Characteristics of autosomal dominant WFS1-associated optic neuropathy and its comparability to OPA1-associated autosomal dominant optic atrophy.

This study aims to describe the ophthalmic characteristics of autosomal dominant (AD) WFS1-associated optic atrophy (AD WFS1-OA), and to explore phenotypic differences with dominant optic atrophy (DOA) caused by mutations in the OPA1-gene. WFS1-associated diseases, or 'wolframinopathies', exhibit a spectrum of ocular and systemic phenotypes, of which the autosomal recessive Wolfram syndrome has been the most extensively studied. AD mutations in WFS1 also cause various phenotypical changes including OA. The most common phenotype in AD WFS1-associated disease, the combination of OA and hearing loss (HL), clinically resembles the 'plus' phenotype of DOA. We performed a comprehensive medical record review across tertiary referral centers in the Netherlands and Belgium resulting in 22 patients with heterozygous WFS1 variants. Eighteen (82%) had HL in addition to OA. Diabetes mellitus was found in 7 (32%). Four patients had isolated OA. One patient had an unusual phenotype with anterior chamber abnormalities and malformations of the extremities. Compared to DOA, AD WFS1-OA patients had different color vision abnormalities (red-green vs blue-yellow in DOA), abnormal OPL lamination on macular OCT (absent in DOA), more generalized thinning of the retinal nerve fiber layer, and more reduced and delayed pattern reversal visual evoked potentials.

Diabetic Charcot neuroarthropathy: A threat to both limb and life.

Diabetic Charcot neuroarthropathy (DCN), first described in 1936, occurs in less than 1% of diabetic patients, but in those diabetic subjects with distal symmetrical polyneuropathy, the overall incidence increases to 30% and the risk is even greater in those with type 1 diabetes. Factors that precipitate DCN are trauma, ischaemia due to arterio-venous shunting, increased osteoclastic activity and inflammation. DCN usually presents with a painless swollen foot and/or ankle which is 'hot to the touch'. These clinical findings are soon followed by characteristic magnetic resonance imaging (MRI) abnormalities and later X-ray changes. The joints that are most typically involved in chronological order are the tarsometatarsals followed by the naviculocuniform, sub-tarsal, talonavicular and metatarsal and tarsophalangeal. The cornerstone of therapy is prolonged (3-12 months) offloading with immobilization. Bisphosphonates may possibly accelerate recovery, whereas other unproven possible therapies include rhPTH, 1-34, calcitonin and methylprednisolone, which are not only ineffective but in some cases may also prolong the time to healing. Denosumab is potentially an efficacious, if unproven, therapy to accelerate healing. The risk of amputation is high and increases in the presence of a foot ulcer. DCN is associated with manifestations of autonomic neuropathy, including cardiac denervation, so that the risks of a cardiac event and heart failure are increased with DCN. Mortality is also increased with DCN, especially in the presence of a foot ulcer. To avoid the recurrence of DCN and especially to lower the risk of the recurrence of a foot ulcer recurrence reconstructive, surgery may be needed.

Leukemic occult infiltrative optic neuropathy presenting as optic neuritis: a case report.

Isolated ocular relapses of leukemia are rare and typically present as infiltrative lesions of the optic nerve. This report presents a case of an isolated ocular relapse of leukemia in a female patient, characterized by occult infiltrative optic neuropathy. Despite the absence of leukemic cell infiltration on MRI, a 33-year-old female patient presented with optic neuritis, which resolved after intrathecal administration of chemotherapeutic agents. However, due to her non-compliance with the treatment regimen, leukemia progressed to infiltrative optic neuropathy. She refused radiation therapy, and while intrathecal injections provided temporary stabilization, they were insufficient for sustained disease control. This case uniquely documents the extended progression of an isolated ocular relapse of leukemia, evolving from an occult infiltrative lesion initially presenting as optic neuritis to a more pronounced infiltrative lesion. It suggests that leukemic optic nerve infiltration can occur in patients with leukemia even in the absence of MRI-detectable abnormalities. Radiation therapy emerges as a critical modality in the management of infiltrative lesions of the optic nerve.

