Congenital cytomegalovirus infection: the impact of cerebral cortical malformations.

AIM: Cytomegalovirus has been suggested to have a teratogenous influence during the migration of neural cells from the ventricular zones to the cortex during the gestational period. The aim of this study was to investigate the prevalence of congenital cytomegalovirus infections in a cohort of children with neurological disability and cerebral cortical malformations recognized by neuroimaging. METHODS: Twenty-six children with neurological disability and cerebral cortical malformations were investigated retrospectively for congenital cytomegalovirus infection by analysing the dried blood spot samples for cytomegalovirus deoxynucleic acid using qualitative polymerase chain reaction. RESULTS: CMV DNA in the dried blood spot samples was found in four out of 26 children. Two of these four had severe disabilities with mental retardation, autism, spastic cerebral palsy, epilepsy and deafness. A third child had epilepsy and unilateral cerebral palsy, while the fourth had a mild motor coordination dysfunction and hearing deficit. CONCLUSION: In our study, the number of congenital cytomegalovirus infections in children with cerebral cortical malformations was higher (4/26) than expected with reference to the birth prevalence (0.2-0.5%) of congenital cytomegalovirus infection in Sweden. We thus conclude that congenital cytomegalovirus infection should be considered in children with cortical malformations of unknown origin.

Cranial ultrasound and MRI at term age in extremely preterm infants.

OBJECTIVES: Conventional MRI at term age has been reported to be superior to cranial ultrasound (cUS) in detecting white matter (WM) abnormalities and predicting outcome in preterm infants. However, in a previous study cUS was performed during the first 6 weeks only and not in parallel to MRI at term age. Therefore, the aim of the present work was to study brain injuries in preterm infants performing concomitant cUS and MRI at full-term age. METHODS: In a population-based cohort of 72 extremely low gestational age infants paired cUS and conventional MRI were performed at term age. Abnormalities on MRI were graded according to a previously published scoring system. On cUS images the lateral ventricles, the corpus callosum, the interhemispheric fissure and the subarachnoidal spaces were measured and the presence of cysts, grey matter abnormalities and gyral folding were scored. RESULTS: Moderate or severe WM abnormalities were detected on MRI in 17% of infants and abnormalities of the grey matter in 11% of infants. Among infants with normal ultrasound (n=28, 39%) none had moderate or severe WM abnormalities or abnormal grey matter on MRI. All infants with severe abnormalities (n=3, 4%) were identified as severe on MRI and cUS. CONCLUSIONS: All severe WM abnormalities identified on MRI at term age were also detected by cUS at term, providing the examinations were performed on the same day. Infants with normal cUS at term age were found to have a normal MRI or only mild WM abnormalities on MRI at term age.

A child with muscle-eye-brain disease. Ophthalmological and neurological characteristics.

PURPOSE: To describe a child with Muscle-Eye-Brain disease (MEB), one of three types of congenital muscular dystrophy associated with ocular abnormalities. METHODS: Case report. RESULTS: The child showed severe visual impairment due to progressive myopia and retinal degeneration, a pachygyria-type of migration disorder of the brain with a nodular cortical surface, i.e. cobblestone cortex, as well as muscular weakness and severe mental retardation. CONCLUSION: Ophthalmological assessments are important to help to diagnose and follow children with congenital muscular dystrophy.

Periventricular band of increased echogenicity: edema or calcification?

This paper illustrates the cases of two infants with an identical appearance of a periventricular band (PVB) of increased echogenicity on cranial sonography, shown on CT to be due to edema in one and calcification in the other. Such a PVB due to edema has not been reported previously, and its similarity to calcification on sonography is emphasized.

Unique desmoplastic cerebral tumor in a patient with complex partial seizures.

