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Late vascular effects of whole brain X-irradiation in the mouse.

The whole brains of mice were irradiated with 250 kVp X-rays at 120 rads min-1 (1.6 mm Cu HVL, TSD 50 cm), and a histological study was carried out. The dose range of X-irradiation was from 1,300 to 2,500 rads, i.e., 1,300, 1,500, 1,750, 2,000, and 2,500 rads. Eighty-six mice were used for histological examination. For microscopic examination, the mice were killed at regular postirradiation intervals between 15 and 20, 31 and 40, 41 and 50, 51 and 60, 61 and 70, 71 and 80, 81 and 90, 139 and 177 weeks. The brains were removed immediately thereafter, fixed in Bouin's solution, and embedded in paraffin. A histological examination was performed by a morphometric estimation of vascular lesions, in which the degree of the damage to the arterial system was scored in whole serial brain sections. Necrosis (encephalomalacia), atrophy, cell infiltration, and telangiectatic vascular change of the brain, caused as a result of the fibrinoid necrosis of the large arteries, were observed. Dose-dependent incidence of the fibrinoid necrosis increased between 41 and 87 weeks after irradiation. Mean score of fibrinoid necrosis increased dose dependently approximately 60 weeks after irradiation. It is suggested that scores of large vessel damage do relate to dose at 41 to 87 weeks, and can be used to quantify the vessel injury, and that fibrinoid necrosis of the large vessels may relate to the incidence of radionecrosis.

Animals↗

CT analysis of missile head injury.

Between August 1991 and December 1992, CT was performed on 154 patients who had suffered missile head injury during the war in the Republic of Croatia. In 54% CT was performed 1-24 h after injury, and in 27% follow-up CT was also obtained. The wounds were penetrating, tangential or perforating (45%, 34% and 21%, respectively). Haemorrhage was the most frequent lesion in the brain (84%). Follow-up CT evolution of haemorrhage, oedema, cerebritis, abscess, secondary vascular lesions, necrosis, encephalomalacia and hydrocephalus. The most dynamic changes occurred 7-14 days after injury. In 14% of cases, deep cerebral lesions were found in the corpus callosum, septum pellucidum periventricular region and pons, although bone and shell fragments were in a different part of the brain parenchyma. Such lesions were found in penetrating injuries only. CT proved very useful for assessing the extent and type of lesions. Although different mechanisms of brain damage in missile head injury are known, here they are, to the best of our knowledge, shown for the first time by CT.

Adult↗

Cranial ultrasonography of neonatal periventricular/intraventricular hemorrhage: who, how, why and when?

The sex, age, and cranial ultrasound (US) findings of 742 premature neonates evaluated over a 3-year period were reviewed retrospectively. Examinations were performed with a mechanical-sector real-time unit using a 5 MHz or 7.5 MHz transducer. The caudothalamic groove was carefully imaged with periventricular/intraventricular hemorrhage diagnosed by previously described criteria. Intracranial hemorrhage occurred in 44% of patients with 20% being Grade 1, 10% Grade 2, 7% Grade 3, and 7% Grade 4. All hemorrhages occurred during the first week of life. Computed tomography is superior to US for demonstrating parenchymal changes and extent of hypoxic damage. Based on our 3-year experience and a review of the literature, we propose an algorithm for cranial imaging of the preterm neonate. This ordered, sequential approach to the premature neonate with possible intracranial hemorrhage permits accurate initial diagnosis as well as appropriate follow-up for potential complications of ventricular dilatation, hydrocephalus, porencephaly, and hypoxic encephalomalacia.

Cerebral Hemorrhage↗

Computed tomography in young children with herpes simplex virus encephalitis.

Computed tomographic (CT) scans were obtained from eight infants and young children with herpes simplex virus encephalitis. In two cases the initial scan showed diffuse edematous changes as a mass effect without laterality. Unilateral localized low attenuation in the initial scan was evident 4 days after the onset in one patient, and high attenuation in the initial scan appeared on the 6th day in another patient, but in general, it was not possible to establish an early diagnosis of herpes simplex virus encephalitis from CT scan. In the longitudinal study the calcification with ventriculomegaly appeared in 3 of 5 survivors, and gyriform calcification in 2 of 3 patients, respectively. The appearance of multicystic encephalomalacia was evident in one patient 6 months after the onset of neonatal herpes simplex encephalitis. It is shown that the CT findings of neonates and young children with herpes simplex encephalitis are different from those of older children and adults, and the importance of longitudinal CT studies was stressed in clarifying the pathophysiology of the central nervous system involvement in survivors.

