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.

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.

Dysfunction of the Neurovascular Unit in Ischemic Stroke: Highlights on microRNAs and Exosomes as Potential Biomarkers and Therapy.

Ischemic stroke is a damaging cerebral vascular disease associated with high disability and mortality rates worldwide. In spite of the continuous development of new diagnostic and prognostic methods, early detection and outcome prediction are often very difficult. The neurovascular unit (NVU) is a complex multicellular entity linking the interactions between neurons, glial cells, and brain vessels. Novel research has revealed that exosome-mediated transfer of microRNAs plays an important role in cell-to-cell communication and, thus, is integral in the multicellular crosstalk within the NVU. After a stroke, NVU homeostasis is altered, which induces the release of several potential biomarkers into the blood vessels. The addition of biological data representing all constituents of the NVU to clinical and neuroradiological findings can significantly advance stroke evaluation and prognosis. In this review, we present the current literature regarding the possible beneficial roles of exosomes derived from the components of the NVU and multipotent mesenchymal stem cells in preclinical studies of ischemic stroke. We also discuss the most relevant clinical trials on the diagnostic and prognostic roles of exosomes in stroke patients.

The Role of Biomarkers in Atherothrombotic Stroke-A Systematic Review.

Stroke represents the primary debilitating disease in adults and is the second-highest cause of death worldwide. Atherosclerosis, the most prevalent etiology for vascular conditions, is a continuous process that gradually creates and develops endothelial lesions known as atherosclerotic plaques. These lesions lead to the appearance of atherothrombotic stroke. In the last decades, the role of biological biomarkers has emerged as either diagnostic, prognostic, or therapeutic targets. This article aims to create a list of potential biomarkers related to atherothrombotic stroke by reviewing the currently available literature. We identified 23 biomarkers and assessed their roles as risk factors, detection markers, prognostic predictors, and therapeutic targets. The central aspect of these biomarkers is related to risk stratification, especially for patients who have not yet suffered a stroke. Other valuable data are focused on the predictive capabilities for stroke patients regarding short-term and long-term prognosis, including their influence over the acute phase treatment, such as rt-PA thrombolysis. Although the role of biomarkers is anticipated to be of extreme value in the future, they cannot yet compete with traditional stroke neuroimaging markers but could be used as additional tools for etiological diagnosis.

Cardiac autonomic neuropathy in type 1 and type 2 diabetes patients.

BACKGROUND: Cardiac autonomic neuropathy (CAN) in diabetes is among the strongest risk markers for future global and cardiovascular mortality. The aim of this study was to analyse CAN prevalence and to compare the associations between CAN, the glycaemic control, cardiovascular risk factors, peripheral neuropathy, retinopathy and macroangiopathy in patients with type 1 (T1DM) and type 2 diabetes mellitus (T2DM). METHODS: One hundred ninety-five diabetic patients were included in this study. All patients were evaluated for detection of CAN (with standardised cardiovascular reflex tests), diabetes-related microvascular complications (polyneuropathy, retinopathy), common carotid artery intima-media thickness (IMT) and ankle-brachial index (ABI). RESULTS: The prevalence of CAN was 39.1% in T2DM and 61.8% in T1DM patients. Multivariate logistic regression analysis demonstrated that in T2DM, the odds [OR (95% confidence intervals)] of CAN increased with diabetes duration [1.67(1.42-1.92)], HbA1c [1.74(1.34-2.27)], cholesterol [1.01(1.00-1.01)], triglycerides [1.01(0.99-1.00)], smoking [2.35(1.23-4.49)], systolic blood pressure [1.01(1.00-1.03)], BMI [1.16(1.08-1.24)], glomerular filtration rate [0.91(0.88-0.93)], peripheral neuropathy [25.94(11.04-44.25)], retinopathy [13.13(3.03-84.73)] and IMT [10.12 (7.21-15.32)]. In T1DM, the odds of CAN increased with diabetes duration [1.62(1.13-2.31)], HbA1c [4.49(1.27-15.9)], age of patients [1.14(1.03-1.27)], glomerular filtration rate [0.94(0.89-0.99)], peripheral neuropathy [31.6(4.5-45.8)] and IMT [5.5(2.3-8.3)]. CONCLUSION: This study indicated that CAN is a more frequent complication in T1DM. Apart from glycaemic control, the existence of CAN is associated with potentially modifiable cardiovascular risk only in T2DM patients. The presence of other micro- and macrovascular complications increases the probability of having CAN in both types of DM (but more pronounced in T2DM).