Primary brain tumors with prominent desmoplasia include the gliofibroma, desmoplastic infantile ganglioglioma (DIG), pleomorphic xanthoastrocytoma (PXA), and desmoplastic cerebral astrocytoma. In the present report, we describe unusual pathological appearances in two successive resections of a left temporal tumor in a patient with complex partial seizures. Both tumors showed focal astroglial and very prominent neuronal differentiation. In the first resection at age 11 years, the tumor showed only focal desmoplastic areas and prominent neuronal differentiation with bizarre atypical giant cells. In the second resection at age 14 years, the morphology was dramatically different. Now the tumor showed marked desmoplasia with tumor cells coexpressing neuronal and glial markers. Electron microscopy showed prominent neuronal differentiation in both resections and presence of basal lamina around tumor cells. Our case represents a unique example of an extraordinary degree of neuronal differentiation in a desmoplastic cerebral tumor. While cellular pleomorphism in a desmoplastic tumor traditionally suggests the diagnosis of PXA, we wish to underscore that many cells exhibiting marked cytologic atypia may in fact be of neuronal rather than of glial origin as in our case.

Positron emission tomography compared with magnetic resonance imaging and computed tomography in supratentorial gliomas using multiple stereotactic biopsies as reference.

Ten patients with findings at computed tomography (CT) suggesting intracranial supratentorial glioma were investigated to compare the diagnostic efficacy of this technique with that of positron emission tomography (PET) using 11C-methionine and examinations with magnetic resonance (MR). The findings were related to histopathologic examination of serial stereotactic biopsies, which were guided by the appearance of the lesions on PET examination. To obtain corresponding slice orientation with the different examination techniques, an individually shaped helmet fixation was used. However, in 3 cases this fixation device could not be used for MR. Histopathologic diagnosis, obtained in all cases from multiple target stereotactic biopsies, included glioma in 9 patients and reactive gliosis in one case. A detailed comparison of the three imaging techniques and the findings at stereotactic biopsies was possible in 7 patients, while in 3 patients comparison with MR was less exact due to the patient's refusal to wear the helmet during this examination. MR was the most accurate method for outlining the total extent of a lesion, i.e. the tumor and the edema surrounding it. Four lesions had homogeneous signal characteristics and in 6 lesions two (or more) compartments could be distinguished with MR. In 5 cases the MR findings were in complete agreement with the histopathologic findings. However, a thorough correlation between signal characteristics and histology was not possible. Using PET the occurrence and the extent of tumor tissue was correctly predicted in 7 patients. The PET was normal in one case. Findings at CT were in agreement with the histopathologic diagnosis in 5 patients. MR was the most sensitive method for the detection of lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Positron emission tomography with 11C-methionine and computed tomography of intracranial tumours compared with histopathologic examination of multiple biopsies.

A selected group of 36 patients with suspected supratentorial gliomas were investigated with positron emission tomography (PET) using 11C-methionine and transmission computed tomography (CT) before and after intravenous injection of contrast medium. Every examination was performed with the head fixed in a plastic helmet and a baseplate to guarantee that the slice orientation was the same at examinations with the two modalities and over time. Guided by the examinations, multiple stereotactic biopsies were performed with the biopsy instrument mounted on the baseplate. Regional accumulation of methionine was compared with histology of the corresponding samples and with attenuation before and after injection of contrast medium as well as mass effect on CT. Typically, there was a low attenuating lesion with a slight mass effect on CT. There was an increased accumulation compared with normal brain tissue in 31 cases of tumours and ordinary or decreased accumulation in 3 cases of tumours. In 22 cases with increased accumulation of methionine the extension of the tumour judged by PET corresponded with that of histology. In 4 cases tumour cells were found outside the area with pathologic methionine uptake. In 5 patients there were areas with increased methionine accumulation where no tumour cells were found. In 22 cases PET using methionine was more accurate than CT in defining the tumour boundaries as determined from the histologic findings. Four groups of biopsy specimens with different amounts of methionine accumulation are described. The uptake in a single biopsy gives good but not exact information about the histology of the specimen.

PET study of methionine accumulation in glioma and normal brain tissue: competition with branched chain amino acids.

