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Abusive head trauma (AHT) is the leading cause of fatal head injuries in children younger than 2 years. A multidisciplinary team bases this diagnosis on history, physical examination, imaging and laboratory findings. Because the etiology of the injury is multifactorial (shaking, shaking and impact, impact, etc.) the current best and inclusive term is AHT. There is no controversy concerning the medical validity of the existence of AHT, with multiple components including subdural hematoma, intracranial and spinal changes, complex retinal hemorrhages, and rib and other fractures that are inconsistent with the provided mechanism of trauma. The workup must exclude medical diseases that can mimic AHT. However, the courtroom has become a forum for speculative theories that cannot be reconciled with generally accepted medical literature. There is no reliable medical evidence that the following processes are causative in the constellation of injuries of AHT: cerebral sinovenous thrombosis, hypoxic-ischemic injury, lumbar puncture or dysphagic choking/vomiting. There is no substantiation, at a time remote from birth, that an asymptomatic birth-related subdural hemorrhage can result in rebleeding and sudden collapse. Further, a diagnosis of AHT is a medical conclusion, not a legal determination of the intent of the perpetrator or a diagnosis of murder. We hope that this consensus document reduces confusion by recommending to judges and jurors the tools necessary to distinguish genuine evidence-based opinions of the relevant medical community from legal arguments or etiological speculations that are unwarranted by the clinical findings, medical evidence and evidence-based literature.

Background Hutchinson-Gilford progeria syndrome is an extremely rare, fatal, segmental premature aging syndrome caused by a mutation in LMNA yielding the farnesylated aberrant protein, progerin. Without progerin-specific treatment, death occurs at an average age of 14.6 years from an accelerated atherosclerosis. A previous single-arm clinical trial demonstrated that the protein farnesyltransferase inhibitor, lonafarnib, ameliorates some aspects of cardiovascular and bone disease. This present trial sought to further improve disease by additionally inhibiting progerin prenylation. Methods Thirty-seven participants with HGPS received pravastatin, zoledronic acid and lonafarnib. This combination therapy was evaluated, in addition to descriptive comparisons with the prior lonafarnib monotherapy trial. Results No participants withdrew due to side effects. Primary outcome success was pre-defined by improved per patient rate of weight gain or carotid artery echodensity; 71.0% of participants succeeded (P<0.0001). Key cardiovascular and skeletal secondary variables were pre-defined. Secondary improvements included increased areal (P=0.001) and volumetric (P<0.001–0.006) bone mineral density, and 1.5–1.8-fold radial bone structure increases (P<0.001). Median carotid artery wall echodensity and carotid-femoral pulse wave velocity demonstrated no significant changes. Percentages of participants with carotid (5% to 50%; P=0.001) and femoral (0 to 12%; P=0.13) artery plaques and extraskeletal calcifications (34.4% to 65.6%; P=0.006) increased. Other than increased bone mineral density, no improvement rates exceeded those of the prior lonafarnib monotherapy treatment trial. Conclusions Comparisons with lonafarnib monotherapy treatment reveal additional bone mineral density benefit, but likely no added cardiovascular benefit with addition of pravastatin and zoledronic acid. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00879034 and NCT00916747.