Idiopathic Neuropathy Research Articles

Caídas frecuentes y neuroimágenes en paciente con parálisis supranuclear progresiva. Presentación de caso y revisión de la literatura

Las caídas en los adultos mayores son comunes, peligrosas y frecuentemente incapacitantes. Con frecuencia son multifactoriales y requieren un amplio abordaje diagnóstico. Las demencias, la enfermedad de Parkinson idiopática (EP), la enfermedad cerebrovascular y las neuropatías se encuentran entre las condiciones neurológicas que con mayor frecuencia se asocian a caídas. Sin embargo, cuando estas se presentan con recurrencia en el contexto de un síndrome parkinsoniano, particularmente al inicio de la enfermedad, deben sugerir el diagnóstico de una parálisis supranuclear progresiva (PSP). Esta entidad es de diagnóstico esencialmente clínico; sin embargo, dado su pronóstico sombrío, se realizan imágenes por resonancia magnética (IRM) de cerebro a todos los pacientes para excluir otros diagnósticos alternativos y buscar hallazgos característicos de PSP. Estos son, principalmente, atrofia del mesencéfalo, borramiento de la sustancia nigra, atrofia del putamen y atrofia con aumento de la señal del globo pálido.
 Se presenta a continuación el caso de un paciente adulto mayor que presentaba demencia y parkinsonismo refractario a levodopa, con caídas frecuentes, en quien la realización de una resonancia magnética sirvió para aclarar el diagnóstico al evidenciar los hallazgos típicos de PSP. Además, se hace una breve revisión de los principales hallazgos con imágenes, de demencias parkinsonianas, y la prevención de caídas en estos pacientes.

Efficacy and safety of vixotrigine in idiopathic or diabetes-associated painful small fibre neuropathy (CONVEY): a phase 2 placebo-controlled enriched-enrolment randomised withdrawal study.

No pharmacological treatments are specifically indicated for painful small fibre neuropathy (SFN). CONVEY, a phase 2 enriched-enrolment study, evaluated the efficacy and safety of vixotrigine, a voltage- and use-dependent sodium channel blocker, in participants with idiopathic or diabetes-associated painful SFN. CONVEY was a phase 2, multicentre, placebo-controlled, double-blind (DB), enriched-enrolment, randomised withdrawal study. The study was conducted at 68 sites in 13 countries (Europe and Canada) between May 17, 2018, and April 12, 2021. Following a 4-week open-label period in which 265 adults with painful SFN (a mixture of large and small fibre neuropathy was not exclusionary) received oral vixotrigine 350mg twice daily (BID), 123 participants (with a ≥30% reduction from baseline in average daily pain [ADP] score during the open-label period) were randomised 1:1:1 to receive 200mg BID, 350mg BID or placebo for a 12-week double-blind (DB) period. Primary endpoint was change from baseline in ADP at DB Week 12. Secondary endpoints included the proportion of participants with a ≥30% reduction from baseline in ADP and the proportion of Patient Global Impression of Pain (PGIC) responders at DB Week 12. Treatment-emergent adverse events (AEs) were monitored. Statistical significance was set at 0.10 (2-sided). The trial was registered on ClinicalTrials.gov (NCT03339336) and on ClinicalTrialsregister.eu (2017-000991-27). A statistically significant difference from placebo in least squares mean reduction in ADP score from baseline to DB Week 12 was observed with vixotrigine 200mg BID (-0.85; SE, 0.43; 95% CI,-1.71 to 0.00; p=0.050) but not 350mg BID (-0.17; SE, 0.43; 95% CI,-1.01 to 0.68; p=0.70). Numerically, but not statistically significantly, more participants who received vixotrigine vs placebo experienced a ≥30% ADP reduction from baseline (68.3-72.5% vs 52.5%), and only the 350mg BID group had significantly more PGIC responders vs placebo (48.8% vs 30.0%; odds ratio=2.60; 95% CI, 0.97-6.99; p=0.058) at DB Week 12. AEs were mostly mild to moderate in the vixotrigine groups. The most common AEs (≥5% of vixotrigine-treated participants) in the DB 200mg BID and 350mg BID vixotrigine groups were falls, nasopharyngitis, muscle spasm, and urinary tract infection. In our study, vixotrigine 200mg BID, but not 350mg BID, met the primary endpoint; more vixotrigine-treated participants experienced a ≥30% reduction from baseline in ADP at DB Week 12. Vixotrigine (at both dosages) was well tolerated in participants with SFN. Biogen, Inc.

Clinical profile of autoimmune nodopathy with anti-neurofascin 186 antibody.

