Serum SARM1 Levels and Diabetic Peripheral Neuropathy in Type 2 Diabetes: Correlation with Clinical Neuropathy Scales and Nerve Conduction Studies and Impact of COVID-19 vaccination.

Patients with peripheral neuropathy with type 2 diabetes mellitus (T2DM) are more likely to have functional impairments. Recently, the gene for serum sterile alpha and toll/interleukin receptor motif-containing protein 1 (SARM1), which may contribute to the pathogenesis of Wallerian degeneration, was discovered in mice models of peripheral neuropathy. We set out to assess serum SARM1's activity as a potential biomarker for the early identification of diabetic peripheral neuropathy in T2DM patients while also examining the impact of the COVID-19 vaccine on SARM1 levels. We assessed the cross-sectional relationships between the SARM1 biomarker, clinical neuropathy scales, and nerve conduction parameters in 80 participants aged between 30 years and 60 years. The analysis was carried out after the patients were split into two groups since we discovered a significant increase in SARM1 levels following the second dose of the COVID-19 vaccination, where group A received one dose of the COVID-19 vaccine inoculation, and group B received two doses of the COVID-19 vaccine. SARM1 was correlated significantly (p < 0.05) with MNSIe and NSS in group A and showed a consistent positive correlation with the other neuropathy clinical scales in group A and group B without reaching statistical significance. Additionally, SARM1 was negatively correlated significantly (p < 0.05) with the median sensory amplitude in group A and showed a consistent negative correlation with the six other sensory and motor nerves' potential amplitude in group A and group B without reaching statistical significance. In conclusion, SARM1 showed a consistent correlation with clinical neuropathy scales and nerve conduction parameters after accounting for the influence of COVID-19 vaccination doses.

Association of Hematological Parameters and Diabetic Neuropathy: A Retrospective Study.

Background: Diabetic neuropathy (DN) is a common complication of type 2 diabetes (T2DM) and is characterized by persistent inflammation. Hematological parameters have emerged as a novel marker for detecting chronic inflammatory conditions, including diabetes. Aim: We aim to examine the association between HbA1c levels, which can indicate the presence of diabetic neuropathy, and hematological parameters to explore the possibility of using hematological parameters as a new indicator for DN in T2DM patients. Methods: This was a retrospective study of 768 (483 males and 284 females) medical records of adult T2DM patients with or without neuropathy who attending the outpatient neuromuscular clinic at King Abdul-Aziz University Hospital from January 2016 to December 2021. Results: The results showed significant increases in HbA1c levels (p=0.000), lymphocyte levels (p=0.028), and the neutrophil-lymphocyte ratio (NLR) (p=0.011). In the T2DM group, HBA1C levels were found to be positively correlated with age (r=0.306, p=0.000), neutrophil (NEUT) (r=0. 287, p=0.000), platelet (PLT) (r=0. 148, p=0.039), and neutrophil-lymphocyte ratio (NLR) (r=0.306193, p=0.0007), and negatively correlated with gender (r=-0.306193, p=0.0007). In the T2DMN group, HBA1C levels showed a positive correlation with hemoglobin (HB) (r=0.084, p=0.045), PLT (r=0.087, p=0.037), and PLT/mean corpuscular hemoglobin (MCH) ratio (PLT/MCH ratio) (r=0.12, p=0.004), and a negative correlation with age (r=-0.204, p=0.000), gender (r=-0.086, p=0.041), weight (WT) (r=-0.113, p=0.007), Body Surface Area (BSA) (r=-0.09, p=0.031), mean corpuscular volume (MCV) (r=-0.292, p=0.000), and MCH (r=-0.186, p=0.000). Conclusion: Our study found a significant association between HbA1c, a biomarker for diabetic neuropathy, and various hematological parameters (HB, MCV, MCH, PLT, PLT/MCH ratio) in T2DMN patients. By effectively controlling and monitoring these variables, it may be feasible to prevent or delay the progression of peripheral neuropathy in diabetic patients. However, further research is needed to validate these findings.

Values and diagnostic accuracy of sensory nerve action potentials in control participants and participants with diabetes with and without clinical diabetic neuropathy, based on neuropathy scale measurements.

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.

Utility of Initial Arterial Blood Gas in Neuromuscular versus Non-Neuromuscular Acute Respiratory Failure in Intensive Care Unit Patients.

