Laser interstitial thermal therapy for in-field recurrence of brain metastasis after stereotactic radiosurgery: does treatment with LITT prevent a neurologic death?

Brain metastasis (BM) affects up to one-third of adults with cancer and carries a historically bleak prognosis. Despite advances in stereotactic radiosurgery (SRS), rates of in-field recurrence (IFR) after SRS range from 10 to 25%. High rates of neurologic death have been reported after SRS failure, particularly for recurrences deep in the brain and surgically inaccessible. Laser interstitial thermal therapy (LITT) is an emerging option in this setting, but its ability to prevent a neurologic death is unknown. In this study, we investigate the causes of death among patients with BM who undergo LITT for IFR after SRS. We conducted a single institution retrospective case series of patients with BM who underwent LITT for IFR after SRS. Clinical and demographic data were collected via chart review. The primary endpoint was cause of death. Between 2010 and 2018, 70 patients with BM underwent LITT for IFR after SRS. Median follow-up after LITT was 12.0 months. At analysis, 49 patients died; a cause was determined in 44. Death was neurologic in 20 patients and non-neurologic in 24. The 24-month cumulative incidence of neurologic and non-neurologic death was 35.1% and 38.6%, respectively. Etiologies of neurologic death included local recurrence (n = 7), recovery failure (n = 7), distant progression (n = 5), and other (n = 1). Among our patient population, LITT provided the ability to stabilize neurologic disease in up to 2/3 of patients. For IFR after SRS, LITT may represent a reasonable treatment strategy for select patients. Additional work is necessary to determine the extent to which LITT can prevent neurologic death after recurrence of BM.

Hypothalamic-Pituitary Function in Brain Death: A Review.

The Uniform Determination of Death Act (UDDA) states that an individual is dead when "all functions of the entire brain" have ceased irreversibly. However, it has been questioned whether some functions of the hypothalamus, particularly osmoregulation, can continue after the clinical diagnosis of brain death (BD). In order to learn whether parts of the hypothalamus can continue to function after the diagnosis of BD, we performed 2 separate systematic searches of the MEDLINE database, corresponding to the functions of the posterior and anterior pituitary. No meta-analysis is possible due to nonuniformity in the clinical literature. However, some modest generalizations can reasonably be drawn from a narrative review and from anatomic considerations that explain why these findings should be expected. We found evidence suggesting the preservation of hypothalamic function, including secretion of hypophysiotropic hormones, responsiveness to anterior pituitary stimulation, and osmoregulation, in a substantial proportion of patients declared dead by neurological criteria. We discuss several possible explanations for these findings. We conclude by suggesting that additional clinical research with strict inclusion criteria is necessary and further that a more nuanced and forthright public dialogue is needed, particularly since standard diagnostic practices and the UDDA may not be entirely in accord.

[Neuropathology required from "brain death"].

We have pathoanatomically investigated Japanese 84 autopsied patients who had been clinically judged to be in a state of "brain death". 1) The finding observed in all the cases was that the brains revealed a severe state of increased intracranial pressure (IICP) with secondary hemorrhages involving the brain stem tegmentum. 2) Autolysis was observed in all the brains, especially in their brain stems, and the degree was always severer than in the visceral organs (VOs). 3) We considered that in all the cases cessation of cerebral blood flow occurred at least in the brain stem tegmentum by the time of the judgements. 4) We pointed out that like the VOs, the spinal cord under a certain level of the cervical segments continued to live until the cardiac stop. 5) We also considered that in nearly half the cases the neurons of the hypothalamus, especially of its supraoptic nucleus, tended to live long, for 3 to 4 days, even after the judgements.

Magnetic resonance: a noninvasive approach to metabolism, circulation, and morphology in human brain death.

Phosphorus (31P) magnetic resonance spectroscopy and magnetic resonance imaging were used to study the intracellular metabolism, circulation, and morphology in the brains of 3 patients with clinical brain death syndrome due to traumatic brain damage, subarachnoid hemorrhage, and acute occlusive hydrocephalus caused by a colloid cyst. Magnetic resonance spectra were characterized by a complete absence of ATP and were dominated by an intense inorganic phosphate signal. Magnetic resonance imaging revealed a uniform pattern of diffuse brain swelling and tentorial and foraminal herniation. Intracranial blood flow was absent on the magnetic resonance angiography projections. These preliminary findings suggest an important impact of magnetic resonance in the determination of human brain death.

[Hypothalamic and pituitary function in brain death].

Hypothalamic and pituitary hormone levels were measured in 56 patients meeting the criteria of brain death proposed by the Japanese Ministry of Welfare. Pituitary hormone releasing tests were carried out in 39 patients. In addition, cerebral angiography and transcranial Doppler (TCD) were performed in 13 and six patients, respectively, just after hormone measurements. Serum hypothalamic and pituitary hormone levels were inconsistently high based on the half life time in the presumed absence of cerebral blood flow shown by angiography. The responses to releasing hormones were normal in 16 patients. TCD detected cerebral blood flow in the middle cerebral artery or ophthalmic artery in three patients who showed non-filling on angiography. Postmortem microscopic examination of the hypothalamus and anterior pituitary lobe revealed normal structure and cells intermingled with lytic changes and necrosis. This series suggests that some part of the hypothalamus and hypophysis may still be alive after brain death, although the function of these regions may be clinically insignificant.