Nodal/paranodal autoantibodies identified a group of peripheral neuropathies independent from chronic inflammatory demyelinating polyneuropathy (CIDP). However, nodopathy with antibody against neurofascin 186 (NF186) was rarely reported. We presented a cohort of patients with anti-NF186 antibody and described the clinical profile of them. In this retrospective study, 195 patients diagnosed with CIDP and immune mediated idiopathic neuropathies were enrolled. Cell-based assay was used to screen anti-NF186 and anti-NF155 antibodies in serum samples. Teased-fiber immunofluorescence were used as a confirmatory assay. Clinical data of seropositive patients were collected and analyzed. Among the patients with anti-NF186 antibody, seven patients (58.3%) presented acute or subacute disorder onset. Four patients (33.3%) were found to have asymmetric weakness or numbness. Distal weakness and/or numbness was the core feature. Sensory ataxia, tremor and central nervous system demyelination were rarely observed. Nerve conduction studies revealed predominant demyelinating with/without axonal loss. Brachial plexus MRI was normal in the majority of patients (6/7, 85.7%). Five patients (5/9, 55.6%) showed response to intravenous immunoglobulin. Eight patients (8/10, 80.0%) improved after corticosteroids. All patients (3/3,100%) responded to rituximab. In the study, we depicted the clinical profile of nodopathy with anti-NF186 antibody. The diversity of clinical features, electrophysiology results and pathological findings was specific in nodopathy with anti-NF186 antibody. Screening of autoantibody against NF186 in acute-onset neuropathy is recommended.

MP52-16 POST-OPERATIVE OUTCOMES IN "MONTI" CONSTRUCTION FOR NEUROGENIC BLADDERS IN AN ADULT POPULATION

You have accessJournal of UrologyCME1 Apr 2023MP52-16 POST-OPERATIVE OUTCOMES IN "MONTI" CONSTRUCTION FOR NEUROGENIC BLADDERS IN AN ADULT POPULATION Minna Blottner, Ashley Matthew, Sarah Krzastek, and Adam Klausner Minna BlottnerMinna Blottner More articles by this author , Ashley MatthewAshley Matthew More articles by this author , Sarah KrzastekSarah Krzastek More articles by this author , and Adam KlausnerAdam Klausner More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003300.16AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Various diversion techniques exist for the management of neurogenic bladders. In pediatrics, the appendicovesicostomy is a successful approach but may not be applicable for all patients. An alternative is the Yang-Monti (“Monti”) catheterizable conduit, created using a section of small bowel. Although commonly used in pediatrics, there are very few series evaluating adults. This study aims to evaluate “Monti” outcomes in an adult population. METHODS: Between 1999 and 2022, “Monti” procedures at a single institution were identified using CPT codes, and the list was reviewed to select for adult patients with neurogenic bladder dysfunction. Preoperative data included indications for surgery and patient demographics. Perioperative (day 0 to end of hospital stay) data included time to return of bowel function, length of stay, and perioperative complications. Long-term complications included infections, hospital admissions, and reoperations. Data are presented as means or percentages. RESULTS: 21 adult patients (male n=8; female n=13) with neurogenic bladder dysfunction were identified. 14 patients developed neurogenic bladder secondary to trauma, while other indications for surgery included idiopathic urinary retention (n=1), tumors (n=2), congenital abnormalities (n=2), multiple sclerosis (n=1), and autoimmune neuropathy (n=1). The mean follow-up time was 3.13 years and mean age at surgery was 35.5 years. The mean time to return of bowel function was 2.7 days (n=14) and postoperative hospital stay was 4.3 days (n=16). Perioperative complications occurred in 10 patients (47.6%) in the first 30 days including UTIs (n=3), surgical site infection (n=3), ileus (n=1), small bowel obstruction (n=1), and suprapubic tube related complications (n=3). Five emergency room admissions for urologic concerns occurred within this period with a total of 28 visits overall. At six month follow-up, a total of six (28.6%) patients had longer-term complications. These included a takedown, a scheduled revision, a hospitalization for complicated UTI, and three patients who were unable to catheterize. Overall, nine patients (42.9%) required reoperation, including three revisions and one cystectomy with conversion to ileal conduit. Two patients expired during the course of this study due to COVID pneumonia and suspected sepsis. CONCLUSIONS: “Monti” procedures are useful for adult patients with neurogenic bladder dysfunction. However, these procedures are associated with significant complications. This information should be used to aid in presurgical counseling. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e709 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Minna Blottner More articles by this author Ashley Matthew More articles by this author Sarah Krzastek More articles by this author Adam Klausner More articles by this author Expand All Advertisement PDF downloadLoading ...

Interosseous Membrane Stimulation: A Treatment for Painful Peripheral Neuropathy.

