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Charcot-Marie-Tooth disease (CMT) is one of the most common and genetically heterogeneous inherited neurological diseases, with more than 130 disease-causing genes. Whole genome sequencing (WGS) has improved diagnosis across genetic diseases, but the diagnostic impact in CMT is yet to be fully reported. We present the diagnostic results from a single specialist inherited neuropathy centre, including the impact of WGS diagnostic testing. Patients were assessed at our specialist inherited neuropathy centre from 2009 to 2023. Genetic testing was performed using single gene testing, next-generation sequencing targeted panels, research whole exome sequencing and WGS and, latterly, WGS through the UK National Health Service. Variants were assessed using the American College of Medical Genetics and Genomics and Association for Clinical Genomic Science criteria. Excluding patients with hereditary ATTR amyloidosis, 1515 patients with a clinical diagnosis of CMT and related disorders were recruited. In summary, 621 patients had CMT1 (41.0%), 294 CMT2 (19.4%), 205 intermediate CMT (CMTi, 13.5%), 139 hereditary motor neuropathy (HMN, 9.2%), 93 hereditary sensory neuropathy (HSN, 6.1%), 38 sensory ataxic neuropathy (2.5%), 72 hereditary neuropathy with liability to pressure palsies (HNPP, 4.8%) and 53 'complex' neuropathy (3.5%). Overall, a genetic diagnosis was reached in 76.9% (1165/1515). A diagnosis was most likely in CMT1 (96.8%, 601/621), followed by CMTi (81.0%, 166/205) and then HSN (69.9%, 65/93). Diagnostic rates remained less than 50% in CMT2, HMN and complex neuropathies. The most common genetic diagnosis was PMP22 duplication (CMT1A; 505/1165, 43.3%), then GJB1 (CMTX1; 151/1165, 13.0%), PMP22 deletion (HNPP; 72/1165, 6.2%) and MFN2 (CMT2A; 46/1165, 3.9%). We recruited 233 cases to the UK 100 000 Genomes Project (100KGP), of which 74 (31.8%) achieved a diagnosis; 28 had been otherwise diagnosed since recruitment, leaving a true diagnostic rate of WGS through the 100KGP of 19.7% (46/233). However, almost half of the solved cases (35/74) received a negative report from the study, and the diagnosis was made through our research access to the WGS data. The overall diagnostic uplift of WGS for the entire cohort was 3.5%. Our diagnostic rate is the highest reported from a single centre and has benefitted from the use of WGS, particularly access to the raw data. However, almost one-quarter of all cases remain unsolved, and a new reference genome and novel technologies will be important to narrow the 'diagnostic gap'. [ABSTRACT FROM AUTHOR]

The development of combination antiretroviral therapy (cART) has transformed human immunodeficiency virus (HIV) infection from a lethal diagnosis into a chronic disease, and people living with HIV on cART can experience an almost normal life expectancy. However, these individuals often develop various complications that lead to a decreased quality of life, some of the most significant of which are neuropathic pain and the development of painful peripheral sensory neuropathy (PSN). Critically, although cART is thought to induce pain pathogenesis, the relative contribution of different classes of antiretrovirals has not been systematically investigated. In this study, we measured the development of pathological pain and peripheral neuropathy in mice orally treated with distinct antiretrovirals at their translational dosages. Our results show that only nucleoside reverse transcriptase inhibitors (NRTIs), not other types of antiretrovirals such as proteinase inhibitors, non-nucleoside reverse transcriptase inhibitors, integrase strand transfer inhibitors, and CCR5 antagonists, induce pathological pain and PSN. Thus, these findings suggest that NRTIs are the major class of antiretrovirals in cART that promote the development of neuropathic pain. As NRTIs form the essential backbone of multiple different current cART regimens, it is of paramount clinical importance to better understand the underlying mechanism to facilitate the design of less toxic forms of these drugs and/or potential mitigation strategies. [ABSTRACT FROM AUTHOR]

Neuropathy is a damage, disease, or dysfunction of one or more nerves especially of the peripheral nervous system. One of the most common disease causing neuropathy is diabetes mellitus. Diabetic neuropathy is a serious consequence that arises when nerve tissue is damaged by prolonged hyperglycemia. It affects a considerable portion of those who have the disease. This article covers every component of this complexed disease. We will discuss the definition, etiology, risk factors that patients can control and that are uncontrollable, and forms of neuropathies linked to diabetes such as peripheral, autonomic and focal. For more clinical approach signs and symptoms, diagnostic methods which are a mix of clinical evaluations, neurological exams, electrophysiological testing, and, in certain situations, imaging modalities and complicated nature of treating diabetic neuropathy will be explored. Moreover, challenges in treating this disease and future directions and research will be elaborated. What is more it interdisciplinary care will be explored as a key element in addressing complexed nature of diabetic neuropathy. In addition to highlighting the complexity of neuropathy in diabetes mellitus and emphasizing the vital significance of early recognition and specialized interventions for the best possible patient outcomes, the article aims to present a thorough grasp of diabetic neuropathy. [ABSTRACT FROM AUTHOR]