Background: The arterial blood gas (ABG) parameters of patients admitted to intensive care units (ICUs) with acute neuromuscular respiratory failure (NMRF) and non-NMRF have not been defined or compared in the literature. Methods: We retrospectively collected the initial ABG parameters (pH, PaCO2, PaO2, and HCO3) of patients admitted to ICUs with acute respiratory failure. We compared ABG parameter ranges and the prevalence of abnormalities in NMRF versus non-NMRF and its categories, including primary pulmonary disease (PPD) (chronic obstructive pulmonary disease, asthma, and bronchiectasis), pneumonia, and pulmonary edema. Results: We included 287 patients (NMRF, n = 69; non-NMRF, n = 218). The difference between NMRF and non-NMRF included the median (interquartile range (IQR)) of pH (7.39 (7.32−7.43), 7.33 (7.22−7.39), p < 0.001), PaO2 (86.9 (71.4−123), 79.6 (64.6−99.1) mmHg, p = 0.02), and HCO3 (24.85 (22.9−27.8), 23.4 (19.4−26.8) mmol/L, p = 0.006). We found differences in the median of PaCO2 in NMRF (41.5 mmHg) versus PPD (63.3 mmHg), PaO2 in NMRF (86.9 mmHg) versus pneumonia (74.3 mmHg), and HCO3 in NMRF (24.8 mmol/L) versus pulmonary edema (20.9 mmol/L) (all p < 0.01). NMRF compared to non-NMRF patients had a lower frequency of hypercarbia (24.6% versus 39.9%) and hypoxia (33.8% versus 50.5%) (all p < 0.05). NMRF compared to PPD patients had lower frequency of combined hypoxia and hypercarbia (13.2% versus 37.8%) but more frequently isolated high bicarbonate (33.8% versus 8.9%) (all p < 0.001). Conclusions: The ranges of ABG changes in NMRF patients differed from those of non-NMRF patients, with a greater reduction in PaO2 in non-NMRF than in NMRF patients. Combined hypoxemia and hypercarbia were most frequent in PPD patients, whereas isolated high bicarbonate was most frequent in NMRF patients.

Translation, validation, and diagnostic accuracy of the Arabic version of the Michigan neuropathy screening instrument.

ABSTRACT: The Michigan Neuropathy Screening Instrument (MNSI) is used to screen patients for diabetic neuropathy (DNP). We aimed to translate the MNSI questionnaire into Arabic (MNSIq-Ar) and to assess the validity and diagnostic performance of the MNSI Arabic version (MNSI-Ar).Cronbach alpha α and the interclass correlation coefficient were used to measure the reliability and reproducibility of the MNSIq-Ar. The instrument's validity was assessed by Spearman correlation with the Utah Early Neuropathy Scale (UENS), the Modified Toronto Neuropathy Score (mTCNS), diabetic neuropathy symptoms (DNS), and sural nerve amplitude (SNA). The construct validity of the MNSI-Ar was assessed by its ability to differentiate the severity of DNP (using the Kruskal-Wallis test). The diagnostic performance was assessed through the receiver operator curve area.We recruited 89 participants (mean [SD] age, 50.8 [12.3] years; 48% men). The MNSIq-Ar showed an α of 0.81 and intraclass correlation coefficient = 0.94, and the correlation coefficients with UENS, mTCNS, DNS, and sural nerve amplitude were 0.67, 0.83, 0.73, and -0.49, respectively (all P < .0001). The MNSI-Ar was able to differentiate the different severities of DNP. The receiver operator curve area was 0.93 with a high sensitivity of 95.9% and 100% for probable and confirmed DNP, respectively.MNSI-Ar is a reliable and valid tool to screen for diabetic neuropathy in the Arabic language with a good diagnostic performance and high sensitivity.

Clinical features and outcome of Guillain-Barre syndrome in Saudi Arabia: a multicenter, retrospective study.

