High-resolution diffusion tensor magnetic resonance imaging of the brainstem safe entry zones.

Operative management of intrinsic brainstem lesions remains challenging despite advances in electrophysiological monitoring, neuroimaging, and neuroanatomical knowledge. Surgical intervention in this region requires detailed knowledge of adjacent critical white matter tracts, brainstem nuclei, brainstem vessels, and risks associated with each surgical approach. Our aim was to systematically verify internal anatomy associated with each brainstem safety entry zone (BSEZ) via neuroimaging modalities commonly used in pre-operative planning, namely high-resolution magnetic resonance imaging (MRI) and diffusion tensor tractography (DTT). Twelve BSEZs were simulated in eight, formalin-fixed, cadaveric brains. Specimens then underwent radiological investigation including T2-weighted imaging and DTT using 4.7 T MRI to verify internal anatomic relationships between simulated BSEZs and adjacent critical white matter tracts and nuclei. The distance between simulated BSEZs and pre-defined, adjacent critical structures was systemically recorded. Entry points and anatomic limits on the surface of the brainstem are described for each BSEZ, along with description of potential neurological sequelae if such limits are violated. With high-resolution imaging, we verified a maximal depth for each BSEZ. The relationship between proposed safe entry corridors and adjacent critical structures within the brainstem is quantified. In combination with tissue dissection, high-resolution MR diffusion tensor imaging allows the surgeon to develop a better understanding of the internal architecture of the brainstem, particularly as related to BSEZs, prior to surgical intervention. Through a careful study of such imaging and use of optimal surgical corridors, a more accurate and safe surgery of brainstem lesions may be achieved.

Clinical-pathological correlations in three patients with fibrodysplasia ossificans progressiva.

OBJECTIVE: Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder in which heterotopic bone forms in the soft tissues. This often occurs in response to injury or inflammation, leading to joint immobilization and significant disability. There are currently no definitive treatment options for this devastating disease. Although the most dramatic phenotype in FOP is the episodic and progressive heterotopic ossification, patients report a number of symptoms that affect other organ systems. Post-mortem examination of FOP patients may contribute to our understanding of the underlying pathophysiology and complications of this disease. Here, we present the autopsy findings from three patients with FOP. FINDINGS: Autopsy findings in two of the three patients confirmed that the cause of death was cardiorespiratory failure in the setting of severe thoracic insufficiency from heterotopic ossification. Both of these patients also had evidence of right ventricular dilatation likely secondary to thoracic insufficiency. The third patient died from complications of a traumatic head injury after a fall but also had post-mortem evidence of thoracic insufficiency syndrome. All three patients had extensive, widespread heterotopic ossification and joint deformities consistent with FOP. There was extensive ossification of the spinal ligament in these patients, which may contribute to cervical spine rigidity. One patient was diagnosed post-mortem with a brainstem malformation. No additional significant abnormalities were noted in the other organ systems. Finally, we also demonstrate that cadaveric skin fibroblasts can be isolated for use as a potential source for future in vitro cell culture studies. CONCLUSIONS: This autopsy case series provides valuable information about the underlying complications of FOP and contributes significantly to our knowledge of this rare yet debilitating disorder. Thoracic insufficiency syndrome, right heart dysfunction, widespread heterotopic ossification, spinal ligament ossification, and CNS malformations were clearly evident; however, most other non-bone tissues appeared to be spared from gross malformations. Finally, the ability to isolate live cells from cadaveric skin is an important technique that will facilitate future studies, particularly as induced pluripotent stem cells and other cell-based technologies evolve. This case series highlights the importance of post-mortem examinations and their contribution to our current knowledge of disease pathophysiology and comorbidities.