Clinical Spectrum and Neuroimagistic Features in Hospitalized Patients with Neurological Disorders and Concomitant Coronavirus-19 Infection.

In the first months of the COVID-19 pandemic, several research studies focused on understanding the damage to the respiratory and circulatory systems. However, the evidence of neurological manifestations as part of the clinical spectrum of the disease has increased. The aim of this retrospective study was to determine the potential association of neurological disorders with concomitant COVID-19 infection. We reviewed 101 patients (mean age, 70.05 years; 62.37% men) diagnosed with different neurological disorders and COVID-19 who were referred to the Department of Neurology between March 2020 and May 2021. The protocol included demographic, clinical, and neuroimagistic features, biochemical evaluation data, and prognosis. In the first group of patients with non-severe COVID-19 infection (<50% lung damage), we enrolled 75 cases (mean age, 69.13 years; 65.33% men), and the second group, with 26 patients (mean age, 72.69 years; 53.84% men), developed severe COVID-19 infection (>50% lung damage). Severe COVID-19 infection was significantly correlated with an increased highly sensitive C-reactive protein level (hsCRP) (p < 0.05), lactate dehydrogenase level (LDH) (p < 0.05), erythrocyte sedimentation rate (ESR) (p < 0.05), D-dimer (p < 0.05), fibrinogen level (p < 0.05), and blood glucose (p < 0.05) when compared to the first group. These biochemical parameters were increased in both groups, but the levels were much higher in the second group. Headaches (72.27%) and dizziness (14.85%) were present in the early stage of infection. Cerebrovascular events were also reported: ischemic stroke (48% vs. 57.69%; p < 0.05), cerebral hemorrhage (4.95%), and cerebral venous sinus thrombosis (1.98%). Encephalitis (1.98%) and Guillain-Barré Syndrome (1.98%) were found but less frequently. Cranial nerve abnormalities were statistically more common in the non-severe group: anosmia (32% vs. 26.92%; p < 0.05), dysgeusia/ageusia (48% vs. 42.30%; p < 0.05), impaired eye movement (1.33% vs. 0%), and facial nerve palsy (2.66% vs. 0%). Seizures (13.33% vs. 11.53%; p < 0.05) and a depressed level of consciousness (31.68%) occurred commonly. We detected the neuropsychiatric symptoms of anxiety (23.76%) and depression (14.85%). Mortality was increased in both groups but was much higher in the second group (46.15% vs. 21.33%). Neurological complications during COVID-19 infection are common in hospitalized patients, but the mechanism of these complications is not fully understood, representing a continuous challenge for neurologists.

Respiratory Dysfunctions in Parkinson's Disease Patients.

Respiratory dysfunctions have been associated with Parkinson's disease since the first observations of the disease in 1817. Patients with Parkinson's disease frequently present respiratory disorders with obstructive ventilatory patterns and restrictive modifications, as well as limitations in respiratory volumes. In addition, respiratory impairments are observed due to the rigidity and kyphosis that Parkinson's disease patients experience. Subsidiary pulmonary complications can also appear as side effects of medication. Silent aspiration can be the cause of pneumonia in Parkinson's disease. Pulmonary dysfunction is one of the main factors that leads to the morbidity and mortality of patients with Parkinson's disease. Here, we performed a narrative review of the literature and reviewed studies on dyspnea, lung volumes, respiratory muscle function, sleep breathing disorders, and subsidiary speech and swallow impairments related to pulmonary dysfunction in patients with Parkinson's disease.

Clinical spectrum of symptoms in cerebral Toxocariasis (Review).

Human helminth zoonosis is one of the most encountered helminthiases worldwide. Representative diseases include Toxocara canis and Toxocara cati, which are common nematodes prevalent in dogs and cats. The infiltration of these roundworms in the human body through contaminated food or nematode eggs could lead to central nervous system injury as the roundworms can cross the blood-brain barrier leading to neurotoxocariasis. Among the neurological and neuropsychological disturbances produced by Toxocara infection, in humans, the most representative are meningitis, encephalitis, myelitis and cerebral vasculitis, but asymptomatic central nervous system infection is probably the most prevalent. The present review examines the clinical symptomatology of neurotoxocariasis in case reports in the literature in the last 7 decades (1950-2020). The available evidence was retrieved from PubMed and Medline electronic databases. The present review reports the most prevalent clinical symptomatology in the cases of detected and diagnosed Toxocara infection with neuroinvasion. Thus, the present review aims to raise the awareness of neurological cases of Toxocara infection with the potential to at least establish differential diagnosis of neurotoxocariasis.

