Elif Simin Issı

Background: Bedside prognostication after acute ischemic stroke remains challenging despite the availability of several composite scores, which often demand variables not routinely obtained at admission. Whether the combination of baseline neurological severity and early non-contrast computed tomography findings can support parsimonious, contemporaneous prediction of 3-month functional outcome is an open question, particularly given the well-documented overlap between clinical and imaging measures of stroke extent. Methods: We retrospectively analyzed 432 consecutive adults admitted with confirmed anterior-circulation acute ischemic stroke to a Turkish tertiary care university hospital between January 2022 and December 2025. The primary outcome was a poor functional outcome, defined as modified Rankin Scale (mRS) score 3–6 at 3 months. A prespecified multivariable logistic regression model incorporated three admission variables: baseline National Institutes of Health Stroke Scale (NIHSS) per five-point increment, Alberta Stroke Program Early CT Score (ASPECTS) per one-point increment, and age dichotomized at 65 years. Model performance was assessed with the area under the receiver operating characteristic curve (AUC), five-fold stratified cross-validation, and calibration testing. We additionally performed DeLong tests, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) analyses to evaluate the incremental contribution of ASPECTS, and compared the parsimonious model against a comprehensive multivariable model containing ten predictors. Results: At 3 months, 252 patients (58.3%) had poor functional outcome, with 177 deaths (41.0%). Baseline NIHSS emerged as the dominant predictor (adjusted odds ratio [aOR] 4.16 per five-point increase, 95% confidence interval [CI] 2.79–6.22, p < 0.001), whereas ASPECTS retained no independent prognostic value after adjustment (aOR 0.99 per point, 95% CI 0.73–1.34, p = 0.952). Age ≥ 65 years was likewise non-significant (aOR 0.79, 95% CI 0.46–1.37, p = 0.405). The parsimonious model achieved excellent discrimination (AUC 0.904, 95% CI 0.876–0.932; cross-validated AUC 0.899, 95% CI 0.873–0.926) and good overall calibration on internal validation (calibration slope 0.958; calibration-in-the-large 0.009), although the Hosmer–Lemeshow test was significant (p = 0.001), reflecting localized miscalibration in the intermediate-risk range. Adding ASPECTS to a reduced model containing only NIHSS and age produced no meaningful discrimination gain (ΔAUC + 0.0003, DeLong p = 0.50; IDI ≈ 0), consistent with substantial variance sharing between NIHSS and ASPECTS (Spearman ρ = −0.89). A comprehensive model including infarct volume, Glasgow Coma Scale, reperfusion therapy, and comorbidities did not improve discrimination (AUC 0.905) and yielded a worse Akaike information criterion, supporting the sufficiency of the parsimonious model. Conclusions: In this Turkish tertiary center cohort, baseline NIHSS captured most of the prognostic information available at admission, and early ASPECTS added minimal independent value once neurological severity was accounted for. Findings should be interpreted in the context of the high case-mix severity of this referral population; external validation in independent, multicenter cohorts is required before clinical implementation is considered.

Background: Trigeminal neuralgia (TN) is a severe neuropathic pain disorder primarily diagnosed on clinical grounds, and objective molecular biomarkers that could support diagnosis remain limited. Increasing evidence suggests that inflammation–apoptosis interactions contribute to TN pathophysiology. Methods: In this exploratory prospective case–control study, circulating apoptosis-related microRNAs (miRNAs) were analyzed in 30 patients with idiopathic TN and 20 healthy controls. Plasma miRNA expression levels were quantified using quantitative real-time polymerase chain reaction. Diagnostic performance of individual miRNAs was assessed using receiver operating characteristic (ROC) curve analysis. A multivariable logistic regression model integrating multiple miRNAs was constructed to evaluate combined diagnostic performance, with internal validation performed using five-fold cross-validation. Results: Circulating miRNA expression profiles differed between TN patients and controls. Among individual markers, hsa-miR-183-5p demonstrated the highest diagnostic accuracy (AUC = 0.72), followed by hsa-miR-23a-3p (AUC = 0.65). hsa-miR-223-3p showed reversed directionality (AUC = 0.28), consistent with lower expression in TN and high specificity but low sensitivity at the optimal threshold. The combined miRNA panel achieved an apparent AUC of 0.86, with a mean cross-validated AUC of 0.84 ± 0.12, suggesting improved discrimination over single miRNAs but with variability consistent with the limited sample size. Conclusions: Apoptosis-related circulating miRNAs exhibit distinct expression patterns in idiopathic TN. While individual miRNAs show modest diagnostic performance, integration into a multi-miRNA panel improved discrimination between TN patients and healthy controls in this pilot dataset. These findings support the potential of apoptosis-based miRNA signatures as candidate minimally invasive biomarkers for TN, warranting further validation in larger, independent cohorts, ideally including clinically relevant disease-control facial pain conditions.