Painful peripheral neuropathy is a condition that may be associated with diabetes as well as other causes of neuropathy. Common treatments for the pain include topical application of capsaicin as well as using oral medications, typically gabapentin. The results are variable and rarely provide substantial lasting relief. This report describes how a simple and easy to perform acupuncture technique-interosseous membrane stimulation-was used to treat painful neuropathy in 3 patients: 1 with painful diabetic neuropathy; 1 with idiopathic painful neuropathy; and 1 with painful neuropathy caused by exposure to Agent Orange while serving in Vietnam. The 3 patients had much relief from the pain associated with their neuropathy for several weeks at a time. With regular treatments, sustained relief was obtained any without the addition of new medication. Interosseous membrane stimulation is safe, simple, and effective for treatment of painful neuropathy. This treatment should be considered for patients who are suffering with painful neuropathy.

RFC1 repeat expansions and cerebellar ataxia, neuropathy and vestibular areflexia syndrome: Experience and perspectives from a neuromuscular disorders unit

IntroductionPathogenic expansions in RFC1 have been described as a cause of a spectrum of disorders including late-onset ataxia, chronic cough, and cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS). Sensory neuronopathy/neuropathy appears to be a major symptom of RFC1-disorder, and RFC1 expansions are common in patients with sensory chronic idiopathic axonal neuropathy or sensory ganglionopathy. We aimed to investigate RFC1 expansions in patients with suspected RFC1-related disease followed-up in a Neuromuscular Diseases Unit, with a particular interest in the involvement of the peripheral nervous system. MethodsWe recruited twenty consecutive patients based on the presence of at least two of the following features: progressive ataxia, sensory neuropathy/neuronopathy, vestibulopathy and chronic cough. Medical records were retrospectively reviewed for a detailed clinical description. More extensive phenotyping of the RFC1-positive patients and clinical comparison between RFC1 positive and negative patients were performed. ResultsBiallelic AAGGG repeat expansions were identified in 13 patients (65%). The most frequent symptoms were chronic cough and sensory disturbances in the lower extremities (12/13). Only 4 patients (31%) had complete CANVAS. The phenotypes were sensory ataxia and sensory symptoms in extremities in 4/13; sensory ataxia, sensory symptoms, and vestibulopathy in 3/13; sensory symptoms plus chronic cough in 2/13. Chronic cough and isolated sensory neuronopathy were significantly more prevalent in RFC1-positive patients. ConclusionPathogenic RFC1 expansions are a common cause of sensory neuropathy/neuronopathy and should be considered in the approach to these patients. Identification of key symptoms or detailed interpretation of nerve conduction studies may improve patient selection for genetic testing.

No Difference in Risk of Amputation or Frequency of Surgical Interventions Between Patients With Diabetic and Nondiabetic Charcot Arthropathy.