BACKGROUND: Guillain-Barre syndrome (GBS) is an inflammatory polyradiculoneuropathy characterized by rapidly evolving weakness and areflexia, reaching nadir within 4 weeks. Data on the characteristic of GBS in Saudi Arabia are limited. This study aimed to describe the clinical, electrophysiological, and laboratory characteristics and outcome of a multicenter cohort of patients with GBS. METHODS: This is a retrospective multicenter nationwide study. Patients who had GBS, identified through Brighton Criteria, between January 2015 and December 2019 were included. Data collected included demographics, clinical features, cerebrospinal fluid profile, reported electrophysiological patterns, treatment, and outcome. Reported GBS subtypes were compared using chi-square, Fisher's exact, or Mann-Whitney U tests, as appropriate. RESULTS: A total of 156 patients with GBS were included (men, 61.5%), with a median age of 38 (interquartile range, 26.25-53.5) years. The most commonly reported antecedent illnesses were upper respiratory tract infection (39.1%) and diarrhea (27.8%). All but two patients (98.7%) had weakness, 64.1% had sensory symptoms, 43.1% had facial diplegia, 33.8% had oropharyngeal weakness, 12.4% had ophthalmoplegia, and 26.3% needed mechanical ventilation. Cytoalbuminological dissociation was observed in 69.1% of the patients. GBS-specific therapy was administered in 96.8% of the patients, of whom 88.1% had intravenous immunoglobulin, and 11.9% had plasmapheresis. Approximately half of the patients were able to walk independently within 9 months after discharge, and a third regained the ability to walk independently thereafter. Death of one patient was caused by septicemia. Acute inflammatory demyelinating polyradiculoneuropathy was the most commonly reported GBS subtype (37.7%), followed by acute motor axonal neuropathy (29.5%), and acute motor-sensory axonal neuropathy (19.2%). CONCLUSION: The clinical and laboratory characteristics and outcome of GBS in the Arab population of Saudi Arabia are similar to the international cohorts. The overall prognosis is favorable.

A novel DOK7 mutation causing congenital myasthenic syndrome with limb-girdle weakness: case series of three family members.

Congenital myasthenia syndrome (CMS) is a group of heterogeneous diseases affecting the neuromuscular endplate. CMS has a considerably different phenotypic presentations, with the onset time ranging from early infancy to late adulthood. Here, we report a case of a CMS due to a new DOK7 mutation in a 28-year-old man and two of his sisters, who have a pure limb-girdle weakness. DOK7 CMS has a varying presentation. Typically, the onset occurs in childhood with ptosis, bulbar symptoms, difficulty walking, weakness, and gait abnormality. This case sheds light on a novel DOK7 gene mutation with a unique presentation of CMS and provides insight into its unique phenotypic presentation.

The Assessment of Major Histocompatibility Complex (MHC) Class-I Expression in Different Neuromuscular Diseases.

BACKGROUND: Major histocompatibility complex (MHC) class-1 antigen is a glycoprotein expressed in all nucleated cells. The aim of this study was to assess MHC class-I expression in different neuromuscular diseases. METHODS: The authors reviewed the data of 54 patients with neuromuscular diseases. Anti MHC class-I antibody was performed on the frozen muscle tissues using immunohistochemistry. MHC class-I was scored based on its expression on muscle fibers (0: normal, 1: expression <5 fibers, 2: expression in 5-10 fibers, 3: expression in >10 fibers). The pattern was only assessed in cases with MHC class-I scored 3 as: (1: Sarcocapillary, 2: Sarcocapillary and necrotic fibers, 3: Perifascicular). The relationship between MHC class-I expression and neuromuscular diseases was statistically analyzed. RESULTS: The mean age of the patients was 39.1 ± 18.5 years. Around 50% of patients showed normal CK levels and 5% of the cases showed elevated CK levels. There was a significance difference in MHC class-I expression between cases with normal and elevated CK levels when MHC class-I score was 3 (p= 0.020). There was a significant difference in MHC class-I expression among different neuromuscular diseases (p<0.001). All cases with idiopathic inflammatory myopathies (IIMs) have expressed MHC class-I in more than 10 fibers. MHC class-I was expressed in 15 cases of non-IIMs. CONCLUSION: MHC class-I cannot be solely used as a biomarker to distinguish IIMs from non-IIMs. The presence of MHC class-I molecules in non-IIMs might be related to immunoproteasomes mechanism. Further studies, with different muscle proteins expression and genomic sequencing, must be conducted to understand the role of MHC Class-I in neuromuscular diseases.