Child, Preschool↗

Computed tomography (CT) in children with herpes simplex encephalitis.

Computed Tomography (CT) scans were obtained from nine infants with herpes simplex virus encephalitis (HSE). The early CT findings were generalized or localized edematous change and a mass effect was also seen in two cases. In the follow-up study two patients showed bilateral gyriform calcification, a rare occurrence in association with intracranial infection. The appearance of multicystic encephalomalacia was evident in one patient 3 months after the onset of disease. It is shown that the CT findings of neonates and young children with HSE are different from those of adults.

Child↗

[Multiple cerebral infarcts caused by spontaneous, synchronous cholesterol embolisms].

We report on a 68-year-old patient who was admitted with hemiparesis and disorientation. Computed tomography showed several old, mostly lacunar infarcts. One week after admission, the patient became comatose. A repeat computed tomography revealed several new hypodense lesions in both hemispheres compatible with acute cerebral infarctions. Autopsy confirmed the diagnosis of numerous acute encephalomalacias of the same age which were found in different territories of the anterior cerebral circulation. Histologic examination showed the extraordinary result of multiple cholesterol emboli with a maximum in the peripheral leptomeningeal vessels. The source of the emboli was severe atherosclerosis with an ulcerated and thrombotic surface of the aorta and both carotid arteries. This case is remarkable because of its severe and synchronous emboli of cholesterol in several different cerebral territories. One has to suspect a so far unknown physical or metabolic factor responsible for the shower of emboli.

Aged↗

Spin-echo MRI of chronic intracerebral haematomas.

Our purpose was to characterise the MRI appearances of clinically non-neoplastic chronic intracerebral haematomas (ICH). We examined 25 patients with a history of clinically non-neoplastic 0.5-to 1.5-year-old ICH who underwent prospective follow-up 1.0-T spin-echo MRI of the brain. On T1-weighted images most lesions gave lower signal than white matter and were isointense with cerebrospinal fluid (CSF). On T2-weighted images most were either totally low-signal and slit-like, or had a high-signal centre and a low-signal margin. The low-signal (haemosiderin) rim showed areas of discontinuity in 7 cases. Of 24 lesions, 4 showed small enhancing areas on contrast-enhanced images. In 10 cases the brain parenchyma surrounding the lesion showed high-signal on T2- and low signal on T1-weighted images, probably representing encephalomalacia. In 20 cases enlargement of a nearby CSF space was observed, and 14 cases showed atrophy of the brain stem ipsilateral to the lesion. We thus found more variation on MRI of clinically non-neoplastic chronic ICH than previously described.

Adult↗

Serial MR observation of cortical laminar necrosis caused by brain infarction.

To examine the chronological changes characteristic of cortical laminar necrosis caused by brain infarction, 16 patients were repeatedly examined using T1-, T2-weighted spin-echo, T2*-weighted gradient echo, fluid attenuated inversion recovery (FLAIR) images, and contrast enhanced T1-weighted images at 1.0 or 1.5 T. High intensity cortical lesions were visible on the T1-weighted images from 2 weeks after ictus and became prominent at 1 to 3 months, then became less apparent, but occasionally remained at high intensity for 2 years. High intensity cortical lesions on FLAIR images became prominent from 1 month, and then became less prominent from 1 year, but occasionally remained at high intensity for 2 years. Subcortical lesions did not display high intensity on T1-weighted images at any stage. On FLAIR images, subcortical lesions initially showed slightly high intensity and then low intensity from 6 months due to encephalomalacia. Cortical lesions showed prominent contrast enhancement from 2 weeks to 3 months, but subcortical lesions were prominent from 2 weeks only up to 1 month. T2*-weighted images disclosed haemosiderin in 3 of 7 patients, but there was no correlation with cortical short T1 lesions. Cortical laminar necrosis showed characteristic chronological signal changes on T1-weighted images and FLAIR images. Cortical short T1 lesions were found not to be caused by haemorrhagic infarction.

Adult↗

High-resolution cranial ultrasound in the shaken-baby syndrome.

