Long-Term Disability Outcomes in Relapsing-Remitting Multiple Sclerosis Patients: Impact of Clinical and Demographic Factors on Disease Progression.

Background: Multiple sclerosis (MS) is a prevalent chronic inflammatory and neurodegenerative disease of the central nervous system. The main evolving forms, relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS), lack clear delineation. Methods: We conducted an observational study on 523 Caucasian RRMS patients receiving first-line disease-modifying therapies (DMTs), analyzing demographic, clinical, and geographical data. Results: RRMS patients experienced a statistically significant reduction in relapse rates post-DMT initiation. Significant differences in time to reach an Expanded Disability Status Score (EDSS) of 3.0 and 6.0 were observed based on demographics and onset topography. Kaplan-Meier analysis revealed that the onset with optic or supratentorial symptoms is linked to a longer time until EDSS = 3.0 is reached. Urban origin correlated with a prolonged time until EDSS = 3.0. Gender and environment showed no significant associations with the hazard of reaching an EDSS = 6.0. Cox regression analysis revealed no significant impact of relapses on the time to reach EDSS scores of 3.0 and 6.0 in our study cohort. Conclusions: Multivariate analysis identified several predictive factors for disability progression, including environment, age at onset, and disability level at DMT initiation.

The Immunomodulatory Potential of Short-Chain Fatty Acids in Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative central nervous system (CNS) disorder, characterized by focal inflammation, demyelination, irreversible axonal loss and neurodegeneration. The proposed mechanism involves auto-reactive T lymphocytes crossing the blood-brain barrier (BBB), contributing to inflammation and demyelination. Pro-inflammatory Th1 and Th17 lymphocytes are pivotal in MS pathogenesis, highlighting an imbalanced interaction with regulatory T cells. Dysbiosis in the gut microbiota, characterized by microbial imbalance is implicated in systemic inflammation, yet its exact role in MS remains elusive. Short-chain fatty acids (SCFAs), including valerate, butyrate, propionate, and acetate, produced through dietary fiber fermentation by the gut microbiota, modulate inflammation and immune responses. Particularly, butyrate and propionate exhibit pronounced anti-inflammatory effects in both the gut and CNS. These SCFAs influence regulatory T lymphocyte expression and BBB permeability. This review discusses the potential therapeutic implications of SCFA in MS, highlighting their ability to modulate the gut-brain axis and restore immune balance.

Physiotherapy Intervention on Premature Infants-A Pilot Study.

Background and Objectives: Considering the fact that prematurity echoes in terms of motor development even up to the age of adolescence, through the presence of deficiencies, the importance of starting kinetotherapeutic treatment as soon as possible is highlighted, even in the absence of brain damage or obvious motor delays. Therefore, the objectives of this study are to analyze the factors that influence the level of motor development of premature babies up to 9 months and identify the motor development curve of premature babies according to the three stages of motor development: the position of symmetrical support on the elbows at 3 months, sitting with support at 6 months, and verticalization at 9 months. Materials and Methods: This prospective pilot study was conducted within a rehabilitation facility located in Targu Mureș, Romania, spanning a duration of 2 years from June 2021 to 2023. Results: The study involved a population of 78 children, all premature infants, selected from the patient pool of the rehabilitation facility, specifically chosen based on adherence to the predetermined inclusion and exclusion criteria outlined in the study protocol. Two physiotherapists specialized in child recovery were involved in the study, and one performed the assessments and the other applied the Bobath therapy. Conclusions: Early physiotherapy interventions can have a positive influence in terms of reducing differences in motor development between preterm and full-term infants. This study identified several factors that influence the motor development of premature infants. Among these, the most prominent biological factors were gestational age and birth weight.

Factors Influencing the Duration of Rehabilitation in Infants with Torticollis-A Pilot Study.