Complete progressive ophthalmoplegia and numb chin syndrome, the first clinical manifestations of a lethal abdominal Burkitt lymphoma.

A 57-year-old patient was admitted to the Neurology Clinic for hypoesthesia, intense pain in the right chin and double vision. During the hospitalization, the patient developed progressive complete bilateral ophthalmoplegia and numbness of both sides of the chin. Brain CT and MRI scans with gadolinium were normal. Standard laboratory tests on admission were normal. The cerebral spinal fluid examination and the infectious and autoimmune workup were also normal. A thoracic-abdominal and pelvic CT scan revealed two hypodense lesions in the liver, irregular thickening of the gastric and ileal wall, and multiple abdominal adenopathies. Meanwhile, the patient developed marked fatigue, fever, sweats, nausea, vomiting and abdominal pain. An exploratory laparotomy was performed that showed multiple tumours of the small intestinal wall, stomach wall, multiple liver masses in both lobes and appendicular tumour. Histopathological findings of the liver biopsy and appendicular walls revealed Burkitt lymphoma. The patient died two days after surgery by cardiopulmonary arrest. This case underscores the importance of keeping BL in the differential diagnosis of patients with rapidly progressive ophthalmoplegia and numb chin syndrome, with normal brain MRI and CSF examinations.

The role of ultrasound in the diagnosis of temporal arteritis.

Temporal arteritis (TA), also known as giant cell arteritis, is a chronic vasculitis of medium and large-sized blood vessels, in particular the main cervical branches of the aorta, with particular affinity to the temporal arteries and eye-supplying arteries. Temporal artery biopsy is still a gold standard for diagnosis, however in recent years colour duplex ultrasound examination has been proposed as a useful diagnostic screening tool in cases of TA suspicion. We report three cases of TA in which the ultrasonographical examination of the temporal arteries had a decisive role in the diagnosis.

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.

Characteristics of Developmental and Epileptic Encephalopathy Associated with PACS2 p.Glu209Lys Pathogenic Variant-Our Experience and Systematic Review of the Literature.

BACKGROUND: Developmental and epileptic encephalopathies (DEE) encompass a group of rare diseases with hereditary and genetic causes as well as acquired causes such as brain injuries or metabolic abnormalities. The phosphofurin acidic cluster sorting protein 2 (PACS2) is a multifunctional protein with nuclear gene expression. The first cases of the recurrent c.625G>A pathogenic variant of PACS2 gene were reported in 2018 by Olson et al. Since then, several case reports and case series have been published. METHODS: We performed a systematic review of the PUBMED and SCOPUS databases using Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Our search parameters included DEE66 with a pathogenic PACS2 gene p.Glu209Lys mutation published cases to which we added our own clinical experience regarding this pathology. RESULTS: A total of 11 articles and 29 patients were included in this review, to which we added our own experience for a total of 30 patients. There was not a significant difference between sexes regarding the incidence of this pathology (M/F: 16/14). The most common neurological and psychiatric symptoms presented by the patients were: early onset epileptic seizures, delayed global development (including motor and speech delays), behavioral disturbances, limited intellectual capacity, nystagmus, hypotonia, and a wide-based gait. Facial dysmorphism and other organs' involvement were also frequently reported. Brain MRIs evidenced anomalies of the posterior cerebellar fossa, foliar distortion of the cerebellum, vermis hypoplasia, white matter reduction, and lateral ventricles enlargement. Genetic testing is more frequent in children. Only 4 cases have been reported in adults to date. CONCLUSIONS: It is important to maintain a high suspicion of new pathogenic gene variants in adult patients presenting with a characteristic clinical picture correlated with radiologic changes. The neurologist must gradually recognize the distinct evolving phenotype of DEE66 in adult patients, and genetic testing must become a scenario with which the neurologist attending adult patients should be familiar. Accurate diagnosis is required for adequate treatment, genetic counseling, and an improved long-term prognosis.

Serum levels of IL-17A in patients with relapsing-remitting multiple sclerosis treated with interferon-ß.

