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Introduction: Guillain‐Barré Syndrome (GBS) is a spectrum of peripheral neuropathies characterized by rapid symmetrical limb weakness and sensory symptoms. GBS can be life‐threatening and requires intensive care, particularly for patients with imminent respiratory failure. In Africa, limited research and high therapy costs pose challenges. This literature review aims to comprehensively address GBS in Africa to improve understanding and outcomes. Aim: This literature review aims to provide an extensive overview of GBS in Africa, encompassing its clinical presentation, impact, management approaches, and challenges faced. It also highlights the need for increased research and awareness to enhance patient care and outcomes. Methods: A comprehensive review of existing literature on GBS in Africa was conducted, focusing on clinical presentation, diagnosis, management, and its impact on patients and communities. Data sources included medical databases, research articles, and reports. Data was scoured from databases such as PubMed, Medline and Embase. A total of four hundred and fifty‐five articles and case studies were screened, with broader topic margins into GBS and different triggers, demographics, statistics, and variations in treatments across the world. These articles were further screened to match our inclusion criteria which focused on articles published after 2000 and which gave clearer insights into the presentations and situation of GBS in the African continent. Results: GBS in Africa is characterized by a range of clinical presentations, with limited diagnostic resources and healthcare infrastructure. Patients often face long intervals between symptom onset and hospitalization, impacting outcomes. The syndrome's impact extends beyond physical symptoms, affecting patients' quality of life, employment, and community roles. Management involves immunotherapy, physiotherapy, and psychosocial support, but high therapy costs and incomplete recovery pose challenges. Research in Africa has grown in recent years but remains limited compared to other regions. Efforts are needed to expand research capacity, introduce early screening programs, and improve healthcare infrastructure. Conclusion: GBS presents a significant healthcare challenge in Africa, with the potential for severe clinical outcomes. This literature review underscores the importance of enhancing research, awareness, and healthcare infrastructure. African‐led research initiatives offer hope for improved patient outcomes and healthcare system strengthening. By advocating for increased government support and resources, Africa can address the pressing needs of GBS patients and foster a brighter and healthier future for affected individuals on the continent. [ABSTRACT FROM AUTHOR]

Paired pulses' technique using a conventional electrodiagnostic machine applied in healthy volunteers (n = 40) and patients with Charco-Marie-Tooth disease type 1A (n = 10). [Display omitted] • The study of the axonal excitability recovery cycle with a conventional machine is feasible and reliable. • In patients with Charcot-Marie-Tooth (CMT) disease type 1A, the refractory periods and the superexcitable period are reduced. • The most relevant parameter to discriminate CMT1A from the control group is the area under the curve during superexcitability. To validate the 'paired pulses' technique with a conventional electrodiagnostic machine (CEM) for studying the axonal excitability recovery cycle (ERC). Paired pulses, with a variable inter-stimulus interval, were delivered at the wrist along the median nerve. The CEM repeatability was verified in a group of 15 healthy volunteers (test/retest analysis). ERC was then applied in 40 healthy volunteers and 10 patients with Charcot-Marie-Tooth type 1A (CMT1A), using both the threshold tracking (TT) reference method and CEM (basal condition, during and after ischemia). CEM parameters evaluating absolute refractory and supernormal periods were reproducible (interclass correlation coefficient > 0.75). CEM results were consistent with TT method and literature data. In CMT1A, refractory and superexcitable periods were significantly reduced. According to receiving operator characteristic analysis, the CEM supernormal period area was the most relevant parameter for discriminating CMT1A from healthy volunteers (area under the curve = 0.98). CEM was a valid procedure for studying ERC. CMT1A patients exhibited ERC alterations due to modifications in passive membrane properties and of nodal ion channel distribution resulting from demyelination. Studying ERC with CEM could be performed in routine practice in patients with peripheral neuropathies to provide information on motor axonal excitability. [ABSTRACT FROM AUTHOR]

This review explores diverse infectious etiologies of peripheral nervous system (PNS) dysfunction, spanning sensory and motor neurons, nerves, and associated structures. Progress in viral and bacterial infections reveals multifaceted mechanisms underlying neuropathies, including viral neurotoxicity and immune-mediated responses. Latest diagnostic advances facilitate early PNS complication detection, with ongoing research offering promising treatment avenues. Emerging pathogens like severe acute respiratory syndrome coronavirus 2, Zika virus, and EV-D68 highlight the evolving infectious neuropathy paradigm. Recognizing characteristic patterns and integrating clinical factors are pivotal for precise diagnosis and tailored intervention. Challenges persist in assessment and management due to varied pathogenic mechanisms. Advancements in understanding pathogenesis have improved targeted therapies, yet gaps remain in effective treatments. Ongoing research is crucial for optimizing approaches and improving patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Positron emission tomography (PET) has been reported as effective in diagnosing peripheral nerve injury (PNI). However, there is a lack of studies evaluating different degrees of PNI using PET within the same individual to reduce errors due to interindividual differences. Purpose: To evaluate the recovery process in the same rat after sciatic nerve injury using PET/magnetic resonance imaging (MRI). Material and Methods: Crushing nerve injuries were induced in the left sciatic nerves of six male rats, preserving the right ones. The degree of nerve damage was measured at one, two, three, four, and five weeks postoperatively using three assessment methods: paw withdrawal threshold test (RevWT); PET (SUVR); and MRI (MRSIR). All the representing values of each method are presented as ratio values of the right and left sides in each rat. Results: Significant gradual recovery of all rats was observed over time in all the methods. No significant differences in RevWT and MRSIR were observed between before and more than four weeks after injury, whereas a significant difference in SUVR was still observed between before and five weeks after injury (P = 0.0007). The parameters of all methods decreased significantly over time (P = 0.000, all), and the explanatory power was significant in RevWT, SUVR, and MRSIR. Conclusion: PET and MRI could be valuable non-invasive techniques for diagnosing neuropathic pain resulting from PNI. PET/MRI would be expected to be a more accurate and informative diagnostic tool for PNI than MRI alone. [ABSTRACT FROM AUTHOR]

Neuropathies secondary to tophus compression in gout patients are well known; however, limited data exist on other types of peripheral neuropathies (PN). Our aim was to describe PN frequency, characteristics, distribution, patterns, and associated factors in gout patients through clinical evaluation, a PN questionnaire, and nerve conduction studies (NCS). This cross-sectional descriptive study included consecutive gout patients (ACR/EULAR 2015 criteria) from our clinic. All underwent evaluation by Rheumatology and Rehabilitation departments, with IRB approval. Based on NCS, patients were categorized as PN + (presence) or PN- (absence). PN + patients were further classified as local peripheral neuropathy (LPN) or generalized somatic peripheral neuropathy (GPN). We enrolled 162 patients, 98% male (72% tophaceous gout). Mean age (SD): 49.4 (12) years; mean BMI: 27.9 (6.0) kg/m2. Comorbidities included dyslipidemia (53%), hypertension (28%), and obesity (23.5%). Abnormal NCS: 65% (n = 106); 52% LPN, 48% GPN. PN + patients were older, had lower education, and severe tophaceous gout. GPN patients were older, had lower education, and higher DN4 scores compared to LPN or PN- groups (p = 0.05); other risk factors were not significant. Over half of gout patients experienced neuropathy, with 48% having multiplex mononeuropathy or polyneuropathy. This was associated with joint damage and functional impairment. Mechanisms and risk factors remain unclear. Early recognition and management are crucial for optimizing clinical outcomes and quality of life in these patients. Key Points Peripheral neuropathies in gout patients had been scarcely reported and studied. This paper report that: • PN in gout is more frequent and more diverse than previously reported. • Mononeuropathies are frequent, median but also ulnar, peroneal and tibial nerves could be injured. • Unexpected, generalized neuropathies (polyneuropathy and multiplex mononeuropathy) are frequent and associated to severe gout. • The direct role of hyperuricemia /or gout in peripheral nerves require further studies. [ABSTRACT FROM AUTHOR]

