Determination of hemorrhagic transformation risk in acute ischemic cerebrovascular disease: The relationship between ADC values and GRE hemo sequence microhemorrhage.

Background and purpose:

To determine the risk of hemorrhagic transformation in patients with acute ischemic cerebrovascular disease, we investigated the relationship between Apparent Diffusion Coefficient Magnetic Resonance Imaging values measured within the infarct area and microbleeds observed on Gradient Echo Sequence Magnetic Resonance Imaging.

A total of 172 patients who were hospitalized to the Neurology Clinic of the Istanbul Provincial Directorate of Health Erenkoy Mental and Nervous Diseases Training and Research Hospital between June 2019 and March 2020 were included in this cross-sectional study. The patients were classified according to their demographic and clinical characteristics, by age, gender, hypertension, diabetes mellitus, smoking, and alcohol use. In the Cranial Magnetic Resonance Imaging taken in the application for the diagnosis of acute ischemic cerebrovascular disease, the infarction area in Apparent Diffusion Coefficient sequences with the Region of Interest value and the relationship between microhemorrhage observed in Gradient Echo hemo-sequence was evaluated in Magnetic Resonance Imaging applied between 3-7 days. While calculating spherical Region of Interest values, 5 Region of Interest values were obtained for lesions larger than 1.5x1.5 cm, and their arithmetic mean was obtained, and single spherical Region of Interest value was taken for smaller ones. Apparent Diffusion Coefficient Magnetic Resonance Imaging Region of Interest mean values were divided into 2 groups as <500x10–6 mm2 /s and >500x10–6 mm2/s. 

Patients in the group with Apparent Diffusion Coefficient Region of Interest mean values below 500x10-6 mm2/s, had a significantly higher probability for microhemorrhage observes in Gradient Echo Sequence Magnetic Resonance Imaging (p: 0.001) and also more likely to experience microhemorrhage in other areas, which was statistically significant (p: 0.001).The probability of another micro-bleeding observed in patients with microhemorrhage Gradient Echo Sequence Magnetic Resonance Imaging was also statistically significant (p: 0,001). The risk of microbleeding in areas other than ischemia was also found to be significantly higher in patients with microbleeding in the ischemia area in Gradient Echo Sequence Magnetic Resonance Imaging.

In our study, a statistically significant relationship was found between the microhemorrhage in the infarct area and the Apparent Diffusion Coefficient Region of Interest values. When the literature was reviewed, no such study was found to determine the risk of bleeding.

Real-life experiences with galcanezumab and predictors for treatment response in Turkey.

BACKGROUND: The complexity of clinical practice extends far beyond the controlled settings of trials, and there is a need for real-world studies aimed at identifying which patients will respond to anti-CGRP monoclonal antibodies in different countries. This study aimed to investigate the efficacy and safety of galcanezumab in treating migraine in a real-life setting in Turkey, as well as identify predictors of treatment response. METHODS: A total of 476 patients who diagnosed with migraine according to ICHD-3 criteria and treated with galcanezumab by headache specialists were voluntarily participated in this cross-sectional study. Galcanezumab is indicated for the prevention of migraine in adults who have at least 4 monthly migraine days in Turkey. All patients filled out a survey on Google Form that comprised 54 questions, addressing various aspects such as demographics, migraine characteristics, previous use of acute symptomatic medication, failures with preventive drug classes, comorbidities, most bothersome symptoms, as well as the interictal burden of migraine. RESULTS: Among the participants, 89.3% reported that galcanezumab treatment was beneficial for them. A decrease in the frequency (80.0%), severity (85.7%), and acute medication usage for migraine attacks (71.4%) was reported with galcanezumab treatment. An adverse effect related to galcanezumab was reported in 16.3% of cases, but no serious adverse reactions were observed. Remarkably, 14.3% of participants reported no longer experiencing any headaches, and 18.9% did not require any acute treatment while receiving galcanezumab treatment. A logistic regression model showed that male gender, lack of ictal nausea, and previous failure of more than 2 prophylactic agents may predict the non-responders. CONCLUSIONS: The first large series from Turkey showed that galcanezumab treatment is safe and effective in most of the patients diagnosed with migraine by headache experts in the real-life setting. Patients reported a significant decrease in both ictal and interictal burden of migraine and expressed satisfaction with this treatment.

