These observations suggest that apoptosis represents a prominent form of cell death associated with ICH in the perihematoma region. Further studies are required to define the mediators of apoptosis in ICH.

These observations suggest that apoptosis represents a prominent form of cell death associated with ICH in the perihematoma region. Further studies are required to define the mediators of apoptosis in ICH.

In a kindred of 122 individuals we found 5 individuals with cerebral vascular malformation, 3 representing typical cavernous angiomas. The condition was inherited as an autosomal dominant trait with variable expressivity. Forty-three relatives were examined prospectively by cranial computed tomography (CCT) and lesions were found in 15; 7 were followed prospectively with CCT scans for 5 years. Angiography in 5 of these cases failed to demonstrate the lesion. In 3 patients with previously normal CCT scans a change in blood volume or membrane permeability allowed visualization of the lesion on contrast scans. In 2 individuals, both parents of affected children, a normal CCT scan was found. This emphasizes the limitations of CCT in detecting this disorder. Biochemical and red blood cell immunological genetic linkage studies were done in 36 persons. No linkage was found with any of the markers. The natural history of this disorder, characterized by marked clinical and radiographic variation in site of lesion, and the timing and severity of intracranial hemorrhage, make it a useful model for investigating contributing factors and consequences of intracranial hemorrhage in general. For at-risk and affected patients early and sequential CCTs are necessary. Familial cavernous angioma should be included in the differential diagnosis of all young persons presenting with cerebrovascular impairment, seizures, intracranial calcifications or hemorrhage.

No abstract

Acute hemorrhagic leukoencephalitis (AHL) is characterized by an acute, rapidly progressive, monophasic, fulminant inflammatory hemorrhagic demyelination of white matter, usually postinfectious and associated with death or severe morbidity within a few days. 1-3 We report MRI and neuropathology in a case of AHL.Case report. A 19-year-old white man was admitted with acute onset of fever, headache, and progressive lethargy. He had developed mild upper respiratory symptoms and cough 2 weeks earlier.Examination showed lethargy and meningismus, but he was arousable and oriented to person, place, and time. Brainstem responses were intact. Serum white blood count was 17.9 cells/uL. Head CT (not shown) revealed a left parietal hypodensity with mild mass effect. He was started on levofloxacin, ceftriaxone, and dexamethasone treatment. Brain MRI (figure, A) was performed while the patient was able to communicate and brainstem function was intact. Six hours later, he had a cardiopulmonary arrest and required resuscitation, intubation, and mechanical ventilation, after which he lost all brainstem function. He was treated with mannitol and hyperventilation, yet he was declared brain dead 12 hours after resuscitation and pronounced dead another 3 hours later. Blood cultures were negative. Nasopharyngeal cultures and serum antigens were negative for Streptococcus Pneumoniae, Neisseria meningitidis, and Haemophilus influenza. On gross examination, autopsy showed that the brain was markedly swollen, weighing 1,810 grams, with uncal and tonsillar herniations and loss of gray-white demarcation, possibly related to "respirator brain." The deep white matter had a mottled gray appearance with posterior predominant focal hemorrhages, conforming to MRI lesions. Microscopic findings are shown (see figure, B).Discussion. By the combination of clinical, MRI, and pathology findings, this case is typical of AHL, which is usually triggered by infectious respiratory antigens. 1-3 The prodromal infection is usually followed 1 to 20 days later by the acute onset of symptoms and signs of meningitis and neurologic deficits (most commonly hemiparesis, aphasia, brainstem dysfunction, and seizures followed by coma and brain death). [1][2][3] AHL is felt to be a hyperacute form of the more common acute disseminated encephalomyelitis (ADEM); both seem to result from an autoimmune process directed against the CNS myelin. 3 The course of AHL is more fulminant than ADEM, with rapid progression that is more frequently fatal. 3 On MRI, the lesions of AHL tend to be larger and associated with more edema and mass effect 2,5,6 than in ADEM. 4 Perivenular demyelination and inflammation largely confined to the white matter are seen in both processes. The infiltrates in ADEM contain mostly lymphocytes, whereas AHL produces a predominantly neutrophilic infiltrate, with pericapillary ball and ring hemorrhages and hematomas.We report the third case in the literature of MRI findings in a patient with pathologically confirmed AHL. MRI in our patient showed confluent n...

Background and Purpose This study explored the correlation between duration of focal ischemia and infarct volume in spontaneously hypertensive rats as a measure of outcome after neuroprotective intervention.Methods We used 2,3,5 -triphenyltetrazolium chloride staining to discriminate infarcted tissue and calculate infarct volume 24 hours after temporary tandem common carotid/ middle cerebral artery occlusion lasting 5 to 150 minutes. We used a graded bioassay described by logistic function and executed by computer program (ALLFIT) to evaluate changes in infarct volume after increasing durations of ischemia. The method allowed us to calculate the maximal infarct volume (VoL^) and the duration of ischemia before reperfusion producing half-maximal infarct size (T,,,). Hypothermia and the N-methyl-D-aspartate antagonist CNS-1102 begun after

Background and Purpose Evidence linking changes in calcium/calmodulin-dependent protein kinase II activity with ischemic cell death has been reported in animal models of global ischemia. The purpose of this study was to delineate the course of these changes after focal ischemia and to clarify the relation of changes in activity of calcium/calmodulin-dependent protein kinase II to the process of ischemic cell death.Methods Change in calcium/calmodulin-dependent protein kinase II activity was evaluated in a rat model of focal ischemia after 5 minutes, 30 minutes, and 1 hour of tandem middle cerebral artery and common carotid artery occlusion both with and without reperfusion.Results Calcium/calmodulin-dependent protein kinase II activity was significantly decreased after all three durations of ischemia followed by immediate decapitation compared with sham-operated animals, in both ischemic core and borderzone regions (P<.05 for all groups). Depression of activity occurred in a regionally graded fashion, with the most severe decrease in infarct core and progressively smaller decreases in

We evaluated several doses of cis-4-(phosphonomethyl)-2-piperidine-carboxylic acid (CGS-19755), a potent competitive N-methyl-D-aspartate (NMDA) receptor antagonist, systemically administered either before or after 20 to 30 minutes of global ischemia in rats. We measured outcome by mortality, histological damage by light microscopy, and learning ability on an eight-arm maze, and determined the drug's mechanism of action by an immunohistochemical assay of calcium-calmodulin binding. High-dose treatment begun prior to ischemia resulted in reduced cellular damage in severely ischemic hippocampal tissue, but also caused high mortality due to respiratory depression. Treatment begun 30 minutes after ischemia resulted in little histological protection but significantly improved learning ability when tested 1 month after ischemia, and did not increase mortality. Furthermore, CGS-19755, 10 mg/kg intraperitoneally, begun either before or after ischemia substantially reduced calcium influx into ischemic neurons as evidenced by reduced calcium-calmodulin binding. We conclude that CGS-19755 prevents calcium entry into ischemic neurons and may be effective therapy for very acute cerebral ischemia.