Alexander disease is a progressive, usually fatal neurological disorder defined by the widespread and abundant presence in astrocytes of protein aggregates called Rosenthal fibers. The disease most often occurs in infants younger than 2 years and has been labeled a leukodystrophy because of an accompanying severe myelin deficit in the frontal lobes. Later onset forms have also been recognized based on the presence of abundant Rosenthal fibers. In these cases, clinical signs and pathology can be quite different from the infantile form, raising the question whether they share the same underlying cause. Recently, we and others have found pathogenic, de novo missense mutations in the glial fibrillary acidic protein gene in most infantile patients examined and in a few later onset patients. To obtain further information about the role of glial fibrillary acidic protein mutations in Alexander disease, we analyzed 41 new patients and another 3 previously described clinically, including 18 later onset patients. Our results show that dominant missense glial fibrillary acidic protein mutations account for nearly all forms of this disorder. They also significantly expand the catalog of responsible mutations, verify the value of magnetic resonance imaging diagnosis, indicate an unexpected male predominance for the juvenile form, and provide insights into phenotype-genotype relations.

Plasma cell granulomas (inflammatory pseudotumors) are benign inflammatory masses that have been observed in virtually every organ system but are most often described in the lung. Rare cases have been reported in which the brain and spinal cord are affected. We present the case of a 5-year-old girl with personality and behavioral changes, discovered to be harboring an intracerebral plasma cell granuloma. The literature on plasma cell granuloma of the central nervous system is discussed with emphasis on the clinical, radiological, and pathological features of these lesions.

Ehlers-Danlos syndrome (EDS) type IV is a connective tissue disorder characterized by the inability to produce sufficient amounts of collagen or a defect in the structure of collagen. The most serious complications include a rupture of a viscus or vascular rupture with or without mural dissection. Death may result from internal hemorrhage. This report describes three cases of sudden and unexpected death caused by EDS type IV. Two cases involved hemothorax as a result of dissection of the subclavian artery and aorta, respectively. The third case represented spontaneous pulmonary rupture and hemorrhage. A detailed family history should be sought, and additional specimens collected to confirm the diagnosis, including skin fibroblasts for collagen testing and blood for DNA testing. The forensic pathologist should consider the possibility of EDS type IV upon discovery of spontaneous visceral or arterial rupture and should alert the family members of this hereditary and potentially fatal condition.

Excited delirium denotes a life-threatening medical condition characterized by the acute onset of agitated and violent behavior that often results in a sudden and unexplained death. Cocaine-induced excited delirium refers to fatal cocaine intoxication with the following symptoms occurring sequentially: hyperthermia, delirium with agitation, respiratory arrest, and death. We present a case of cocaine-induced excited delirium in a cocaine "body packer" or a "mule", specifically an individual who attempts to smuggle cocaine within the body. Investigators at the scene initially suspected homicide due to the victim's sharp and blunt force injuries. Three rubber packets containing cocaine were removed from the victim's rectum. Blood toxicological analysis revealed an alcohol concentration of 0.016 g/100 and cocaine >1 mg/L. The forensic pathologist should consider cocaine-induced excited delirium when an individual exhibits aggressive behavior, unexpected strength, and resistance to pain who dies suddenly. Further analysis should be performed during the scene investigation and autopsy for evidence of body packing.