ABSTRACT Introduction Guillain‐Barré Syndrome (GBS) is a spectrum of peripheral neuropathies characterized by rapid symmetrical limb weakness and sensory symptoms. GBS can be life‐threatening and requires intensive care, particularly for patients with imminent respiratory failure. In Africa, limited research and high therapy costs pose challenges. This literature review aims to comprehensively address GBS in Africa to improve understanding and outcomes. Aim This literature review aims to provide an extensive overview of GBS in Africa, encompassing its clinical presentation, impact, management approaches, and challenges faced. It also highlights the need for increased research and awareness to enhance patient care and outcomes. Methods A comprehensive review of existing literature on GBS in Africa was conducted, focusing on clinical presentation, diagnosis, management, and its impact on patients and communities. Data sources included medical databases, research articles, and reports. Data was scoured from databases such as PubMed, Medline and Embase. A total of four hundred and fifty‐five articles and case studies were screened, with broader topic margins into GBS and different triggers, demographics, statistics, and variations in treatments across the world. These articles were further screened to match our inclusion criteria which focused on articles published after 2000 and which gave clearer insights into the presentations and situation of GBS in the African continent. Results GBS in Africa is characterized by a range of clinical presentations, with limited diagnostic resources and healthcare infrastructure. Patients often face long intervals between symptom onset and hospitalization, impacting outcomes. The syndrome's impact extends beyond physical symptoms, affecting patients' quality of life, employment, and community roles. Management involves immunotherapy, physiotherapy, and psychosocial support, but high therapy costs and incomplete recovery pose challenges. Research in Africa has grown in recent years but remains limited compared to other regions. Efforts are needed to expand research capacity, introduce early screening programs, and improve healthcare infrastructure. Conclusion GBS presents a significant healthcare challenge in Africa, with the potential for severe clinical outcomes. This literature review underscores the importance of enhancing research, awareness, and healthcare infrastructure. African‐led research initiatives offer hope for improved patient outcomes and healthcare system strengthening. By advocating for increased government support and resources, Africa can address the pressing needs of GBS patients and foster a brighter and healthier future for affected individuals on the continent.

Copyright of Revista de la Facultad de Medicina Humana is the property of Instituto de Investigaciones en Ciencias Biomedicas de la Universidad Ricardo Palma and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Peripheral neuropathies in mitochondrial disease are caused by mutations in nuclear genes encoding mitochondrial proteins, or in the mitochondrial genome. Whole exome or genome sequencing enable parallel testing of nuclear and mtDNA genes, and it has significantly advanced the genetic diagnosis of inherited diseases. Despite this, approximately 40% of all Charcot-Marie-Tooth (CMT) cases remain undiagnosed. Methods: The genome-phenome analysis platform (GPAP) in RD-Connect was utilised to create a cohort of 2087 patients with at least one Human Phenotype Ontology (HPO) term suggestive of a peripheral neuropathy, from a total of 10,935 patients. These patients' genetic data were then analysed and searched for variants in known mitochondrial disease genes. Results: A total of 1,379 rare variants were identified, 44 of which were included in this study as either reported pathogenic or likely causative in 42 patients from 36 families. The most common genes found to be likely causative for an autosomal dominant neuropathy were GDAP1 and GARS1. We also detected heterozygous likely pathogenic variants in DNA2, MFN2, DNM2, PDHA1, SDHA, and UCHL1. Biallelic variants in SACS, SPG7, GDAP1, C12orf65, UCHL1, NDUFS6, ETFDH and DARS2 and variants in the mitochondrial DNA (mtDNA)-encoded MT-ATP6 and MT-TK were also causative for mitochondrial CMT. Only 50% of these variants were already reported as solved in GPAP. Conclusion: Variants in mitochondrial disease genes are frequent in patients with inherited peripheral neuropathies. Due to the clinical overlap between mitochondrial disease and CMT, agnostic exome or genome sequencing have better diagnostic yields than targeted gene panels. [ABSTRACT FROM AUTHOR]

Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of inherited peripheral neuropathies. Although the typical disease onset is reported in the second decade, earlier onsets are not uncommon. To date, few studies on pediatric populations have been conducted and the achievement of molecular diagnosis remains challenging. During the last 24 years we recruited 223 patients with early-onset hereditary peripheral neuropathies (EOHPN), negative for PMP22 duplication, 72 of them referred by a specialized pediatric hospital. Genetic testing for CMT-associated genes has been carried out with a range of different techniques. Of the 223 EOHPN cases, 43% were classified as CMT1 (demyelinating), 49% as CMT2 (axonal), and 8% as CMTi (intermediate). Genetic diagnosis was reached in 51% of patients, but the diagnostic yield increased to 67% when focusing only on cases from the specialized pediatric neuromuscular centers. Excluding PMP22 rearrangements, no significant difference in diagnostic rate between demyelinating and axonal forms was identified. De novo mutations account for 38% of cases. This study describes an exhaustive picture of EOHPN in an Italian referral genetic center and analyzes the molecular diagnostic rate of a heterogeneous cohort compared with one referred by a specialized pediatric center. Our data identify MPZ , MFN2 , GDAP1 , and SH3TC2 genes as the most frequent players in EOHPN. Our study underlines the relevance of a specific neurological pediatric expertise to address the genetic testing and highlights its importance to clarify possible unexpected results when neuropathy is only a secondary clinical sign of a more complex phenotype. [ABSTRACT FROM AUTHOR]

Background: Posterior interosseous nerve (PIN) compression in the forearm without motor paralysis is a challenging clinical diagnosis. This retrospective study evaluated the clinical assessment, diagnostic studies, and outcomes following surgical decompression of the PIN in the forearm. Methods: This study reviewed 182 patients' medical charts following PIN decompression between 2000 and 2020 by a single surgeon. After exclusion of combined nerve entrapments, polyneuropathy, motor palsy, or lateral epicondylitis, the study included 14 patients. Data collected included: clinical presentation and pain drawings, provocative testing, functional outcomes, and Disabilities of the Arm, Shoulder, and Hand (DASH) scores. Results: There were 15 PIN decompressions (14 patients, mean follow-up = 11.9 months). Clinical presentation included pain (n = 14) (proximal dorsal forearm, n = 14; distal forearm over radial sensory nerve, n = 3) and positive clinical tests (sensory collapse test over the radial tunnel, n = 8; pain with forearm pronation and compression over the radial tunnel, n = 10; Tinel sign, n = 5). Postoperatively, there were significant improvements in Visual Analog Scale pain scores (6.7 to 3.3, P =.0006), quality-of-life scores (74.7 to 32.7, P =.0001), and DASH scores (46.3 to 33.6, P =.02). Conclusions: The PIN compression in the forearm without motor paralysis is a clinical diagnosis supported by pain drawings, pain quality, and provocative tests. Patients with persistent, therapy-resistant dorsal forearm pain should be evaluated for PIN compression. Surgical decompression provides statistically significant quantifiable improvement in pain and quality of life. [ABSTRACT FROM AUTHOR]