Case report: MEK inhibitor as treatment for multi-lineage mosaic KRAS G12D-associated epidermal nevus syndrome in a pediatric patient.

The RASopathies, collectively, are a spectrum of genetic syndromes caused by mutations in genes involved in the RAS/ mitogen-activated protein kinase (MAPK) pathway, including but not limited to PTPN11, NRAS, KRAS, HRAS, BRAF, and MAP2K1. Recognized RASopathy conditions include neurofibromatosis type 1 (NF1), Noonan syndrome, capillary malformation-arteriovenous malformation syndrome, Costello syndrome, cardiofacio-cutaneous (CFC) syndrome, LEOPARD syndrome and Legius syndrome. The RASopathies often display overlapping clinical features, presumably owing to common RAS-MAPK signaling pathway activation driving dysregulated cell proliferation. Epidermal nevus syndromes (ENS) are described as the presence of epidermal nevi, in individuals also affected by extra-cutaneous organ system involvement, and there is recent recognition of mosaic RAS mutations as molecular drivers of ENS. Currently, no curative treatments exist for RASopathy driven conditions, but rather symptom-directed management is the currently accepted standard. Here, we detail a unique case of a child exhibiting diffuse spinal nerve root hypertrophy in the context of epidermal nevus syndrome driven by molecularly confirmed KRAS G12D mosaicism, treated with the MEK 1/2 inhibitor selumetinib. Herein, we report the response of this patient to targeted therapy of more than two years' duration, including stabilization of multilevel nerve root hypertrophy as well as significant improvement in epidermal nevi. While the effectiveness of MEK inhibitors such as selumetinib is established in NF1-associated inoperable plexiform neurofibromas, their use in managing hyperactive KRAS-driven epidermal nevi and hypertrophic neuropathy remains unproven, and this case, to our knowledge, is the first such case to be reported. Shared molecular dysregulation and overlapping clinical features between these conditions suggest potential for effective therapeutic application of MEK directed therapy to address a range of conditions resulting from germline and/ or mosaic expression of aberrantly regulated RAS signaling.

Neuropharmacology of Neuropathic Pain: A Systematic Review.

Neuropathic pain, a debilitating condition, remains challenging to manage effectively. An insight into neuropharmacological mechanisms is critical for optimizing treatment strategies. This systematic review aims to evaluate the role of neuropharmacological agents based on their efficacy, involved neurotransmitters, and receptors. A manual literature search was undertaken in PubMed including Medline, Cochrane Library, Google Scholar, Plos One, Science Direct, and clinicaltrials.gov from 2013 until 2023. Out of the 13 included studies, seven evaluated the role of gabapentinoids. Two main drugs from this group, gabapentin and pregabalin, function by binding voltage-gated calcium channels, lowering neuronal hyperexcitability and pain signal transmission, thereby relieving neuropathic pain. Four of the pooled studies reported the use of tricyclic antidepressants (TCAs) including amitriptyline and nortriptyline which work by blocking the reuptake of norepinephrine and serotonin, their increased concentration is thought to be central to their analgesic effect. Three articles assessed the use of serotonin-norepinephrine reuptake inhibitors (SNRIs) and reported them as effective as the TCAs in managing neuropathic pain. They work by augmenting serotonin and norepinephrine. Three studies focused on the use of selective serotonin reuptake inhibitors (SSRIs), modulating their effect by increasing serotonin levels; however, they were reported as not a highly effective treatment option for neuropathic pain. One of the studies outlined the use of cannabinoids for neuropathic pain by binding to cannabinoid receptors with only mild adverse effects. It is concluded that gabapentinoids, TCAs, and SNRIs were reported as the most effective therapy for neuropathic pain; however, for trigeminal neuralgia, anticonvulsants like carbamazepine were considered the most effective. Opioids were considered second-line drugs for neuropathic pain as they come with adverse effects and a risk of dependence. Ongoing research is exploring novel drugs like ion channels and agents modulating pain pathways for neuropathic pain management. Our review hopes to inspire further research into patient stratification by their physiology, aiding quicker and more accurate management of neuropathic pain while minimizing inadvertent side effects.