IVIg-induced headache: prospective study of a large cohort with neurological disorders.

BACKGROUND: Intravenous immune globulin (IVIg) is frequently used in some neurological diseases and is also the first-line therapy in Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, and multifocal motor neuropathy. We aimed to evaluate the frequency and characteristics of headaches, which is one of the most common side effects of IVIg treatment. METHODS: Patients who received IVIg treatment for neurological diseases were prospectively enrolled in 23 centers. Firstly, the characteristics of patients with and without IVIg-induced headaches were analyzed statistically. Then, patients with IVIg-induced headaches were classified into three subgroups determined by their history: no primary headache, tension-type headache (TTH), and migraine. RESULTS: A total of 464 patients (214 women) and 1548 IVIg infusions were enrolled between January and August 2022. The frequency of IVIg-related headaches was 27.37% (127/464). A binary logistic regression analysis performed with significant clinical features disclosed that female sex and fatigue as a side effect were statistically more common in the IVIg-induced headache group. IVIg-related headache duration was long and affected daily living activities more in patients with migraine compared to no primary headache and TTH groups (p = 0.01, respectively). CONCLUSION: Headache is more likely to occur in female patients receiving IVIg and those who develop fatigue as a side effect during the infusion. Clinicians' awareness of IVIg-related headache characteristics, especially in patients with migraine, may increase treatment compliance.

CD4+ and CD25+ T-cell response to short-time interferon-beta therapy on IL10, IL23A and FOXP3 genes in multiple sclerosis patients.

AIM OF THE STUDY: Interferon-beta (IFN-ß), multiple sclerosis (MS) drug for years, does not have therapeutic effects on each patient. Yet, a considerable portion has experienced no therapeutic response to IFN-ß. Therefore, it is necessary to determine disease-specific biomarkers that affect drug response. Here, we aimed to determine the effects of interleukin 10 (IL10) and 23 (IL23A), as well as forkhead box P3 (FOXP3) genes on MS after IFN-ß therapy. MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMCs) of 42 MS patients were isolated to obtain CD4+ and CD25+ T cells. Both cell types were characterised by flow cytometry. To determine optimum drug concentration of IFN-ß, cytotoxicity assays were assessed on each cell type for 4, 16, 24 and 48 hours respectively. Then, cells were cultured in the presence of 500 IU/mL of IFN-ß. cDNA synthesis was performed after mRNA extraction. RT-PCR was performed to measure gene expressions of IL10, IL23A and FOXP3. Results were evaluated statistically. RESULTS: It was found that the cytotoxic effect of IFN-ß was more efficient as the exposure time was expanded regardless of drug concentration. Moreover, CD25+ T lymphocytes were more resistant to IFN-ß. IL23A was down-regulated, whereas FOXP3 was up-regulated at 48 hours in CD4+ T cells. For CD25+ T cells, the graded increase in FOXP3 was obtained while IL10 expression was gradually decreased throughout the drug intake. CONCLUSION: Although a considerable change in expression was obtained, the long-term IFN-ß effect on both genes and cells should be determined by follow-up at least a year.

ε2 , ε3 , and ε4 variants of ApoE; rs2228570 (VDR), rs4588 and rs7041 (VDBP) polymorphisms in patients with multiple sclerosis: A case-control study in Turkish population.