Charcot-Marie-Tooth disease (CMT) is a group of inherited peripheral neuropathies related to variants in the mitochondrial transfer RNA (mt-tRNAval) gene. Here, we report a Chinese family harboring the m.1661A>G variant in the mt-tRNAval gene. Clinical evaluation, neuroelectrodiagnostic testing, and nerve biopsy were performed on four affected family members. Weakness, spasms, and pain in the limbs (especially in the lower limbs) were the main complaints of the proband. Physical examination revealed atrophy and weakness in the distal limbs, increased muscle tone, and hyperreflexia in four limbs. Neuroelectrodiagnostic tests and nerve biopsy supported an axonal polyneuropathy. This study furthers the understanding of phenotype diversity caused by variants in the mt-tRNAval gene in CMT. [ABSTRACT FROM AUTHOR]

Summary: Peripheral neuropathy is a well‐described side effect of certain chemotherapeutic agents, including taxanes, and often improves in the weeks following treatment. The recurrence of motor and sensory neuropathies after anaesthesia has not yet been described to our knowledge. We present a case of transient recurrence of chemotherapy‐induced peripheral neuropathy following general anaesthesia. Although an exact mechanism has not yet been described and is likely multifactorial in nature, anaesthetists should be prepared to address this phenomenon in the growing population of patients on chemotherapeutic agents. [ABSTRACT FROM AUTHOR]

Abstract Background We proposed to investigate high-dose pharmaceutical-grade biotin in a population of demyelinating neuropathies of different aetiologies, as a proof-of-concept. Methods Phase IIb open label, uncontrolled, single center, pilot study in 15 patients (three groups of five patients) with chronic demyelinating peripheral neuropathy, i.e. chronic inflammatory demyelinating polyradiculoneuropathy, anti-myelin-associated glycoprotein neuropathy and Charcot-Marie-Tooth 1a or 1b. The investigational product was high-dose pharmaceutical-grade biotin (100 mg taken orally three times a day over a maximum of 52 weeks. The primary endpoint was a 10% relative improvement in 2 of the following 4 electrophysiological variables: motor nerve conduction velocity, distal motor latency, F wave latency, duration of the compound muscle action potential. The secondary endpoints included Overall Neuropathy Limitations Scale (ONLS) score, Medical Research Council (MRC) sum score, Inflammatory Neuropathy Cause and Treatment (INCAT) sensory sum score, 10-m walk test, 6-min walk test, posturography parameters, and nerve excitability variables. Results The primary endpoint was reached in one patient. In the full population analysis, some secondary endpoints parameters improved: MRC score, INCAT sensory sum score, 6-min walk distance, strength-duration time constant, and rheobase. There was a positive correlation between the improvement in the 6-min walk distance and the strength-duration time constant. Regarding the safety results, 42 adverse events occurred, of which three were of severe intensity but none was considered as related to the investigational product. Conclusions Even if the primary endpoint was not met, administration of high-dose pharmaceutical-grade biotin led to an improvement in various sensory and motor parameters, gait abilities, and nerve excitability parameters. The tolerance of the treatment was satisfactory. Trial registration ClinicalTrials.gov Identifier: NCT02967679; date 2016/12/05.

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Background and Aims: POLR3B gene encodes a subunit of RNA polymerase III (Pol III). Biallelic mutations in POLR3B are associated with leukodystrophies, but recently de novo heterozygous mutations have been described in early onset peripheral demyelinating neuropathies with or without central involvement. Here, we report the first Italian case carrying a de novo variant in POLR3B with a pure neuropathy phenotype and primary axonal involvement of the largest nerve fibers. Methods: Nerve conduction studies, sympathetic skin response, dynamic sweat test, tactile and thermal quantitative sensory testing and brain magnetic resonance imaging were performed according to standard procedures. Histopathological examination was performed on skin and sural nerve biopsies. Molecular analysis of the proband and his relatives was performed with Next Generation Sequencing. The impact of the identified variant on the overall protein structure was evaluated through rotamers method. Results: Since his early adolescence, the patient presented with signs of polyneuropathy with severe distal weakness, atrophy, and reduced sensation. Neurophysiological studies showed a sensory‐motor axonal polyneuropathy, with confirmed small fiber involvement. In addition, skin biopsy and sural nerve biopsy showed predominant large fibers involvement. A trio's whole exome sequencing revealed a novel de novo variant p.(Arg1046Cys) in POLR3B, which was classified as Probably Pathogenic. Molecular modeling data confirmed a deleterious effect of the variant on protein structure. Interpretation: Neurophysiological and morphological findings suggest a primary axonal involvement of the largest nerve fibers in POLR3B‐related neuropathies. A partial loss of function mechanism is proposed for both neuropathy and leukodystrophy phenotypes. [ABSTRACT FROM AUTHOR]

Background: We proposed to investigate high-dose pharmaceutical-grade biotin in a population of demyelinating neuropathies of different aetiologies, as a proof-of-concept. Methods: Phase IIb open label, uncontrolled, single center, pilot study in 15 patients (three groups of five patients) with chronic demyelinating peripheral neuropathy, i.e. chronic inflammatory demyelinating polyradiculoneuropathy, anti-myelin-associated glycoprotein neuropathy and Charcot-Marie-Tooth 1a or 1b. The investigational product was high-dose pharmaceutical-grade biotin (100 mg taken orally three times a day over a maximum of 52 weeks. The primary endpoint was a 10% relative improvement in 2 of the following 4 electrophysiological variables: motor nerve conduction velocity, distal motor latency, F wave latency, duration of the compound muscle action potential. The secondary endpoints included Overall Neuropathy Limitations Scale (ONLS) score, Medical Research Council (MRC) sum score, Inflammatory Neuropathy Cause and Treatment (INCAT) sensory sum score, 10-m walk test, 6-min walk test, posturography parameters, and nerve excitability variables. Results: The primary endpoint was reached in one patient. In the full population analysis, some secondary endpoints parameters improved: MRC score, INCAT sensory sum score, 6-min walk distance, strength-duration time constant, and rheobase. There was a positive correlation between the improvement in the 6-min walk distance and the strength-duration time constant. Regarding the safety results, 42 adverse events occurred, of which three were of severe intensity but none was considered as related to the investigational product. Conclusions: Even if the primary endpoint was not met, administration of high-dose pharmaceutical-grade biotin led to an improvement in various sensory and motor parameters, gait abilities, and nerve excitability parameters. The tolerance of the treatment was satisfactory. Trial registration: ClinicalTrials.gov Identifier: NCT02967679; date 2016/12/05. [ABSTRACT FROM AUTHOR]

Background: Many patients being investigated for Guillain-Barré syndrome (GBS) undergo unnecessary neuroimaging. The objective of this study was to determine the proportion of patients with GBS undergoing neuroimaging investigation, and to investigate any association with different GBS variants using the Brighton criteria. Methods: This cross-sectional observational study was conducted in the leading tertiary care hospital in Pakistan; 148 patients being investigated for, and subsequently diagnosed with GBS between January 2017 and March 2020 were enrolled. Participants were asked if they had undergone neuroimaging of the craniospinal axis before or during hospital admission, and the purpose of any computed tomography (CT) scan was investigated. We enquired whether fundoscopy had been performed before lumbar puncture (LP) and determined the level of certainty based on the Brighton criteria. Results: The majority of participants were men (n = 107, 73%), with a mean age of 42.85 ± 18.40 years. The mean waiting time to their first interaction with a neurologist was 5.20 ± 4.01 days, and the demyelinating variant of GBS was more common than the axonal variant (1.6:1). Most patients were diagnosed with level I certainty using the Brighton criteria (n = 113, 76%). Brain and spine magnetic resonance imaging (MRI) were performed ahead of admission in 48 (32%) and 59 (39%) patients, respectively. Brain CT scan was performed in 121 (82%) patients before LP, while 27 (18%) only underwent fundoscopic examination before LP. Conclusion: Clinical examination is fundamental in the diagnosis of GBS. Neuroimaging may be inappropriate and unnecessary, and may detract attention from crucial peripheral neuropathy measures while misusing limited resources. [ABSTRACT FROM AUTHOR]