Trigeminal neuralgia (TN) is a debilitating neuropathic pain disorder characterized by severe paroxysmal facial pain. Increasing evidence indicates that Schwann cell dysfunction and altered nerve repair mechanisms contribute to TN pathology. MicroRNAs (miRNAs), as key regulators of Schwann cell plasticity, myelination, inflammation, and nerve regeneration, represent promising biomarker candidates. This study aimed to investigate differential expression patterns of Schwann cell-associated miRNAs (miR-221-3p, miR-132-3p, miR-210-5p, miR-340-3p, miR-98-5p, miR-182-5p) in patients with trigeminal neuralgia and evaluate their diagnostic biomarker potential. Expression analysis was performed using quantitative real-time PCR with 5s rRNA as the reference gene. miRNA expression levels were evaluated by qRT-PCR. Differential expression was calculated using ΔCt, ΔΔCt, and fold-change analyses. Diagnostic performance was assessed using ROC curve analysis. Integrated visualization was carried out using scatter plots, volcano plots, and z-score-normalized heatmaps. miR-221-3p was significantly upregulated in patients with trigeminal neuralgia (TN), whereas miR-340-3p and miR-182-5p were downregulated. Hierarchical clustering and principal component analysis (PCA) demonstrated a clear separation between patient and control miRNA expression profiles. In receiver operating characteristic (ROC) analyses, miR-221-3p emerged as the most powerful individual biomarker (AUC = 0.699), while the combined miRNA panel achieved high diagnostic performance (AUC = 0.89). Downregulated miRNAs reflect suppressed inhibitory signaling pathways, suggesting that miRNA profiling may provide valuable insights into Schwann cell pathology in TN. The selected miRNAs, which are implicated in impaired Schwann cell repair mechanisms, represent promising molecular biomarker candidates for the diagnosis of TN and potentially for guiding therapeutic strategies.

Purpose: This study aimed to investigate autonomic alterations associated with periodic limb movements during sleep (PLMS) by comparing linear and non-linear heart rate variability (HRV) parameters across whole-night recordings and stage N2 non-rapid eye movement (NREM) sleep (N2). Methods: From 8082 polysomnographic (PSG) recordings, we identified 21 patients with PLMS and 28 age- and sex-matched controls. Linear and non-linear HRV indices were analyzed for whole-night recordings and the longest N2 segment. Periodic limb movement (PLM) indices and arousal-related parameters were also evaluated. Results: Compared with controls, patients with PLMS showed significantly higher standard deviation of normal-to-normal intervals (SDNN) and root mean square of successive differences (RMSSD), increased low-frequency (LF) power, and reduced approximate entropy (ApEn) and sample entropy (SampEn) across the whole night, together with a lower Stress Index (SI). No significant group differences were observed in high-frequency (HF) power or in the composite sympathetic/parasympathetic nervous system (SNS/PNS) indices. During stage N2, the PLM group exhibited significantly greater SDNN, Poincaré plot long-axis standard deviation (SD2), detrended fluctuation analysis alpha-1 exponent (DFA α1), and very-low-frequency (VLF) power, along with lower ApEn values. A significant increase in the SD2/SD1 ratio was also observed specifically during N2, whereas the LF/HF ratio showed only a non-significant upward trend. PLMS counts, indices, and arousal-related parameters were markedly elevated during stage N2. Conclusions: PLMS are characterized by increased autonomic variability (SDNN, SD2, DFA α1) but reduced complexity (ApEn, SampEn), particularly during stage N2. Stage-specific HRV assessment may provide novel insights into the cardiovascular implications of PLMS.