AIM OF THE STUDY: Multiple sclerosis (MS) is a degenerative disease characterized by autoimmune demyelination in the central nervous system. Yet, underlined genetics or environmental markers are still controversial. The impact of vitamin D and cholesterol on disease activity has been phrased by many studies; however, the data available for the Turkish population are very limited. This study aimed to investigate the effect of vitamin D-related polymorphisms (VDBP and VDR) and cholesterol-related variants of ApoE on Turkish MS patients. MATERIALS AND METHODS: Total DNAs were extracted from peripheral blood samples of 51 MS patients and 50 healthy volunteers. rs4588 and rs7041 polymorphisms of VDBP, rs2228570 of VDR, as well as ε2, ε3, and ε4 variants of ApoE, were investigated by RT-PCR. Biochemical parameters which thought to be associated with MS were also measured. Results were evaluated statistically. RESULTS: Homozygous mutant genotype and G allele of rs2228570 in VDR, as well as heterozygous genotype of rs4588 in VDBP, were found statistically high in patients. Total cholesterol, triglyceride, and LDL-C levels were found significantly high, whereas HDL-C and vitamin D levels were low in patients. An association was found between rs4588 variation and high triglyceride levels. Similar correlations were found between ε2 genotype and low LDL-C level; ε3 genotype and higher LDL-C. Gender, triglyceride, HDL-C, and AA genotype in rs4588 had a significant effect on MS progression. CONCLUSION: The variations of rs2228570 and rs4588, vitamin D deficiency, and biological parameters related to cholesterol metabolism may be associated with MS risk.

Assessment of Patients with Intracerebral Hemorrhage or Hemorrhagic Transformation in the VENOST Study.

INTRODUCTION: Cerebral venous and sinus thrombosis (CVST) may lead to cerebral edema and increased intracranial pressure; besides, ischemic or hemorrhagic lesions may develop. Intracerebral hemorrhages occur in approximately one-third of CVST patients. We assessed and compared the findings of the cerebral hemorrhage (CH) group and the CVST group. MATERIALS AND METHODS: In the VENOST study, medical records of 1,193 patients with CVST, aged over 18 years, were obtained from 35 national stroke centers. Demographic characteristics, clinical symptoms, signs at the admission, radiological findings, etiologic factors, acute and maintenance treatment, and outcome results were reported. The number of involved sinuses or veins, localizations of thrombus, and lesions on CT and MRI scans were recorded. RESULTS: CH was detected in the brain imaging of 241 (21.1%) patients, as hemorrhagic infarction in 198 patients and intracerebral hemorrhage in 43 patients. Gynecologic causes comprised the largest percentage (41.7%) of etiology and risk factors in the CVST group. In the CH group, headache associated with other neurological symptoms was more frequent. These neurological symptoms were epileptic seizures (46.9%), nausea and/or vomiting (36.5%), altered consciousness (36.5%), and focal neurological deficits (33.6%). mRS was ≥3 in 23.1% of the patients in the CH group. DISCUSSION AND CONCLUSION: CVST, an important cause of stroke in the young, should be monitored closely if the patients have additional symptoms of headache, multiple sinus involvement, and CH. Older age and parenchymal lesion, either hemorrhagic infarction or intracerebral hemorrhage, imply poor outcome.

Sleep quality, excessive daytime sleepiness, and depression in Parkinson's disease: implications for improved patient outcomes.

OBJECTIVES: Sleep disorders are frequently encountered non-motor symptoms that significantly impact the lifestyle quality of individuals with Parkinson's disease (PD). Our research endeavors to research the sleep quality of PD patients and define the occurrence of excessive daytime sleepiness (EDS) and nocturnal difficulties within this population. METHODS: We incorporated 140 patients diagnosed with PD and 75 healthy individuals as controls. The modified Hoehn & Yahr Staging Scale (HYS) was employed for the clinical classification of PD stages, while the evaluation of clinical intensity utilized the Unified Parkinson's Disease Rating Scale (UPDRS). The assessment of sleep quality utilized the Pittsburgh Sleep Quality Index (PSQI), along with the Parkinson's Disease Sleep Scale (PDSS), and the Epworth Sleepiness Scale (ESS). Additionally, the subjective depression levels of attendees were assessed by the Beck Depression Inventory. RESULTS: In contrast to the healthy controls, the patient cohort demonstrated notably higher scores across the PSQI scale, ESS, and Beck Depression Scale (p < 0.05). Within the PD patient group, 66.4% exhibited poor sleep quality, and 17.1% reported excessive daytime sleepiness. A significant positive correlation was between poor sleep quality and factors such as H&Y stage, duration of levodopa exposure, scores on the ESS, and the BDI (p < 0.05). Additionally, EDS was positively correlated with UPDRS-I scores, Levodopa equivalent daily dose, PSQI, and BDI scores (p < 0.05). DISCUSSION: Addressing the specific etiology of sleep disorders in Parkinson's patients has the potential to result in improved treatment outcomes and enhanced functionality in their daily lives.

