Sriwijaya Journal of Neurology

Terminal Insomnia as a Phenotypic Biomarker of Geriatric Depression in a Balinese Cohort: A Cross-Sectional Analysis of Circadian Disruption and Sleep Continuity

Made Citra Riesti Wulan — 2025-12-17

Introduction: Sleep architecture undergoes significant fragmentation during aging, yet the specific phenotypic expression of insomnia in the context of geriatric depression remains under-characterized. While the bidirectional relationship between depression and sleep is established, few studies distinguish between initial, middle, and terminal insomnia subtypes in Southeast Asian geriatric populations. This study aims to characterize the predominant insomnia phenotypes among elderly patients with depression and investigate the association between sociodemographic determinants, chronic morbidity, and specific sleep continuity disturbances.

Methods: A cross-sectional analytical study was conducted at the Geriatric Outpatient Clinic of Karangasem Regional General Hospital, Bali, Indonesia (N=58). Psychometric evaluation utilized the Geriatric Depression Scale (GDS-15) to screen for depressive symptoms and the Pittsburgh Sleep Quality Index (PSQI) to assess global sleep quality. Insomnia phenotypes were clinically adjudicated based on diagnostic interviews. To account for potential confounders, body mass index (BMI) and chronic pain scores were included in the analysis. Data were analyzed using Firth’s Penalized Likelihood Logistic Regression to stabilize estimates given the sample size.

Results: The prevalence of depression in the cohort was 58.3%. Among depressed elderly patients, terminal (Late) Insomnia was the predominant phenotype, affecting 76.0% of the subgroup, followed by middle insomnia (66.7%) and initial insomnia (36.4%). Multivariate analysis adjusted for age, chronic disease status, BMI, and pain demonstrated that Terminal Insomnia was the strongest independent predictor of depression (Adjusted OR 6.42; 95% CI 2.15–14.8; p<0.001).

Conclusion: Terminal insomnia represents a distinct and dominant clinical phenotype of depression in this geriatric cohort, potentially reflecting underlying circadian phase advances and HPA-axis hyperactivity characteristic of melancholic depression. Clinicians should prioritize sleep maintenance strategies over sleep induction pharmacotherapy in this population.

Tenecteplase versus Alteplase or Standard Care for Improving Functional Outcomes in Acute Ischaemic Stroke: A Systematic Review and Meta-Analysis

Steffanny Regina Maria Andini — 2026-05-22

Introduction: Intravenous alteplase is the standard fibrinolytic for acute ischaemic stroke, but tenecteplase offers practical advantages as a single-bolus alternative. This systematic review and meta-analysis aimed to consolidate recent randomised controlled trial (RCT) evidence on the effectiveness of tenecteplase for improving functional outcomes, with explicit attention to dose stratification.

Methods: Following the PRISMA 2020 framework, we searched PubMed for RCTs published between January 2017 and May 2026 comparing tenecteplase with alteplase or standard care. The primary efficacy outcome was an excellent functional outcome at 90 days (modified Rankin Scale 0–1). Trial-level effects were harmonised on a standardised mean-difference scale (Hedges g) and pooled using a DerSimonian–Laird random-effects model. Pre-specified subgroup analyses examined dose (0.25 vs 0.40 mg/kg).

Results: Ten RCTs (n=7,118) met eligibility, and eight contributed dichotomous data to the quantitative synthesis. The pooled Hedges g was 0.063 (95% CI –0.067 to 0.192; p=0.344) with substantial heterogeneity (I²=77.1%). Tenecteplase 0.25 mg/kg produced a small but statistically significant favourable effect (Hedges g 0.108; 95% CI 0.0001 to 0.215), whereas the 0.40 mg/kg dose was directionally inferior. Excluding the prematurely terminated NOR-TEST 2 Part A trial yielded a pooled Hedges g of 0.088 (p=0.029) and reduced heterogeneity (I²=39.7%).

Conclusion: Intravenous tenecteplase performed at least as well as alteplase or standard medical care for 90-day functional recovery, with the most favourable signal confined to the 0.25 mg/kg dose. The findings supported the integration of tenecteplase 0.25 mg/kg into standard acute neurology pathways, particularly where bolus administration simplified workflow.

Efficacy and Safety of Melatonin on Pain Intensity and Sleep Quality in Adults with Neuropathic Pain: A Systematic Review and Meta-Analysis of Randomised Controlled Trials

Maria Pamela Tiffani — 2026-05-25

Introduction: Neuropathic pain frequently coexists with sleep disturbance, and current pharmacotherapy is constrained by limited efficacy and adverse effects. Melatonin, a pleiotropic neurohormone with analgesic, antioxidant, anti-inflammatory and chronobiotic properties, has been proposed as an adjunctive treatment, but its magnitude of clinical benefit on pain and sleep across heterogeneous neuropathic-pain populations had not previously been quantitatively synthesised in a meta-analysis specific to neurology practice.

