Thaabit Raziq

Despite decades of investigation, delayed cerebral ischemia (DCI) remains the principal cause of secondary neurological injury following aneurysmal subarachnoid hemorrhage (aSAH). Successive paradigms including angiographic vasospasm, early brain injury, neuroinflammation, blood–brain barrier disruption, cortical spreading depolarization, microvascular dysfunction, oxidative stress, and metabolic failure have each explained important aspects of disease biology. However, these mechanisms have largely evolved as parallel explanations rather than components of an integrated model, leaving the dissociation between vasospasm and DCI, delayed onset, interpatient heterogeneity, and limited efficacy of vasospasm-directed therapies incompletely explained. This perspective proposes, as a hypothesis, progressive neurovascular unit (NVU) failure as a conceptual framework for DCI after aSAH. We integrate experimental, translational, and clinical evidence spanning vascular biology, neuroimmunology, cerebrovascular physiology, electrophysiology, metabolism, biomarker research, and therapeutic trials to develop a hypothesis-generating framework. The established mechanisms of DCI may represent interacting manifestations of progressive disruption of coordinated signaling among endothelial, vascular smooth muscle, pericyte, astrocytic, microglial, and neuronal compartments of the neurovascular unit. Within this framework, early brain injury may initiate NVU dysfunction, which is amplified by interacting vascular, barrier, inflammatory, electrophysiological, and metabolic disturbances, culminating in neuronal metabolic failure and tissue injury. Vasospasm is therefore positioned as one contributor to this process rather than a sufficient explanation for DCI. This framework offers a possible basis for interpreting clinical heterogeneity and therapeutic discordance while generating testable predictions for multimodal biomarker development, biological phenotyping, and mechanism-informed therapeutic strategies. The framework does not introduce new mechanisms; rather, it proposes a testable distinction between compensated NVU dysfunction and NVU failure, frames compartment-specific non-additive interactions as an empirical question, and organizes biomarkers by the NVU compartment they reflect. These proposals remain to be validated.

Endovascular thrombectomy [EVT] has revolutionized acute ischemic stroke care by restoring macrovascular reperfusion in large vessel occlusion; however, a persistent “reperfusion–outcome gap” remains, leaving nearly half of successfully recanalized patients without functional independence. This review aims to bridge this translational gap by establishing a mechanistic and procedural framework for adjunctive pharmacotherapy designed to target the microvascular, thromboinflammatory, and reperfusion-related injuries left unaddressed by purely mechanical models. Synthesis of recent literature reveals that futile recanalization is driven by three distinct anatomical and biological bottlenecks: distal microembolization, microcirculatory no-reflow, and ischemia–reperfusion injury. Furthermore, the inconsistency of clinical trial results reflects a critical precision deficit, including dilution of treatment effects across heterogeneous reperfusion grades, inadequate stroke etiology stratification, delayed pharmacologic intervention relative to evolving microvascular injury, and reliance on functional endpoints that inadequately capture tissue-level reperfusion. To address these limitations, this review outlines a tri-axial clinical decision framework integrating reperfusion status, stroke etiology and hemorrhagic risk, which maps specific patient phenotypes, such as incomplete macrovascular reperfusion or underlying intracranial atherosclerotic disease, to targeted pharmacologic strategies including microcatheter-directed intra-arterial thrombolytics and glycoprotein IIb/IIIa inhibitors. The review further argues that future progress will require imaging-guided identification of residual hypoperfusion, mechanistically enriched patient enrolment, and incorporation of biological and tissue-level reperfusion endpoints alongside conventional functional outcomes. Ultimately, closing the reperfusion–outcome gap will require moving beyond empirical, universal drug administration toward a precision, pharmacologically augmented EVT paradigm that aligns adjunctive therapy with mechanism-specific procedural phenotypes and prioritizes true tissue-level recovery over angiographic success alone.

Primary parapharyngeal space (PPS) tumors are rare neoplasms comprising 0.5% of head and neck tumors. Their complex anatomical location and proximity to critical neurovascular structures pose significant surgical challenges. While transcervical and transcervical-combined approaches represent the primary surgical techniques, no comprehensive systematic comparison exists. This systematic review compared surgical success, complications, functional outcomes, and recurrence rates between these approaches. Following PROSPERO registration (CRD420251037201), we searched PubMed, Cochrane, Web of Science, Google Scholar, and ScienceDirect without date restrictions. Independent dual screening identified retrospective cohort studies and case series comparing both approaches. Data extraction and risk of bias assessment employed standardized tools, with synthesis conducted per PRISMA 2020 guidelines using narrative analysis. Ten studies encompassing 505 patients with 508 tumors met inclusion criteria. Both approaches achieved excellent complete resection rates (95–100%). Transcervical approaches demonstrated lower overall complication rates (4.8–52.6%) versus transcervical-combined approaches (7.7–100%), though rates varied substantially by tumor type, and differences likely reflect case selection rather than approach-specific effects. Cranial nerve injuries (VII, X, XII) constituted predominant complications. Infratemporal fossa approaches showed the highest morbidity. Recurrence rates ranged from 0–30.3% without consistent patterns favoring either approach. Transcervical-combined approaches were essential for superior compartment extension and for skull base involvement. Both transcervical and transcervical-combined approaches achieve excellent tumor resection with acceptable morbidity when appropriately selected. For most benign PPS tumors, a transcervical approach may be preferred. Combined approaches may be considered in specific anatomic scenarios that require enhanced exposure, particularly when the superior compartment and skull base are involved, although the decision is always highly individual.