Increased brain iron deposition in the basial ganglia is associated with cognitive and motor dysfunction in type 2 diabetes mellitus.

OBJECTIVE: Compared with those in type 2 diabetes mellitus (T2DM) patients without diabetic peripheral neuropathy (DPN), alterations in brain iron levels in the basal ganglia (an iron-rich region) and motor and cognitive dysfunction in T2DM patients with DPN have not been fully elucidated. We aimed to explore changes in brain iron levels in the basal ganglia in T2DM patients with DPN using quantitative susceptibility mapping (QSM). METHODS: Thirty-four patients with DPN, fifty-five patients with diabetes without DPN (non-DPN, NDPN), and fifty-one healthy controls (HCs) were recruited and underwent cognitive and motor assessments, blood biochemical tests, and brain QSM imaging. One-way ANOVA was applied to evaluate the variations in cognitive, motor and blood biochemical indicators across the three groups. Then, we performed multiple linear regression analysis to identify the possible factors associated with the significant differences in susceptibility values of the basal ganglia subregions between the two T2DM groups. RESULTS: Susceptibility values in the putamen and the caudate nucleus were greater in the T2DM patients than in the HCs (DPN patients vs. HCs, p < 0.05; NDPN patients vs. HCs, p < 0.05, FDR correction), and there were no significant differences between the DPN patients and NDPN patients. Multiple linear regression analysis revealed that age and history of diabetes played crucialroles in brain iron deposition in the putamen and the caudate nucleus. Notably, DPN in T2DM patients had no effect on brain iron deposition in the putamen or the caudate nucleus. The susceptibility values of the putamen was positively correlated with the Timed Up and Go test score and negatively correlated with gait speed, the Montreal Cognitive Assessment score, and the Symbol Digit Modalities Test score in T2DM patients. CONCLUSIONS: Iron-based susceptibility in the putamen, measured by QSM, can reflect motor function in T2DM patients and might indicate micropathological changes in brain tissue in T2DM patients.

Low muscle strength rather than low muscle mass is associated with cardiovascular autonomic neuropathy in patients with type 2 diabetes.

Several studies have investigated whether sarcopenia is associated with diabetic microvascular complications, but very few have examined associations between sarcopenia and cardiovascular autonomic neuropathy (CAN) in patients with type 2 diabetes mellitus (T2DM). Therefore, we investigated associations of muscle strength (handgrip strength [HGS]) and mass (appendicular skeletal muscle mass index [ASMI]) and CAN in patients with T2DM. We enrolled 342 patients in this retrospective, cross-sectional study. Cardiovascular reflex tests were used to assess CAN according to Ewing's protocol. Relative HGS was determined after normalizing absolute HGS to body weight (HGS/body weight [kg]). We defined low HGS and low ASMI according to a consensus report of the Asian Group for Sarcopenia. Logistic regression analyses were carried out to assess the associations between relative HGS or ASMI quartiles and the presence of CAN in patients with T2DM. The prevalence rates of CAN, low HGS, and low ASMI in the study subjects were 34.8%, 17.3%, and 18.7%, respectively. Low HGS was significantly more prevalent in patients with CAN than those without CAN (23.5% vs. 13.9%, p = 0.025). The CAN scores were significantly and negatively correlated with relative HGS but not with ASMI. Relative HGS was negative correlated with age, glycated hemoglobin, fasting plasma glucose, hsCRP, body mass index, and HOMA-IR and positively correlated with ASMI. The prevalence of CAN gradually increased with decreasing quartile of relative HGS (28.4% in Q4, 31.8% in Q3, 34.2% in Q2, and 45.3% in Q1, p = 0.02 for trend). Multivariable-adjusted prevalence ratios (PRs) for CAN, determined by comparing the first, second, and third quartiles with the fourth quartile of relative HGS, were 4.4 with a 95% confidence interval (95% CI) of [1.1 to 17.3]), 2.3 (95% CI [0.8 to 6.9]), and 1.2 (95% CI [0.4 to 3.7]), respectively. The prevalence of CAN and the PRs (95% [CI]) for CAN based on ASMI were not statistically significant. Our findings suggest that low muscle strength rather than low muscle mass was significantly associated with the presence of CAN. Therefore, HGS testing could help identify patients who would benefit from screening for earlier diagnosis of CAN.