Efficacy and safety of mirogabalin treatment in patients with diabetic peripheral neuropathic pain: A systematic review and meta-analysis of randomised controlled trials.

AIM: We aimed to perform a systematic review and meta-analysis to examine the efficacy and safety of mirogabalin in patients with diabetic peripheral neuropathic pain (DPNP). METHODS: We searched four databases from inception to 1st July 2020. We included all randomised controlled trials (RCTs) which assessed the effectiveness and safety of mirogabalin in patients with DPNP. We evaluated the quality of the included RCTs using the Cochrane risk of bias assessment tool. We pooled dichotomous outcomes as risk ratios and continuous outcomes as mean differences with 95% confidence intervals, both under the random- or fixed-effects model. RESULTS: Three RCTs matched our inclusion criteria with a total of 1732 patients with DPNP: 1057, 534 and 141 patients received mirogabalin, placebo and pregabalin, respectively. The quality of included RCTs was marked as moderate-to-high. Mirogabalin treatment was significantly associated with a significant reduction in the average daily pain score (ADPS) compared with placebo over 7 weeks. Compared with pregabalin, mirogabalin was significantly associated with more decrease in ADPS only after 3, 4 and 5 weeks. The proportion of patients with ≥30% and ≥50% reduction in the ADPS was significantly higher in the mirogabalin vs placebo and pregabalin groups. Compared with placebo, mirogabalin was significantly associated with more adverse events of dizziness, increased weight, peripheral oedema and somnolence. The safety profile was comparable between mirogabalin and pregabalin. CONCLUSIONS: Our systematic review and meta-analysis revealed that in patients with DPNP, mirogabalin treatment was superior to placebo and pregabalin in decreasing the ADPS over time. Besides, mirogabalin was largely safe and associated with some adverse events that could be managed conservatively.

Amyotrophic lateral sclerosis care in Saudi Arabia: A survey of providers' perceptions.

OBJECTIVE: Provision of care for patients with amyotrophic lateral sclerosis (ALS) is complex and requires the contribution of multiple healthcare professionals. Several international ALS care measures were developed to ensure optimal care for ALS patients. We looked at the rate of inconsistency in providing standard ALS care measures in Saudi Arabia (SA). METHODS: A 5-point response survey was distributed to practicing neurologists in SA. They were asked to grade their perceived consistency of accessibility for 19 items of ALS care measures at their center. The list of ALS care measures items was derived from international ALS guidelines. RESULTS: The response rate from neurologists was 47.3% (62/131), and the responses of 39 neurologists who follow ALS cases were included. Most of the selected ALS care measure items, 63.1% (12/19), were perceived by 50% or more of the ALS care providers to be not consistently accessible to their patients. The perception of ALS care providers of the inconsistent accessibility for ALS patients to ALS care measures was high for communication devices (92.3%), supportive equipment such as motorized wheelchairs (76.9%), end-of-life discussion (74.4%), and respiratory monitoring (66.7%). CONCLUSION: Our data show that ALS patients in SA do not have consistent access to the recommended ALS care measures.

Stiff-Person Syndrome Outpatient Rehabilitation: Case Report.

Stiff-person syndrome (SPS) is a rare neurological disorder that causes muscle rigidity and stiffness of the trunk and proximal limb muscles, leading to movement difficulties and impaired function. Due to the rarity of the disease, studies on the benefit of rehabilitation for this disorder are quite limited. A 46-year-old female patient diagnosed with SPS complained of imbalance and movement difficulty. We prescribed therapeutic exercises aimed to reduce the stiffness of the trunk and proximal limbs and improve her function. Baseline measurement of the patient's range of motion, muscle power and tone, balance and functional abilities were taken pre- and post-program. Outcome measures showed a general improvement in the patient's muscle flexibility, balance, and functionality.

Brucellosis causing subacute motor polyradiculopathy and the pathological correlation of pseudomyopathic electromyography: A case report.