Background and Objectives: Torticollis is a common pediatric condition, with an incidence of 0.3-2.0%. Studies show that an adequate, tailored, and early treatment helps 90% to 95% of children recover before the first year of life and 97% of patients recover if treatment starts before the first six months. To identify the relationships between variables considered essential in the recovery process of infants with torticollis, we included factors such as the type of torticollis, age at onset of treatment, gender, birth weight, mode of delivery, fetal position in the uterus, the presence of craniofacial deformities, regions affected by postural asymmetries, and duration of the rehabilitation program. The hypothesis of the study is that early initiation of therapy can contribute to achieving favorable outcomes in the recovery process. Material and Methods: This retrospective cohort pilot study was conducted within a rehabilitation facility, spanning a duration of 1 year. The study involved a population of 41 children aged between 0 and 6 months. The rehabilitation program consisted of the application of Vojta therapy. Each session lasted 20 min, with a frequency of three times per week. Results: A total of 41% of those who started therapy in the first 3 months of life were fully recovered after 4-6 weeks of therapy. Of infants who started therapy at 5 and 6 months of age, 15% showed no improvement in measurements from 14 to 16 weeks of age, at which point the use of a cranial orthosis was recommended, and 23% experienced a plateau in measurements from 10 to 14 weeks, requiring the use of a cervical collar in conjunction with therapy. Conclusions: The findings from the study suggest that there may be a correlation between early initiation of therapy and favorable outcomes in the recovery process. The primary factors influencing the duration of recovery were identified as the presence of body asymmetries and the age at which therapy was initiated.

Astrocyte Involvement in Blood-Brain Barrier Function: A Critical Update Highlighting Novel, Complex, Neurovascular Interactions.

Neurological disorders have been linked to a defective blood-brain barrier (BBB), with dysfunctions triggered by stage-specific disease mechanisms, some of these being generated through interactions in the neurovascular unit (NVU). Advanced knowledge of molecular and signaling mechanisms in the NVU and the emergence of improved experimental models allow BBB permeability prediction and the development of new brain-targeted therapies. As NVU constituents, astrocytes are the most numerous glial cells, characterized by a heterogeneity that occurs as a result of developmental and context-based gene expression profiles and the differential expression of non-coding ribonucleic acids (RNAs). Due to their heterogeneity and dynamic responses to different signals, astrocytes may have a beneficial or detrimental role in the BBB's barrier function, with deep effects on the pathophysiology of (and on the progression of) central nervous system diseases. The implication of astrocytic-derived extracellular vesicles in pathological mechanisms, due to their ability to pass the BBB, must also be considered. The molecular mechanisms of astrocytes' interaction with endothelial cells at the BBB level are considered promising therapeutic targets in different neurological conditions. Nevertheless, a personalized and well-founded approach must be addressed, due to the temporal and spatial heterogeneity of reactive astrogliosis states during disease.

The Benefits of Combining Bobath and Vojta Therapies in Infants with Motor Development Impairment-A Pilot Study.

Background: In infants presenting with motor development impairment, early kinesiotherapeutic interventions aim to normalise the pattern of movements and improve recovery. By applying Bobath and Vojta methods, we aimed to identify a combined approach regarding motor deficit in infants with neurological disabilities. Methods: We designed a prospective interventional study on 108 infants with motor developmental delay and applied Bobath, Vojta, or combined Bobath and Vojta therapy in three equal groups. Results: In the combined Bobath and Vojta group, complete motor recovery was achieved for 50% of the participants, with full recovery after six months, whereas in Bobath- or Vojta-only therapy groups, the total recovery for all participants was achieved at seven months. Regarding infants with muscular hypertonia, Bobath therapy initiation demonstrated complete recovery in 5 months in more than 50% of the cases, while for Vojta this was achieved in only 33.57% of the cases. Conclusions: The comparative evaluation conducted by analysing the data regarding the application of the Bobath and Vojta methods showed that combining these two therapies results in a shorter motor deficit recovery time than if a single therapy is applied. These findings have important implications for the selection of rehabilitation therapies in infants with neurological motor development issues.

Delayed Demyelinating Disease of the Central Nervous System Following Low-Voltage Alternating Current Electrical Injury: A Case Report and Review of the Literature.