Exploring Outcomes and Mediating Factors Following Supercharged End-to-Side Anterior Interosseous Nerve to Ulnar Nerve Transfer: A Scoping Review With Expert Insight.

Purpose: This scoping review with expert insight aims to map outcome measures following supercharged end-to-side anterior interosseous nerve to ulnar nerve transfer procedures, integrating clinical, patient-reported, and electrodiagnostic measures. It also explores surgical rationale and recovery trajectories, aiming to standardize methodologies and enhance patient care in nerve transfer surgeries. Methods: Our search encompassed multiple online databases, including MEDLINE, Embase, PubMed, and Google Scholar, ensuring rigor and comprehensiveness in identifying relevant literature. Results: Through scrutiny of 17 studies involving 300 patients from 300 articles, along with expert consultations on supercharged end-to-side nerve transfer for ulnar nerve entrapment, promising outcomes emerge, particularly in cubital tunnel syndrome. Primary measures such as Medical Research Council scale assessments and Disabilities of the Arm, Shoulder, and Hand scores demonstrate notable postsurgery improvements, with minor complications noted. Factors influencing recovery include preoperative dysfunction duration and surgical technique. Surgery indications prioritize high ulnar nerve injuries and severe cubital tunnel syndrome. Conclusions: The review highlights the importance of standardized outcome measures, early intervention, and comprehensive rehabilitation for optimizing supercharged end-to-side anterior interosseous nerve to ulnar nerve transfer outcomes. Type of study/level of evidence: Therapeutic IIIa.

Transgenic zebrafish as a model for investigating diabetic peripheral neuropathy: investigation of the role of insulin signaling.

Diabetic peripheral neuropathy (DPN), a complication of diabetes mellitus (DM), is a neurodegenerative disorder that results from hyperglycemic damage and deficient insulin receptor (IR) signaling in peripheral nerves, triggered by failure of insulin production and insulin resistance. IR signaling plays an important role in nutrient metabolism and synaptic formation and maintenance in peripheral neurons. Although several animal models of DPN have been developed to identify new drug candidates using cytotoxic reagents, nutrient-rich diets, and genetic manipulations, a model showing beneficial effects remains to be established. In this study, we aimed to develop a DPN animal model using zebrafish to validate the effects of drug candidates on sensory neuropathy through in vivo imaging during the early larval stage. To achieve this, we generated Tg (ins:gal4p16);Tg (5uas:epNTR-p2a-mcherry) zebrafish using an enhanced potency nitroreductase (epNTR)-mediated chemogenetic ablation system, which showed highly efficient ablation of pancreatic ß-cells following treatment with low-dose metronidazole (MTZ). Using in vivo live imaging, we observed that sensory nerve endings and postsynaptic formation in the peripheral lateral line (PLL) were defective, followed by a disturbance in rheotaxis behavior without any locomotory behavioral changes. Despite defects in sensory nerves and elevated glucose levels, both reactive oxygen species (ROS) levels, a primary cause of DPN, and the number of ganglion cells, remained normal. Furthermore, we found that the activity of mTOR, a downstream target of IR signaling, was decreased in the PLL ganglion cells of the transgenic zebrafish. Our data indicates that peripheral neuropathy results from the loss of IR signaling due to insulin deficiency rather than hyperglycemia alone.

Neurobartonelloses: emerging from obscurity!