The cause of Charcot neuro-osteoarthropathy (CN) is diabetes in approximately 75% of patients. Most reports on the clinical course and complications of CN focus on diabetic CN, and reports on nondiabetic CN are scarce. No study, to our knowledge, has compared the clinical course of patients initially treated nonoperatively for diabetic and nondiabetic CN. Among patients with CN, are there differences between patients with diabetes and those without in terms of (1) the frequency of major amputation as ascertained by a competing risks survivorship estimator; (2) the frequency of surgery as ascertained by a competing risks survivorship estimator; (3) frequency of reactivation, as above; or (4) other complications (contralateral CN development or ulcers)? Between January 1, 2006, and December 31, 2018, we treated 199 patients for diabetic CN. Eleven percent (22 of 199) were lost before the minimum study follow-up of 2 years or had incomplete datasets and could not be analyzed, and another 9% (18 of 199) were excluded for other prespecified reasons, leaving 80% (159 of 199) for analysis in this retrospective study at a mean follow-up duration since diagnosis of 6 ± 4 years. During that period, we also treated 78 patients for nondiabetic Charcot arthropathy. Eighteen percent (14 of 78) were lost before the minimum study follow-up and another 5% (four of 78 patients) were excluded for other prespecified reasons, leaving 77% (60 of 78) of patients for analysis here at a mean of 5 ± 3 years. Patients with diabetic CN were younger (59 ± 11 years versus 68 ± 11 years; p < 0.01), more likely to smoke cigarettes (37% [59 of 159] versus 20% [12 of 60]; p = 0.02), and had longer follow-up (6 ± 4 years versus 5 ± 3 years; p = 0.02) than those with nondiabetic CN. Gender, BMI, overall renal failure, dialysis, and presence of peripheral arterial disease did not differ between the groups. Age difference and length of follow-up were not considered disqualifying problems because of the later onset of idiopathic neuropathy and longer available patient follow-up in patients with diabetes, because our program adheres to the follow-up recommendations suggested by the International Working Group on the Diabetic Foot. Treatment was the same in both groups and included serial total-contact casting and restricted weightbearing until CN had resolved. Then, patients subsequently transitioned to orthopaedic footwear. CN reactivation was defined as clinical signs of the recurrence of CN activity and confirmation on MRI. Group-specific risks of the frequencies of major amputation, surgery, and CN reactivation were calculated, accounting for competing events. Group comparisons and confounder analyses were conducted on these data with a Cox regression analysis. Other complications (contralateral CN development and ulcers) are described descriptively to avoid pooling of complications with varying severity, which could be misleading. The risk of major amputation (defined as an above-ankle amputation), estimated using a competing risks survivorship estimator, was not different between the diabetic CN group and nondiabetic CN group at 10 years (8.8% [95% confidence interval 4.2% to 15%] versus 6.9% [95% CI 0.9% to 22%]; p = 0.4) after controlling for potentially confounding variables such as smoking and peripheral artery disease. The risk of any surgery was no different between the groups as estimated by the survivorship function at 10 years (53% [95% CI 42% to 63%] versus 58% [95% CI 23% to 82%]; p = 0.3), with smoking (hazard ratio 2.4 [95% CI 1.6 to 3.6]) and peripheral artery disease (HR 2.2 [95% CI 1.4 to 3.4]) being associated with diabetic CN. Likewise, there was no between-group difference in CN reactivation at 10 years (16% [95% CI 9% to 23%] versus 11% [95% CI 4.5% to 22%]; p = 0.7) after controlling for potentially confounding variables such as smoking and peripheral artery disease. Contralateral CN occurred in 17% (27 of 159) of patients in the diabetic group and in 10% (six of 60) of those in the nondiabetic group. Ulcers occurred in 74% (117 of 159) of patients in the diabetic group and in 65% (39 of 60) of those in the nondiabetic group. Irrespective of whether the etiology of CN is diabetic or nondiabetic, our results suggest that orthopaedic surgeons should use similar nonsurgical treatments, with total-contact casting until CN activity has resolved, and then proceed with orthopaedic footwear. A high frequency of foot ulcers must be anticipated and addressed as part of the treatment approach. Level III, prognostic study.

Electrodiagnostic test results in people with a working diagnosis of cubital tunnel syndrome

BackgroundElectrodiagnostic tests (EDx) can determine when symptoms and signs suggestive of idiopathic ulnar neuropathy at the elbow (cubital tunnel syndrome; CubTS) is due to measurable ulnar neuropathy at the elbow (UNE), cervical radiculopathy, or median neuropathy at the carpal tunnel, and when there is no measurable neuropathology associated with the symptoms. The role of EDx in management of CubTS is debated. Questions(1) What is the percentage of patients with CubTS (both including and excluding patients with a previous electrodiagnosis of idiopathic UNE) that have EDx results consistent with idiopathic UNE, other neuropathology, and no detectable neuropathology (2) What factors (e.g. age and gender); are independently associated with electrodiagnosis of UNE. MethodsWe retrospectively reviewed all medical records of 133 patients with a working diagnosis of CubTS sent for EDx over a 5-year period in one large urban medical center. We recorded data on patient demographics, comorbidities, non-specialist or specialist referring physician, and EDx results. ResultsAmong 133 patients, 61% (N = 81) of EDx identified idiopathic UNE, 14% (N = 18) identified other neuropathology, and for 26% (N = 34) there was no measurable neuropathology. Among the 14 patients with a previous ipsilateral or contralateral electrodiagnosis of UNE, all 14 had electrodiagnosis of UNE. Older age and men were independently associated with an increased likelihood of UNE. ConclusionsThe observation that people diagnosed with CubTS often do not have UNE, particularly if they are relatively young, suggests that the diagnosis of CubTS may benefit from a more stringent clinical prediction rule. Level of EvidenceDiagnostic; Retrospective cohort study; Level III.

Medication sparing after medical cannabis initiation: A case study of a chronic pain patient in Project Twenty21