Electrical injuries are relatively common types of mechanical trauma associated with significant morbidity and mortality. These injuries occur most commonly in adult men and account for approximately 3-7% of admissions to burn units. The type and amount of current, voltage, tissue resistance, and duration of current flow all influence the extent of injury and the patient outcome. A broad spectrum of central nervous system (CNS) and peripheral nervous systems (PNS) disorders caused by electrocution have been described in the literature. Here, we present a rare case of a 45-year-old man, electrocuted with a 240 V low-voltage alternating current (AC), four years prior to presentation, who has been admitted to our neurology clinic with a positive Lhermitte sign, paraparesis, proximal muscle pain, and distal paresthesia of the lower limbs, symptoms that had appeared one year after the electrocution. Magnetic resonance imaging (MRI) of the brain and spinal cord revealed multiple demyelinating lesions involving pons, juxtacortical and periventricular regions of the brain, and cervical and upper thoracic spinal cord. Given that other etiologies of demyelinating diseases of the CNS were excluded, we have interpreted this case and all accompanying pathologic findings as a consequence of electrical injury. Although the general epidemiologic reports regarding age, sex, type of current, circumstances, and site of electrocution correspond to the data of our reported case, this patient presents a delayed, rare neurologic complication with a nonspecific MRI pattern that we did not find in the literature. These patients should be carefully monitored not only during the acute phase but also over a longer period, because, as reported in this case, neurological complications may occur later after electrocution.

The peripheral profile of the chitinase 3-like-1 in benign multiple sclerosis - a single centre's experience.

BACKGROUND: A limited subgroup of multiple sclerosis (MS) patients present with a long-term disease evolution characterized by a limited disease progression, known as benign MS (BMS). Chitinase 3-like-1 (CHI3L1) levels are sensitive to inflammatory processes and may play a role in the pathogenesis of MS. In this observational, cross-sectional study, we aimed to evaluate the implications of serum CHI3L1 and inflammatory cytokines in BMS patients treated with interferon ß-1b for over a decade. METHODS: We collected serum samples from 17 BMS patients and 17 healthy controls (HC) to measure serum CHI3L1 levels and a Th17 panel of inflammatory cytokines. Serum levels of CHI3L1 were analysed using the sandwich ELISA method and the Th17 panel was assessed using the multiplex XMap technology on a Flexmap 3D Analyzer. RESULTS: Serum CHI3L1 levels did not differ significantly from HC. We identified a positive correlation between CHI3L1 levels and relapses during treatment. CONCLUSIONS: Our findings suggest that there are no differences in serum CHI3L1 levels between BMS patients and HC. However, serum CHI3L1 levels are sensitive to clinical inflammatory activity and may be associated with relapses in BMS patients.

Recent Progress in the Identification of Early Transition Biomarkers from Relapsing-Remitting to Progressive Multiple Sclerosis.

Despite extensive research into the pathophysiology of multiple sclerosis (MS) and recent developments in potent disease-modifying therapies (DMTs), two-thirds of relapsing-remitting MS patients transition to progressive MS (PMS). The main pathogenic mechanism in PMS is represented not by inflammation but by neurodegeneration, which leads to irreversible neurological disability. For this reason, this transition represents a critical factor for the long-term prognosis. Currently, the diagnosis of PMS can only be established retrospectively based on the progressive worsening of the disability over a period of at least 6 months. In some cases, the diagnosis of PMS is delayed for up to 3 years. With the approval of highly effective DMTs, some with proven effects on neurodegeneration, there is an urgent need for reliable biomarkers to identify this transition phase early and to select patients at a high risk of conversion to PMS. The purpose of this review is to discuss the progress made in the last decade in an attempt to find such a biomarker in the molecular field (serum and cerebrospinal fluid) between the magnetic resonance imaging parameters and optical coherence tomography measures.

Non-Aneurysmal Perimesencephalic Subarachnoid Hemorrhage: A Literature Review.

Spontaneous non-aneurysmal subarachnoid haemorrhage (NAPMSAH) (addressing point 1) is a relatively rare occurrence in clinical settings as it is rarely misdiagnosed and usually involves a significantly better prognosis than the classical aneurysmal pattern. We hereby focused on a comprehensive analysis of this distinct pathological entity with the purpose of analysing possible pathophysiological entities, outcomes and treatment options involving this diagnosis with a focus on demographical, epidemiological and clinical data. The clinical setting includes focal neurological signs related to the anatomical structures, while computer tomography followed by tomographic angiography are the most common diagnosis tools, with a typical hyperdense lesion involving the midbrain, fourth ventricle and subthalamic areas without an angiographic correspondent, such as an aneurysmal pathology. Further investigations can also be used to highlight this diagnosis, such as interventional angiography or magnetic resonance imaging. Given the rarity of this condition and its relatively better prognosis, treatment options usually remain conservative. In the present review, the main characteristics of NAPMSAH are discussed.

Cervical Artery Dissections-A Demographical Analysis of Risk Factors, Clinical Characteristics Treatment Procedures, and Outcomes-A Single Centre Study of 54 Consecutive Cases.