BACKGROUND: Bartonella species are fastidious, intracellular bacteria responsible for an expanding array of human pathologies. Most are considered to be transmitted by direct inoculation with infected bodily fluids from a mammalian reservoir species or vector-transmitted through a variety of arthropod species and their excrement. However, there are mounting reports of infection in the absence of documented animal or vector contact. A variety of Bartonella species have been documented in conditions affecting both the peripheral and central nervous systems. More common conditions, including neuroretinitis, are often associated with Bartonella henselae. However, Bartonella quintana, the agent of trench fever, as well as emerging pathogens related to rodent reservoir species, B. grahamii and B. elizabethae, have also been documented. Encephalitis and encephalopathy, also most often associated with B. henselae, have been reported with B. quintana, B. washoensis (ground squirrels) and B. vinsonii subsp. vinsonii (voles) infections. Bartonella infections have also been associated with peripheral neuropathies, such as cranial nerve paresis and neuropathic pain, including infection with less commonly encountered species such as Bartonella koehlerae. Recently, molecular diagnostic testing revealed that DNA from Bartonella spp. was found to be more prevalent in blood of patients with neuropsychiatric disorders such as schizophrenia and psychoses compared to healthy controls. METHODS: A systematic literature search was conducted on PubMed, Google Scholar and Web of Science. Search terms included Bartonella and specific neurological conditions and focused on peer-reviewed case reports published after 2012 pursuant to a prior review, with limited exceptions for conditions not previously covered. Published diagnostic testing, serology, molecular testing or pathology, were necessary for inclusion, except for one case which had clinical and epidemiological evidence consistent with diagnosis along with follow-up. RESULTS: Neurobartonelloses included neuralgic amyotrophy, complex regional pain syndrome, chronic inflammatory demyelinating polyneuropathy, cranial nerve paralysis, Guillain-Barré syndrome, peripheral vasculitic polyneuropathy, acute transverse myelopathy, neuroretinitis, encephalitis/encephalopathy, cerebral vasculitis/aneurysm and neuropsychiatric conditions. CONCLUSIONS: The breadth of reported symptoms and clinical syndromes associated with an increasing number of Bartonella species continues to expand. Increased clinical awareness of this important zoonotic pathogen is necessary to advance One Health among the medical and veterinary communities.

Exploring social determinants of health on chemotherapy-induced peripheral neuropathy severity in ovarian cancer: An integrative review.

Ovarian cancer remains a significant public health concern for women despite advancements in cancer management. Despite comprising only 2.5 % of cancers in women, ovarian cancer ranks as the fifth leading cause of cancer-related deaths among women, with patients frequently receiving late diagnoses. Chemotherapy, a primary treatment, frequently causes chemotherapy-induced peripheral neuropathy (CIPN), affecting over 60 % of patients and leading to severe sensory, motor, and autonomic nerve impairments. This often necessitates dosage reduction or discontinuation of treatment, thereby increasing mortality. While CIPN's impact on patients is well-documented, there is a paucity of knowledge of how structural and intermediary social determinants of health factors (SDOH), such as socioeconomic and political context, material circumstances such as living and walking conditions, area deprivation, and food availability, affect CIPN severity. The aim of this article was to explore the association between various SDOH and CIPN severity in ovarian cancer, identifying potential research gaps and future research directions. This article seeks to inform targeted interventions to mitigate CIPN's impact by elucidating these associations.

Isolated Trigeminal Mononeuropathy: A Possible COVID-19 Sequelae.

COVID-19 infections have been linked with multiple neurological manifestations. One of the infrequent complications of post-COVID-19 infection is trigeminal neuropathy. Despite its infrequency, few cases of trigeminal neuropathy following COVID-19 infection have been documented in the literature. However, there remains a paucity of evidence regarding isolated trigeminal neuropathy following COVID-19, particularly in cases devoid of pain but characterized by sensory deficits such as loss of sensation and paresthesia only. We describe a clinical case of trigeminal neuropathy that emerged after a COVID-19 infection at our institution. Our case report delves into the clinical presentation of such trigeminal neuropathy that would aid clinicians in including this pathology in their differential diagnosis.

A RETREG1 variant is associated with hereditary sensory and autonomic neuropathy with acral self-mutilation in purebred German Spitz.