Prescribed cannabinoids are legal in the UK and are increasingly being used for a variety of conditions, with one of the most frequent conditions being chronic pain. Within this cohort, there is developing evidence that cannabis-based medicinal products are associated with opioid and other medication sparing. However, at present, the National Institute for Health and Care Excellence (NICE) does not recommend the prescription of cannabis-based medicinal products to treat chronic pain due to the lack of randomised controlled trial evidence for this condition. Here we present a case study of a 61-year-old woman with idiopathic small fibre neuropathy, who was prescribed the gabapentinoid pregabalin, in combination at different times with various other agents including amitriptyline, duloxetine, lamotrigine, meloxicam and topical capsaicin, over a 17-year period for the associated neuropathic pain. Although her pain was relatively well controlled, the patient reported hearing loss, sleepiness, tinnitus, confusion and worsening anxiety possibly as a result of prolonged pregabalin use. Efforts were made to reduce the pregabalin dose but any attempts to reduce below a total daily dose of 350 mg resulted in unacceptable pain for the patient. In 2021, the patient was enrolled in Project Twenty21, the UK's first medical cannabis registry, and prescribed full plant extract delta-9-tetrahydrocannabinol 10 mg: cannabidiol 15 mg/mL of oil, prescribed at a dose range of 0.1–0.5 mL twice daily. As a result, the patient managed to reduce her pregabalin down to 37.5 mg total daily dose. The patient now feels she has ‘been given a second chance at life’ and her husband describes her as ‘a new woman’. This patient feels that she is in a position to finally stop treatment with pregabalin, as a result of medical cannabis controlling her pain. Highlighting the potential benefits of cannabis-based medicinal products to treat chronic pain, our case study indicates the value of including real-world evidence when assessing the benefits and safety of cannabis-based medicinal products.

Functional and structural markers of peripheral microvascular autonomic neuropathy.

Autonomic dysfunction is a common complication of small-fiber neuropathy (SFN). In this study we aimed to assess the applicability of autonomic microvascular indices as a potential marker for SFN assessment. Fifteen patients with confirmed SFN (idiopathic neuropathy [n=10], chemotherapy-induced peripheral neuropathy [n=2], impaired glucose tolerance [n=1], hereditary transthyretin amyloidosis (hATTR) [n=1], pulmonary sarcoidosis [n=1]) and 15 matched control subjects underwent assessment of vascular skin responses assessed through laser Doppler flowmetry and evaluation of microvascular vessel and nerve density in skin biopsies. All participants underwent peripheral autonomic evaluation by quantitative sudomotor axon reflex testing (QSART). We found no significant differences in vascular skin responses, or in any microvascular skin biopsy markers, when comparing SFN with control subjects. We found no correlation between vascular skin responses and skin biopsy indices. We saw no significant difference in any microvascular indices when comparing subjects with and without impaired sudomotor function. Our findings suggest markers of peripheral microvascular innervation and function are not associated with the diagnosis of SFN. Furthermore, we saw no association between microvascular markers and sudomotor function, suggesting that these are independent and unrelated components of the autonomic nervous system.

Surgical reinnervation of the dentate anterior muscle in long-term idiopathic neuropathy of the long thoracic nerve: a case report

Cases of pterygoid deviation (deviation) of the scapula are associated with dysfunction of the muscles of the primary stabilizers of its superior medial and inferior medial edges. One of the factors of KDL is idiopathic neuropathy of the long thoracic nerve (LPN). The ineffectiveness of therapeutic methods of treatment of KDL can be compensated by the use of surgical correction methods. Carrying out decompression of the DGN makes it possible to achieve partial regression in 87 % of patients and complete regression of the deficiency — in 62 % in terms of up to 6 months. The method of selective targeted reinnervation of nerve structures — neurotization is devoid of a number of disadvantages of traditional surgical methods, makes it possible to eliminate the influence of the time factor on the complex process of denervation/reinnervation and ensures the predictability of the outcome. A 27‑year‑old male attended the department with pain in the right shoulder joint, limitation of flexion in the right shoulder joint to 130°, external rotation of the shoulder to 75°, abduction of the right shoulder to 150°. The function of the right deltoid muscle is within the normal range (M5 according to the British MRC scale), KDL at rest (static) and during movements (dynamic). The duration of the disease is about 7 months. Electroneuromyography (EMG) revealed a violation of the conduction of motor fibers of the DGN and a long‑standing denervation process without signs of reinnervation in the dentate anterior muscle (DAM). The patient underwent neurotization of the DGN with the anterior portion of the thoraco‑spinal nerve (PP GSN) according to the method of C. B. Novak and S. E. Mackinnon. A follow‑up examination of the patient was carried out 9, 15 and 19 months after surgical reinnervation. In addition to clinical neurological examination, ENMG was performed. The pain in the right shoulder girdle regressed completely. Full regression of the KDL at rest (static) and partial during movements (dynamic) of the right upper limb was noted. The ENMG data confirmed the reinnervation of the PZM. The use of a more aggressive surgical approach — neurotization made it possible to bring the axons with preserved function (PP GSN) closer to the end motor plates of the non‑functioning nerve (DGN), which contributed to achieving a positive functional result — the restoration of PZM. Selective use of PP GSN made it possible to preserve the functionality of the latissimus dorsi muscle at the expense of preserving the posterior portion of the nerve donor.