Cervical artery dissections (CAD) are a common cause of ischemic cerebrovascular events among the younger and middle-aged population. Altogether, CAD counts for up to 15% of all causes of stroke in patients aged 50 or younger. Among the known etiological causes, especially addressing the younger population with mechanical traumas and whiplash injuries are regarded as the main culprits. However, cases of spontaneous dissection are also widespread, with risk factors such as hypertension, migraine, and lifestyle factors increasing the risk of occurrence. Clinically, the symptoms associated with a cerebrovascular event caused by CADs are highly variable and can be classified as either compressive symptoms (such as Horner's syndrome and cervical pain) or stroke syndromes attributable to cerebral ischemia. Therefore, establishing an early diagnosis might be particularly challenging as it requires particular attention and quick clinical reasoning when interviewing the patient. With these certain particularities, our main focus was to conduct a prospective study involving up to 54 patients who were diagnosed with CAD in our clinical facility between January 2015 and December 2022, with the focus of assessing certain individual parameters attributable to each patient and their influence and prognosis value for their short and long term evolution. An important emphasis was placed on parameters such as topographical localization, clinical presentation, severity of the questioned cerebrovascular event, outcomes, and causative factors. Statistical validity tools were applied when possible.

Cytokine Secretion Dynamics of Isolated PBMC after Cladribine Exposure in RRMS Patients.

Cladribine (CLD) treats multiple sclerosis (MS) by selectively and transiently depleting B and T cells with a secondary long-term reconstruction of the immune system. This study provides evidence of CLD's immunomodulatory role in peripheral blood mononuclear cells (PBMCs) harvested from 40 patients with untreated relapsing-remitting MS (RRMS) exposed to CLD. We quantified cytokine secretion from PBMCs isolated by density gradient centrifugation with Ficoll−Paque using xMAP technology on a FlexMap 3D analyzer with a highly sensitive multiplex immunoassay kit. The PBMC secretory profile was evaluated with and without CLD exposure. PBMCs isolated from patients with RRMS for ≤12 months had significantly higher IL-4 but significantly lower IFN-γ and TNF-α secretion after CLD exposure. PBMCs isolated from patients with RRMS for >12 months had altered inflammatory ratios toward an anti-inflammatory profile and increased IL-4 but decreased TNF-α secretion after CLD exposure. CLD induced nonsignificant changes in IL-17 secretion in both RRMS groups. Our findings reaffirm CLD's immunomodulatory effect that induces an anti-inflammatory phenotype.

Oxidative Stress in Amyotrophic Lateral Sclerosis: Synergy of Genetic and Environmental Factors.

Amyotrophic lateral sclerosis (ALS) is a grievous neurodegenerative disease whose survival is limited to only a few years. In spite of intensive research to discover the underlying mechanisms, the results are fairly inconclusive. Multiple hypotheses have been regarded, including genetic, molecular, and cellular processes. Notably, oxidative stress has been demonstrated to play a crucial role in ALS pathogenesis. In addition to already recognized and exhaustively studied genetic mutations involved in oxidative stress production, exposure to various environmental factors (e.g., electromagnetic fields, solvents, pesticides, heavy metals) has been suggested to enhance oxidative damage. This review aims to describe the main processes influenced by the most frequent genetic mutations and environmental factors concurring in oxidative stress occurrence in ALS and the potential therapeutic molecules capable of diminishing the ALS related pro-oxidative status.

Autoimmune Encephalitis in COVID-19 Infection: Our Experience and Systematic Review of the Literature.

The neurologic complications of COVID-19 infection are frequent in hospitalized patients; a high percentage of them present neurologic manifestations at some point during the course of their disease. Headache, muscle pain, encephalopathy and dizziness are among the most common complications. Encephalitis is an inflammatory condition with many etiologies. There are several forms of encephalitis associated with antibodies against intracellular neuronal proteins, cell surfaces or synaptic proteins, referred to as autoimmune encephalitis. Several case reports published in the literature document autoimmune encephalitis cases triggered by COVID-19 infection. Our paper first presents our experience in this issue and then systematically reviews the literature on autoimmune encephalitis that developed in the background of SARS-CoV-2 infections and also discusses the possible pathophysiological mechanisms of auto-immune-mediated damage to the nervous system. This review contributes to improve the management and prognosis of COVID-19-related autoimmune encephalitis.