Hereditary sensory and autonomic neuropathies (HSAN) represent a group of genetic diseases affecting the peripheral nervous system. In humans, at least 16 loci have been associated with the disorder but do not explain the disease origin of all patients. In dogs, similar conditions have been documented for decades in various breeds with a severe impact on life quality and are often referred to as acral mutilation syndrome (AMS). Causal variants in three genes have been identified to date, suggesting larger genetic heterogeneity in the dog population. Our aim was to explain the genetic etiology of an early-onset HSAN/AMS in a purebred German Spitz. The affected dog showed progressive loss of pain sensation in the distal extremities, which led to intense licking, biting, and self-mutilation of digits and paw pads. Whole-genome sequencing identified a single candidate causal variant on chromosome 4 in the RETREG1 gene (c.656C>T, p.Pro219Leu). This missense variant was previously recognized as deleterious in a mixed breed dog family with similar clinical signs. Haplotype analyses and targeted genotyping revealed a likely German Spitz ancestry of these mixed breed dogs. Further screening of an extensive cohort of ~900 000 dogs of various breeds hinted at the variant allele origin in the German Spitz breed. Disruption of RETREG1 inhibits endoplasmic reticulum turnover and leads to neuron degeneration. Our findings provide evidence that this variant underlies the recessive form of HSAN/AMS in the German Spitz and support the use of whole-genome sequencing-based veterinary precision medicine for early diagnosis and prevention via a genetic test.

Acupuncture as Adjuvant Therapy for Glaucoma: Protocol for a Randomized Controlled Trial.

BACKGROUND: Glaucoma is a chronic progressive optic neuropathy that necessitates lifelong treatment to reduce the decline of the optic nerve. Due to the extended and continuous treatments required for patients, complementary therapies are often considered alongside conventional treatments to enhance the effectiveness of the treatment. Acupuncture has demonstrated the potential to lower intraocular pressure in previous clinical trials, making it a promising glaucoma intervention. OBJECTIVE: The primary objective of this study is to conduct a single-center randomized control trial involving patients with glaucoma. Acupuncture will be evaluated as an adjunctive therapy. The trial aims to explore its effectiveness for glaucoma. METHODS: In this single-center randomized controlled trial, participants (N=50) with primary open-angle glaucoma will be randomly assigned to the treatment group, receiving ophthalmic acupuncture with "De Qi" sensation, or the control group, receiving minimum acupuncture stimulation on nonophthalmic acupoints. The intervention will consist of weekly acupuncture treatments for a total of 6 sessions. Participants will be assessed at 8 time points, which are baseline, during the intervention (6 times), and at a 3-month follow-up. The primary outcome measure is a change in the intraocular pressure before and after each acupuncture treatment. Secondary outcomes will include measurements of heart rate and blood pressure before and after acupuncture, best-corrected visual acuity, visual field, optical coherence tomography, optical coherence tomography angiography, the Glaucoma Symptom Scale, and the Glaucoma Quality of Life-15 questionnaire. RESULTS: Recruitment of participants for the trial commenced on June 28, 2023. A total of 10 participants have been enrolled to test the feasibility of the experiment. We anticipate that the preliminary data from this trial will be completed by December 2025. CONCLUSIONS: This trial uses rigorous methodology and comprehensive outcome measurements to assess the clinical efficacy of acupuncture as an adjunctive therapy for glaucoma, providing valuable insights for future clinical treatment guidelines. TRIAL REGISTRATION: ClinicalTrials.gov NCT05753137; https://clinicaltrials.gov/study/NCT05753137. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/57888.

Pedal Vessel Calcification and Risk of Major Adverse Foot Events in the Diabetic Neuropathic, Nephropathic Foot.

AIMS: We aimed to determine the relative risk of pedal vessel calcification (PVC) on major adverse foot events (MAFEs) and chronic kidney disease (CKD) stage in patients with diabetes mellitus (DM) and peripheral neuropathy (PN). METHODS: Retrospective electronic medical record review of 152 patients with diagnoses of DM, PN, and CKD stages 1-5 who had at least one foot x-ray obtained. PVC was scored (from 0-4) based on foot anatomic location and radiology reported MAFEs, which includes foot fracture, Charcot neuroarthropathy, foot ulcer, osteomyelitis, or minor amputation. Risk ratios (RR) with 95% confidence intervals (95% CI) and Poisson regressions were performed assessing the risk of sustaining MAFEs with number of PVCs and stage of CKD. RESULTS: The risk of any MAFE increased as PVC score increased (RR = 1.23); the risk of any MAFE increased as CKD stage increased (RR = 1.35); and risk of any PVC increased as CKD stage increased (RR = 1.71). CONCLUSIONS: Pedal vessel calcification (PVC) on a foot radiograph increases the risk of any MAFE and increases with progressive stage of CKD. PVC may serve as a gateway to prompt investigation, treatment, or referral for at-risk diabetic neuropathic, nephropathic patients.