Background/Objectives: Vitamin B12 deficiency can cause variable symptoms, which may be irreversible if not diagnosed and treated in a timely manner. We aimed to develop a widely accepted expert consensus to guide the practice of diagnosing and treating B12 deficiency. Methods: We conducted a scoping review of the literature published in PubMed since January 2003. Data were used to design a two-round Delphi survey to study the level of consensus among 42 experts. Results: The panelists agreed on the need for educational and organizational changes in the current medical practices for diagnosing and treating B12 deficiency. Recognition of clinical symptoms should receive the highest priority in establishing the diagnosis. There is agreement that the serum B12 concentration is useful as a screening marker and methylmalonic acid or homocysteine can support the diagnosis. Patient lifestyle, disease history, and medications can provide clues to the cause of B12 deficiency. Regardless of the cause of the deficiency, initial treatment with parenteral B12 was regarded as the first choice for patients with acute and severe manifestations of B12 deficiency. The use of high-dose oral B12 at different frequencies may be considered for long-term treatment. Prophylactic B12 supplementation should be considered for specific high-risk groups. Conclusions: There is a consensus that clinical symptoms need to receive more attention in establishing the diagnosis of B12 deficiency. B12 laboratory markers can support the diagnosis. The severity of clinical symptoms, the causes of B12 deficiency, and the treatment goals govern decisions regarding the route and dose of B12 therapy. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the feasibility and capability of UT in detecting musculoskeletal system lesions in the limbs and to explore its image quality. Materials and Methods: The Institutional Review Board has approved this prospective single-center study. This study included participants with various musculoskeletal and neurologic disorders in the limbs who provided written consent from October 2022 to April 2023. In addition to other radiological examinations (X-rays, CT, or MRI) and conventional handheld ultrasound scans requested by clinicians based on the conditions, each participant also underwent UT scanning using our developed limb ultrasound imaging system during the same period. Four radiologists and ultrasound physicians with more than five years of experience in musculoskeletal diagnostics analyzed the two-dimensional and three-dimensional images of the examination area. Results: Overall, 50 participants were evaluated (mean age, 36 years ± 18 [SD]; 26 males). The conditions included musculoskeletal tumors (n = 10), postoperative follow-up of musculoskeletal tumors (n = 20), peripheral nerve disorders in the limbs (n = 10) and postoperative pain in orthopedic surgery (n = 10). In all UT images, the region of interest was completely displayed, and internal structures such as muscles and nerves were clearly visible. Compared to conventional ultrasound images, the reconstructed three-dimensional images intuitively displayed the relationship between the lesions and surrounding tissues. Furthermore, UT did not exhibit metal artifacts when observing soft tissues around metallic implants, providing more comprehensive soft tissue information and more intuitive stereoscopic images. Conclusion: Clinical results of the UT system have demonstrated its feasibility as an automated and standardized imaging technique for musculoskeletal imaging, providing a new imaging modality for the diagnosis of musculoskeletal diseases in the human body. [ABSTRACT FROM AUTHOR]

Autoimmune autonomic ganglionopathy (AAG) is a disease of autonomic failure caused by ganglionic acetylcholine receptor (gAChR) autoantibodies. Although the detection of autoantibodies is important for distinguishing the disease from other neuropathies that present with autonomic dysfunction, other factors are important for accurate diagnosis. Here, we provide a comprehensive review of the clinical features of AAG, highlighting differences in clinical course, clinical presentation, and laboratory findings from other neuropathies presenting with autonomic symptoms. The first step in diagnosing AAG is careful history taking, which should reveal whether the mode of onset is acute or chronic, followed by an examination of the time course of disease progression, including the presentation of autonomic and extra-autonomic symptoms. AAG is a neuropathy that should be differentiated from other neuropathies when the patient presents with autonomic dysfunction. Immune-mediated neuropathies, such as acute autonomic sensory neuropathy, are sometimes difficult to differentiate, and therefore, differences in clinical and laboratory findings should be well understood. Other non-neuropathic conditions, such as postural orthostatic tachycardia syndrome, chronic fatigue syndrome, and long COVID, also present with symptoms similar to those of AAG. Although often challenging, efforts should be made to differentiate among the disease candidates. [ABSTRACT FROM AUTHOR]

Background: The assessment of the normative values of sensory nerve action potentials (SNAP) and their diagnostic accuracies using validated neuropathy‐assessment tools to classify participants into groups with and without neuropathy was not previously described in the literature. Methods: The Utah Early Neuropathy Scale (UENS), Michigan neuropathy‐screening instrument, and nerve conduction data were collected prospectively. We described and compared the values of the sural, superficial peroneal sensory (SPS), and superficial radial SNAP amplitude in different age groups for three groups. Group 1 (G1)—control participants (UENS <5), group 2 (G2)—participants with diabetes without clinical diabetic neuropathy (UENS <5), and group 3 (G3)—participants with clinical diabetic neuropathy (UENS ≥5). We also described the diagnostic accuracy of single‐nerve amplitude and a combined sensory polyneuropathy index (CSPNI) that consists of four total points (one point for each of the following nerves if their amplitude was <25% lower limit of normal: right sural, left sural, right SPS, and left SPS potentials). Results: We assessed 135 participants, including 41, 37, and 57 participants in G1, G2, and G3, respectively, with age median (interquartile ranges) of 51 (45–56), 47 (38–56), and 54 (51–61) years, respectively, whereas 19 (46.3%), 18 (48.7%), and 32 (56.14%) of them were males, respectively. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) scores were 68.4%, 92.3%, 86.7%, and 80% for the sural amplitude; 86%, 58.3%, 62%, and 84% for the SPS amplitude; 66.7%, 94.4%, 90.5%, and 78.2% for the CSPNI of 3; and 54.4%, 98.6%, 96.9%, and 73.2% for the CSPNI of 4, respectively. Conclusion: Sural nerve had a high specificity for neuropathy; however, the CSPNI had the highest specificity and PPV, whereas the SPS had the highest sensitivity and NPV. We described the sensitivity, specificity, positive predictive value, and negative predictive values of sensory nerve action potentials. We used a validated neuropathy scales to classify our participants into neuropathy and no neuropathy groups. These diagnostic accuracies were not reported in the previous literature. [ABSTRACT FROM AUTHOR]

Leber's hereditary optic neuropathy (LHON) is a mitochondrial genetic disease with central vision loss as the main symptom. It is one of the diseases that cause vision loss and optic atrophy in young and middle-aged people. The mutations of these three primary mitochondrial mutations, m.11778G>A, m.14484T>C, and m.3460G>A, are the main molecular basis, but their pathogenesis is also affected by nuclear genes, mitochondrial genetic background, and environmental factors. This article summarizes the research progress on molecular pathogenesis, clinical symptoms, and treatment of LHON in recent years, aiming to summarize the genetic pathogenesis and clinical treatment points of LHON. [ABSTRACT FROM AUTHOR]