BACKGROUND: Interleukin-17 (IL-17), which is secreted by Th17 cells, is a proinflammatory cytokine that is implicated in the pathogenesis of multiple sclerosis (MS) and plays a role in nonresponse of MS patients to interferon-ß (IFN-ß) therapy. OBJECTIVES: The purpose of this study was to establish a correlation between nonresponders (NR) and IL-17A serum titers and binding antibodies (BAbs) to IFN-ß, as well as to find a correlation between IL-17A serum levels and other features of MS patients. METHODS: Our prospective study included 72 inactive relapsing-remitting multiple sclerosis (RRMS) patients that had been treated for at least 18 months with IFN-ß and 15 healthy subjects. We determined the serum levels of IL-17A and of BAbs. IL-17A levels were considered elevated (IL-17A+) if the recorded value was greater than 1.6 pg/ml. RESULTS: Twenty-seven patients (37.5%) were NR and had a significantly higher serum IL-17A level compared to the responders group. Nineteen patients (26.4%) were IL-17A+ and had had a significantly higher number of relapses in the previous year and a higher Expanded Disability Status Score. The majority of IL-17A+ patients were NR and had a shorter MS duration. CONCLUSIONS: RRMS patients with high serum IL-17A levels do not respond well to IFN-ß therapy and have shorter MS duration compared to patients with low IL-17A levels. This response is not influenced by the presence of BAbs.

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.

Serum Fatty Acids Are Associated with a Higher Risk of Ischemic Stroke.

Stroke prevention, a significant public-health concern, begins with recognizing and addressing risk factors. Interventions targeted at modifiable risk factors can effectively prevent ischemic stroke, while Omega-3 fatty acids have been shown to improve stroke outcomes. Our study aimed to investigate the relationship between ischemic-stroke risk factors and fatty acids using a prospective observational study with 274 patients. We collected clinical data on risk factors and measured fatty-acid levels using high-performance liquid chromatography coupled with mass spectrometry. We found that several risk factors, including age, sex, smoking, atrial fibrillation, dyslipidemia, and previous stroke history, had a direct relationship with fatty acids. Of these, smoking had the most significant impact, negatively impacting levels of docosahexaenoic and eicosapentaenoic acid. Conversely, dyslipidemia and atrial fibrillation positively correlated with fatty acids, particularly in female patients and those with recurrent strokes. Age was found to directly correlate with other risk factors and variations in fatty-acid ratios. The stroke rate was higher in males than females before the age of 70, but this trend reversed. Our findings suggest that better management of risk factors, particularly modifiable lifestyle factors, could improve fatty-acid profiles and the balance of Omega-3 and Omega-6 in patients with ischemic stroke.

The Occurrence of Acute Disseminated Encephalomyelitis in SARS-CoV-2 Infection/Vaccination: Our Experience and a Systematic Review of the Literature.

BACKGROUND: The neurological complications of coronavirus disease 2019 (COVID-19) infection and the side effects of vaccination include immune-mediated diseases of the central nervous system (CNS) such as acute disseminated encephalomyelitis (ADEM). It is an acute-onset demyelinating disease that involves a rapid evolution and multifocal neurological deficits that develops following a viral or bacterial infection or, less frequently, following vaccination. Acute hemorrhagic leukoencephalitis (AHLE) is the hemorrhagic variant of ADEM that presents a more severe evolution which can be followed by coma and death. The objectives of this study consist in evaluating the diagnosis, clinical characteristics, imaging and laboratory features, evolution, and treatment of ADEM and AHLE following COVID-19 infection or vaccination. METHODS: We performed a systematic review of the medical literature according to PRISMA guidelines that included ADEM cases published between 1 January 2020 and 30 November 2022 following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination and also included our own clinical experience regarding this pathology. RESULTS: A total number of 74 patients were diagnosed with ADEM, 45 following COVID-19 infection and 29 after a SARS-CoV-2 vaccine. A total of 13 patients (17.33%) presented AHLE. The moderate form of COVID-19 presented a positive correlation with AHLE (r = 0.691, p < 0.001). The existence of coma and AHLE was correlated with poor outcomes. The following more aggressive immunomodulatory therapies applied in severe cases were correlated with poor outcomes (major sequelae and death): therapeutic plasma exchange (TPE) treatment (r = 382, p = 0.01) and combined therapy with corticosteroids and TPE (r = 0.337, p = 0.03). CONCLUSIONS: Vaccinations are essential to reduce the spread of the COVID-19 pandemic, and the monitoring of adverse events is an important part of the strategic fight against SARS-CoV-2. The general benefits and the overall good evolution outweigh the risks, and prompt diagnosis is associated with a better prognosis in these patients.

Sociodemographic and Clinical Determinants of Fatigue in Multiple Sclerosis.