The Association Between Vitamin B12 Deficiency and Diabetic Foot Ulcer in Type 2 Diabetic Patients in Qassim Province, Saudi Arabia: A Case-Control Study.

Background Diabetic foot ulcer (DFU) is a major complication of diabetes with many identified risk factors. These include poor control of diabetes, cardiovascular disease, smoking, and end-stage kidney disease. This study aims to shed light on the micronutrient status of diabetic patients and its effect on DFU, particularly, the association between vitamin B12 deficiency and DFU. Methodology This retrospective case-control study included adults in Buraydah who were at least 18 years old and had type 2 diabetes mellitus. Data were obtained from the electronic files of the patients who visited the diabetes center from January 2018 to August 2023 and were analyzed using SPSS version 27.0.1 (IBM Corp., Armonk, NY, USA). Results The research involved 221 participants, with 114 controls (individuals with diabetes but no DFU), and 107 cases (individuals with diabetes affected by DFU). Vitamin B12 levels varied, with 79.2% falling within the normal range of 187-883 pg/mL. The average age of cases (58.5 years, SD = 11.3) was notably higher than that of controls (54.1 years, SD = 14.1). Glycated hemoglobin levels were significantly higher in cases (8.7, SD = 2.0) compared to controls (7.6, SD = 2.2) (p < 0.001). Regarding physical activity, cases showed a significantly higher percentage of inactivity (62.1%) compared to controls (39.1%) (p = 0.046). Neuropathy exhibited a significant association with ulcer development, with 59.1% of cases having neuropathy compared to 23.5% of controls (p < 0.001). Furthermore, complications such as dry foot and fissures (60.0% vs. 6.3%), Charcot joint (36.8% vs. 12.2%), and foot trauma (40.9% vs. 3.9%) were significantly more prevalent in cases compared to controls (p < 0.001 for all). Conclusions The significant associations observed with advanced age, uncontrolled diabetes, longer diabetes duration, neuropathy, and specific foot complications underscore the multifactorial nature of ulcer development. The normal levels of vitamin B12 in most patients reflect no positive impact of normalized vitamin B12 levels on DFU. However, further observational studies with multiple vitamin B12 readings over a longer period are needed to establish its association with DFU development.

Periocular Involvement in Trigeminal Trophic Syndrome.

Trigeminal trophic syndrome (TTS) is an uncommon condition resulting from trigeminal nerve damage, characterized by persistent facial ulceration, loss of sensation, and paresthesia within the trigeminal dermatome, with ala nasi involvement being a key feature. Lesions develop from repeated self-inflicted manipulation and trauma of the dysesthetic skin. This report details three cases of TTS, highlighting periocular changes, with etiologies varying from cerebrovascular accidents to herpes zoster ophthalmicus.

Isoniazid-historical development, metabolism associated toxicity and a perspective on its pharmacological improvement.

Despite the extraordinary anti-tubercular activity of isoniazid (INH), the drug-induced hepatotoxicity and peripheral neuropathy pose a significant challenge to its wider clinical use. The primary cause of INH-induced hepatotoxicity is in vivo metabolism involving biotransformation on its terminal -NH2 group owing to its high nucleophilic nature. The human N-acetyltransferase-2 enzyme (NAT-2) exploits the reactivity of INH's terminal -NH2 functional group and inactivates it by transferring the acetyl group, which subsequently converts to toxic metabolites. This -NH2 group also tends to react with vital endogenous molecules such as pyridoxine, leading to their deficiency, a major cause of peripheral neuropathy. The elevation of liver functional markers is observed in 10%-20% of subjects on INH treatment. INH-induced risk of fatal hepatitis is about 0.05%-1%. The incidence of peripheral neuropathy is 2%-6.5%. In this review, we discuss the genesis and historical development of INH, and different reported mechanisms of action of INH. This is followed by a brief review of various clinical trials in chronological order, highlighting treatment-associated adverse events and their occurrence rates, including details such as geographical location, number of subjects, dosing concentration, and regimen used in these clinical studies. Further, we elaborated on various known metabolic transformations highlighting the involvement of the terminal -NH2 group of INH and corresponding host enzymes, the structure of different metabolites/conjugates, and their association with hepatotoxicity or neuritis. Post this deliberation, we propose a hydrolysable chemical derivatives-based approach as a way forward to restrict this metabolism.

