Histotripsy is a novel, noninvasive, non-thermal technology invented in 2004 for the precise destruction of biologic tissue. It offers a powerful alternative to more conventional thermal or surgical interventions. Using short-pulse, low-duty cycle ultrasonic waves, histotripsy creates cavitation bubble clouds that selectively and precisely destroy targeted tissue in a predefined volume while sparing critical structures like bile ducts, ureters, and blood vessels. Such precision is of value when treating tumors near vital structures. The FDA has cleared histotripsy for the treatment of all liver tumors. Major medical centers are currently spearheading clinical trials, and some institutions have already integrated the technology into patient care. Histotripsy is now being studied for a host of other cancers, including primary kidney and pancreatic tumors. Preclinical murine and porcine models have already revealed promising outcomes. One of histotripsy’s primary advantages is its non-thermal mechanical actuation. This feature allows it to circumvent the limitations of heat-based techniques, including the heat sink effect and unpredictable treatment margins near sensitive tissues. In addition to its non-invasive ablative capacities, it is being preliminarily explored for its potential to induce immunomodulation and promote abscopal inhibition of distant, untreated tumors through CD8+ T cell responses. Thus, it may provide a multilayered therapeutic effect in the treatment of cancer. Histotripsy has the potential to improve precision and outcomes across a multitude of specialties, from oncology to cardiovascular medicine. Continued trials are crucial to further expand its applications and validate its long-term efficacy. Due to the speed of recent developments, the goal of this review is to provide a comprehensive and updated overview of histotripsy. It will explore its physics-based mechanisms, differentiating it from similar technologies, discuss its clinical applications, and examine its advantages, limitations, and future.

A previously espoused notion that the brain is an immune-privileged organ has been challenged by evidence of bidirectional communication between the central nervous system and the periphery. A well-described “glymphatic” system in the brain and the meningeal lymphatic system serve as conduits through which antigens, immune cells, and metabolic waste travel from the brain to the deep cervical lymph nodes. These nodes, which are more than passive drainage points, serve as locales where dendritic cells, T cells, and B cells interact with central nervous system-derived signals and modulate immune responses that can influence the brain itself. Disruption of clearance mechanisms to deep cervical nodes—due to intracranial vascular disease, aging, poor sleep, chronic inflammation, or other etiologies—may lead to immune dysregulation. Abnormalities in lymphatic drainage can also alter the presentation of antigens from the central nervous system, affect lymphocyte trafficking, and contribute to the aggregation of proteins like β-amyloid, tau, and α-synuclein. This review synthesizes current knowledge on glymphatic and meningeal lymphatic anatomy and function, highlights how impaired drainage contributes to disorders including multiple sclerosis, Alzheimer disease, and Parkinson disease, and discusses the emerging role of deep cervical lymph node imaging and immunophenotyping in assessing neuroinflammation. Finally, we consider how modulation of meningeal lymphatic and nodal function, through pharmacologic or physical interventions, may impair or restore drainage and alter the course of disease in various ways. The integration of advanced imaging with immunological analysis ultimately may enhance the diagnosis, monitoring, and treatment of neuroinflammatory and neurodegenerative diseases. We propose that deep cervical lymph nodes represent an understudied locale, and, potentially, a therapeutic target for peripheral interventions to influence brain disease trajectories.

South-Asians comprise one-quarter of the world’s population, yet account for 40% of global stroke deaths ¹ . They experience earlier stroke onset than whites, a 1.5-fold higher stroke mortality than Europeans, and a higher risk relative to other Asian populations. However, most studies aggregate South-Asians with other Asian populations or compare native South-Asians with other immigrant groups. This review synthesizes current evidence on the burden of stroke, epidemiology, risk factors, clinical presentation, subtypes, mechanisms, and treatment in South-Asians, with an emphasis on disparities compared to other ethnic groups. We discuss risk factors including distinct cardiometabolic profiles, genetic polymorphisms that affect homocysteine levels and drug metabolism, dietary patterns, and lifestyle factors. We review stroke subtypes in South-Asians and explore treatment and prevention strategies. Finally, we offer recommendations to target the multifactorial origins of elevated stroke burden in South-Asians, including improvements in screening, pharmacogenomic testing, and thresholds for intracranial vessel imaging. To address this disparity and reduce the high burden of stroke in these communities, it is important to develop tailored management strategies, increase clinical trial representation, and establish South-Asian stroke registries.

A 68-year-old left-handed woman with a history of hypertension presented with writing difficulties initially affecting numbers and then progressing to include letters. She described an inability to form the shape of numbers and found her hand drifting towards incorrect keys on her phone despite knowing what she wanted to select. Neurological examination revealed fluent but mildly slowed speech without paraphasic errors, intact comprehension and naming, and mild temporal disorientation, where she often stated the wrong year. Her writing was characterized by hesitation, poor spatial planning, and irregular letter and number formation. She also demonstrated constructional apraxia when attempting to draw cubes and finger agnosia. Oral calculation, bedside language functions, and reading were intact. MRI revealed multifocal enhancing lesions in the corpus callosum and left inferior frontal lobe, after which brain biopsy confirmed primary CNS lymphoma. This case illustrates how isolated disturbances of writing and praxis can arise from multifocal lesions involving visuospatial-motor integration networks.