INTRODUCTION: Brucellosis is a rare cause of polyradiculopathy. We aim to present a case of subacute motor polyradiculopathy (SAMPR), along with the electromyographic pseudomyopathic changes, and their histopathological correlation. CASE PRESENTATION: A 24-year-old man presented with gradually progressive bilateral lower limb weakness for three weeks that progressed to a loss of ambulation in seven weeks. He had no ocular, facial, or sphincteric weakness and no sensory symptoms. He showed normal cognitive, cranial nerve, and upper limb exams. His lower limb power was medical research council (MRC) grade 3 proximally, and 4 distally. His reflexes were grade 2+ in the upper limbs and grade 0 in the lower limbs. The nerve conduction studies were normal. Electromyography (EMG) showed active denervation with a short-duration motor unit potential (MUP) and early recruitment. MRI showed a diffuse enhancement of the lumbosacral nerve roots. Cerebrospinal fluid (CSF) showed a protein of 2.7 g/L and a white blood cells (WBC) count of 420 cells per microliter. Muscle biopsy revealed neurogenic changes with secondary degenerating and regenerating fibers, explaining the small and short MUPs in the EMG. CSF grew Brucella after fourteen days of incubation. Serum showed high antibody titers for the Brucella species "Melitensis" and "Abortus". The patient started to walk again, ten months after starting a course of antibiotics. CONCLUSION: Neurobrucellosis can present primarily as SAMPR, sparing the sensory system. SAMPR, with ongoing degenerating and regenerating muscle fibers, may explain the pseudomyopathic changes found in electromyographic studies.

Carpal Tunnel Decompression Surgery Outcome and Effect of Diabetes.

OBJECTIVE: The benefits of carpal tunnel decompressive surgery (CTDS) among diabetic patients with carpal tunnel syndrome (CTS) were previously investigated through comparing the outcome before and after CTDS, and in comparison to nondiabetic CTS. We sought to investigate if diabetes mitigates the benefits of CTDS compared to not receiving CTDS. METHODS: In this retrospective study, we compared the risk of reporting any unfavorable outcomes among CTS patients (diabetic and nondiabetic) who underwent CTDS versus no CTDS after controlling for diabetes. We also compared the risk of reporting any unfavorable outcomes (waking up at night, pain during the day or during daily activities, or hand weakness) among diabetic CTS patients who underwent CTDS versus no CTDS after controlling for severity. RESULTS: We included 207 patients; of these, 105 patients had CTDS and 102 did not. There were 60 diabetic and 147 nondiabetic patients. The risk of any unfavorable outcomes was reduced by CTDS from 83.3 to 66.6%, with an odds ratio (OR), after controlling for diabetes, of 0.39 (95% confidence interval [CI] 0.20-0.78). Among diabetic patients, there was no difference between the CTDS and non-CTDS groups in the risk of reporting any unfavorable outcomes; however, after adjustment for severity, the risk of hand weakness was less with CTDS, with an OR of 0.13 (95% CI 0.02-0.86). CONCLUSION: Diabetes did not mitigate the benefits of CTDS. CTDS may prevent hand weakness among diabetic CTS patients.

Acute Paralytic Post-Bariatric Surgery Axonal Polyneuropathy: Clinical Features and Outcome.

INTRODUCTION: The syndrome of post-bariatric surgery axonal polyneuropathy (PAP) may present with various sensory and motor symptoms including paralysis. We aim to describe the diagnostic features and outcome of treatment of the acute paralytic form of PAP (acute paralytic PAP [APPAP]) as it was not described in a separate cohort previously. METHODS: We retrospectively reviewed medical charts and described the clinical, electrodiagnostic features, treatment, and outcome for patients who presented to our clinical neurophysiology unit with disabling weakness within 24 months post-bariatric surgery. The main outcome measure was the percent of patients who are able to walk independently at the last visit and comparing the group who resumed walking independently at 6 months to the group who did not, in regards to the use of intravenous immunoglobulin (IVIg). RESULTS: Thirteen patients were included (10 women and 3 men) with a mean age of 29.8 years (SD 12.5). All presented with loss of ambulation resembling Guillain-Barre Syndrome. The median time of onset was 4 months (interquartile range [IQR] 3-6) post-surgery, and the median time to weakness nadir was 3 weeks (IQR 3-3.5) with an average weight loss of 38.6 kg (SD 17.09). All patients regained their ability to ambulate; however, the ability to walk independently was achieved in 66.7% of patients. The percent of patients who were able to ambulate independently at 6 months were 16% with IVIg versus 66.7% without IVIg. CONCLUSION: The syndrome of -APPAP develops in the first-year post-bariatric surgery. The majority of patients regain independent ambulation.