Background: Sudomotor dysfunction is one of the earliest manifestations of small fiber neuropathy (SFN), reflecting the alteration of sympathetic C fiber innervation of the sweat glands. Among other techniques, such innervation can be assessed by measuring electrochemical skin conductance (ESC) in microsiemens (µS). In this study, ESC was measured at the feet to detect distal SFN. For this objective, the performance of a new device, the Body Scan® (Withings, France), intended for home use, was compared with that of a reference device, the Sudoscan® (Impeto Medical, France), which requires a hospital setting. Methods: In patients with diabetes with or without neuropathy or non-diabetic patients with lower-limb neuropathy, the diagnostic performance of the Body Scan® measurement was assessed by calculating its sensitivity (Se) and specificity (Sp) to detect at least moderate SFN (Se70 and Sp70), defined by a value of feet ESC ≤ 70 µS and > 50 µS on the Sudoscan® measure, or severe SFN (Se50 and Sp50), defined by a value of feet ESC ≤ 50 µS on the Sudoscan® measure. The agreement between the two devices was assessed with the analysis of Bland-Altman plots, mean absolute error (MAE), and root mean squared error (RMSE) calculations. The repeatability of the measurements was also compared between the two devices. Results: A total of 147 patients (52% men, mean age 59 years old, 76% diabetic) were included in the analysis. The sensitivity and specificity to detect at least moderate or severe SFN were: Se70 = 0.91 ([0.83, 0.96]), Sp70 = 0.97 ([0.88, 0.99]), Se50 = 0.91 ([0.80, 0.98]), and Sp50 = 0.99 ([0.94, 1]), respectively. The bias and 95% limits of agreement were 1.5 [-5.4, 8.4]. The MAE was 2.9 and the RMSE 3.8. The intra-sample variability was 2.0 for the Body Scan® and 2.3 for the Sudoscan®. Conclusion: The ESC measurements provided by the Body Scan® were in almost perfect agreement with those provided by the reference device, the Sudoscan®, which validates the accuracy of the Body Scan® for the detection of SFN. By enabling simple, rapid, and autonomous use by the patient at home, this new technique will facilitate screening and monitoring of SFN in daily practice. [ABSTRACT FROM AUTHOR]

Abstract Background The assessment of the normative values of sensory nerve action potentials (SNAP) and their diagnostic accuracies using validated neuropathy‐assessment tools to classify participants into groups with and without neuropathy was not previously described in the literature. Methods The Utah Early Neuropathy Scale (UENS), Michigan neuropathy‐screening instrument, and nerve conduction data were collected prospectively. We described and compared the values of the sural, superficial peroneal sensory (SPS), and superficial radial SNAP amplitude in different age groups for three groups. Group 1 (G1)—control participants (UENS

Neuropathy is a damage, disease, or dysfunction of one or more nerves especially of the peripheral nervous system. One of the most common disease causing neuropathy is diabetes mellitus. Diabetic neuropathy is a serious consequence that arises when nerve tissue is damaged by prolonged hyperglycemia. It affects a considerable portion of those who have the disease. This article covers every component of this complexed disease. We will discuss the definition, etiology, risk factors that patients can control and that are uncontrollable, and forms of neuropathies linked to diabetes such as peripheral, autonomic and focal. For more clinical approach signs and symptoms, diagnostic methods which are a mix of clinical evaluations, neurological exams, electrophysiological testing, and, in certain situations, imaging modalities and complicated nature of treating diabetic neuropathy will be explored. Moreover, challenges in treating this disease and future directions and research will be elaborated. What is more it interdisciplinary care will be explored as a key element in addressing complexed nature of diabetic neuropathy. In addition to highlighting the complexity of neuropathy in diabetes mellitus and emphasizing the vital significance of early recognition and specialized interventions for the best possible patient outcomes, the article aims to present a thorough grasp of diabetic neuropathy.

Background/Objectives: Vitamin B12 deficiency can cause variable symptoms, which may be irreversible if not diagnosed and treated in a timely manner. We aimed to develop a widely accepted expert consensus to guide the practice of diagnosing and treating B12 deficiency. Methods: We conducted a scoping review of the literature published in PubMed since January 2003. Data were used to design a two-round Delphi survey to study the level of consensus among 42 experts. Results: The panelists agreed on the need for educational and organizational changes in the current medical practices for diagnosing and treating B12 deficiency. Recognition of clinical symptoms should receive the highest priority in establishing the diagnosis. There is agreement that the serum B12 concentration is useful as a screening marker and methylmalonic acid or homocysteine can support the diagnosis. Patient lifestyle, disease history, and medications can provide clues to the cause of B12 deficiency. Regardless of the cause of the deficiency, initial treatment with parenteral B12 was regarded as the first choice for patients with acute and severe manifestations of B12 deficiency. The use of high-dose oral B12 at different frequencies may be considered for long-term treatment. Prophylactic B12 supplementation should be considered for specific high-risk groups. Conclusions: There is a consensus that clinical symptoms need to receive more attention in establishing the diagnosis of B12 deficiency. B12 laboratory markers can support the diagnosis. The severity of clinical symptoms, the causes of B12 deficiency, and the treatment goals govern decisions regarding the route and dose of B12 therapy.