Quantitative gastrointestinal function and corresponding symptom profiles in autonomic neuropathy.

Peripheral neuropathies with autonomic nervous system involvement are a recognized cause of gastrointestinal dysmotility for a wide spectrum of diseases. Recent advances in wireless motility capsule testing allow improved sampling of regional and whole gut motility to aid in the diagnosis of gastrointestinal motility disorders and may provide additional insight into segment-specific enteric involvement of peripheral neuropathies affecting autonomic nervous system function. We utilized standardized autonomic nervous system (ANS) reflex assessment and wireless motility capsule testing to evaluate 20 individuals with idiopathic autonomic neuropathy and unexplained gastrointestinal symptoms. Additionally, we examined the relationship between quantifiable autonomic neuropathy and gastrointestinal dysmotility at specific neuroanatomical levels. Symptom profiles were evaluated using the 31-item Composite Autonomic Symptom Score questionnaire (COMPASS-31) and compared to wireless motility capsule data. We found that transit times were predominately abnormal (delayed) in the foregut (10 of 20; 50%), while contractility abnormalities were far more prominent in the hindgut (17 of 20; 85%), and that motility and symptom patterns, as assessed by the COMPASS-31 GI domain items, generally corresponded. Finally, we also found that there was neuroanatomical overlap in the presence of autonomic reflex abnormalities and WMC-based transit and/or contractility abnormalities. We found that transit times were predominately abnormal in the foregut and midgut, while contractility abnormalities were far more prominent in the hindgut in individuals with idiopathic autonomic neuropathy. There was a high rate of agreement in segmental wireless motility capsule data with neuroanatomically corresponding standardized ANS function measures (e.g., cardiovagal, sudomotor, adrenergic). Expanded sudomotor testing, including additional neuroanatomical segments, could provide additional indirect assessment of visceral involvement in ANS dysfunction.

Editors' Note: Part 3: Intravenous Immunoglobulin Therapy in Patients With Painful Idiopathic Small Fiber Neuropathy.

“Intravenous Immunoglobulin Therapy in Patients With Painful Idiopathic Small Fiber Neuropathy” by Geerts et al. compared the administration of IVIG with placebo for patients with idiopathic small fiber neuropathy (SFN) and found no significant difference in the Pain Intensity Numerical Rating Scale score. We summarized (1) an exchange about these findings between Wilder-Smith and Spoendlin and Faber (a coauthor on the article) in the October 19, 2021, Editors' Note and (2) an exchange between Wilder-Smith et al. and Faber et al. in the January 18, 2022, Editors' Note.[1][1],[2][2] Oaklander et al. now comment that while the trial used a subjective outcome (pain intensity), an objective assessment (such as autonomic function test scores) could have enhanced the methodology. They also advocate against the extrapolation of these results to all patients with SFN, noting that patients with autoimmune disorders who may benefit from IVIG may not be readily apparent, so it is beneficial to create guidelines triaging patients with SFN who may benefit from a time-limited trial of IVIG. Finally, they express concern that payors may deny treatment to some patients who could benefit, particularly those who are immune-mediated. Faber et al. respond that changes in the Pain Intensity Numerical Rating Scale score are clinically relevant and the sensitivity of autonomic function testing results in isolation to detect autonomic dysfunction in SFN is low in clinical practice. They agree that patients with immune-mediated SFN may benefit from IVIG and emphasize that their study was not intended to focus on that patient population. However, they suggest that randomized studies with valid and reliable outcome measures are needed to evaluate the role of IVIG in patients with SFN that could potentially be immune-mediated. “Intravenous Immunoglobulin Therapy in Patients With Painful Idiopathic Small Fiber Neuropathy” by Geerts et al. compared the administration of IVIG with placebo for patients with idiopathic small fiber neuropathy (SFN) and found no significant difference in the Pain Intensity Numerical Rating Scale score. We summarized (1) an exchange about these findings between Wilder-Smith and Spoendlin and Faber (a coauthor on the article) in the October 19, 2021, Editors' Note and (2) an exchange between Wilder-Smith et al. and Faber et al. in the January 18, 2022, Editors' Note.1,2 Oaklander et al. now comment that while the trial used a subjective outcome (pain intensity), an objective assessment (such as autonomic function test scores) could have enhanced the methodology. They also advocate against the extrapolation of these results to all patients with SFN, noting that patients with autoimmune disorders who may benefit from IVIG may not be readily apparent, so it is beneficial to create guidelines triaging patients with SFN who may benefit from a time-limited trial of IVIG. Finally, they express concern that payors may deny treatment to some patients who could benefit, particularly those who are immune-mediated. Faber et al. respond that changes in the Pain Intensity Numerical Rating Scale score are clinically relevant and the sensitivity of autonomic function testing results in isolation to detect autonomic dysfunction in SFN is low in clinical practice. They agree that patients with immune-mediated SFN may benefit from IVIG and emphasize that their study was not intended to focus on that patient population. However, they suggest that randomized studies with valid and reliable outcome measures are needed to evaluate the role of IVIG in patients with SFN that could potentially be immune-mediated. [1]: #ref-1 [2]: #ref-2

Author Response: Intravenous Immunoglobulin Therapy in Patients With Painful Idiopathic Small Fiber Neuropathy.