Methods: PubMed, Embase, Web of Science and the Cochrane Central Register of Controlled Trials were searched for randomised controlled trials of oral melatonin versus placebo or active control in adults with neuropathic pain, in accordance with PRISMA 2020. Two reviewers independently screened, extracted and assessed risk of bias using Cochrane RoB 2.0 with the crossover extension where applicable. The primary outcome was change in pain intensity (NRS or VAS); secondary outcomes were sleep quality (PSQI, ESS, sleep-interference NRS), responder rate (≥ 50 % pain reduction) and adverse events. Standardised mean differences (Hedges’ g) were pooled under a random-effects model with restricted maximum likelihood and Knapp–Hartung adjustment, with parallel raw mean differences on the NRS where instruments matched. Heterogeneity was quantified with I² and τ². Pre-specified subgroups examined etiology, dose and duration; sensitivity analyses used leave-one-out resampling and exclusion of the open-label and the mechanism-only trials.

Results: Ten randomised controlled trials enrolling 491 participants were included. The exploratory primary pooled SMD across the two trials with extractable continuous pain data was −0.43 (95 % CI −4.86 to 4.00; I² = 77.8 %; P = 0.436); the wide interval reflects the Knapp–Hartung correction with k = 2 and is a structural feature of the methodology. The corresponding raw mean difference on the NRS 0–10 scale was −0.70 (95 % CI −1.99 to 0.59). Substantial heterogeneity was driven by divergent results in painful diabetic neuropathy (SMD −0.76, 95 % CI −1.16 to −0.36; raw NRS difference 1.3 points; P < 0.001) and mixed neuropathic pain (SMD −0.06, 95 % CI −0.57 to 0.45; P = 0.8). Sleep favoured melatonin in painful diabetic neuropathy (sleep-interference SMD −0.81, 95 % CI −1.21 to −0.41) and in multiple-sclerosis-related neuropathic pain (PSQI ↓ 55.9 %, P < 0.001). The ≥ 50 % responder rate in painful diabetic neuropathy was higher with melatonin (RR 1.47, 95 % CI 1.01 to 2.14). Risk of bias was low for six trials, raised some concerns for three trials and was high for one open-label trial. Adverse events were infrequent and did not differ from placebo.

Conclusion: Current evidence indicates that melatonin reduces pain and improves sleep in painful diabetic peripheral neuropathy with concomitant sleep disturbance and may benefit selected post-surgical neurosensory deficits and multiple-sclerosis-related neuropathic pain, but is unlikely to benefit unselected mixed neuropathic pain in tertiary chronic-pain settings. Substantial clinical heterogeneity and the small number of pooled trials preclude routine recommendation. Adequately powered, etiology-stratified trials with harmonised pain and sleep endpoints are required.

Inflammatory and Neuroendocrine Biomarkers of Insomnia in Acute Ischaemic Stroke: A Systematic Review and Meta-Analysis

Alinda Weka Danastuti — 2026-05-28

Introduction: Insomnia complicates 40-75 % of acute ischaemic strokes (AIS) yet its biological determinants remain incompletely synthesised. We aimed to quantify the association between inflammatory and neuroendocrine biomarkers and post-stroke insomnia in AIS.

Methods: PubMed/MEDLINE, Scopus, Web of Science and Cochrane Central were searched systematically. Observational studies reporting cortisol, the neutrophil-to-lymphocyte ratio (NLR), composite indices (PLR, SII, MHR) or cytokines (IL-6, IL-18, TNF-alpha, hs-CRP) alongside a validated sleep outcome (PSQI, ISI or HAMD insomnia items) in adult AIS were eligible. Risk of bias was appraised with the Newcastle-Ottawa Scale, JBI checklist and the ROBINS-I framework. Standardised mean differences (Hedges g) were pooled in a DerSimonian-Laird random-effects model, with Hartung-Knapp confirmation.

Results:Thirteen studies entered qualitative synthesis; eight cohorts (n = 2 455) contributed 12 effects to the primary meta-analysis. The pooled g was 0.79 (95 % CI 0.52-1.05; p < 0.0001), with high heterogeneity (I²= 86.2 %). The composite-inflammation subgroup gave the most reproducible estimate (g = 0.53, 95 % CI 0.33-0.72, I² = 17.5 %). Leave-one-out g was 0.69-0.83 (all p < 1 × 10⁻⁷); Egger (p = 0.887) and Begg (p = 0.79) detected no small-study effect.

Conclusion: Cortisol, NLR and composite inflammatory indices are robustly associated with insomnia in AIS, with composite indices the most reproducible biomarker class, supporting early biomarker-based identification of patients at risk for post-stroke insomnia.