Aim: To determine the demographic, etiological, and clinical features and treatment modalities of patients with neuro-ophthalmological disorders starting at a later age. Materials and Methods: We retrospectively reviewed the clinical data related to the neuro-ophthalmology patients who presented at the geriatric age at two tertiary eye care referral centers from 2004 to 2022. Results: Of the 2,127 patients who applied to the Neuro-Ophthalmology Department during this period, 162 (7.6%) were ≥ 65 years old at the time of diagnosis, and their data were analyzed. The mean age at the onset of the disease was 73.2 ± 6.7 (65-95) years, and the mean follow-up time was 1.1±0.4 (1-3) years. Non-arteritic anterior ischemic optic neuropathy (NAAION) (n=85, 52.5%), isolated cranial nerve palsies (n=28, 17.3%), and cerebral vascular disorders (CVD) (n=14, 8.6%) were the most frequent diagnosis. The most common symptoms were as follows: sudden visual loss in 79 (48.8%), diplopia in 31 (19.1%), and blurred vision in 21 (13%) cases. The most common accompanying systemic disease was hypertension (HT) and diabetes mellitus (DM) in 31 (27.4%), followed by HT in 29 (25.7%) cases. There was no accompanying systemic disease in 49 (30.2%) patients. The diagnosis of NAAION and AAION resulted in poor visual outcomes, while CVD presented with homonymous hemianopsia. Conclusion: NATION and CVD were the most common age-related neuroophthalmological disorders that cause visual acuity loss and a visual field defect at an advanced age. Identifying these disorders and managing the visual problems are essential to protect the patient's quality of life. [ABSTRACT FROM AUTHOR]

A case of anteromedial leg pain diagnosed and treated for 10 years as "shin splints" (medial tibial stress syndrome) is described. A history and examination was performed focused on anatomy, biomechanics, and peripheral nerves. Detailed sensory testing was performed in the painful area, and imaging was obtained to confirm the diagnosis. The clinical investigation was consistent with dynamic stenosis of the left L4-5 intervertebral foramen, causing a mixed partial mononeuropathy of the L4 spinal nerve that presented as pain and hypersensitivity in the anteromedial shin. Manual therapy maneuvers intended to open the intervertebral foramen led to resolution of the pain and sensory deficits. After three additional treatments performed within a month, resolution was maintained for >3 years. This case highlights how concepts from preclinical studies, coupled with basic anatomical, neurological, and biomechanical investigations, can be critical for accurate diagnosis and treatment for a case previously considered unresponsive to care. [ABSTRACT FROM AUTHOR]

Background: India is sometimes called the "diabetic capital of the world" due to the country's alarmingly rising rate of diabetes mellitus. Worldwide, Type 2 Diabetes has become a serious health issue. Material and Methods: From the pool of Type 2 Diabetics receiving care at NRIIMS's General Medicine Department in Visakhapatnam, 100 patients met the study's inclusion and exclusion criteria. From October 2021 to December 2022, a full year of data was collected for this investigation. Results: This study's findings add to the growing body of evidence showing that cardiac autonomic dysfunction is widespread among diabetic patients. Multiple investigations, some of which were carried out in India, have found findings that are consistent with one another. Using validated but basic measures of cardiovascular autonomic function, this study showed severe anomalies in autonomic function. Conclusion: The study found the following results, our hospital's research group found a high prevalence of cardiovascular autonomic neuropathy among type 2 diabetes. As diabetes progresses, so does the risk of developing CAN. [ABSTRACT FROM AUTHOR]

Background: Leprosy (or Hansen's disease) continues to present considerable challenges regarding containment and early diagnosis. Leprosy is considered to be primarily a neural disease that first affects the sensory function of small fibres. Although the condition is well described in terms of clinical manifestations and histology, few studies have been undertaken to detect damage done to small-fibre sensory nerves. In vivo confocal microscopy is a useful tool for conducting a detailed evaluation of these structures, although its use in individuals affected by leprosy has still not been explored. Objective: To evaluate in vivo confocal microscopy findings in Hansen's disease patients and their association with clinical variables relating to this disease. Method: A cross-sectional case-series type study was carried out between October 2019 and May 2021, in Recife, Pernambuco, Brazil. Socio-demographic and clinical data were gathered from 21 patients with leprosy. The douleur neuropathique 4 neuropathic pain questionnaire was used to evaluate pain. In vivo confocal microscopy of the cornea was employed to evaluate the small-calibre fibres. Findings were compared with those for a control group of 23 healthy individuals. Results: In relation to clinical parameters, 90.5% of the patients were classified as "multibacillary" according to the World Health Organization criteria, and 70% as dimorphic or borderline, in accordance with the Madrid classification. Around 52.4% had received a diagnosis after one year or less of living with the disease, while 95.2% presented alterations in small-fibre sensory function and 35% presented such alterations in the large fibre. Neuropathic pain was present in 81% of the patients. In vivo confocal microscopy found no statistically significant difference in mean age and distribution according to sex between the Hansen disease patients and the control group of healthy individuals. The median-of-means for dendritic cells and volume of sub-basal nerve fibres in the control group were used to test for normality. Both eyes of all leprosy patients examined contained higher number of dendritic cells than the median value and a volume of sub-basal nerve fibres lower than the mean. These differences were statistically significant (P < 0.001 and P < 0.001, respectively). Multibacillary individuals had a median number of dendritic cells two times that of paucibacillary individuals (P = 0.035). Limitations: No association was found between the variables examined using in vivo confocal microscopy and clinical variables relating to small-fibre damage, the neuropathic pain questionnaire or alterations detected by the neurological examination. We believe, however, that Cochet-Bonnet esthesiometry of the cornea may have revealed such an association. Conclusion: In vivo confocal microscopy is a useful diagnostic tool for detecting small fibre loss in individuals affected by leprosy and may constitute a useful addition to the range of tools available to help curb the effects of neuropathy in these patients. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the utility of isolated-check visual evoked potential (icVEP) for discriminating between eyes with dysthyroid optic neuropathy (DON) and eyes with thyroid-associated ophthalmopathy (TAO) but not DON. Methods: Forty-three eyes with TAO but not DON (as non-DON), fifty-three eyes with DON, and sixty healthy eyes (as controls) were included. Comprehensive ophthalmic examinations, including best-corrected visual acuity, refraction, color vision test, intraocular pressure measurement, slit-lamp biomicroscopy, ophthalmoscopy, RAPD, exophthalmometry measurements, pVEP test, icVEP test, standard automated perimetry, and clinical activity score classification of TAO, as well as demographic information, were collected and analyzed. Results: In the DON group, the signal-to-noise ratio (SNR) value of icVEPs decreased significantly compared with that of the non-DON group as well as control (p < 0.05). The SNR values under 8%, 16% and 32% depth of modulation (DOM) were significantly negatively correlated with BCVA (p < 0.05, r = − 0.9 ~ − 0.6), papilledema (Y/N) (p < 0.05, r = − 0.8 ~ 0.4) and DON (Y/N) (p < 0.001, r = − 0.7 ~ − 0.5). The 8% DOM of icVEP had the largest area under the receiver operating characteristic curve (AUC) (0.842) for discriminating DON from non-DONs. Meanwhile, decision curve analysis (DCA) showed that patients clinically benefit most from 8% DOM of icVEP. Furthermore, the 8% DOM of icVEP combing with papilledema (Y/N) and BCVA (Model 1) has significantly larger AUC than the 8% DOM of icVEP (p = 0.0364), and has better clinical benefit in DCA analysis. Conclusions: The SNR of 8% DOM from icVEP may represent a significant ancillary diagnostic method for DON detection. Furthermore, icVEP combined with papilledema (Y/N) and BCVA should be considered as a diagnostic model in future clinical practice. [ABSTRACT FROM AUTHOR]