We appreciate the comments on our article by Drs. Oaklander and Dalakas.1 We agree that immune-related forms of painful small fiber neuropathy (SFN) could potentially benefit from IV immunoglobulins (IVIg), and as mentioned, there are case series that underline the positive effect of IVIg. The group of autoimmune-related SFN was not the focus of our study. Our study cohort was targeted on patients with I-SFN because no underlying condition is found in 53% of the SFN population, which is a large proportion of clinical patients and clinically relevant.2

Idiopathic progressive polyneuropathy presented with frequently acute pulmonary oedema: a case report

Neuropathy is when nerve damage interferes with the functioning of the peripheral nervous system (PNS). When the cause can’t be determined, it’s called idiopathic neuropathy(Idiopathic neuropathy, now designated as chronic idiopathic axonal polyneuropathy (CIAP). There are three kinds of nerves within the PNS. Sensory nerves relay messages from the sense organs to the brain. This allows sensations of temperature and touch. Motor nerves transmit signals from the brain to the muscles. This helps the brain control the muscles. Autonomic nerves control body functions like heart rate, breathing, and digestion. Damage to nerve cells can affect how the PNS communicates with the rest of the body. Symptoms can include numbness, pain, and balance issues. It’s called acute neuropathy when symptoms develop suddenly. Alternately, it’s called chronic neuropathy when symptoms start slowly and increase over time. Diagnosis involves physical examination and review of medical history. Diagnostic testing may include blood tests, nerve testing, and imaging tests. There is no cure for idiopathic neuropathy. Treatments including medication, physical therapy, and lifestyle modifications can help you function and feel better. We report a case of idiopathic polyneuropathy presented with frequent acute pulmonary edema for a year.

Sensory neuronopathies, diagnostic criteria and causes.

To stress on the diagnostic strategy of sensory neuronopathies (SNN), including new genes and antibodies. SNN involve paraneoplastic, dysimmune, toxic, viral and genetic mechanisms. About one-third remains idiopathic. Recently, new antibodies and genes have reduced this proportion. Anti-FGFR3 and anti-AGO antibodies are not specific of SNN, although SNN is predominant and may occur with systemic autoimmune diseases. These antibodies are the only marker of an underlying dysimmune context in two-thirds (anti-FGFR3 antibodies) and one-third of the cases (anti-AGO antibodies), respectively. Patients with anti-AGO antibodies may improve with treatment, which is less clear with anti-FGFR3 antibodies. A biallelic expansion in the RFC1 gene is responsible for the cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) in which SNN is a predominant manifestation. Most of the patients have an adult onset and are sporadic. The RFC1 mutation may represent one-third of idiopathic sensory neuropathies. Finally, the criteria for the diagnosis of paraneoplastic SNN have recently been updated. The diagnostic of SNN relies on criteria distinguishing SNN from other neuropathies. The strategy in search of their cause now needs to include these recent findings.

Dysautonomia in RFC1-related disorder: Clinical and neurophysiological evaluation

ObjectiveTo characterize and quantify autonomic involvement in patients with RFC1-related disorder of adult-onset cerebellar ataxia and idiopathic sensory neuropathy. MethodsWe enrolled 16 subjects with biallelic RFC1 (AAGGG)n expansions and 16 age and sex-matched healthy controls that underwent comprehensive clinical and neurophysiological evaluation. Scales for Outcomes in Parkinson’s Disease Autonomic Dysfunction (SCOPA-AUT) score was used to assess autonomic symptoms. Electrophysiological testing included assessment of heart rate variability and quantitative sudomotor axon reflex test (QSART). Between-group comparisons were assessed using non-parametric tests. ResultsIn the patient group, there were 9 men/7 women and the median age was 60.5 years. SCOPA-AUT scores were significantly higher in the RFC1 group compared to controls (22 vs 10, p < 0.001). Half of patients had cardiac autonomic neuropathy. In neurophysiology, there was resting tachycardia combined with abnormal responses during Valsalva maneuver and deep breathing among patients. QSART responses were also significantly reduced in the RFC1 group, especially in the lower limbs. ConclusionsAutonomic dysfunction is frequent, clinically relevant and involves multiple domains in RFC1-related disorder. Patients have both sympathetic and parasympathetic involvement. From a topographical perspective, this condition is characterized by a small fiber autonomic axonopathy. SignificanceDysautonomia is frequent, severe and related to peripheral damage in RFC1-related disorder.