This study aimed to evaluate macro- and micro-architectural parameters of the N3 sleep stage in patients with REM-dependent obstructive sleep apnea (OSA). This single-center retrospective study compared the macroarchitecture and delta band measures of Non-Rapid Eye Movement sleep stage 3 (N3) between healthy individuals (n=20), patients with Sleep-stage independent obstructive sleep apnea (OSA, n=20), and those with Rapid Eye Movement (REM)-dependent OSA (n=20). REM-dependent OSA was defined by an apnea–hypopnea index (AHI) ≥5/hour, a REM/NREM AHI ratio ≥2, and a REM duration of at least 30 minutes. Analyses were performed on the longest artifact-free 5-minute N3 segment in the first half of the night, using the F3–A2 derivation and a Welch-based spectral method. Absolute delta power (1–4 Hz, µV²) and % Slow-Wave Activity (SWA)-N3 (1–4/1–50 Hz) were calculated. The N3 duration and percentage showed significant differences between groups (p=0.004 and p=0.002, respectively), with longer and higher values in the control group. However, absolute delta power (p=0.396) and %SWA-N3 (p=0.122) showed no significant differences between groups. These findings indicate that N3 duration is significantly reduced in OSAS phenotypes, but N3 depth remains at the same level as in controls. To our knowledge, this study is among the few to directly assess N3 delta power in the REM-dependent OSA subgroup, thus contributing novel evidence to the field. Future research is needed in larger cohorts using multiple N3 segments and covariance-adjusted models (e.g., age, BMI, hypoxemia indices).

OBJECTIVE: Inflammation has been investigated as a possible mechanism for underlying migraine. Many studies continue to be conducted on the role of obesity and adipokines in inflammation and their relationship with migraine. Our objective was to determine the relationship between plasma adiponectin (ADP) levels, body mass index (BMI), and C-reactive protein (CRP), with the frequency and severity of migraine attacks in premenopausal women during the interictal period. MATERIAL AND METHODS: The study included 38 premenopausal women receiving outpatient treatment for migraine and 32 age-matched healthy controls. The patients were diagnosed with migraine according to the International Headache Society criteria. The patients' CRP, ADP levels, leukocyte counts during the headache-free period, and BMI were compared with those of the control group. RESULTS: A positive and statistically significant correlation was observed in the comparison of BMI and CRP levels in both the patient and control groups (p=0.01, p=0.03, respectively). No correlation could be established in terms of the comparison of BMI and ADP levels in either group (p=0.053 for controls, p=0.285 for patients). No statistically significant association was found in the comparison of the frequency of migraine attacks with the BMI, CRP, and ADP levels of the patients (p=0.669, p=0.989, p=0.201, respectively). A positive and significant relationship was determined between BMI and pain severity (p=0.017). However, no relationship between CRP, ADP levels, and pain severity was found (p=0.827, p=0.359, respectively). CONCLUSIONS: CRP, as an established marker of inflammation, increases in relation to a rise in BMI. High BMI may contribute to the development of severe migraine attacks. In conclusion, preventing weight gain and advising weight loss may be a therapeutic strategy for managing severe headache attacks.

Background: Intramuscular injections are routine interventions worldwide, yet when executed incorrectly they can cause sciatic nerve injury (SNI) that leaves patients with lifelong motor-sensory disability. Although international guidelines recommend the ventrogluteal site, the dorsogluteal region remains dominant in Turkey, potentially elevating risk. This study analysed Turkish Supreme Court decisions on injection-induced SNI from public-health, ethical and legal perspectives. Methods: We conducted a retrospective cross-sectional content analysis of all publicly available Supreme Court criminal and civil decisions issued between January 2006 and April 2025 that contained SNI-related keywords. After deduplication and relevance screening, 92 unique cases were eligible. Two investigators independently coded each judgment; disagreements were resolved by consensus. Variables recorded were legal category, injection site, clinical indication, drug class, injector profession, defendant identity, symptom latency, electrophysiological pattern, first-instance verdict and Supreme Court outcome. Frequencies and percentages were calculated with SPSS v.29. Results: Negligent bodily injury was the leading charge (50/92, 54%); 32% of files also sought monetary compensation. Gluteal injections accounted for 79% of cases, most administered for postoperative analgesia (33%) or antibiotic therapy (27%). Nurses performed 60% of injections, physicians 9%. Individual health professionals (physicians ± nurses) were defendants in 65% of lawsuits, while hospitals (alone or jointly) appeared in 23%. Symptoms emerged immediately or within 1 h in 76% of plaintiffs, and electromyography typically revealed severe axonal damage—predominantly of the peroneal division. The Supreme Court overturned 100% of firstinstance convictions and 32% of acquittals, most often citing inadequate expert evaluation (35%), contradictory reports (20%), uncertainty over negligence versus complication (18%) or missing informedconsent documentation (10%). Conclusions: Injection-related sciatic nerve injuries in Turkey remain potentially preventable. The entrenched use of the dorsogluteal site, limited anatomical awareness, inadequate informed consent practices, and inconsistencies in medico-legal evaluations continue to contribute to both patient harm and an increased burden of litigation. Transitioning to the ventrogluteal technique, mandating annual refresher training, standardising consent forms, and accrediting neurophysiology expert panels could help reduce both injury incidence and courtroom burden—advancing the WHO’s “zero harm” patient safety goal.