Ultrasound has emerged as a highly valuable tool in imaging peripheral nerve lesions in the wrist region, particularly for common pathologies such as carpal tunnel and Guyon's canal syndromes. Extensive research has demonstrated nerve swelling proximal to the entrapment site, an unclear border, and flattening as features of nerve entrapments. However, there is a dearth of information regarding small or terminal nerves in the wrist and hand. This article aims to bridge this knowledge gap by providing a comprehensive overview concerning scanning techniques, pathology, and guided-injection methods for those nerve entrapments. The median nerve (main trunk, palmar cutaneous branch, and recurrent motor branch), ulnar nerve (main trunk, superficial branch, deep branch, palmar ulnar cutaneous branch, and dorsal ulnar cutaneous branch), superficial radial nerve, posterior interosseous nerve, palmar common/proper digital nerves, and dorsal common/proper digital nerves are elaborated in this review. A series of ultrasound images are used to illustrate these techniques in detail. Finally, sonographic findings complement electrodiagnostic studies, providing better insight into understanding the whole clinical scenario, while ultrasound-guided interventions are safe and effective for treating relevant nerve pathologies. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Although intravascular lymphoma rarely presents with peripheral neuropathy, learning about this presentation can lead to timely diagnosis and improved prognosis in patients with intravascular lymphoma. A 64‐year‐old man presented with asymmetric paresthesia and subsequent weakness of his feet and a 10 kg weight loss over 40 days. Electrodiagnostic studies revealed distal axonal sensory‐motor polyneuropathy with ongoing axonal loss. A peroneal nerve biopsy showed intravascular proliferation of CD‐20 positive lymphocytes, which suggested intravascular large B‐cell lymphoma. [ABSTRACT FROM AUTHOR]

Objective: To investigate the clinical efficacy and prognostic factors of transnasal endoscopic optic decompression in the treatment of traumatic optic neuropathy (TON). Methods: A retrospective analysis was performed on 13 TON patients in The Seventh Affiliated Hospital of Sun Yat-sen University and Shenzhen Eye Hospital in Shenzhen City (China) from June 2020 to April 2022. These patients had received transnasal endoscopic optic decompression, and hormonal and neurotrophic drugs were given after surgery. Visual acuity (VA) improvement was used as the criterion to judge clinical efficacy. Results: In a total of 13 patients, 13 injured eyes (12 men and 1 woman; mean age, 28.0 ± 11.8 years) received transnasal endoscopic optic decompression. After surgery, nine patients had improved VA, whereas four patients failed to show any improvement, resulting in a total effective rate of 69.2%. Of the six patients with no light perception preoperatively, three had effective results after the operation, giving an effective rate of 50.0%. Of the seven patients with residual light sensation preoperatively, six had effective results after the operation, giving an effective rate of 85.7%. Of the 10 patients operated on within 7 days after injury, seven had effective results, giving an effective rate of 70%. Of the three patients injured and operated on after 7 days, two had effective results, giving an effective rate of 66.7%. Conclusion: Transnasal endoscopic optic nerve decompression is an effective treatment method for TON. The presence of residual light perception and the timing of surgery within 7 days are crucial to the prognosis. [ABSTRACT FROM AUTHOR]

Background: We report an enhancement of the dorsal roots on gadolinium-enhanced cervical magnetic resonance imaging (MRI) in a patient with acute autonomic and sensory neuropathy (AASN). Case presentation: A 38-year-old woman visited our university hospital for dizziness and fainting while rising from sitting or lying down and a tingling sensation in the whole body, including her limbs, torso, and abdomen, which was sustained for 15 days. The patient had hyperalgesia in nearly her entire body and slight motor weakness in her bilateral upper and lower limbs. Autonomic dysfunction was confirmed using autonomic testing. Furthermore, the nerve conduction study showed an absence of sensory nerve action potentials in all evaluated peripheral nerves. Cervical MRI was performed 18 days after dysautonomia onset. In the axial T1-gadolinum-enhanced MRIs, enhancement in cervical ventral and dorsal nerve roots and the posterior column of the spinal cord were observed, and the axial T2-weighted MRI showed high signal intensity in the posterior column of the cervical spinal cord. Considering the clinical, electrophysiological and imaging findings, the patient was diagnosed with AASN. A total dose of 90 g (2 g/kg) of intravenous immunoglobulin was administered over 5 days. At the follow-up at 4 years after AASN symptom onset, the hyperalgesia and orthostatic hypotension symptoms improved. However, her systolic blood pressure intermittently decreased to < 80 mmHg. Conclusion: Gadolinium-enhanced MRI may facilitate the accurate and prompt diagnosis of AASN. [ABSTRACT FROM AUTHOR]