Neuroprotection in Stroke-Focus on the Renin-Angiotensin System: A Systematic Review.

Stroke is the primary cause of disability in the adult population. Hypertension represents the leading risk factor being present in almost half the patients. The renin-angiotensin system is involved in the physiopathology of stroke and has an essential impact on hypertension as a risk factor. This article targeted the role of the renin-angiotensin system in stroke neuroprotection by reviewing the current literature available. The mechanism of action of the renin-angiotensin system was observed through the effects on AT1, AT2, and Mas receptors. The neuroprotective properties ascertained by angiotensin in stroke seem to be independent of the blood pressure reduction mechanism, and include neuroregeneration, angiogenesis, and increased neuronal resistance to hypoxia. The future relationship of stroke and the renin-angiotensin system is full of possibilities, as new agonist molecules emerge as potential candidates to restrict the impairment caused by stroke.

Rivaroxaban for the treatment of cerebral venous thrombosis: a single-center experience.

The mainstay of cerebral venous thrombosis (CVT) treatment according to current guidelines is parenteral anticoagulation with unfractionated heparin or low-molecular-weight heparin followed by long-term oral anticoagulation with vitamin K antagonists. Direct oral anticoagulants (DOACs), including the factor Xa inhibitor rivaroxaban, are used occasionally off-label for CVT based on individual treatment plans. This publication sought to report our experience with rivaroxaban for the indication of CVT and to review the relevant literature data concerning this topic. We performed a single-center retrospective analysis including patients from our institution with the diagnosis of cerebral venous thrombosis treated with rivaroxaban. Among 12,500 stroke patients over an 11-year period, we identified 87 cases with a diagnosis of CVT (0.7%). As long-term anticoagulation, 80 of these patients were receiving vitamin K antagonists and seven were receiving DOACs, including six receiving rivaroxaban and one receiving apixaban. Of the six patients receiving rivaroxaban, at least 6 months of clinical follow-up data were available for five of them. Excellent clinical outcomes were obtained in four of these five cases (modified Rankin scale score: 0-1 points). No hemorrhagic events, recurrent thrombosis, or other relevant complications were recorded during the follow-up period. Despite our small study sample size, our positive results support that rivaroxaban may be a safe and effective treatment option for patients with CVT. Hopefully, ongoing randomized clinical trials will better clarify the role of rivaroxaban in the treatment of CVT so as to provide a more convenient and safer alternative to vitamin K antagonists in this context.

Severe Acute Motor Axonal Neuropathy associated with Influenza-A (H1N1) Infection and Prolonged Respiratory Failure - A Case Report.

Acute Motor Axonal Neuropathy (AMAN) is an immune-mediated disorder of the peripheral nervous system, part of the spectrum of the Guillain-Barre syndrome (GBS). An infectious event most often triggers it reported a few weeks before the onset. The reported case is of a 56 years-old woman who developed acute motor axonal neuropathy three weeks after respiratory infection with influenza A virus subtype H1N1. Despite early treatment with plasmapheresis and intravenous immunoglobulins, the patient remained tetraplegic, mechanically ventilated for five months, with repetitive unsuccessful weaning trails. The probable cause was considered to be phrenic nerve palsy in the context of acute motor axonal neuropathy. This case highlights that acute motor axonal neuropathy is a severe and life-threatening form of Guillain-Barre syndrome associated with significant mortality and morbidity. Neurological and physical recovery strongly depend on the inter-professional effort in an intensive care unit and neurology professionals.

Postpartum Acute Basilar Artery Occlusion Secondary to Vertebral Artery Dissection. Case Report and Literature Review.

Female patients in the peripartum and postpartum periods have an increased risk of stroke than nonpregnant women. Cerebrovascular complications of pregnancy represent a significant cause of maternal mortality and morbidity and are potentially disabling. Acute basilar artery occlusion secondary to spontaneous vertebral artery dissection in the postpartum period is an infrequent entity and a major diagnostic and treatment challenge. In the present case, a 37-year-old female patient, eight weeks after caesarean delivery, presented with a history of sudden cervical pain, followed by headache and dizziness. Some hours later, she was found unconscious by her family and was transferred to the emergency department, where a neurological status assessment suggested vertebrobasilar stroke. The imagistic workup revealed right vertebral artery dissection and basilar artery occlusion without constituted ischemic lesions. The patient underwent endovascular intervention with dilation of the narrowed vertebral artery and stent retriever basilar artery thrombectomy, with a favourable clinical outcome. This report first presents the details of this case and the relevant literature data on postpartum arterial dissections and the subsequent ischemic complications and available treatment options.