Cluster Analysis Revealed Two Hidden Phenotypes of Cluster Headache.

Objective: To investigate the possible subgroups of patients with Cluster Headache (CH) by using K-means cluster analysis. Methods: A total of 209 individuals (mean (SD) age: 39.8 (11.3) years), diagnosed with CH by headache experts, participated in this cross-sectional multi-center study. All patients completed a semi-structured survey either face to face, preferably, or through phone interviews with a physician. The survey was composed of questions that addressed sociodemographic characteristics as well as detailed clinical features and treatment experiences. Results: Cluster analysis revealed two subgroups. Cluster one patients (n = 81) had younger age at diagnosis (31.04 (9.68) vs. 35.05 (11.02) years; p = 0.009), a higher number of autonomic symptoms (3.28 (1.16) vs. 1.99(0.95); p < 0.001), and showed a better response to triptans (50.00% vs. 28.00; p < 0.001) during attacks, compared with the cluster two subgroup (n = 122). Cluster two patients had higher rates of current smoking (76.0 vs. 33.0%; p=0.002), higher rates of smoking at diagnosis (78.0 vs. 32.0%; p=0.006), higher rates of parental smoking/tobacco exposure during childhood (72.0 vs. 33.0%; p = 0.010), longer duration of attacks with (44.21 (34.44) min. vs. 34.51 (24.97) min; p=0.005) and without (97.50 (63.58) min. vs. (83.95 (49.07) min; p = 0.035) treatment and higher rates of emergency department visits in the last year (81.0 vs. 26.0%; p< 0.001). Conclusions: Cluster one and cluster two patients had different phenotypic features, possibly indicating different underlying genetic mechanisms. The cluster 1 phenotype may suggest a genetic or biology-based etiology, whereas the cluster two phenotype may be related to epigenetic mechanisms. Toxic exposure to cigarettes, either personally or secondarily, seems to be an important factor in the cluster two subgroup, inducing drug resistance and longer attacks. We need more studies to elaborate the causal relationship and the missing links of neurobiological pathways of cigarette smoking regarding the identified distinct phenotypic classes of patients with CH.

Prognostic role of mean platelet volume and platelet count in ischemic and hemorrhagic stroke.

BACKGROUND: Mean platelet volume (MPV) is an indicator of platelet function or reactivity. Platelets play an important role in the pathophysiology of ischemic stroke but the effect of platelet count (PC) and dysfunction in the pathogenesis of hemorrhagic stroke is poorly understood. We have investigated the possibility of MPV and PC being an independent risk factor of ischemic and haemorrhagic stroke and their effect on prognosis. METHODS: We prospectively studied 692 patients with either ischemic or hemorrhagic stroke and compared them with 208 control subjects with similar risk factors, but without evidence of vascular events. The association of MPV and PC with cause, localization, and size of the infarct or hemorrhage was examined. Prognosis was determined by Glasgow Outcome Scale. By multivariate logistic regression analysis, the influence of MPV and PC on stroke subtype and prognosis was determined. RESULTS: MPV and PC were observed as independent risk factors for ischemic stroke (P = .007, odds ratio [OR] = 0.866; P = .000, OR = 0.996; 95% confidence interval [CI], respectively). There was a negative and significant correlation between PC and hemorrhagic stroke (P = .001), but no association was found with MPV (P > .05). MPV and PC were not statistically significant related to etiological subgroups, localization, and size of the infarct or hemorrhage (P > .05). Ischemic group MPV (P = .013, OR = 1.02, 95% CI) and hemorrhagic group PC were in correlation with worse outcome (P = .001, OR = 1.004, 95% CI). CONCLUSION: MPV, may be an early and important predictor for the prognosis of ischemic stroke, whereas for hemorrhagic stroke PC has a role for outcome.

Primary headache associated with sexual activity: A case series of 13 patients.