Abstract Aims/Introduction Neuropathy is a common complication of diabetes that reduces balance by disrupting vision, and the sensory and vestibular systems. This is important in older adults who are more at risk of falling. Studies show that improving the sensory mechanisms through insoles can improve balance in people with balance disorders. As textured insoles have recently been considered for improving balance disorders, this study aimed to investigate the immediate effect of textured insoles on the balance of patients with diabetic neuropathy. Materials and Methods A total of 17 patients with diabetic neuropathy participated in this quasi‐experimental study. The studied variables were the general balance index, posterior–anterior balance index and medial‐lateral balance index, which were measured in three conditions: (i) soft textured insoles; (ii) hard textured insoles; and (iii) without textured insoles. A Biodex balance device was used for this purpose. Results In the general balance index, there was a significant difference between all the studied conditions. In the posterior–anterior balance index, there was a significant difference between without textured insole and hard textured insoles, and also soft and hard textured insoles. In the medial‐lateral balance index, there was a significant difference between the hard textured insoles and without textured insoles, and also soft and hard textured insoles (P

Action potential propagation along myelinated axons depends on the geometry of the myelin unit and the division of the underlying axon to specialized domains. The latter include the nodes of Ranvier (NOR), the paranodal junction (PNJ) flanking the nodes, and the adjacent juxtaparanodal region that is located below the compact myelin of the internode. Each of these domains contains a unique composition of axoglial adhesion molecules (CAMs) and cytoskeletal scaffolding proteins, which together direct the placement of specific ion channels at the nodal and juxtaparanodal axolemma. In the last decade it has become increasingly clear that antibodies to some of these axoglial CAMs cause immune‐mediated neuropathies. In the current review we detail the molecular composition of the NOR and adjacent membrane domains, describe the function of different CAM complexes that mediate axon‐glia interactions along the myelin unit, and discuss their involvement and the underlying mechanisms taking place in peripheral nerve pathologies. This growing group of pathologies represent a new type of neuropathies termed "nodopathies" or "paranodopathies" that are characterized by unique clinical and molecular features which together reflect the mechanisms underlying the molecular assembly and maintenance of this specialized membrane domain. [ABSTRACT FROM AUTHOR]

Copyright of Revista Mexicana de Endocrinología, Metabolismo y Nutrición is the property of Publicidad Permanyer SLU and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Mutations in the neurofilament polypeptide light chain (NEFL) gene account for <1% of all forms of Charcot-Marie-Tooth (CMT) diseases and present with different phenotypes, including demyelinating, axonal and intermediate neuropathies, and with diverse pattern of transmission, with dominant and recessive inheritance being described. Methods: Here, we present clinical and molecular data in two new unrelated Italian families, affected with CMT. Results: We studied fifteen subjects (11 women, 4 men), age range 23–62 year. Onset of symptoms was mainly in childhood, with running/walking difficulties; some patients were pauci-asymptomatic; almost all shared variably distributed features of absent/reduced deep tendon reflexes, impaired gait, reduced sensation, and distal weakness in the legs. Skeletal deformities were seldom documented and were of mild degree. Additional features included sensorineural hearing loss in 3 patients, underactive bladder in 2 patients, and cardiac conduction abnormalities, requiring pacemaker implantation, in one child. Central nervous system (CNS) impairment was not documented in any subject. Neurophysiological investigation disclosed feature suggestive of demyelinating sensory-motor polyneuropathy in one family and resembling an intermediate form in the other. Multigene panel analysis of all known CMT genes revealed two heterozygous variants in NEFL: p.E488K and p.P440L. While the latter change segregated with the phenotype, the p.E488K variant appeared to act as a modifier factor being associated with axonal nerve damage. Conclusions: CMT related to P440L mutation in NEFL is associated with a mild, childhood-onset phenotype, showing prevalently sensory distal limbs involving and with motor impairment predominantly involving anterolateral leg muscles, in the absence of CNS involvement. Additional findings, never reported so far in patients with NEFL mutation, are cardiological and urinary dysfunctions. Our study expands the array of clinical features associated with NEFL-related CMT. [ABSTRACT FROM AUTHOR]

Although the immunotherapy advent has revolutionized cancer treatment, it, unfortunately, does not spare cancer patients from possible immune-related adverse events (irAEs), which can also involve the peripheral nervous system. Immune checkpoint inhibitors (ICIs), blocking cytotoxic T-lymphocyteassociated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), or programmed cell death ligand 1 (PD-L1), can induce an immune imbalance and cause different peripheral neuropathies (PNs). Considering the wide range of PNs and their high impact on the safety and quality of life for cancer patients and the availability of large post-marketing surveillance databases, we chose to analyze the characteristics of ICI-related PNs reported as suspected drug reactions from 2010 to 2020 in the European real-world context. We analyzed data collected in the European pharmacovigilance database, Eudravigilance, and conducted a systematic and disproportionality analysis. In our study, we found 735 reports describing 766 PNs occurred in patients treated with ICIs. These PNs included Guillain-Barré syndrome, Miller-Fisher syndrome, neuritis, and chronic inflammatory demyelinating polyradiculoneuropathy. These ADRs were often serious, resulting in patient disability or hospitalization. Moreover, our disproportionality analysis revealed an increased reporting frequency of PNs with tezolizumab compared to other ICIs. Guillain-Barré syndrome is a notable potential PN related to ICIs, as it is associated with a significant impact on patient safety and has had unfavorable outcomes, including a fatal one. Continued monitoring of the safety profile of ICIs in real-life settings is necessary, especially considering the increased frequency of PNs associated with atezolizumab compared with other ICIs. [ABSTRACT FROM AUTHOR]

Copyright of Somnologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aims/Introduction: Neuropathy is a common complication of diabetes that reduces balance by disrupting vision, and the sensory and vestibular systems. This is important in older adults who are more at risk of falling. Studies show that improving the sensory mechanisms through insoles can improve balance in people with balance disorders. As textured insoles have recently been considered for improving balance disorders, this study aimed to investigate the immediate effect of textured insoles on the balance of patients with diabetic neuropathy. Materials and Methods: A total of 17 patients with diabetic neuropathy participated in this quasi‐experimental study. The studied variables were the general balance index, posterior–anterior balance index and medial‐lateral balance index, which were measured in three conditions: (i) soft textured insoles; (ii) hard textured insoles; and (iii) without textured insoles. A Biodex balance device was used for this purpose. Results: In the general balance index, there was a significant difference between all the studied conditions. In the posterior–anterior balance index, there was a significant difference between without textured insole and hard textured insoles, and also soft and hard textured insoles. In the medial‐lateral balance index, there was a significant difference between the hard textured insoles and without textured insoles, and also soft and hard textured insoles (P < 0.05). Conclusions: Wearing textured insoles can increase the balance in patients with diabetic neuropathy. This can be due to its effect on the sensory feedback of the soles, improving the proprioception and tactile sensors that are the main sources of balance. [ABSTRACT FROM AUTHOR]