Assessing the values of circulating immune complexes in multiple sclerosis patients following immunomodulator or corticosteroid treatment.

Multiple sclerosis is defined as an immune-mediated disease that affects the central nervous system, and also is characterized by the presence of immune cells and mediators which contribute to the subsidiary neuroinflammation associated with multiple sclerosis. Throughout the evolution of multiple sclerosis, it has been observed that circulating immune complexes (CICs) have higher values in these patients, especially in the acute phase of the disease. Thus, the aim of the present study was to observe, if in acute attack, relapsing-remitting multiple sclerosis patients still present high values of CICs after treatment with glatiramer and prednisone. We divided 70 patients with multiple sclerosis with high values of CICs into two treatment groups, one treated with glatiramer (Copaxone) (immunomodulatory treatment) and the other with prednisone (corticosteroid treatment). After three months of treatment, we assessed the levels of CICs of the two multiple sclerosis groups and we observed that the patients that followed the immunomodulatory treatment had lower values of CICs than the group that followed the corticosteroid treatment. In addition, another observation established was that the glatiramer treatment group had higher levels of vitamin D in the serum than the prednisone group of multiple sclerosis patients. To conclude, better outcomes, from the point of view of the results obtained from the comparative analysis of the values of CICs and vitamin D, were demonstrated by following immunomodulatory treatment.

Plasminogen Activator Inhibitor-1 (PAI-1) Gene Polymorphisms Associated with Cardiovascular Risk Factors Involved in Cerebral Venous Sinus Thrombosis.

Cerebral venous sinus thrombosis (CVST), accounting for less than 1% of stroke cases, is characterized by various causes, heterogeneous clinical presentation and different outcome. The plasminogen activator inhibitor-1 (PAI-1) gene polymorphisms has been found to be associated with CVST. The aim of this retrospective study was to determine the potential association of PAI-1 675 4G/5G polymorphisms and homocysteine levels with cardiovascular risk factors in a group of young patients with CVST. Eighty patients with CVST and an equal number of age and sex matched controls were enrolled. The protocol included demographic and clinical baseline characteristics, neuroimagistic aspects, genetic testing (PAI-1 675 4G/5G polymorphisms), biochemical evaluation (homocysteine-tHcy, the lipid profile, blood glucose, glycohemoglobin-HbA1c, high-sensitive C-reactive protein-hsCRP) data, therapy and prognosis. The PAI-1 675 4G/5G gene polymorphisms were significantly correlated with increased homocysteine level (tHcy) (p < 0.05), higher total cholesterol (TC) (p < 0.05), low- density lipoprotein cholesterol (LDLc) (p = 0.05) and high- sensitive C- reactive protein (hsCRP) (p < 0.05) in patients with CVST when compared with controls. From the PAI-1 gene polymorphisms, the PAI-1 675 4G/5G genotype presented statistically significant values regarding the comparisons of the blood lipids values between the CVST group and control group. The homocysteine (tHcy) was increased in both groups, patients versus controls, in cases with the homozygous variant 4G/4G but the level was much higher in the group with CVST (50.56 µmol/L vs. 20.22 µmol/L; p = 0.03). The most common clinical presentation was headache (91.25%), followed by seizures (43.75%) and focal motor deficits (37.5%). The superior sagittal sinus (SSS) was the most commonly involved dural sinus (56.25%), followed by the lateral sinus (LS) (28.75%). Intima-media thickness (IMT) values were higher in the patients' group with CVST (0.95 mm vs. 0.88 mm; p < 0.05). The fatal outcome occurred 2.5% of the time. PAI-1 675 4G/5G gene polymorphisms and higher homocysteine concentrations were found to be significantly associated with CVST in young patients.

MTHFR Gene Polymorphisms and Cardiovascular Risk Factors, Clinical-Imagistic Features and Outcome in Cerebral Venous Sinus Thrombosis.