Potential Misinformation in the Official Disability Guidelines About the Diagnosis and Treatment of Carpal Tunnel Syndrome.

Workers' compensation guidelines may reinforce unhelpful thoughts regarding symptoms that are known to increase symptom intensity and magnitude of incapability. One guideline commonly used (the Official Disability Guidelines) was reviewed regarding carpal tunnel syndrome. For 15 statements, we created an alternative statement based on a set of consensus principles for health, value, and quality in care. One hundred eight upper extremity surgeons of the Science of Variation Group reviewed both versions of the statements to indicate their preference. Surgeons preferred seven revised statements and five guideline statements and were neutral on three statements. Favored revisions related to more accurate discernment of symptoms that are clearly related to idiopathic median neuropathy and representative of severity of pathology. There may be important mental health considerations for care under a work claim, such as unhelpful thoughts or distress regarding symptoms, which are not adequately considered by the Official Disability Guidelines.

Surgeons' Recommendations for Neurodiagnostic Testing With High Pretest Probability of Idiopathic Median Neuropathy at the Carpal Tunnel

The utility of electrodiagnostic tests (EDx) for patients with a high pretest probability of idiopathic median neuropathy at the carpal tunnel (IMNCT) based on characteristic symptoms and signs is debated. Decision-making and care strategies could be informed by a better understanding of factors associated with surgeon recommendations for electrodiagnostic testing. Ninety-one upper-extremity surgeons participated in an online, survey-based experiment. Participants viewed 7 vignettes of patients with carpal tunnel syndrome, with the following factors randomized in each vignette: patient age, gender, magnitude of incapability, symptom intensity and the presence of nocturnal symptoms, palmar abduction weakness, and positive provocative tests results. We sought patient and surgeon factors associated with ordering EDx and surgeon-rated comfort with performing carpal tunnel release (CTR) without EDx. Surgeons recommended EDx for over half of the patient vignettes, with notable variation (median, 57%; interquartile range, 14-100), and felt relatively neutral, on average, offering CTR without EDx. Twenty-six (29%) out of 91 surgeons ordered EDx for all patient scenarios, and 18 surgeons (20%) did not order testing for any scenario. A lower likelihood of EDx was associated with older age and positive provocative tests results. Greater surgeon comfort offering CTR without EDx was associated with older patients, the presence of nocturnal symptoms, palmar abduction weakness, and positive provocative tests results. Upper-extremity surgeons are neutral regarding diagnosing IMNCT based on electrodiagnostic evidence of pathology and are relatively more comfortable offering surgery without EDx in older patients that present with key aspects of carpal tunnel syndrome. There is notable variation in care, with half of all surgeons always or never ordering EDx. Future studies can investigate whether a treatment strategy offering surgery to patients with a high pretest probability of IMNCT and only using EDx in intermediate probability scenarios can limit use of testing without affecting patient health.

Tibiotalocalcaneal arthrodesis for the treatment of midfoot Charcot neuroarthropathy

Charcot neuroarthropathy of the foot and ankle is a destructive disorder resulting in severe and debilitating deformity. The goal of surgical reconstruction in Charcot neuroarthropathy is to create a stable, plantigrade foot that is amenable to bracing and offloading. Many reconstruction methods have been described in the literature including ostectomy of osseous prominences, realignment ostoeotmies, intramedullary midfoot beaming, plate fixation and external fixation. In this study we describe the use of tibiotalocalcaneal arthrodesis with intramedullary nail fixation for the treatment of midfoot Charcot neuroarthropathy in 12 consecutive patients. The mean age of our patient population was 61.33 years, mean BMI was 37.03 kg/m2, 9 patients were type II diabetics, 2 patients were type I diabetics and 1 patient had a diagnosis of idiopathic neuropathy without underlying diabetes mellitus (DM). The mean duration of DM diagnosis was 24.73 years. 9 patients within the study population had suffered from chronic or recurrent ulcerations secondary to osseous deformity that had failed conservative treatment and 3 patients had residual ulceration at the time of surgery. Fusion was observed in 10 of 12 patients within the study. All patients had a functional, plantigrade foot post-operatively. Overall, 5 patients are ambulating in custom diabetic shoes without assistive devices while the remaining patients are ambulating with assistive devices. The results of this study indicate that tibiotalocalcaneal arthrodesis with retrograde intramedullary nail fixation for midfoot Charcot neuroarthropathy is a reliable treatment option to provide a stable, plantigrade, braceable foot.