With limited near-field resolution and accessible acoustic windows, sonography has not been advocated for assessing central nervous system injuries in the shaken-baby syndrome. Our purpose was to correlate high-resolution ultrasonographic characteristics of central nervous system injuries in whiplash injuries and the shaken-baby-syndrome with MRI and CT. Ultrasonographic images of 13 infants, aged 2-12 months, with whiplash or shaking cranial trauma were reviewed and compared with MRI in 10 and CT in 10. Five patients had serial ultrasonography and MRI or CT follow-up from 1 to 4 months after the initial injury. With ultrasonography we identified 20 subdural haematomas. MRI and CT in 15 of these showed that four were hyperechoic in the acute stage, three were mildly echogenic in the subacute stage, and that one subacute and seven chronic lesions were echo-free. Five patients had acute focal or diffuse echogenic cortical oedema which evolved into subacute subcortical hyperechoic haemorrhage in four, and well-defined chronic sonolucent cystic or noncystic encephalomalacia was seen at follow-up in two. Using ultrasonography we were unable to detect two posterior cranial fossa subdural haematomas or subarachnoid haemorrhage in the basal cisterns in three cases, but did show blood in the interhemispheric cistern and convexity sulci in two. U1-trasonography has limitations in demonstrating abnormalities remote from the high cerebral convexities but may be a useful adjunct to CT and MRI in monitoring the progression of central nervous system injuries in infants receiving intensive care.

Battered Child Syndrome↗

Innominate artery steal syndrome after stage I palliation for hypoplastic left heart syndrome.

Four neonates with hypoplastic left heart syndrome (HLHS) were found to have innominate artery steal syndrome (IASS) following stage I palliation with a modified Blalock-Taussig (B-T) shunt. All patients presented in the early postoperative period with a persistent supplemental oxygen requirement. Two-dimensional echocardiography with Doppler flow analysis and cardiac catheterization with angiography demonstrated obstruction at the origin of the innominate artery. This obstruction was associated with intermittent retrograde flow through the right vertebral and common carotid arteries into the distal innominate artery and modified B-T shunt. An ascending neoaorta to right pulmonary artery shunt, with takedown of the B-T shunt, was performed in two of the patients. The other two patients were treated with percutaneous balloon dilatation of the obstructed area. Both procedures improved arterial blood oxygen saturations and eliminated the need for supplemental oxygen. In three of four patients, the left common carotid artery was found to be larger than the right. All four patients developed microcephaly, and one patient had encephalomalacia in the distribution of the right anterior and middle cerebral arteries. The development of IASS following stage I palliation for HLHS and the association of neurologic sequelae from this complication are discussed.

Brachiocephalic Trunk↗

CT findings in neonatal hypothermia.

BACKGROUND: Newborn infants are particularly prone to hypothermia, a condition with a high mortality. OBJECTIVE: To study the CT brain patterns in infants with hypothermia and neurological symptoms. MATERIALS AND METHODS: We reviewed the brain CT of nine infants with neonatal hypothermia, multiple organ failure, seizures and coma. RESULTS: Two infants had normal CT scans, acutely and at follow-up, and were clinically normal at follow-up. In seven infants, CT showed diffuse cerebral oedema, with reversal of the normal density relationship between grey and white matter and a relative increased density of the thalami, brainstem and cerebellum - the 'reversal sign'. In six surviving infants with severe developmental delay, follow-up CT revealed cerebral atrophy with multicystic encephalomalacia. CONCLUSIONS: The 'reversal sign' has been described in the abused child, birth asphyxia and anoxia due to drowning. Neonatal hypothermia is offered as a further cause.

Brain↗

Herpes simplex encephalitis: MRI findings in two cases confirmed by polymerase chain reaction assay.

Herpes simplex virus (HSV) type I causes a fulminant necrotising meningoencephalitis distinguished from other encephalitides by its focal and often haemorrhagic nature. Specific antiviral therapy with acyclovir can significantly improve the prognosis. We present MRI findings of two cases of herpes simplex encephalitis (HSE) confirmed by PCR analysis, focusing on the serial changes after acyclovir therapy: gyral swelling, high signal intensity on T2-weighted images in the subfrontal region, temporal lobe and insula in the initial stage, then regional extension with enhancement and haemorrhage despite appropriate acyclovir therapy, and finally encephalomalacia and brain atrophy.

Acyclovir↗

Cerebellar atrophy after severe traumatic head injury in children.

