BACKGROUND: Intravenous thrombolysis is a standard treatment for acute ischemic stroke but has traditionally been limited to 4.5 hours after symptom onset. This time-based restriction may exclude patients with salvageable brain tissue, especially those with wake-up or unknown-onset strokes. Multimodal imaging allows for the identification of viable penumbra beyond traditional treatment windows. This study compiles randomized evidence evaluating intravenous thrombolysis in imaging-selected patients treated after 4.5 hours. METHODS: We conducted a systematic review and meta-analysis in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed, Embase, and Cochrane Central were searched through February 2026 for randomized trials comparing intravenous thrombolysis (alteplase or tenecteplase) with best medical therapy in patients presenting beyond 4.5 hours or with wake-up/unknown-onset stroke selected by imaging. The primary outcome was excellent functional outcome at 90 days (modified Rankin Scale score 0–1). Secondary outcomes included functional independence (modified Rankin Scale score 0–2), symptomatic intracranial hemorrhage, and 90-day mortality. RESULTS: Fourteen trials involving 4192 participants were analyzed. Intravenous thrombolysis improved excellent functional outcomes (modified Rankin Scale score 0–1; risk ratio, 1.22 [95% CI, 1.16–1.29]) and functional independence (modified Rankin Scale score 0–2; risk ratio, 1.12 [95% CI, 1.06–1.18]). Both alteplase and tenecteplase contributed to these benefits. Thrombolysis increased the risk of symptomatic intracranial hemorrhage (risk ratio, 2.58 [95% CI, 1.58–4.22]) but did not significantly affect 90-day mortality (risk ratio, 1.15 [95% CI, 0.97–1.35]). CONCLUSIONS: In patients selected using advanced imaging, intravenous thrombolysis performed after 4.5 hours improves functional outcomes without increasing mortality, supporting a tissue-based rather than strictly time-based approach to treating acute ischemic stroke.

Background: Anti‐NMDA receptor encephalitis is an autoimmune disorder that affects the brain, leading to a combination of neuropsychiatric symptoms, including severe mood changes, agitation, and psychosis, as well as cognitive impairments resembling dementia. It is commonly seen in young individuals and requires early intervention to prevent long‐term neuropsychiatric deficits. Method: Case Study Result: A 20‐year‐old male, born from a non‐consanguineous marriage, presented with a history of multiple episodes of new‐onset focal seizures, which were followed by well‐formed visual hallucinations. Over a period of days, he developed significant behavioral changes, including agitation, anger outbursts, memory disturbances, and a marked decrease in interest in daily activities. His speech output also diminished progressively and eventually led to a mute state. The patient showed increased slowness in activities and a general decline in functional ability. On neurological examination, the patient was found to be in a severe catatonic state, unable to communicate or engage in any purposeful movements. Perioral dyskinesias, characterized by involuntary movements of the mouth, were noted. The remainder of the examination, including cranial nerve function, motor, sensory, cerebellar, and extrapyramidal assessments, was grossly normal. Further investigations included a plain MRI of the brain, which showed a left temporal hyperintensity, suggestive of inflammation, though no other structural abnormalities were identified. EEG was normal, which is not uncommon in early stages of this condition. CSF analysis was normal, with no signs of infection or inflammatory changes. An autoimmune panel was sent, and NMDA receptor antibodies were found to be positive, confirming the diagnosis of anti‐NMDA receptor encephalitis. The patient was started on intravenous immunoglobulin (IVIG) therapy, resulting in a significant improvement in his clinical condition, including resolution of catatonia and gradual restoration of speech and cognitive function. Conclusion: Early recognition of anti‐NMDA receptor encephalitis, characterized by neuropsychiatric and cognitive symptoms, is critical. Timely treatment with immunotherapy like IVIG can significantly improve recovery and prevent irreversible cognitive decline, highlighting the importance of prompt diagnosis in managing this potentially reversible form of encephalitis.

