Multimodality management and outcomes of brain arterio-venous malformations (AVMs) in children: personal experience and review of the literature, with specific emphasis on age at first AVM bleed.

PURPOSE: The purpose of this paper is to study the presentation and analyse the results of multimodality treatment of brain arterio-venous malformations (AVMs) in children at our centre and review age at first AVM rupture in the literature. METHODS: Of 52 patients aged <18 years, 47 with brain AVMs (27 males and 20 females) aged 4-17 years (mean 12.2) were retrospectively reviewed. PubMed search revealed five additional studies including 267 patients where the prevalence of age-related AVMs rupture was analysed. RESULTS: In our study, 37 patients had bled, 9 were symptomatic without haemorrhage and 1 was incidental. Spetzler-Martin score distribution was 5 cases grade I, 18 grade II, 21 grade III and 3 grade IV. Appropriate imaging was performed, either CT/MRI angiogram only (in emergency cases) or catheter angiogram, prior to definitive treatment. There were 40 supratentorial and 7 infratentorial AVMs. Twenty-nine patients had microsurgery alone and 9 patients were treated by radiosurgery only. Three patients were embolised, all followed by radiosurgery, with one requiring surgery too, while 4 patients had combined surgery and radiosurgery. One patient is awaiting radiosurgery while another was not treated. Good outcomes, classified as modified Rankin score (mRS) 0-2 improved significantly after intervention to 89.4% from 38.3% pre-treatment (p value <0.0001). Angiography confirmed 96.6% obliteration after first planned operation. Repeat cerebral angiogram around age 18 was negative in all previously cured patients. Reviewing the literature, 82.0% (95% CI = [77-87]; N = 267) of children diagnosed with brain AVMs (mean age 11.4 ± 0.4) presented with a bleed in the last 22 years. Males significantly outnumbered females (136 vs 84) (p < 0.001). Ninety-five patients underwent surgical intervention alone when compared to other treatment modalities (p < 0.001). CONCLUSIONS: Microsurgical excision of surgically accessible intracranial AVMs remains the primary treatment option with very good outcomes. A significant number of patients' AVMs ruptured around puberty; therefore, understanding the pathophysiology of AVM instability at this age may aid future therapy

Pragmatic trials can be designed as optimal medical care: Principles and methods of care trials

Objectives The way clinical research and care are currently separated encourages the practice of unverifiable medicine. Some pragmatic trials can be designed (1) to guide proper medical conduct in the presence of uncertainty and (2) to govern the distinction between unvalidated and validated care

Pragmatic trials can be designed as optimal medical care: principles and methods of care trials.

OBJECTIVES: The way clinical research and care are currently separated encourages the practice of unverifiable medicine. Some pragmatic trials can be designed (1) to guide proper medical conduct in the presence of uncertainty and (2) to govern the distinction between unvalidated and validated care. METHODS: Care trials are simple randomized trials integrated into a practice they regulate in the interest of present patients. The fundamental principle guiding the design of a care trial is the protection of the patient being offered medical care that has not yet been validated. Selection criteria are inclusive, to assist most current patients confronted with the problem. The trial entails no extra tests or risks beyond what is proven beneficial. Endpoints are pre-defined, simple, valuable and resistant to bias. Follow-up visits and tests are routine. Data is collected in simple case-report forms. RESULTS: Care trials protect present patients from both unverifiable medicine and research performed for extraneous interests. They provide prudent care when evidence is lacking. They should not be obstructed by the need for separate funding, or by bureaucracy. CONCLUSION: Care trials can identify which medical alternative should be standard therapy. In the meantime, they provide optimal care in the presence of uncertainty