Fatigue is the most common and disabling symptom in patients with multiple sclerosis (PwMS), representing one of the main determinants of reduced quality of life among PwMS due to its interference with social activities and work capacity. This study aimed to identify the sociodemographic determinants of fatigue in a cohort of 150 PwMS and 100 healthy controls (HCs). Fatigue was assessed using one of the most suitable and appropriate tools for measuring the degree of fatigue: the Modified Fatigue Impact Scale (MFIS). By comparing the median scores for the MFIS, we observed that the PwMS group had significantly higher MFIS scores than the HCs (p = 0.0001). In PwMS, MFIS scores correlated positively with age, total number of relapses, total disease duration, disability status, and Beck Depression Inventory-II score and negatively with cognitive performance. Patients with relapsing-remitting MS had significantly lower fatigue levels than those with secondary progressive MS (p = 0.0010). Fatigue levels were significantly lower among male than female PwMS (p = 0.0120). Other determinant factors of fatigue in our study proved to be the marital and occupational status, as well as the presence of children, but in a linear multivariate regressions analysis with MFIS score as the dependent variable, the fatigue levels were influenced only by sex, occupational status, marital status, children status, and BDI-II test results. Considering the significant impact of fatigue on the quality of life of PwMS, clinicians must diagnose fatigue as early as possible, identify its modifiable determinants, and manage it effectively to increase their quality of life.

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.

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.

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.

Diagnostic and prognostic computed tomography imaging markers in basilar artery occlusion (Review).

Acute ischemic stroke treatment has been revolutionized by the addition of mechanical and aspiration thrombectomy. Randomized controlled trials have proven beyond doubt, the substantial clinical impact of endovascular interventions in anterior circulation territory strokes. Unfortunately, patients with vertebrobasilar ischemic stroke could not be included in these early trials due to inherent clinical, radiological, and prognostic particularities of posterior circulation ischemia; thus, indications for the treatment of posterior fossa strokes and basilar artery occlusion (BAO) are mainly based on retrospective studies and registries. BAO carries high morbidity and mortality, despite the new improvements in endovascular therapy. Identifying patients who will likely benefit from invasive treatment and have a good clinical outcome resides in discovering clinical, biological, or imaging markers, that have prognostic implications. Such imaging markers have been described, especially in the last decade. Hyperdense Basilar Artery Sign (HDBA), Posterior Circulations-Alberta Stroke Program Early CT Score (pc-ASPECTS), Pons-Midbrain Index (PMI), Posterior Circulation Collateral Score (pc-CS), Posterior Circulation CT Angiography Score (pc-CTA), and Basilar Artery on CT Prognostic Score (BATMAN), are computed tomography (CT) markers with properties that can aid the diagnosis of BAO and can independently predict clinical outcome. This paper aims to present a comprehensive review of these imaging signs to have a thorough understanding of their diagnostic and prognostic attributes.

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.

Ischemic Stroke in Patients with Cancer: a Retrospective Cross-Sectional Study.

INTRODUCTION: An increasing trend of cancer associated stroke has been noticed in the past decade. OBJECTIVES: To evaluate the risk factors and the incidence of neoplasia in stroke patients. MATERIAL AND METHOD: A retrospective, observational study was undertaken on 249 patients with stroke and active cancer (SAC) and 1563 patients with stroke without cancer (SWC). The general cardiovascular risk factors, the site of cancer, and the general clinical data were registered and evaluated. According to the "Oxfordshire Community Stroke Project" (OCSP) classification, all patients were classified into the clinical subtypes of stroke. The aetiology of stroke was considered as large-artery atherosclerosis, small vessel disease, cardio-embolic, cryptogenic or other determined cause. RESULTS: The severity of neurological deficits at admission were significantly higher in the SAC group (p<0.01). The haemoglobin level was significantly lower, and platelet level and erythrocyte sedimentation rate were significantly higher in the SAC group. Glycaemia, cholesterol and triglycerides levels were significantly higher in the SWC group. The personal history of hypertension was more frequent in the SWC group. In the SAC group, 28.9% had a cryptogenic aetiology, compared to 9.1% in SWC group. Cardio-embolic strokes were more frequent in the SAC group (24%) than the SWC group (19.6%). In the SAC group, 15,6% were diagnosed with cancer during the stroke hospitalization, and 78% of the SAC patients were without metastasis. CONCLUSIONS: The most frequent aetiologies of stroke in cancer patients were cryptogenic stroke, followed by large-artery atherosclerosis. SAC patients had more severe neurological deficits and worse clinical outcomes than SWC patients. Stroke in cancer patients appears to be more frequently cryptogenic, probably due to cancer associated thrombosis. The association between stroke and cancer is important, especially in stroke of cryptogenic mechanism, even in the presence of traditional cardiovascular risk factors.