OBJECT: The purpose of this study was to describe late neuropathological MRI findings in pediatric severe head injury and to explore the relationship between these lesions and cognitive sequelae. METHODS: Thirteen infants with severe head trauma (Glasgow 6) were included in this investigation. Clinical examination, a battery of tests designed to assess neurophysiological status, and MRI investigations of the brain were obtained in periods ranging between 8 and 20 months after the accident. Hemosiderin deposits, encephalomalacia, and cerebellar atrophy were the most frequent traumatic sequelae. The lesions were located in frontal lobes, the basal ganglia, and the cerebellum. Six patients had cerebellar atrophy associated with frontal or temporal postraumatic lesions. Cerebellar clinical dysfunction was observed in only 3 of these patients. Performance on tests evaluating frontal lobe functions was depressed in 5 of them. CONCLUSIONS: Late MRI after severe head trauma in our pediatric population showed unexpected cerebellar atrophy. Its correlation with prefrontal dysfunction is difficult to confirm because of its association with other parenchymal post-traumatic lesions. Further research involving a larger sample of patients with brain injury of varying severity is in progress, to investigate whether cerebellar atrophy could be a consequence of severe head trauma.

Adolescent↗

Shaken infant syndrome: developmental neuropathology, progressive cortical dysplasia, and epilepsy.

This study describes the developmental neuropathology of two infants who survived 7 and 9 years, respectively, an episode of violent shaking (shaken infant syndrome) early in their lives. The shaking injuries include cortical and subcortical contusions, hemorrhages, hypoxic/ischemic and axonal damage, and severe edema. The types, distribution, and resolution of these shaking injuries are detailed by sequential radiographic studies and by pathologic examination at postmortem. Despite their severity and extent, these injuries resolved in a relatively short period of time. By 6 months, the original injuries are repaired and the resultant encephaloclastic encephalopathies (e.g., multicystic encephalomalacia, porencephaly, generalized white matter attenuation, diffuse cortical atrophy, microgyria, ulegyria, and hydrocephalus ex vacuo) are well established. No appreciable pathologic differences are detected when radiographic findings at 6 months of age are compared to postmortem observations. On the other hand, undamaged and/or partially damaged cortical regions survive the original insult and undergo post-injury reorganization that transforms the residual cortex structural and presumably functional organization. Prominent features of this post-injury reorganization include progressive cortical dysplasia with cytoarchitectural disorganization, laminar obliteration, morphologic and functional (synaptic reorganization) transformation of some neurons, preservation of layer 1 intrinsic fibers and Cajal-Retzius cells, and the presence of large (hypertrophic) intrinsic neurons with intense neurofilament immunoreactivity. We propose that this progressive dysplastic process modifies the residual cortex structural and functional organization, influences the child's neurological and psychological maturation, and may play a significant role in the pathogenesis of ensuing neurological and/or psychological sequelae.

Brain↗

Consanguineous 3-methylcrotonyl-CoA carboxylase deficiency: early-onset necrotizing encephalopathy with lethal outcome.

A patient with a severe neonatal variant of 3-methylcrotonyl-CoA carboxylase (MCC) deficiency is reported. The first child of healthy consanguineous Turkish parents presented on the second day of life with dehydration, cyanosis, no sucking, generalized muscular hypotonia, encephalopathy, respiratory depression requiring mechanic ventilation, macrocephaly, severe acidosis and hypoglycaemia. Elevated C5-OH-carnitine in dried blood spot by tandem MS and elevated urinary excretion of 3-hydroxyisovaleric acid and 3-methylcrotonylglycine suggested MCC deficiency, confirmed by enzyme analysis in cultured fibroblasts. Cerebral ultrasonography and cranial CT findings revealed progressive changes such as disseminated encephalomalacia, cystic changes, ventricular dilatation and cerebral atrophy. Treatment with high-dose biotin and protein-restricted diet was ineffective and the patient died at the age of 33 days with progressive neurological deterioration. Mutation analysis revealed a homozygous mutation in the splice acceptor site of intron 15 in the MCC beta-subunit. Early-onset severe necrotizing encephalopathy should be included in the differential diagnosis of isolated MCC deficiency.

Carbon-Carbon Ligases↗

Effects of antiperoxidants on FeCl2-induced lipid peroxidation and focal edema in rat brain.