Background: There is little information about neuropsychiatric comorbidities in Charcot-Marie-Tooth disease (CMT). We assessed frequency of anxiety, depression, and general distress in CMT. Methods: We administered online the Hospital Anxiety-Depression Scale (HADS) to CMT patients of the Italian registry and controls. HADS-A and HADS-D scores ≥ 11 defined the presence of anxiety/depression and HADS total score (HADS-T) ≥ 22 of general distress. We analysed correlation with disease severity and clinical characteristics, use of anxiolytics/antidepressants and analgesic/anti-inflammatory drugs. Results: We collected data from 252 CMT patients (137 females) and 56 controls. CMT patient scores for anxiety (mean ± standard deviation, 6.7 ± 4.8), depression (4.5 ± 4.0), and general distress (11.5 ± 8.1) did not differ from controls and the Italian population. However, compared to controls, the percentages of subjects with depression (10% vs 2%) and general distress (14% vs 4%) were significantly higher in CMT patients. We found no association between HADS scores and disease duration or CMT type. Patients with general distress showed more severe disease and higher rate of positive sensory symptoms. Depressed patients also had more severe disease. Nineteen percent of CMT patients took antidepressants/anxiolytics (12% daily) and 70% analgesic/anti-inflammatory drugs. Patients with anxiety, depression, and distress reported higher consumption of anxiolytics/antidepressants. About 50% of patients with depression and/or general distress did not receive any specific pharmacological treatment. Conclusions: An appreciable proportion of CMT patients shows general distress and depression. Both correlated with disease severity and consumption of antidepressants/anxiolytics, suggesting that the disease itself is contributing to general distress and depression. [ABSTRACT FROM AUTHOR]

Background: Hereditary transthyretin amyloidosis (hATTR/ATTRv) results from the deposition of misfolded transthyretin (TTR) throughout the body, including peripheral nerves. Inotersen, an antisense oligonucleotide inhibitor of hepatic TTR production, demonstrated a favorable efficacy and safety profile in patients with the polyneuropathy associated with hATTR in the NEURO-TTR (NCT01737398) study. We report longer-term efficacy and safety data for inotersen, with a median treatment exposure of 3 years. Methods: Patients who satisfactorily completed NEURO-TTR were enrolled in its open-label extension (OLE) study. Efficacy assessments included the modified Neuropathy Impairment Score + 7 (mNIS + 7), Norfolk Quality of Life–Diabetic Neuropathy (Norfolk QoL-DN) questionnaire total score, and the Short Form 36 (SF-36v2) Health Survey Physical Component Summary score. Safety and tolerability were also assessed. Efficacy is reported for patients living in Europe and North America (this cohort completed the study approximately 9 months before the remaining group of patients outside these regions); safety is reported for the full safety dataset, comprising patients living in Europe, North America, and Latin America/Australasia. This study is registered with ClinicalTrials.gov, identifier NCT02175004. Results: In the Europe and North America cohort of the NEURO-TTR study, 113/141 patients (80.1%) completed the study, and 109 patients participated in the OLE study. A total of 70 patients continued to receive inotersen (inotersen–inotersen) and 39 switched from placebo to inotersen (placebo–inotersen). The placebo–inotersen group demonstrated sustained improvement in neurological disease progression as measured by mNIS + 7, compared with predicted worsening based on projection of the NEURO-TTR placebo data (estimated natural history). The inotersen–inotersen group demonstrated sustained benefit, as measured by mNIS + 7, Norfolk QoL-DN, and SF-36v2, compared with estimated natural history as well as compared with the placebo–inotersen group. With a maximum exposure of 6.2 years, inotersen was not associated with any additional safety concerns or increased toxicity in the OLE study. Platelet and renal monitoring were effective in reducing the risk of severe adverse events in the OLE study. Conclusion: Inotersen treatment for > 3 years slowed progression of the polyneuropathy associated with hATTR, and no new safety signals were observed. [ABSTRACT FROM AUTHOR]

Background and Objectives: Choosing the correct site for a nerve biopsy remains a challenge due to nerve sacrifice and major donor site complications, such as neuroma, as seen in sural nerve biopsy. Selecting a deeper donor nerve can help in burying nerve stumps in deep soft tissues, preventing neuroma. Moreover, using an expendable, deeply situated motor nerve can aid indiagnosis when a motor neuropathy is suspected. The authors propose using the pronator quadratus (PQ) branch for this purpose, as it is located deep between the bellies of the flexor muscles and the interosseous membrane in the forearm. This branch is expendable since the denervation of the PQ has a negligible effect on forearm pronation, which is primarily sustained by the pronator teres., Methods: The surgical approach is the same as the approach for anterior interosseous nerve transfer to the motor component of the ulnar nerve in the distal forearm: access is in the midline in the middle third of the forearm under local anesthesia Blunt dissection is performed, separating and retracting the flexor musculotendinous junction to reach the interosseous membrane where the PQ branch is identified. A careful dissection of the nerve branch is performed, allowing a 2 cm long segment to be cut and removed. The proximal stump is then buried into an adjacent muscle belly and the surgical site is closed., Results: The technique is safe and reproducible in experienced hands., Conclusion: This technique may be especially applicable in cases where neurologists need to study motor neuropathies. Contraindications of the technique include wrist instability and high median nerve palsies., (Copyright © 2024. Published by Elsevier B.V.)

This article, published in Frontiers in Molecular Neuroscience, discusses the molecular and cellular bases of peripheral neuropathies. The study focuses on the genetic deletion of the zinc transporter ZnT3 and its effects on cognitive function in mice. The researchers found that ZnT3 knockout mice exhibited progressive cognitive deficits, impaired dendritic spine plasticity, and glucose metabolism abnormalities. They hypothesize that the deficiency of ZnT3 and reduced brain zinc levels may negatively affect glycose metabolism and synaptic plasticity, leading to cognitive impairment. These findings may provide new therapeutic targets for the treatment of neurodegenerative disorders. [Extracted from the article]

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most prevalent and difficult-to-treat symptoms in cancer patients. For this reason, the explore for unused helpful choices able of filling these impediments is essential. Natural products from plants stand out as a valuable source of therapeutic agents, being options for the treatment of this growing public health problem. Therefore, the objective of this study was to report the effects of natural products from plants and the mechanisms of action involved in the reduction of neuropathy caused by chemotherapy. The search was performed in PubMed, Scopus and Web of Science in March/2021. Two reviewers independently selected the articles and extracted data on characteristics, methods, study results and methodological quality (SYRCLE). Twenty-two studies were selected, describing the potential effect of 22 different phytochemicals in the treatment of CIPN, with emphasis on terpenes, flavonoids and alkaloids. The effect of these compounds was demonstrated in different experimental protocols, with several action targets being proposed, such as modulation of inflammatory mediators and reduction of oxidative stress. The studies demonstrated a predominance of the risk of uncertain bias for randomization, baseline characteristics and concealment of the experimental groups. Our findings suggest a potential antinociceptive effect of natural products from plants on CIPN, probably acting in several places of action, being strategic for the development of new therapeutic options for this multifactorial condition. [ABSTRACT FROM AUTHOR]

