic nephropathy. The aim was to analyse these biomarkers to unmask early diabetic complications. Methods: Thirty-three type 1 diabetes patients, aged 20-35 years, and disease duration 20 ± 5.3 years were included. Along with clinical examination, neurophysiological measurements, routine biochemistry, plasma concentrations of TIMP-1, MMP-9 and NGAL were determined with immunoenzymatic techniques. Results: TIMP-1 correlated with abnormal unilateral and bilateral vibratory sense foot perception (r = -0.49 and r = -0.51, respectively), foot neuropathy impairment assessment score (NIA; r = -0.55), neuropathy symptom assessment score (r = 0.42), microalbuminuria (r = 0.50) and eGFR (r = -0.45). MMP-9 correlated with impaired foot NIA (r = 0.51). Multiple regression analysis showed an association for TIMP-1 (p = 0.004) with impaired neurophysiological examinations and renal dysfunction along with NGAL (p = 0.016 and p = 0.015 respectively). Conclusions: This study suggests that plasma levels of TIMP-1, MMP-9 and NGAL may serve as useful biomarkers in unravelling subclinical neuropathy and nephropathy in type 1 diabetes. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and dosage-limited oxaliplatin-related toxicity. To date, there are no successful interventions for CIPN prevention or treatment. A therapeutic role for cannabis in diabetic and HIV-related peripheral neuropathy and a protective role in CIPN have been suggested. We examined the effect of cannabis on oncologic patients with CIPN. Methods: Medical records of 768 consecutive patients treated with oxaliplatin and 5-fluorouracil-based combinations at a tertiary medical center from October 2015 to January 2018 were reviewed. Excluded patients were those with pre-existing neuropathy or patients who received fewer than two cycles of oxaliplatin treatment. CIPN grade, oxaliplatin cumulative dose, and neuropathy-free survival were evaluated. The patients were divided based upon the exposure to cannabis: prior to oxaliplatin (cannabis-first), cannabis following the initiation of oxaliplatin treatment (oxaliplatin-first), and no exposure (control). Results: In total, 513 patients met the inclusion criteria, of whom 248 were treated with cannabis and 265 served as controls. The cannabis-first group included 116 (46.7%) patients and the oxaliplatin-first group included 132 (53.3%) patients. Demographic parameters were comparable between groups. There was a significant difference in CIPN grade 2–3 between cannabis-exposed patients and controls (15.3% and 27.9%, respectively, p < 0.001). The protective effect of cannabis was more pronounced among cannabis-first patients compared to oxaliplatin-first patients (75% and 46.2%, respectively, p < 0.001). The median oxaliplatin cumulative doses were higher in the cannabis-first versus the oxaliplatin-first versus the control groups (545 mg/m2, 340 mg/m2, and 425 mg/m2 respectively, p < 0.001). Conclusion: The rate of neuropathy was reduced among patients treated with cannabis and oxaliplatin. This reduction was more significant in patients who received cannabis prior to treatment with oxaliplatin, suggesting a protective effect. A large prospective trial is planned. [ABSTRACT FROM AUTHOR]

Objectives: We aim to investigate the involvement of the choroid and retinal nerve fiber layer (RNFL) in COVID-19 patients using spectral domain optical coherence tomography. Methods: This cross-sectional study was conducted between April and June 2020. 40 patients (23 female and 17 male) with COVID-19 and 42 healthy individuals (26 female and 16 male) were included in the study. The OCT scans were performed 4 weeks after the COVID-19 diagnosis. Results: In the COVID-19 group, in the right eyes, the mean nasal choroidal thickness was 295.70 ± 7,046 μm (p = 0.017), mean subfoveal choroidal thickness was 333.25 ± 6,353 μm (p = 0.003), mean temporal choroidal thickness was 296.63 ± 6,324 μm (p = 0.039), and mean RNFL was 89.23 ± 1.30 μm (p = 0.227). In the left eyes, mean nasal choroidal thickness was 287.88 ± 9,033 μm (p = 0.267), mean subfoveal choroidal thickness was 333.80 ± 9,457 μm (p = 0.013), mean temporal choroidal thickness was 298.50 ± 9,158 μm (p = 0.079), and mean RNFL was 89.48 ± 1,289 μm (p = 0.092). Compared with the control group, the patient group had significant thickening of the choroidal thickness in all quadrants of the right eyes, and significant thickening of the subfoveal choroidal thickness in the left eyes. There was no significant difference in the RNFL thickness between groups (p > 0.05). Conclusion: COVID-19 may cause a subclinical involvement in the choroidal layer. [ABSTRACT FROM AUTHOR]