Background: Despite the identification of various environmental factors that increase the risk of multiple sclerosis (MS), the effects of many factors on the etiology of MS remain to be elucidated. In this study, we aimed to investigate the effects of radon, a factor previously studied in relation to various other neurodegenerative diseases, on the epidemiology of MS. Methods: A door-to-door field study was conducted in residential areas with relatively high and low radon gas concentrations to determine the prevalence of MS. The study area comprises the Bolvadin and İhsaniye regions, which have different geological characteristics, such as seismic activity, active faults, and distributions of volcanic rocks. CR-39 detectors, with an accepted limit of 300 Bq/m³, were utilized to measure radon gas concentrations. During the screening field, the patients diagnosed with multiple sclerosis were confirmed with their hospital records. Mc Donald’s revised diagnostic criteria were used for multiple sclerosis diagnosis. Results: The regions were grouped into higher radon areas and lower radon areas. The İhsaniye city center, Kayıhan, Kemerkaya, Döğer, and Bolvadin city center were classified as higher radon regions, whereas Dişli, Yaylabağı, Gazlıgöl, and Özburun were identified as lower radon regions. A total of 40,841 individuals were surveyed in the field. The crude MS prevalence was 41.8/100,000 in settlements with high radon gas concentrations and 20.5/100,000 in settlements with low radon gas concentrations. Conclusions: In this study, we revealed that the prevalence of MS was greater in settlements with high radon gas concentrations than in settlements with low radon gas concentrations. These results demonstrated that radon gas is an important environmental risk factor in the etiopathogenesis of MS.

Small fiber neuropathy (SFN) affects thinly myelinated and unmyelinated fibers, often presenting with subtle clinical signs that are undetectable in routine nerve conduction studies. Vitamin B12 deficiency is a known risk factor for SFN, yet early-stage cases frequently remain undiagnosed. Sympathetic skin response (SSR) and cutaneous silent period (CSP) are noninvasive electrophysiological techniques used to assess autonomic and somatic small fiber function.The present study aimed to evaluate the diagnostic utility of SSR and CSP in detecting possible subclinical small-fiber neuropathy (pSFN) in individuals with early-stage vitamin B12 deficiency.The present observational study included 28 patients with vitamin B12 deficiency who had nonspecific complaints, Douleur Neuropathique en 4 Questions (DN4) scores < 4, and normal nerve conduction studies, along with 25 healthy controls. Electrophysiological testing involved SSR recordings from all extremities and CSP measurements from the right median and sural nerves.In the patient group, Median Nerve Cutaneous Silent Period (MN-CSP) and Tibialis Anterior -Sural Cutaneous Silent Period (TA-sural CSP) durations were significantly shorter, while termination and onset latencies were prolonged compared with controls. MN-CSP and TA-sural CSP durations demonstrated high diagnostic accuracy. Sympathetic skin response latencies were significantly prolonged in both hands and feet, indicating autonomic dysfunction. No significant differences were observed in SSR amplitudes.Sympathetic skin response and CSP are valuable tools for detecting possible subclinical SFN in vitamin B12 deficiency. Sympathetic skin response effectively identified autonomic dysfunction, while CSP provided additional diagnostic value for somatic small fiber impairment. Combining SSR and CSP may enhance early detection of pSFN in vitamin B12 deficiency and allow timely intervention.