In recent years, the complexity of cancer and cancer therapies and their interactions with the peripheral nervous system have come into focus, but limitations in experimental models have remained a significant challenge in the field. As evidence, there are currently no therapies approved that target cancer–peripheral nervous system or cancer therapy–peripheral nervous system interactions as an anti‐neoplastic or anti‐neurotoxic agent, respectively. Human pluripotent stem cells offer an appealing model system that, unlike rodent models, is compatible with high throughput, high content applications; techniques that reflect modern drug discovery methodologies. Thus, utilizing the key advantages of stem cell‐based models in tandem with the strengths of traditional animal models offers a complementary and interdisciplinary strategy to advance cancer and cancer therapy‐peripheral nervous system research and drug discovery. In this review, the current status of the cancer‐peripheral nervous system and cancer therapy‐peripheral nervous system research is discussed, examples where stem cell‐based models have been implemented are described, and avenues where stem cell‐based models may further advance the field are proposed. [ABSTRACT FROM AUTHOR]

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most prevalent and difficult-to-treat symptoms in cancer patients. For this reason, the explore for unused helpful choices able of filling these impediments is essential. Natural products from plants stand out as a valuable source of therapeutic agents, being options for the treatment of this growing public health problem. Therefore, the objective of this study was to report the effects of natural products from plants and the mechanisms of action involved in the reduction of neuropathy caused by chemotherapy. The search was performed in PubMed, Scopus and Web of Science in March/2021. Two reviewers independently selected the articles and extracted data on characteristics, methods, study results and methodological quality (SYRCLE). Twenty-two studies were selected, describing the potential effect of 22 different phytochemicals in the treatment of CIPN, with emphasis on terpenes, flavonoids and alkaloids. The effect of these compounds was demonstrated in different experimental protocols, with several action targets being proposed, such as modulation of inflammatory mediators and reduction of oxidative stress. The studies demonstrated a predominance of the risk of uncertain bias for randomization, baseline characteristics and concealment of the experimental groups. Our findings suggest a potential antinociceptive effect of natural products from plants on CIPN, probably acting in several places of action, being strategic for the development of new therapeutic options for this multifactorial condition.

The POLG gene encodes mitochondrial DNA polymerase, and mutations in this gene cause a spectrum of disorders related to mitochondrial DNA depletion or deletion. Dystonia has only rarely been reported as an early and prominent manifestation of POLG mutations. We report a case of a 30-year-old male presenting with lower limb dystonia with peripheral neuropathy and demonstrate that the dystonia was levodopa responsive (with video findings). Whole-genome sequencing revealed biallelic variants in the POLG gene: a known pathogenic variant [NM_001126131.2:c.2209G>C (p.Gly737Arg)] and a novel likely pathogenic variant [NM_001126131.2:c.3305A>C (p.Gln1102Pro)]. A genetic diagnosis was made before the appearance of more readily recognizable features of mitochondrial disease, allowing us to avoid invasive tissue biopsies or potentially deleterious treatments, such as sodium valproate. A POLG-related disorder should be suspected in cases of dystonia with peripheral neuropathy, and this diagnosis may have implications for further investigations and management.

The aim of this study is to determine the effect of hand-foot exercises on chemotherapy-induced peripheral neuropathy-related pain severity, falls, and quality of life in patients with colorectal cancer. The study was conducted in the outpatient chemotherapy unit of a public hospital between 25 April-31 December 2022. The enrolled 39 patients were randomly assigned to the intervention (n:19) and control (n:20) groups. The hand-foot exercises program was applied to the intervention group in three sessions a day and three days a week fashion for 8 weeks at home. No intervention was applied to the control group other than routine treatment and care. Data were collected through face-to-face interviews in the first interview and the 2nd, 4th, 6th, 8th weeks. The exercise program adherence of the intervention group was followed up through telephone/face-to-face interviews in weeks 1–8. Data were collected using the Numerical Pain Rating Scale, Fall Follow-Up Form, the CIPNAT scale, EORTC QLQ-C30 and EORTC QLQ-CR29 scales. Mann-Whitney U Test, Chi-square test, Wilcoxon signed test, and Friedman test were used to analyze the data. The study found that as of week 4th, the intervention group experienced less pain severity than the control group (p < 0.001); at week 8th, the peripheral neuropathy symptoms of the intervention group decreased compared to the control group (p < 0.05); at weeks 2nd,4th,6th,8th, there was no statistically significant difference in falls (p > 0.05); at week 8th, while there was no significant difference between the groups regarding colorectal cancer quality of life (p > 0.05), the overall cancer quality of life improved in the intervention group (p < 0.05). The hand-foot exercises program is effective in chemotherapy-induced peripheral neuropathy-related symptoms, pain severity, and overall cancer quality of life. www.clinicaltrials.gov , NCT05873829. • Hand-foot exercises, effective in alleviating chemotherapy-induced peripheral neuropathy and improving the quality of life in colorectal cancer patients, offer a practical method in nursing care. [ABSTRACT FROM AUTHOR]

Background: Diagnosis of Amyotrophic Lateral Sclerosis (ALS) is challenging as initial presentations are various and diagnostic biomarkers are lacking. The diagnosis relies on the presence of both upper and lower motor neuron signs and thorough exclusion of differential diagnoses, particularly as receiving an ALS diagnosis has major implications for the patient. Sjögren's syndrome may mimic peripheral ALS phenotypes and should be considered in the work-up. Case: A 72-year-old female presented with a mono-neuropathy of the right leg and a complaint of dry eyes and mouth. Initial diagnostic work-up confirmed a regional sensorimotor neuropathy and a Sjögren's syndrome; a causal relationship was assumed. However, motor symptoms spread progressively despite immunosuppressive treatment, eventually including both legs, both arms and the diaphragm. Clinically, unequivocal central signs were lacking, but further along in the disease course, the atrophy pattern followed a split phenotype and deep tendon reflexes were preserved. Nerve biopsy did not show vasculitic infiltration; however, serum neurofilament light chain (sNfL) concentrations were and remained persistently highly elevated despite immunosuppressive treatment. Electrodiagnostic re-evaluation confirmed denervation in 3 regions. A diagnosis of familial ALS was finally confirmed by a C9orf72 repeat expansion. Stationary sensory symptoms were best explained by a neuropathy associated with concomitant Sjögren's syndrome. Discussion: Our instructive case shows the difficulties of diagnosing ALS in the setting of a peripheral symptom onset and a concurrent but unrelated condition also causing neuropathy. Such cases require high clinical vigilance and readiness to reappraise diagnostic findings if the disease course deviates from expectation. Recently proposed simplified diagnostic criteria, genetic testing and body fluid biomarkers such as sNfL may facilitate the diagnostic process and lead to an earlier diagnosis of ALS. [ABSTRACT FROM AUTHOR]

Background and purpose: Mutations in DNAJB2 are associated with autosomal recessive hereditary motor neuropathies/ Charcot‐Marie‐Tooth disease type 2 (CMT2). We describe an Italian family with CMT2 due to a homozygous DNAJB2 mutation and provide insight into the pathomechanisms. Methods: Patients with DNAJB2 mutations were characterized clinically, electrophysiologically and by means of skin biopsy. mRNA and protein levels were studied in lymphoblastoid cells (LCLs) from patients and controls. Results: Three affected siblings were found to carry a homozygous DNAJB2 null mutation segregating with the disease. The disease manifested in the second to third decade of life. Clinical examination showed severe weakness of the thigh muscles and complete loss of movement in the foot and leg muscles. Sensation was reduced in the lower limbs. All patients had severe hearing loss and the proband also had Parkinson's disease (PD). Nerve conduction studies showed an axonal motor and sensory length‐dependent polyneuropathy. DNAJB2 expression studies revealed reduced mRNA levels and the absence of the protein in the homozygous subject in both LCLs and skin biopsy. Interestingly, we detected phospho‐alpha‐synuclein deposits in the proband, as already seen in PD patients, and demonstrated TDP‐43 accumulation in patients' skin. Conclusions: Our results broaden the clinical spectrum of DNAJB2‐related neuropathies and provide evidence that DNAJB2 mutations should be taken into account as another causative gene of CMT2 with hearing loss and parkinsonism. The mutation likely acts through a loss‐of‐function mechanism, leading to toxic protein aggregation such as TDP‐43. The associated parkinsonism resembles the classic PD form with the addition of abnormal accumulation of phospho‐alpha‐synuclein. [ABSTRACT FROM AUTHOR]