Background: Multiple sclerosis (MS), an autoimmune disease, involves peripheral immune activation followed by CNS inflammation in a compartmentalized manner. Although high-efficacy disease-modifying therapies (HE-DMTs) have been effective in suppressing relapses in MS patients, they fail to effectively target chronic microglial activation and smoldering lesions in MS patients. Bruton’s tyrosine kinase inhibitors (BTKis), which are orally active and capable of crossing the blood–brain barrier, have been found to be effective in modulating B cells and CNS-resident myeloid cells. Objective: The objective was to assess the efficacy and safety of Bruton’s tyrosine kinase inhibitors in patients with relapsing, secondary, and primary progressive MS. Methods: We performed a systematic review and meta-analysis according to the Cochrane and PRISMA guidelines (PROSPERO registration number: 1323474). We included randomized controlled trials (RCTs) that assessed fenebrutinib, evobrutinib, or tolebrutinib in adult MS patient populations. The main outcome measures were annualized relapse rate, MRI lesion activity, disability progression (EDSS), and hepatotoxicity. The quality of the included trials was assessed for bias by the RoB2 tool. Results: Six RCTs with 3616 participants were included. BTK inhibitors significantly reduced ARR compared with control therapy (pooled RR 0.24; 95% CI 0.15–0.39). MRI activity was reduced (mean difference −1.45 new/enlarging T2 lesions; 95% CI −2.08 to −0.82). Disability progression was unchanged in short-term relapsing MS trials. Serious hepatotoxicity was reported in 11.0% of BTKi-treated patients compared with 13.7% of control patients (pooled RR 0.80; 95% CI 0.66–0.96). However, increased transaminase elevations were reported in placebo-controlled trials, which indicates that hepatotoxicity remains a clinically relevant safety concern for the class. Conclusions: BTK inhibitors reduce inflammatory disease activity in relapsing MS and have emerging efficacy in progressive MS phenotypes; however, continued monitoring for hepatotoxicity is warranted. Optimization of CNS penetrance and pharmacologic selectivity may influence long-term clinical positioning.

Background: Primary central nervous system histiocytic sarcoma (PCNSHS) is a rare malignant neoplasm of histiocytic origin. Its clinical features, optimal management, and outcomes remain poorly defined. Methods: We systematically reviewed PubMed, MEDLINE, Web of Science, Scopus, and Cochrane Library. Thirty-nine studies (35 case reports, 4 case series) describing 47 patients with PCNSHS were included. Clinical presentation, imaging findings, treatment modalities, and outcomes were analyzed. Results: The mean age at diagnosis was 43.6 years (range 17 months–84 years); 51% were male. Headache (38%), vomiting (23%), and gait instability (23%) were the most frequent presenting symptoms. Lesions were solitary in 55% and multifocal in 44%. Contrast enhancement was reported in 81%, and peritumoral edema in 34%. Surgery was performed in 26 patients (55%), with gross total resection (GTR) in 13 (28%). Chemotherapy and radiotherapy were administered in 51% and 53% of cases, respectively. Median overall survival (OS) was 7.5 months (range 1–70 months). GTR was associated with longer survival compared to non-GTR (median OS 16 vs. 6 months; HR 6.67, 95% CI 1.82–25.0; p = 0.004). Radiotherapy improved survival (8 vs. 4.6 months; HR 2.71, 95% CI 1.31–5.63; p = 0.007). Chemotherapy showed a nonsignificant trend toward benefit (8 vs. 5 months; HR 1.56, 95% CI 0.78–3.12; p = 0.205). Solitary lesions correlated with improved outcomes. Conclusion: PCNSHS is an aggressive tumor with a poor prognosis (median OS 7.5 months). Accurate diagnosis requires comprehensive imaging and immunohistochemistry to exclude mimickers. Multimodal therapy—particularly GTR and radiotherapy- appears to prolong survival, underscoring the need for collaborative efforts and prospective studies.