We present a patient with Pacinian corpuscle hypertrophy and hyperplasia in the hand and discuss the diagnosis and treatment of this rare condition. A 46-year-old woman presented with radiating pain of the left middle finger. A strong Tinel-like sign was elicited between the index and middle fingers. The patient frequently used mobile phone, with the corner of the phone consistently applying pressure on the palm. The surgery was carried out under the microscope and two enlarged cystic lesions under the epineurium were found in the proper digital nerve. Histologic examination revealed hypertrophied Pacinian corpuscle with normal structure. Postoperatively, her symptoms gradually improved. Preoperative diagnosis of this disease is very difficult. Hand surgeons should keep this disease in mind preoperatively. In our case, we would not have been able to identify multiple hypertrophic Pacinian corpuscles without the microscope. An operating microscope is recommended in a surgery of this nature. Level of Evidence: Level V (Therapeutic) [ABSTRACT FROM AUTHOR]

Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disease characterized clinically by eosinophilic hyaline intranuclear inclusions in neuronal and other somatic cells. Skin biopsies are reportedly useful in diagnosing NIID, and the genetic cause of NIID was identified as a GGC repeat expansion in NOTCH2NLC in recent years. The number of adult patients diagnosed via genetic testing has increased; however, there have been no detailed reports of pediatric NIID cases with GGC expansions in NOTCH2NLC. This is the first detailed report of a pediatric patient showing various neurological symptoms from the age of 10 and was ultimately diagnosed with NIID via skin biopsy and triplet repeat primed polymerase chain reaction analyses. This was an 18-year-old female who developed cyclic vomiting, distal dominant muscle weakness, and sustained miosis at 10 years. Nerve conduction studies revealed axonal degeneration, and her neuropathy had slowly progressed despite several rounds of high-dose methylprednisolone and intravenous immunoglobulin therapy. At 13 years, she had an acute encephalopathy-like episode. At 15 years, brain MRI revealed slightly high-intensity lesions on diffusion-weighted and T2-weighted imaging in the subcortical white matter of her frontal lobes that expanded over time. At 16 years, esophagography, upper gastrointestinal endoscopy, and esophageal manometry revealed esophageal achalasia, and per-oral endoscopic myotomy was performed. At 18 years, we diagnosed her with NIID based on the findings of skin specimen analyses and a GGC repeat expansion in NOTCH2NLC. NIID should be considered as a differential diagnosis in pediatric patients with various neurological symptoms. [ABSTRACT FROM AUTHOR]

Key Clinical Message Although intravascular lymphoma rarely presents with peripheral neuropathy, learning about this presentation can lead to timely diagnosis and improved prognosis in patients with intravascular lymphoma. Abstract A 64‐year‐old man presented with asymmetric paresthesia and subsequent weakness of his feet and a 10 kg weight loss over 40 days. Electrodiagnostic studies revealed distal axonal sensory‐motor polyneuropathy with ongoing axonal loss. A peroneal nerve biopsy showed intravascular proliferation of CD‐20 positive lymphocytes, which suggested intravascular large B‐cell lymphoma.

Abstract Background Hereditary transthyretin amyloidosis is an uncommon multisystem disorder caused by mutation of the transthyretin protein, leading to peripheral neuropathy often with autonomic features, cardiomyopathy, or a mixed phenotype. Multiple other organ systems can be involved with ophthalmologic, renal, hematologic, gastrointestinal, and/or genitourinary symptoms and signs. This often results in assessments by multiple specialists and significant delays before the diagnosis is recognized. With the recent advent of potentially lifesaving therapies, early diagnosis has become even more important. Our case highlights the protean aspects of this disease as well as the difficulty of making this diagnosis, especially in the absence of a clear family history. Case presentation We report the case of a 64-year-old man of East-Asian descent who presented with diarrhea, mild anemia, and symptoms of peripheral neuropathy. Numerous investigations and specialist evaluations did not identify a cause. Progression of neurologic symptoms and the development of new hematologic abnormalities ultimately led to consideration of hereditary transthyretin amyloidosis. The diagnosis was confirmed after re-examining previously acquired gastrointestinal biopsies and pursuing genetic testing, which confirmed a pathogenic mutation in the transthyretin gene. He was subsequently started on a novel gene-silencing therapy. On clinical follow-up 8 months after initiation of therapy, the patient described stabilization of previously progressive numbness, weakness, and weight loss with an unchanged neurologic examination and stable repeat electrophysiologic testing. Conclusions Hereditary transthyretin amyloidosis is a challenging disease to recognize in early stages owing to its multisystem and nonspecific manifestations. Recent approval of novel therapies highlights the importance of early diagnosis before irreversible organ damage occurs.

A letter to the editor published in Clinical Orthopaedics & Related Research discusses the discrepancy between diagnosing mild-to-moderate carpal tunnel syndrome based on signs and symptoms versus using electrodiagnostic studies and ultrasound. The authors of the letter agree with a previous study that found a higher prevalence of carpal tunnel syndrome when additional diagnostic tools were used. They emphasize the importance of a multidimensional evaluation and suggest that ultrasound, in particular, can be useful in identifying the condition and assessing nerve integrity. The authors also highlight the need for collaboration between experts in electrodiagnostic examination and ultrasound in the management of orthopedic surgery patients. [Extracted from the article]

This document is a reply to a letter to the editor regarding the diagnosis of mild-to-moderate idiopathic median neuropathy at the carpal tunnel. The authors discuss the Bayesian thinking about diagnosing pathology and the probability of a disease based on signs and symptoms. They argue that even with negative test results, performing carpal tunnel release surgery is still worthwhile due to the potential for permanent nerve damage. The authors also mention the limitations of the diagnostic tests and the time it takes for median nerve swelling to develop. [Extracted from the article]