Controversy exists regarding the influence of breast cancer–related lymphedema (BCRL) in the development of peripheral neuropathies. Our aim was to evaluate the association of secondary lymphedema with peripheral neuropathies in patients with breast cancer. We performed a systematic review by querying PubMed, EMBASE, Ovid Medline and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, and Cochrane Central Register of Controlled Trials databases. The keywords "lymphedema" AND ("neuropathy" OR "carpal tunnel syndrome" OR "cubital tunnel syndrome" OR "neuropathic pain") and synonyms in titles and abstracts were used to perform the search. Seventeen articles met the inclusion criteria. Discrepancies were found in studies that analyzed whether a cause-effect association exists between carpal tunnel syndrome (CTS) and secondary lymphedema. No evidence indicated that lymphedema predisposes to developing peripheral neuropathies such as CTS or brachial plexopathy. No studies found an association between patients with breast cancer at risk of or with lymphedema and the development or worsening of CTS. Carpal tunnel release can be safely performed in patients with BCRL. Neuropathic pain worsens with lymphedema, and treatment seems to improve the pain. Our study did not find enough evidence to conclude that BCRL is associated with the development of peripheral neuropathies. Carpal tunnel release is a safe procedure that can be performed in patients with BCRL and does not influence the development or worsening of lymphedema. Neuropathic pain seems to worsen after development of lymphedema, and treatment has been found to improve neuropathic pain. [ABSTRACT FROM AUTHOR]

Objective: to evaluate the efficacy of limb pneumomassage as one of the components of comprehensive treatment for patients with polyneuropathies of various origins. Material and methods. This study included 77 patients (36 men and 41 women) with limb polyneuropathies treated in the Department of Neurology, Alexander-Mariinsky Regional Clinical Hospital. The mean age of women was 64 ± 9.6 years, while the mean age of men was 58 ± 7.4 years. All study participants were divided into 5 groups depending on the causes of their limb polyneuropathy. Group 1 included 30 patients (14 men and 16 women) with axonal polyneuropathies plus sensologic syndrome, ataxia, toxic polyneuropathies, diabetic polyneuropathies, and chronic inflammatory demyelinating polyneuropathies. Group 2 comprised 16 patients (6 men and 10 women) with multiple sclerosis plus lower paraparesis, cerebellar ataxia. Group 3 included 11 patients (7 men and 4 women) with discogenic vascular myelopathy of the thoracic and lumbosacral spine plus paraparesis and gait disorders. Group 4 comprised 10 patients (4 men and 6 women) after ischemic strokes with hemiparesis. Group 5 was composed of 10 patients (5 men and 5 women) with hereditary diseases, including Charcot-Marie-Tooth disease, CurschmannBatten-Steinert syndrome plus tetraparesis, late-onset cerebellar degeneration with ataxia. All patients received pharmacotherapy that included vascular, neuroprotective, analgesic, antioxidant, and immunomodulatory agents, as well as exercise therapy, acupuncture, and limb pneumomassage. The control group included 21 patients (11 men and 10 women) with polyneuropathies of various origins, who received standard treatment without pneumomassage. The STATISTICA-16 software was used for data amalysis. We performed correlation analysis and calculated Pearson correlation coefficients. Results. We found that limb pneumomassage improved the condition of patients with metabolic, toxic, and inflammatory polyneuropathies. However, limb pneumomassage was ineffective in patients with hereditary polyneuropathies due to more significant and irreversible lesions of the nervous system.

BackgroundDiagnosis of Amyotrophic Lateral Sclerosis (ALS) is challenging as initial presentations are various and diagnostic biomarkers are lacking. The diagnosis relies on the presence of both upper and lower motor neuron signs and thorough exclusion of differential diagnoses, particularly as receiving an ALS diagnosis has major implications for the patient. Sjögren's syndrome may mimic peripheral ALS phenotypes and should be considered in the work-up.CaseA 72-year-old female presented with a mono-neuropathy of the right leg and a complaint of dry eyes and mouth. Initial diagnostic work-up confirmed a regional sensorimotor neuropathy and a Sjögren's syndrome; a causal relationship was assumed. However, motor symptoms spread progressively despite immunosuppressive treatment, eventually including both legs, both arms and the diaphragm. Clinically, unequivocal central signs were lacking, but further along in the disease course, the atrophy pattern followed a split phenotype and deep tendon reflexes were preserved. Nerve biopsy did not show vasculitic infiltration; however, serum neurofilament light chain (sNfL) concentrations were and remained persistently highly elevated despite immunosuppressive treatment. Electrodiagnostic re-evaluation confirmed denervation in 3 regions. A diagnosis of familial ALS was finally confirmed by a C9orf 72 repeat expansion. Stationary sensory symptoms were best explained by a neuropathy associated with concomitant Sjögren's syndromeDiscussionOur instructive case shows the difficulties of diagnosing ALS in the setting of a peripheral symptom onset and a concurrent but unrelated condition also causing neuropathy. Such cases require high clinical vigilance and readiness to reappraise diagnostic findings if the disease course deviates from expectation. Recently proposed simplified diagnostic criteria, genetic testing and body fluid biomarkers such as sNfL may facilitate the diagnostic process and lead to an earlier diagnosis of ALS.

Background and purpose: Guillain–Barré syndrome (GBS) may be fatal in the acute phase but also affect long‐term prognosis due to irreversible sequelae and secondary medical complications. We determined the short‐term, intermediate, and long‐term mortality of GBS compared to the general population. Methods: Individual‐level data from nationwide registries were linked in this matched cohort study of all first‐time hospital‐diagnosed GBS patients in Denmark between 1987 and 2016 and 10 individuals from the general population, matched on age, sex, and index date. We used Cox regression analysis to calculate matched mortality hazard ratios (HRs) following GBS, assessing short‐term (0–6 months), intermediate (>6 months–4 years), and long‐term (>4 years) mortality. Results: We identified 2414 patients with GBS and 23,909 matched individuals from the general population. Short‐term mortality was 4.8% (95% confidence interval [CI] = 4.0–5.8) and 0.8% (95% CI = 0.7–0.9) for GBS patients and general population members, respectively, resulting in an HR of 6.6 (95% CI = 4.0–5.8). Intermediate mortality was 7.6% (95% CI = 6.5–8.9), compared with 5.8% (95% CI = 5.5–6.1) for general population members, corresponding to an HR of 1.5 (95% CI = 1.3–1.8). After the first 4 years, long‐term mortality showed similar results for GBS patients and general population members (HR = 1.1, 95% CI = 0.9–1.2). Conclusions: During the first 6 months after GBS hospital admission, GBS was associated with a 6.6‐fold increased mortality as compared with the background population of the same age. Mortality remained increased for approximately 4 years following GBS, and then leveled off to a similar long‐term mortality rate. [ABSTRACT FROM AUTHOR]