Cerebral venous sinus thrombosis (CVST) as a severe neurological emergency, is represented by variable conditions in its clinic presentation, onset, risk factors, neuroimagistic features and outcome. The genetic polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C was associated with CVST. We aimed to characterize the prevalence of MTHFR gene polymorphisms associated with cardiovascular risk factors in the group of patients with CVST. Also, we studied additional causes associated with CVST including local infections, general infections, obstetric causes (pregnancy, puerperium) and head injury. This is a retrospective study including 114 patients which referred to our hospital between February 2012-February 2020. The protocol included demographic (age, sex), clinical, neuroimagistic features, paraclinic (genetic polymorphism of MTHFR, factor V G1691A-Leiden, prothrombin G20210A, PAI-1 675 4G/5G; Homocysteine level, the lipid profile, blood glucose and Glycohemoglobin HbA1c, high- sensitive C- reactive protein- hsCRP) data, as well as treatment and outcome. The mean age was 37.55 years with a female predominance (65.79%). In the first group of patients with inherited thrombophilia (60 cases; 52.63%) we found genetic mutation includes MTHFR C677T (38.59%) and A1298C (14.03%), factor V G1691A- Leiden (15.78%), prothrombin G20210A (2.63%), PAI-1 675 4G/5G (42.98%), and hyperhomocysteinemia (35.08%). At the second group with other etiology of CVST, except thrombophilia, we included 54 patients (47.36%). The most common sites of thrombosis were the superior sagittal sinus (52.63%). Headache was the most common symptom (91.22%) and seizures were the main clinical presentation (54.38%). The MTHFR polymorphism was significantly correlated with higher total cholesterol (TC) (p = 0.023), low- density lipoprotein cholesterol (LDL) (p = 0.008), homocysteine level (tHcy) (p < 0.001). Inside the first group with MTHFR polymorphism we have found a significant difference between the levels of homocysteine at the patients with MTHFR C677T versus MTHFR A1298C polymorphism (p < 0.001). The high-sensitive C-reactive protein (hsCRP) was increased in both groups of patients, but the level was much higher in the second group (p = 0.046). Mortality rate was of 2.63%. Demographic, clinical and neuroimagistic presentation of CVST in our study was similar with other studies on the matter, with a high frequency of thrombophilia causes. MTHFR gene polymorphisms (C677T and A1298C) are increased in prevalence in CVST. PAI-1 675 4G/5G gene mutation seems to be involved in CVST etiology. Plasma C-reactive protein level and hyperhomocysteinemia should be considered as a prognostic factor in CVST.

Back Pain in Rare Diseases: A Comparison of Neck and Back Pain between Spinal Cord Ischemia and Spinal Dural Arteriovenous Fistula.

Neck and back pain may be noted like a first symptom in rare diseases: spinal cord ischemia and spinal dural arteriovenous fistula (SDAVF). Spinal cord ischemia is a rarer pathology, compared with cerebral ischemia, yet the morbidity and mortality are comparable in both cases; furthermore, classifying the acute loss of function in the spine, encountered in spinal cord ischemia as an important neurological entity. SDAVF presents the same clinical symptoms as spinal cord ischemia, but even though it has a progressive character, the impact in the quality of patients' lives being equally as important. Between August 2012-August 2017 we admitted through the hospital emergency department 21 patients with spinal cord ischemia and 11 patients with SDAVF (only self-casuistry). Demographic (age, gender), clinical, imagistic (Magnetic Resonance Angiography, Magnetic Resonance Imaging), paraclinical data as well as history, time to diagnosis, the visual analogue scale for pain (VAS score), risk factors, surgical and medical treatment, evolution, neurorehabilitation, were all used to compare the two lots of patients. The aim of this study was to observe potential differences in the demographics, symptomatology, VAS scores and treatment in comparison for spinal cord ischemia and SDAVF, to facilitate the further recognition and management in these diseases. In group A we have 21 patients with spinal cord ischemia (14 females, 7 males). The median age was 41.3 years (range 19-64). The median time to diagnosis was 7 h. The most frequent symptoms were acute neck or back pain at onset (100%), motor deficits (95.24%), sensory loss (85.72%), and sphincters problems (90.48%). The most common location was the lumbosacral spine (14 cases; 66.67%; p-value = 0.03) for spinal cord ischemia and the thoracic spine (7 cases, 63.64%; p-value = 0.065) for SDAVF. The treatment of spinal cord ischemia was medical. In group B we included 11 patients (6 females, 5 males). The median age was 52.6 years (range 28-74). The median time to diagnosis was 3 months (range 2 days-14 months). Patients have progressive symptoms: neck or back pain (100%), gait disturbances (100%) and abnormalities of micturition (100%). The treatment of SDAVF was surgical occlusion of fistula. The proportion of severe VAS score (7-10) in patients with spinal cord ischemia was significantly higher than that in patients with SDAVF (100% vs. 18, 19%; p-value = 0.051). Taking into consideration that the usual findings and diagnosis of spinal cord ischemia and SDAVF are still challenging for neurologists and in some cases the difficulties are related to technical limitations, we consider these entities to be rare but very important for the life of our patients. Patients were grouped into spinal cord ischemia and SDAVF status and those with acute or chronic pain conditions, measured by the VAS score. Patients with spinal cord ischemia develop acute neurological symptoms. They are much younger than the patients with SDAVF and the recovery rate is higher. Patients with SDAVF develop a progressive myelopathy and they suffer considerable neurological deficits. Imaging the lesions with MR angiography or MRI, we can confirm the diagnosis.