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a chronic immune‐mediated peripheral form of polyneuropathy. No reliable diagnostic biomarkers are available by which to make the diagnosis of CIDP. As a result, diagnosis of the condition can be challenging. Many patients are not recognized early in the disease course, and on the other end of the spectrum both establishing early and accurate diagnosis as well as avoiding misdiagnosis and overtreatment. Identification of the hallmark clinical, electrophysiological, and laboratory features of the disease are critical to facilitate rapid diagnosis, while an understanding of diagnostic pitfalls can help prevent misdiagnosis. Since the original description of CIDP in the 1970s, over 15 sets of diagnostic criteria have been proposed. The criteria published in 2021 by the European Academy of Neurology / Peripheral Nerve Society (EAN/PNS) were developed for use during routine clinical care and are available in the public domain. These criteria provide clinicians with an invaluable resource by which the data collected during the evaluation of the patient with possible CIDP can be interpreted. One point of importance that bridges diagnosis to treatment is objectification of the treatment response. Interpretation of how patients respond to treatment drives both long‐term treatment paradigms and the diagnosis at which these treatments are aimed. Although no approach is perfect, utilization of strength impairment and disability outcomes in clinical practice can help unravel the difficulties in interpreting response to treatment. Just as improvement in these outcomes is considered diagnostically supportive, the absence of objective benefit argues against it and should prompt reconsideration of a CIDP diagnosis. See Editorial on page 529 in this issue. [ABSTRACT FROM AUTHOR]

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Background: Determining the strategy of surgical treatment for chronic angle closure glaucoma (CACG) is still important. Purpose: To assess the efficacy, rates of successful intraocular pressure (IOP) lowering and the increase in anterior chamber angle for laser peripheral iridotomy (LPI) in patients with CACG. Material and Methods: We examined 31 patients (31 eyes; 18 women and 13 men) who had undergone LPI for CACG. Patient age ranged from 49 to 77 years (mean age, 64.8 ± 5.3 years). The indication for LPI was an anterior chamber angle of Shaffer grade 2 to 3 and the presence of optic neuropathy. Mean Maklakoff intraocular pressure (IOP) was 23.4 ± 1.2 mmHg. Results: Thirteen patients required surgery during the follow-up after LPI. Particularly, 10 eyes required phacoemulsification (PHACO) only, and 3 eyes, PHACO plus goniosynechialysis (GSL), because of decompensated IOP and an anterior chamber angle narrower than Shaffer grade 2 by gonioscopy. Kaplan-Meier survival analysis showed that the rates of successful IOP lowering for laser peripheral iridotomy (without the need for surgery, PHACO alone or PHACO plus GSL) at 12 months, 24 months and 36 months were 87.1%, 71.0% and 58.06%, respectively. Conclusion: The LPI is effective for opening the anterior chamber angle and reducing IOP over 6 months, but is less effective and does not allow opening the anterior chamber angle over a period exceeding 6 months. The LPI may be considered as a preparatory procedure in CACG, particularly in the presence of an acute angle-closure glaucoma attack in the fellow eye. [ABSTRACT FROM AUTHOR]

Background: Increased serum adenosine deaminase (ADA) levels have been shown to be involved in metabolic abnormalities and immune disequilibrium, which may in turn contribute to inflammatory diseases. This study aimed to determine whether increased serum ADA levels are related to diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes (T2D). Methods: This study was part of a series exploring the potential risks for DPN. All patients received DPN assessment based on neuropathic symptoms, neuropathic signs, and nerve conduction studies to calculate the composite Z score of nerve latency, amplitude and conduction velocity (NCV). DPN was confirmed by both at least a presentation of neuropathic symptoms/signs and an abnormal nerve conduction index. Serum ADA levels were also synchronously detected. Results: A total of 384 eligible patients with T2D were recruited for this study, and 24.5% (n=94) were determined to have DPN. Increases in serum ADA levels were closely associated with increases in composite Z score of latency (b=0.263, t=5.273, p<0.001) and decreases in composite Z score of amplitude (b=–0.126, t=–2.352, p=0.019) and NCV (b=–0.201, t=–3.841, p<0.001) after adjusting for other clinical covariates. Moreover, each 5 U/L increase in serum ADA levels was associated with a 1.781-fold increased adjusted odds ratio of having DPN (95% confidence interval: 1.271–2.495). Furthermore, the optimal cut-off value of serum ADA levels to discriminate DPN was ≥14.2 U/L (sensitivity=59.57%, specificity=75.52% and Youden index=0.351) after analysis by receiver operating characteristic curve. Conclusions: Increased serum ADA levels may be a potential risk factor for DPN in patients with T2D. [ABSTRACT FROM AUTHOR]

Blood neurofilament light chain (NfL) is a minimally invasive, but highly sensitive biomarker of neurological diseases. However, diseases and neurological damage associated with increased NfL remain unclear. Therefore, the present study investigated factors associated with increased plasma NfL levels in various neurological diseases, focal lesions and pathological processes. This was a retrospective cohort study on 410 participants with various neurological diseases and 17 healthy and cognitively unimpaired controls (HCU). Plasma samples were analyzed to measure NfL using ECL immunoassay. The focal lesions were classified as the cerebrum, cerebellum, brainstem, meninges, spinal cord, peripheral nerves, neuromuscular junction, and muscles based on medical records. A multiple regression analysis and receiver operating characteristic curve (ROC) analysis were performed to investigate whether plasma NfL levels predict specific diseases and focal lesions. Plasma NfL levels discriminated between the HCU and all disease groups (area under the curve (AUC), 0.97), with a cut-off value of 63.4 pg/mL. A multiple regression analysis of focal lesions adjusted by pathogenic processes showed that brainstem and peripheral nerve involvement was associated with higher plasma NfL levels. A cut-off value of 53.8 pg/mL of NfL discriminated between the HCU and neurological disease group except for brainstem or peripheral disorders (AUC 0.962), while a cut-off value of 208.0 pg/mL distinguished this group from brainstem or peripheral nervous system disorders (AUC 0.716). These results demonstrate that plasma NfL has a potential to be a highly sensitive biomarker for neurological diseases and focal lesions. • Factors associated with increased plasma NfL levels in neurological diseases. • Brainstem and peripheral nerve damage was associated with higher plasma NfL levels. • Plasma NfL could be a biomarker for neurological diseases and focal lesions. [ABSTRACT FROM AUTHOR]