Objectives: Chronic abdominal pain is occasionally caused by an abdominal wall entity such as anterior cutaneous nerve entrapment syndrome (ACNES). This syndrome is thought to occur due to intercostal nerve branches (T7-12) that are entrapped in the rectus abdominis muscles. The diagnosis is largely based on subjective clues in patient history and physical examination. A test referred to as the scratch collapse test (SCT) is used as an additional diagnostic tool in peripheral nerve entrapment syndromes such as the carpal tunnel syndrome. The aim of the present study is to investigate whether an SCT was positive in patients with suspected ACNES. If so, this finding may support its hypothesized neuropathic character., Methods: A prospective, case-control study was performed among patients with ACNES ( n = 20) and two control groups without ACNES (acute intra-abdominal pathology n = 20; healthy n = 20), all were consecutively included. ACNES was diagnosed based on previously published criteria. The SCT test was executed at the painful abdominal area in both patient groups and at a corresponding area in healthy controls. Predictive values, sensitivity, and specificity were calculated. Videos of tests were evaluated by blinded observers., Results: SCT was judged positive in 19 of 20 ACNES patients but not in any of the 40 controls. A 95% sensitivity (confidence interval [CI]: 75-99) and optimal specificity (100%; CI: 83-100) were calculated., Conclusions: The positive SCT supports the hypothesis that ACNES is an entrapment neuropathy. A positive SCT should be considered a major diagnostic criterion for ACNES., (© 2024 the author(s), published by De Gruyter.)

Bacillus Calmette-Guérin (BCG) intravesical infusion therapy is widely used to control recurrence after transurethral resection of bladder tumors. Herein, we report a case of polyneuropathy with transiently positive onconeural antibodies after BCG bladder infusion therapy. A man in his 70s presented with upper and lower extremity weakness 11 weeks after BCG intravesical infusion therapy, a postoperative therapy for superficial bladder cancer. Nerve conduction studies revealed findings that were consistent with demyelinating sensorimotor polyneuropathy. Anti-CV2 antibody was positive; however, contrast-enhanced computed tomography and positron emission tomography revealed no malignancy. The patient's symptoms improved with immunoglobulin therapy. Contrast-enhanced computed tomography showed no malignancy, and the anti-CV-2 antibody test result was negative six months after discharge. The immune response to BCG bladder infusion therapy may have caused the transient CV2 antibody positivity and polyneuropathy. The possibility of transiently positive onconeural antibodies after BCG intravesical infusion therapy should be considered., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Saito et al.)

Les syndromes lymphoprolifératifs (myélomes, maladie de Waldenström, leucémie lymphoïde chronique, lymphomes) peuvent s'associer à la survenue de neuropathies périphériques. Le mécanisme est variable : il peut être dysimmunitaire, associé ou non aux gammapathies monoclonales ; paranéoplasique ; infiltratif ; ou plus communément, iatrogène ou carentiel. Le diagnostic peut être complexe, notamment lorsque la neuropathie est inaugurale, nécessitant une coopération étroite entre internistes et neurologues. Le diagnostic positif de la neuropathie repose sur une enquête électroclinique systématique, qui précise la topographie et le mécanisme de l'atteinte nerveuse, parfois aidé par des examens d'imagerie notamment une IRM nerveuse et/ou plexique. L'imputabilité de la neuropathie à un syndrome lymphoprolifératif repose sur un faisceau d'arguments comprenant le contexte clinique (symptômes B, syndrome tumoral), des examens biologiques de première intention (hémogramme, électrophorèse des protides sériques, sérologies virales, dosage du complément), des auto-anticorps discutés en fonction de la neuropathie (anti-MAG, anti-gangliosides) et parfois des examens plus invasifs (biopsies médullaires ou neuromusculaires). Lymphoproliferative syndromes (multiple myeloma, Waldenström's disease, chronic lymphocytic leukemia, lymphomas) may be associated with peripheral neuropathies. The mechanism can be dysimmune, associated or not with monoclonal gammopathies; paraneoplastic; infiltrative; or more commonly, iatrogenic or due to vitamin deficiency. The diagnosis can be complex, especially when the neuropathy is the presenting manifestation, requiring a close cooperation between internists and neurologists. The positive diagnosis of the neuropathy is based on a systematic electro-clinical investigation, which specifies the topography and the mechanism of the nerve damage, sometimes reinforced by imaging examinations, in particular, nerve and/or plexus MRI. The imputability of the neuropathy to a lymphoproliferative syndrome is based on a set of arguments including the clinical context (B signs, tumour syndrome), first-line laboratory tests (hemogram, protein electrophoresis, viral serologies, complement), auto-antibodies discussed according to the neuropathy (anti-MAG, anti-gangliosides) and sometimes more invasive examinations (bone marrow or neuro-muscular biopsies). [ABSTRACT FROM AUTHOR]

Aims: Diabetic peripheral neuropathy (DPN) is a common and severe complication to type 2 diabetes. The pathogenesis of DPN is not fully known, but several pathways and gene polymorphisms contributing to DPN are described. DPN can be studied using nerve biopsies, but studies on the proteome of the nerve itself, and its surrounding tissue as a whole, are lacking. Studies on the posterior interosseous nerve (PIN) have proposed PIN a useful indicator of DPN. Methods: A quantitative mass spectrometry‐based proteomics analysis was made of peripheral nerves from age‐ and gender‐matched living human male tissue donors; nine type 2 diabetes subjects, with decreased sural nerve action potentials indicating DPN, and six controls without type 2 diabetes, with normal electrophysiology results. Results: A total of 2617 proteins were identified. Linear regression was used to discover which proteins were differentially expressed between type 2 diabetes and controls. Only soft signals were found. Therefore, clustering of the 500 most variable proteins was made to find clusters of similar proteins in type 2 diabetes subjects and healthy controls. Conclusions: This feasibility study shows, for the first time, that the use of quantitative mass spectrometry enables quantification of proteins from nerve biopsies from subjects with and without type 2 diabetes, which may aid in finding biomarkers of importance to DPN development. [ABSTRACT FROM AUTHOR]

Objective To investigate the efficacy of repeated application of capsaicin 179 mg cutaneous patch in nonresponders to the first application. Design Post hoc, as-treated analysis of two prospective trials (STRIDE and PACE) with 52-week follow-up. Blinding Open-label. Setting Multicenter clinical trial. Subjects STRIDE: nondiabetic neuropathic pain; PACE: painful diabetic peripheral neuropathy. Methods Patients were divided according to number of applications needed before attainment of a ≥30% reduction in average pain intensity (question 5 of the Brief Pain Inventory [BPI-Q5]). We assessed the change from baseline in average pain intensity (BPI-Q5), mean "interference with sleep" score, Patient Global Impression of Change, quality of life (QOL) via the EuroQol 5-dimension, and Self-Assessment of Treatment. Results In STRIDE and PACE, respectively, n = 306 and n = 313 received the capsaicin patch; n = 60 and n = 96 had a response after the first application, n = 33 and n = 68 after the second, and n = 11 and n = 43 after the third. Among patients without a ≥30% reduction in pain intensity at 3 months, in STRIDE and PACE, respectively, 23.3% and 28.1% achieved a ≥30% reduction at 6 months, increasing to 33.9% and 45.7% at 12 months. Similar results were obtained when a decrease of ≥50% was used as the responder definition. Progressive improvements in pain intensity in slower responders reached levels similar to those in early responders at month 12 and were accompanied by improvements in sleep, QOL, and patient satisfaction. Conclusions Although some patients with peripheral neuropathic pain experience rapid improvements with a single treatment of capsaicin 179 mg patch, some may require two or three treatments before an initial response is observed. Similar benefits for pain, sleep, and QOL can be achieved in early and late responders. [ABSTRACT FROM AUTHOR]