Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive degeneration of upper and lower motor neurons. The heterogeneous nature of ALS at the clinical, genetic, and pathological levels makes it challenging to develop diagnostic and prognostic tools that fit all disease phenotypes. Limitations associated with the functional scales and the qualitative nature of mainstay electrophysiological testing prompt the investigation of more objective quantitative assessment. Biofluid biomarkers have the potential to fill that gap by providing evidence of a disease process potentially early in the disease, its progression, and its response to therapy. In contrast to other neurodegenerative diseases, no biomarker has yet been validated in clinical use for ALS. Several fluid biomarkers have been investigated in clinical studies in ALS. Biofluid biomarkers reflect the different pathophysiological processes, from protein aggregation to muscle denervation. This review takes a pathophysiologic approach to summarizing the findings of clinical studies utilizing quantitative biofluid biomarkers in ALS, discusses the utility and shortcomings of each biomarker, and highlights the superiority of neurofilaments as biomarkers of neurodegeneration over other candidate biomarkers.

Status epilepticus occurs when a seizure lasts more than five minutes or when multiple seizures occur with incomplete return to baseline. SE induces a myriad of pathological changes involving synaptic and extra-synaptic factors. The transition from a self-limiting seizure to a self-sustaining one is established by maladaptive receptor trafficking, whereby GABA_A receptors are progressively endocytosed while glutamatergic receptors (NMDA and AMPA) are transported to the synaptic membrane, causing excitotoxicity and alteration in glutamate-dependent downstream signaling. The subsequent influx of Ca²⁺ exposes neurons to increased levels of [Ca²⁺]i, which overwhelms mitochondrial buffering, resulting in irreversible mitochondrial membrane depolarization and mitochondrial injury. Oxidative stress resulting from mitochondrial leakage and increased production of reactive oxygen species activates the inflammasome and induces a damage-associated molecular pattern. Neuroinflammation perpetuates oxidative stress and exacerbates mitochondrial injury, thereby jeopardizing mitochondrial energy supply in a state of accelerated ATP consumption. Additionally, Ca²⁺ overload can directly damage neurons by activating enzymes involved in the breakdown of proteins, phospholipids, and nucleic acids. The cumulative effect of these effector pathways is neuronal injury and neuronal death. Surviving neurons undergo long-term alterations that serve as a substrate for epileptogenesis. This review highlights the multifaceted mechanisms underlying SE self-sustainability, pharmacoresistance, and subsequent epileptogenesis.

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. Plain Language Summary: DN is nerve damage induced by elevated blood glucose levels in T2DM. It is a common condition that affects patients by increasing the chance of falling, causing discomfort, and decreasing their quality of life. It is one of the most ubiquitous consequences of diabetes. Symptoms include limb numbness, tingling, weakness, and severe pain and sensitivity. Long-term microvascular effects of diabetes mellitus include retinopathy, nephropathy, and neuropathy. This study was done to evaluate the effects of DN on hematological parameters. The haematological parameters study aims to identify a relationship between HbA1c and DN. The researchers determined clinical data through clinical records including age, gender, WT, BSA, and laboratory data included HbA1c, HB, MCHC, MCV, MCH, PLT, RDW, HCT, NEUT, LYMPH, NLR, PLR, and PLT/MCH ratio. Statistical analysis was applied after data collection. As a result, this retrospective study identified both positive and negative correlations between HbA1c, a biomarker for diabetic neuropathy, and haematological variables in diabetic patients with neuropathy, including HB, MCV, MCH, PLT, and the PLT/MCH ratio. This finding may be used as a prognostic indicator of DN. It is crucial to manage and monitor blood sugar levels for effective treatment of this dangerous condition. Doctors advise regular walking and mild exercise to reduce neuropathy discomfort, build muscle, and regulate blood sugar levels. An in-depth investigation is required to validate the function of these parameters.

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.