Primary headache associated with sexual activity is an infrequent kind of headache mostly seen in the male gender and initiates during the third decade. Although the pathophysiology is still unknown, it is a benign type of headache and must be reminded of the differential diagnosis of the secondary headache. Thirteen patients were diagnosed and assessed by their clinical and demographic data. The mean age was 37.07 ± 7.67. Headache was usually localized at the bilateral occipital area or diffuse, starting with a severe ache and sudden explosive intensity in association with pre orgasm in eight patients and orgasm in five patients with a mean VAS score of 7.8 ± 1.2. The mean duration was 21.53 ± 15.32 min. Five patients had a history of migraine, three had arterial hypertension, and two were diagnosed as primary thunderclap headache with sudden beginning and high-intensity ache. Herein, we present our cases to highlight the importance of differential diagnosis. Patients may have difficulty explaining the problem; therefore, their sexual activity could be limited. Apart from pharmacological prevention, counseling plays an essential role in managing.

Assessment of P wave duration and dispersion in Parkinson's disease.

Cardiovascular disorders such as decreased heart rate variability, orthostatic hypotension, and arrhythmias have been frequently observed in Parkinson's disease (PD) patients. In this study, authors measured P wave duration and dispersion in PD patients and controls. Twenty-three consecutive patients with idiopathic PD and sex-age matched 23 control subjects were included to the study. A 12-lead surface ECG was obtained from each participant. Maximum-minimum P wave duration and P wave dispersion (PWD) were measured in both groups. Maximum P wave duration was found to be higher in PD patients than controls (117+/-12 vs. 105+/-9 ms p=0.001). Minimum P wave duration was similar in PD patients and controls (64+/-11 vs. 63+/-11 ms p=0.7). PWD in PD patients was also found to be higher than those of controls (53+/-11 vs. 43+/-10 ms p=0.0001). P wave duration and PWD did not significantly differ between PD patients taking anti-parkinsonian agents from those who were not (119+/-13 vs. 116+/-13 ms p=0.4 and 55+/-11 vs. 52+/-11 ms p=0.5, respectively). Moreover, when the PD patients taking anti-parkinsonian agents were excluded from the study, PD patients had still higher P wave duration and PWD compared to controls (119+/-11 vs. 105+/-9 ms p=0.004, 52+/-10 vs. 43+/-10 ms p=0.009, respectively). In conclusion, we found that P wave duration and PWD were greater in PD patients compared to control subjects.

Ischemic stroke in the vertebrobasilar system. Risk factors, etiology, and localization.

OBJECTIVE: To investigate and determine the clinical findings, lesions, risk factors, and variety of etiology in Turkish patients suffering from vertebrobasilar ischemia. METHODS: The clinical, radiological, and prognostic features of patients with ischemic stroke in the vertebrobasilar system (VBS) are not homogeneous. The mechanism, localization, and severity of the vascular lesions and the presence of coexisting vascular risk factors influence the prognosis. The study included 134 patients with ischemic strokes in the VBS that were evaluated according to age, gender, clinical findings, risk factors, lesion localization, echocardiography, Doppler sonography, and cervical magnetic resonance angiography at Haydarpasa Numune Education and Research Hospital, Istanbul, Turkey between 1998-2002. RESULTS: Hypertension, heart disease, smoking, diabetes mellitus, and hyperlipidemia were the most commonly observed risk factors. While infratentorial involvement was seen at a higher ratio (75.4%), acute multi-infarcts appearing simultaneously were mostly localized in the thalamus and the brain stem (18.7%). Large and small vessel disease incidences have been found in 32.8% and 20.1% of the patients. Cardioembolism with an incidence rate of 41.8% was the most frequent etiological cause in VBS ischemia. No significant meaning has been developed with age and gender as compared to the relationship between localization and etiological subgroups. CONCLUSION: The most common risk factors were hypertension and cardiac diseases, and the most common localization of the infarcts was the infratentorial region. The cerebellum was seen as the most coexisting localization with all multiple infarcts. Cardioembolism accounted for the largest etiological group in all localizations and in multiple infarcts.