The peripheral nervous system (PNS) relays messages between the central nervous system (brain and spinal cord) and the body. Despite this critical role and widespread distribution, the PNS is often overlooked when investigating disease in diagnostic and experimental pathology. This review highlights key features of neuroanatomy and physiology of the somatic and autonomic PNS, and appropriate PNS sampling and processing techniques. The review considers major classes of PNS lesions including neuronopathy, axonopathy, and myelinopathy, and major categories of PNS disease including toxic, metabolic, and paraneoplastic neuropathies; infectious and inflammatory diseases; and neoplasms. This review describes a broad range of common PNS lesions and their diagnostic criteria and provides many useful references for pathologists who perform PNS evaluations as a regular or occasional task in their comparative pathology practice. [ABSTRACT FROM AUTHOR]

Background: Recurrent painful ophthalmoplegic neuropathy (RPON) is an uncommon disorder characterized by recurrent unilateral headache attacks associated with ipsilateral ophthalmoplegia. We intend to study the clinical picture in our case series along with the published literature to discuss the pathogenesis and propose modified diagnostic criteria for recurrent painful ophthalmoplegic neuropathy. Methods: We reported five cases diagnosed as ophthalmoplegic migraine/RPON in our medical centers and reviewed the published literature related to RPON from the Pubmed database between 2000 and 2020. In one of these cases, a multiplanar reformation was performed to look at the aberrant cranial nerve. Results: The mean onset age for RPON was 22.1 years, and the oculomotor nerve was the most commonly involved cranial nerve (53.9%) in 165 reviewed patients. In most patients, ophthalmoplegia started within 1 week of the headache attack (95.7%, 67/70). Additionally, 27.6% (40/145) of patients presented enhancement of the involved nerve(s) from MRI tests. Finally, 78 patients received corticosteroids, out of which 96.2% benefited from them. Conclusion: This is the first time multiplanar reformation has been performed to reveal the distortion of the oculomotor nerve. Modified diagnostic criteria are proposed. We hope to expand the current knowledge and increase the detection of recurrent painful ophthalmoplegic neuropathy in the future. [ABSTRACT FROM AUTHOR]

Purpose: Neuropathy is one of the most prevalent and dose-limiting side effects of platinum chemotherapeutic agents. N-acetylcysteine is an antioxidant thiol which is able to increase whole blood concentration of glutathione, which may be protective against chemotherapy-induced neuropathy. The aim of this study was to evaluate the effect of N-acetylcysteine on neurotoxicity induced by oxaliplatin in patients with gastric or colorectal cancers. Methods: During this randomized, double‐blinded, placebo‐controlled clinical trial, the preventive effect of N-acetylcysteine effervescent tablets was assessed in comparison with placebo, on neuropathy occurrence. Thirty-two patients with colorectal or gastric cancer randomly received N-acetylcysteine (two 600 mg tablets) or placebo tablets 1 h before receiving oxaliplatin in dose in XELOX (oxaliplatin and capecitabine regimen) for eight courses of chemotherapy. Neuropathy severity was assessed after eight courses of chemotherapy based on National Cancer Institute Common Terminology for Adverse Events (NCI‐CTCAE) criteria neuropathy grading scale and also sensory and motor electrophysiological assessment was performed by a neurologist. Results: The NCI-CTCAE scale grade of patients in intervention group was significantly lower than placebo group after eight course of oxaliplatin (P = 0.01); however, the sensory electrophysiological assessment result was not significantly different (P = 0.501). No patient in both group had motor electrophysiological changes. Conclusion: The results of this study showed that N-acetylcysteine could reduce the incidence of the neuropathy induced by oxaliplatin and delay its occurrence in patients with gastric or colorectal cancers. [ABSTRACT FROM AUTHOR]

Spinal muscular atrophy type 0 is the most severe phenotype of the disease, with patients presenting with contractures, weakness, and respiratory failure at birth, and is typically fatal within weeks. We describe the case of a patient with spinal muscular atrophy type 0 who was treated with both nusinersen and onasemnogene abeparvovec. She has made modest motor improvements since treatment initiation with a 30-point improvement in CHOP-INTEND score, and continues to make motor gains at age 13 months without regression of function, although she remains profoundly weak. Although she has had motor improvements, she has also had continued systemic complications from her spinal muscular atrophy, including chronic respiratory failure, dysphagia, congenital heart malformation, digit necrosis, and diffuse macular rash. This case highlights the challenges in treating those with more severe disease phenotypes and raises questions of how some systemic complications may respond to current SMN replacement therapies. [ABSTRACT FROM AUTHOR]