Head trauma with contusion or cortical laceration and hemorrhage causes focal edema with encephalomalacia and gliosis. Because cerebral hemorrhage ultimately results in deposition of heme compounds and iron into the neuropil, we injected an aqueous solution of iron salts to simulate the decompartmentalization of iron after trauma. We pretreated animals with saline or with 600 mg/kg alpha-tocopherol plus 5 ppm selenium added to the drinking water. Formation of lipid peroxidation products was significantly inhibited within the iron injection site in the antiperoxidant-pretreated rats at 30, 60, and 120 min after injection of iron into the isocortex. The antiperoxidants failed to prevent formation of focal brain edema at the injection site between 1 and 8 h after injection; however, significantly less edema was present in the alpha-tocopherol + selenium-pretreated animals 24 and 48 h after injection. The efficacy of antiperoxidants in preventing lipid peroxidation, and enhancing the resolution of ferrous-induced focal brain edema suggest that tocopherol + selenium administration caused free radical quenching and termination of lipid peroxidation, and increased membrane stabilization, an effect similar to the action of glucocorticoids.

Animals↗

Lipoxygenase activity in the brain regions of young chicks: isolation and some properties.

1. The lipoxygenase (LOX) oxygenation pathway of arachidonic acid was investigated in the cerebellum and cerebral hemispheres of young chicks. 2. Lipoxygenase products consisted mainly of 15-hydroxyeicosatetraenoic acid (15-HETE), accompanied by the 15-hydroperoxy analog (15-HPETE) and the 5-HETE product. 3. The yield of 15-HETE was 3 times greater in the cerebellar system than in the cerebrum. 4. PLA2 activity of the cerebellum was twice that of the cerebrum. 5. Affinity chromatography revealed 2 brain fractions with LOX activity which were assayed with either linoleic or arachidonic acid as substrate. 6. The fraction eluted with 0.2 M sodium acetate pH 5.0, produced a higher yield and enrichment of LOX activity than the eluate obtained with 0.1 M Tris-HCl buffer (pH 8.0). 7. A considerably higher yield and enrichment of the enzyme was achieved when the starting material was the cerebellum, compared to the cerebrum. 8. The optimal pH for both purified fractions from cerebrum and cerebellum was 6.5, with either linoleic or arachidonic acid as substrate. 9. The cerebral LOX yielded Michaelis-Menten kinetics when linoleic acid was the substrate, while the corresponding plots for the cerebellar enzyme were sigmoidal. 10. Arachidonic acid as substrate produced sigmoidal plots, except at pH 5.0, where Michaelis-Menten kinetics were observed. 11. These results and the elevated activities of PLA2 and 15-LOX could be significant in relation to the special vulnerability of the cerebellum in chick nutritional encephalomalacia.

Animals↗

Toxic effects of solstitialin A 13-acetate and cynaropicrin from Centaurea solstitialis L. (Asteraceae) in cell cultures of foetal rat brain.

Extracts of the aerial parts of the yellow star thistle (Centaurea solstitialis L.) were prepared using petroleum ether, chloroform and methanol and toxicity assessed in primary cell cultures of striatum, frontal cortex and mesencephalon, containing the substantia nigra or raphe nucleus from the brain of the foetal rat. Chloroform extracts significantly reduced the percentage of live cells whereas the petroleum ether extract was inactive. The ability of the methanol extract to reduce the percentage of live cells could not be distinguished from the effects of the vehicle controls for methanol. Subsequently, the plant material was extracted with dichloromethane and 10 fractions were obtained by column chromatography. Fractions 5, 6, 7 and 8 caused concentration-dependent cell death in the culture of substantia nigra, the other fractions were not toxic at the concentrations used. In further studies, solstitialin A was isolated from fraction 9, solstitialin A 13-acetate from fraction 6 and solstitialin A-3 acetate and cynaropicrin from fraction 7. Solstitialin A 13-acetate and cynaropicrin were toxic to cultures of substantia nigra cells. It is concluded that, of the compounds identified, solstitialin A 13-acetate and cynaropicrin have toxic potential in cell cultures, containing cells from the substantia nigra of the rat, the specificity of action to cells of the substantia nigra remains to be shown, and that a toxic action in the midbrain may contribute to the nigro-pallidal encephalomalacia, caused by the ingestion of the yellow star thistle by horses.

Animals↗