Treatment With Cladribine Selects IFNγ+IL17+ T Cells in RRMS Patients - An In Vitro Study.

Background: Multiple sclerosis (MS) is an incurable autoimmune disease mediated by a heterogeneous T cell population (CD3+CD161+CXCR3-CCR6+IFNγ-IL17+, CD3+CXCR3+CCR6+IFNγ+IL17+, and CD3+CXCR3+IFNγ+IL17- phenotypes) that infiltrates the central nervous system, eliciting local inflammation, demyelination and neurodegeneration. Cladribine is a lymphocyte-depleting deoxyadenosine analogue recently introduced for MS therapy as a Disease Modifying Drug (DMD). Our aim was to establish a method for the early identification and prediction of cladribine responsiveness among MS patients. Methods: An experimental model was designed to study the cytotoxic and immunomodulatory effect of cladribine. T cell subsets of naïve relapsing-remitting MS (RRMS) patients were analyzed ex vivo and in vitro comparatively to healthy controls (HC). Surviving cells were stimulated with rh-interleukin-2 for up to 14days. Cell proliferation and immunophenotype changes were analyzed after maximal (phorbol myristate acetate/ionomycin/monensin) and physiological T-cell receptor (CD3/CD28) activation, using multiparametric flow cytometry and xMAP technology. Results: Ex vivo CD161+Th17 cells were increased in RRMS patients. Ex vivo to in vitro phenotype shifts included: decreased CD3+CCR6+ and CD3+CD161+ in all subjects and increased CD3+CXCR3+ in RRMS patients only; Th17.1 showed increased proliferation vs Th17 in all subjects; CD3+IL17+ and CD3+IFNγ+IL17+ continued to proliferate till day 14, CD3+IFNγ+ only till day 7. Regarding cladribine exposure: RRMS CD3+ cells were more resistant compared to HC; treated CD3+ cells proliferated continuously for up to 14 days, while untreated cells only up to 7 days; both HC/RRMS CD3+CXCR3+ populations increased from baseline till day 14; in RRMS patients vs HC, IL17 secretion from cladribine-treated cells increased significantly, in line with the observed proliferation of CD3+IL17+ and CD3+IFNγ+IL17+ cells; in both HC/RRMS, cladribine led to a significant increase in CD3+IFNγ+ cells at day 7 only, having no further effect at day14. IFNγ and IL17 secreted in culture media decreased significantly from ex vivo to in vitro. Conclusions: CD3+ subtypes showed different responsiveness due to selectivity of cladribine action, in most patients leading to in vitro survival/proliferation of lymphocyte subsets known as pathogenic in MS. This in vitro experimental model is a promising tool for the prediction of individual responsiveness of MS patients to cladribine and other DMDs.

Autonomic and Somatic Nerve Functions in Type 2 Diabetes Mellitus Patients: Electrophysiological Aspects.

OBJECTIVES: To investigate the relationship between neurophysiological sensory and motor nerve function parameters, assessed by nerve conduction studies (NCS) with parasympathetic autonomic function and by heart rate variability (HRV) tests in patients with type 2 diabetes mellitus (T2DM). MATERIAL AND METHODS: A total of 161 T2DM patients underwent NCS. Cardiac autonomic response was assessed by HRV tests to deep breathing (HRV DB), to Valsalva manoeuvre, and during postural change from lying to standing. RESULTS: The amplitude of motor response in the median nerve, tibial nerve, and peroneal nerve was associated with reduced HRV DB (p = 0.0001). The amplitude of motor response in the median nerve, tibial nerve, and peroneal nerve was associated with reduced HRV Valsalva (p = 0.0001). The correlation between the amplitude of response in all sensory nerves (sural, median, and ulnar) and HRV DB was statistically significant (p = 0.0001). CONCLUSION: The results indicate that there is a correlation in T2DM patients between the damage of small myelinated and unmyelinated nerve fibres from cardiac autonomic nerves, assessed by HRV tests and damage of large motor and sensory fibres, assessed by NCS. Based on the above results, a combination of NCS and HRV tests should be considered in the neurophysiological approach to diabetic neuropathy.