Primary burning mouth syndrome (BMS) is a chronic pain of a burning quality affecting the tongue and intraoral mucosa. Currently, there are no definite diagnostic criteria; therefore, the diagnosis is made by exclusion of potential local and systemic causes that could justify the burning sensation. The etiology behind primary BMS remains unclear; however, the most acceptable theories link primary BMS with neuropathic pain. This article provides a review of primary BMS diagnosis, mechanisms, and treatment with focus on the association of BMS with pain modulation. Preliminary data are presented suggesting a link between primary BMS and a faulty inhibitory pain system. [ABSTRACT FROM AUTHOR]

Inflammatory pseudotumor (IPT) is a non-neoplastic condition of unknown etiology. IPT with lower cranial nerve (CN IX, X, XI, XII) neuropathies is extremely rare. In this study, we systematically reviewed all previously reported cases regarding the management of IPT with lower cranial nerve neuropathies. We searched the PubMed/MEDLINE database for reports related to IPT with lower cranial nerve neuropathies. A total of six papers with 10 cases met the inclusion criteria (mean age 51.6 years, 70% male). The mean follow-up period was 15.4 months (range: 1–60 months). The most frequent treatment was corticosteroids alone (60%), followed by surgery alone (20%), and multimodal treatment (20%). Corticosteroid therapy was associated with an excellent (100%) response rate at 6 months of follow-up, and half of the patients were in complete remission after 9 months. Both cases who received surgery had persistent neurological deficits. Immediate complete remission of neurological symptoms and resolution on imaging after decompression surgery via an endoscopic endonasal approach (EEA) with corticosteroids was demonstrated in our representative case. This review suggests that EEA is a preferred method for diagnosis and treatment, a promising approach associated with favorable outcomes, and a viable first-line treatment for selected cases, followed by multimodal therapy. [ABSTRACT FROM AUTHOR]

Background: Increased plasma D-dimer levels have been reported to be associated with a range of adverse health outcomes. This study aimed to determine whether plasma D-dimer is connected to diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes (T2D). Methods: This study was part of a series exploring the potential risks for DPN. All patients were questioned for neurologic symptoms, examined for neurologic signs, and received nerve conduction studies to collect nerve action potential onset latency, amplitude, and nerve conduction velocity (NCV). Composite Z scores of latency, amplitude, and NCV were calculated. DPN was confirmed as both at least a neurologic symptom/sign and an abnormality of nerve conduction studies. Coagulation function indices, such as plasma D-dimer levels, were also synchronously detected. Results: We finally recruited 393 eligible patients for this study, of whom 24.7% (n = 97) were determined to have DPN. The plasma D-dimer level was found to be closely associated with the composite Z score of latency, amplitude, and NCV after adjusting for other coagulation function indices and clinical covariates (latency: b = 0.134, t = 2.299, p = 0.022; amplitude: b = -0.138, t = -2.286, p = 0.023; NCV: b = -0.139, t = -2.433, p = 0.016). Moreover, the prevalence of DPN in the first, second, third, and fourth quartiles (Q1, Q2, Q3, and Q4) of the D-dimer level was 15.2%, 15.9%, 26.4%, and 42.7%, respectively (p for trend < 0.001). The corresponding adjusted odds ratios and 95% CIs for DPN in D-dimer quartiles were 1, 0.79 (0.21-2.99), 1.75 (0.49-6.26), and 5.17 (1.38-19.42), respectively. Furthermore, the optimal cutoff value of the plasma D-dimer level to discriminate DPN was ≥0.22 mg/L (sensitivity = 67.01%, specificity = 58.78%, and Youden index = 0.26) after analysis by the receiver operating characteristic curve. Conclusions: Increased plasma D-dimer levels may be a promising indicator for DPN in patients with T2D. [ABSTRACT FROM AUTHOR]

For the preoperative evaluation of infraorbital nerve injury, most clinicians depend on the patient's subjective symptoms or judgements, lacking a generalized and objective evaluation method. Due to the limitations in subjective evaluations for accurate diagnosis of infraorbital nerve injury, we used the blink reflex to objectively evaluate injury to the infraorbital nerve. A 49-year-old female, who had previously undergone midface augmentation with alloplastic implants, presented with sensory loss in the left upper lip, nose tip, and lower palatal area. Physical examination revealed sensation loss in the area innervated by the infraorbital nerve. Facial three-dimensional computed tomography did not identify compression of the infraorbital nerve. The blink reflex study of the infraorbital nerve was evaluated preoperatively. After the patient was diagnosed with injury along the infraorbital nerve pathway from alloplastic facial implants, she underwent facial implant removal with decompression surgery. The patient experienced a significant decrease in hypoesthesia, and her sensory function improved. The blink reflex study was an effective method to objectively diagnose infraorbital neuropathy. Therefore, clinical use of the blink reflex study as an electrophysiological diagnostic tool is recommended to investigate infraorbital nerve injuries. [ABSTRACT FROM AUTHOR]

Ultrasound has emerged as a highly valuable tool in imaging peripheral nerve lesions in the wrist region, particularly for common pathologies such as carpal tunnel and Guyon’s canal syndromes. Extensive research has demonstrated nerve swelling proximal to the entrapment site, an unclear border, and flattening as features of nerve entrapments. However, there is a dearth of information regarding small or terminal nerves in the wrist and hand. This article aims to bridge this knowledge gap by providing a comprehensive overview concerning scanning techniques, pathology, and guided-injection methods for those nerve entrapments. The median nerve (main trunk, palmar cutaneous branch, and recurrent motor branch), ulnar nerve (main trunk, superficial branch, deep branch, palmar ulnar cutaneous branch, and dorsal ulnar cutaneous branch), superficial radial nerve, posterior interosseous nerve, palmar common/proper digital nerves, and dorsal common/proper digital nerves are elaborated in this review. A series of ultrasound images are used to illustrate these techniques in detail. Finally, sonographic findings complement electrodiagnostic studies, providing better insight into understanding the whole clinical scenario, while ultrasound-guided interventions are safe and effective for treating relevant nerve pathologies.