MTHFR Gene Polymorphisms Prevalence and Cardiovascular Risk Factors Involved in Cardioembolic Stroke Type and Severity.

BACKGROUND: Cardioembolic stroke (CES), generally known as the most severe subtype of ischemic stroke, is related to many factors, including diabetes mellitus (DM), hypertension (HTN), smoking, hyperlipidemia and atrial fibrillation (AF). Genetic mutations of the methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C have been recently associated with ischemic stroke. The purpose of this study was to analyze the prevalence of MTHFR gene polymorphisms correlated with cardiovascular risk factors in a selected population of patients with CES due to non-valvular AF (NVAF). METHODS: This cross-sectional study was performed on 67 consecutive patients with acute cardioembolic stroke admitted to our hospital. The protocol included general physical examination, neurological clinical status and stroke severity evaluation, imagistic evaluation and genetic testing of MTHFRC677T and A1298C polymorphisms. RESULTS: The prevalence of MTHFR polymorphisms in the study population was 38.2% for C677T and 40.3% for A1298C. The C677T mutation was significantly correlated with increased diastolic blood pressure (DBP) values (p = 0.007), higher total cholesterol (TC) (p = 0.003), low-density lipoprotein cholesterol (LDLc) (p = 0.003) and triglycerides (TGL) (p = 0.001), increased high-sensitive C-reactive protein (hsCRP) values (p = 0.015), HbA1c (p = 0.004) and left ventricle ejection fraction (LVEF) (p = 0.047) and lower high-density lipoprotein cholesterol (HDLc) (p < 0.001) compared to patients without this genetic variant. This genetic profile also included significantly higher CHA2DS2VASC (p = 0.029) and HASBLED (Hypertension, Abnormal liver/renal function, Stroke, Bleeding, Labile INR, Elderly age(>65 years), Drug/Alcohol usage history/Medication usage with bleeding predisposition) (p = 0.025) scores. Stroke severity in patients with MTHFRA1298C mutation was significantly increased when applying National Institutes of Health Stroke Scale (NIHSS) (p = 0.006) and modified Rankin scale (mRS) (p = 0.020) scores. The presence of A1298C mutation as a dependent variable was associated with significantly higher TGL values (odds ratio (OR) = 2.983, 95%CI = (1.972, 7.994)). CONCLUSIONS: The results obtained in this study demonstrate that MTHFR gene polymorphisms have a high prevalence in an NVAF cardioembolic stroke population. Moreover, an association between C677T mutation and stroke severity was highlighted. The C677T mutation in patients with NVAF was correlated with a higher incidence of cardiovascular comorbidities (hypertension HTN, heart failure (HF), dyslipidemia, type II diabetes mellitus (T2DM) with high HbA1c and increased inflammatory state). The A1298CMTHFR gene mutation was associated with a higher incidence of previous lacunar stroke and stroke recurrence rate, while dyslipidemia was the main cardiovascular comorbidity in this category.