Recognizing Leber's Hereditary Optic Neuropathy to avoid delayed diagnosis and misdiagnosis.

Leber's Hereditary Optic Neuropathy (LHON) is a maternally inherited optic nerve disease primarily caused by mutations in mitochondrial DNA (mtDNA). The peak of onset is typically between 15 and 30 years, but variability exists. Misdiagnosis, often as inflammatory optic neuritis, delays treatment, compounded by challenges in timely genetic diagnosis. Given the availability of a specific treatment for LHON, its early diagnosis is imperative to ensure therapeutic appropriateness. This work gives an updated guidance about LHON differential diagnosis to clinicians dealing also with multiple sclerosi and neuromyelitis optica spectrtum disorders-related optic neuritis. LHON diagnosis relies on clinical signs and paraclinical evaluations. Differential diagnosis in the acute phase primarily involves distinguishing inflammatory optic neuropathies, considering clinical clues such as ocular pain, fundus appearance and visual recovery. Imaging analysis obtained with Optical Coherence Tomography (OCT) assists clinicians in early recognition of LHON and help avoiding misdiagnosis. Genetic testing for the three most common LHON mutations is recommended initially, followed by comprehensive mtDNA sequencing if suspicion persists despite negative results. We present and discuss crucial strategies for accurate diagnosis and management of LHON cases.

Clinical Profile, Risk Factors, and Complications in Young-Onset Type 2 Diabetes Mellitus.

Background Young-onset type 2 diabetes mellitus (T2DM), defined as a diagnosis before the age of 45, is an increasingly common and aggressive form of diabetes. This population is at a heightened risk of developing complications earlier in life due to longer disease duration and often suboptimal glycemic control. Complications such as diabetic neuropathy, retinopathy, and nephropathy are significant concerns, leading to reduced quality of life and increased morbidity. Objective To investigate the clinical profile and risk factors associated with complications of young-onset T2DM and to analyze the correlation between the age of onset and other parameters and the development of these complications. Methods We conducted a cross-sectional study on young-onset T2DM patients (<45 years) to investigate the prevalence and associated factors of diabetic complications. Variables analyzed included age, gender, BMI, waist-hip ratio, duration of diabetes, age at diagnosis, proteinuria, and glycosuria, along with biochemical markers such as HbA1C (glycated hemoglobin), serum cholesterol, triglycerides, and C-peptide levels. Results The average age of participants in our study was 34.76 ± 6.91 years. The mean BMI was 26.68 ± 3.35, with a mean cholesterol level of 169.84 ± 55.64 and a mean triglyceride level of 205.79 ± 67.49. The average HbA1c level was 9.82 ± 2.44. Diabetic neuropathy was found to increase significantly with advancing age (p < 0.001), longer duration of diabetes (p < 0.001), higher mean levels of HbA1C (p < 0.001), serum cholesterol (p = 0.006), and serum triglycerides (p = 0.010), as well as with lower levels of serum C-peptide (p = 0.025). The severity of kidney damage showed a significant association with older age (p = 0.049), longer diabetes duration (p < 0.01), elevated mean levels of HbA1C (p = 0.0002), and serum cholesterol (p = 0.0310). Diabetic retinopathy increased significantly with advancing age (p < 0.001), longer diabetes duration (p < 0.001), higher mean levels of HbA1C (p < 0.001), and serum triglycerides (p = 0.013). Conclusion Young-onset T2DM is associated with significant risks for neuropathy, retinopathy, and nephropathy, particularly with increasing age and longer disease duration. Higher HbA1C, serum cholesterol, and triglyceride levels are prevalent among those with complications. These findings underscore the need for early intervention and targeted management strategies to mitigate complications in this high-risk population.