Five patients with glioma were examined with positron emission tomography using ([11C]methyl)-L-methionine. The study was repeated while the patient was being infused with branched chain amino acids (BCAA), 250 mumol/min. The accumulation rates of methionine in tumor tissue and in normal brain tissue were compared without and with the infusion of amino acids. Both tumor tissue and normal brain tissue showed a reduction in the methionine accumulation by 35% while the patient received the infusion. In one patient with a severe blood-tissue barrier disruption the tumor accumulation rate was unaffected. It is concluded that in gliomas without severe blood-tissue barrier disruption, the accumulation of methionine is governed by processes exhibiting similar properties regarding competition with BCAA as in normal brain tissue.

11C-labelled glycine: synthesis and preliminary report on its use in the investigation of intracranial tumours using positron emission tomography.

Carbon-11-labelled glycine has been prepared by a Bücherer-Strecker synthesis using [11C]cyanide, formaldehyde and ammonium carbonate. Total synthesis time, including chromatographic purification, was 30-35 min from end-of-bombardment. Radiochemical yield was 35%, based on [11C]cyanide and radiochemical purity was shown to be greater than 98% by analytical HPLC. The 11C-labelled glycine thus prepared was used along with [68Ga]EDTA and L-[methyl-11C]methionine in the visualization of an anaplastic astrocytoma by positron emission tomography.

Positron emission tomography of cavernous haemangiomas of the brain.

Four cases with lesions suspected to be low-grade intracerebral tumours but later proved to be cavernous haemangiomas are described. The patients were examined with contrast enhanced CT and with positron emission tomography (PET). The lesions were partly calcified with a mild or no mass effect and a slight contrast enhancement at CT. There were signs of disrupture of the blood-lesion barrier also on radionuclide studies. PET with 11C-methionine and 11C-glucose showed a normal or decreased accumulation of the tracers. This combination of findings has not been encountered in intracranial tumours. As a comparison, one case of glioblastoma is described. In this patient, the CT findings suggested a cavernous haemangioma. However, PET showed a markedly increased accumulation of 11C-methionine, which is compatible with brain tumour but not with haemangioma.

Peripheral benzodiazepine binding sites in human gliomas evaluated with positron emission tomography.

A specific ligand for peripheral type benzodiazepine receptors, Ro5-4864, was synthesised and labelled with 11C for use in positron emission tomography (PET). Four patients with suspected glioma, two patients with high grade astrocytoma and two with low grade astrocytoma, as well as one patient with meningioma were examined with PET after the administration of 200 MBq 11C-Ro5-4864. The images as well as kinetic analyses revealed lower uptake of the ligand in tumor as compared with cortical tissue. Markedly elevated uptake in the thalamus suggests a functional role of the ligand.

Positron emission tomography with 11C-methionine of intracranial tumours compared with histology of multiple biopsies.

Thirty-eight patients with suspected supratentorial gliomas have been investigated with positron emission tomography (PET) using 11C-methionine and computed tomography (CT) before and after intravenous injection of contrast medium. Every examination was performed with the head fixed in a plastic helmet and a baseplate to guarantee that the slices were corresponding in the different examinations and from time to time. After the examinations multiple stereotactic biopsies were performed with the biopsy instrument mounted on the baseplate. Accumulation of methionine was compared with normal brain in 32 cases of tumours and ordinary or decreased accumulation in 4 cases of tumours. In 22 cases with increased accumulation of methionine the extension of the tumour judged by PET corresponded with that of histology. In 5 cases tumour cells were found outside the area with pathologic methionine uptake. In 5 patients there were areas with increased methionine accumulation where no tumour cells were found. In 24 cases PET using methionine was more accurate than CT.

The blood tumour barrier in intracranial tumours studied with X-ray computed tomography and positron emission tomography using 68-Ga-EDTA.

Disruption of the blood brain barrier or rather blood tumour barrier in cerebral tumours was studied with CT after intravenous injection of contrast medium and with PET after intravenous administration of 68-Ga-EDTA. Histology from stereotactic biopsies or open surgery is compared with the radiologic findings and advantages of the respective methods are discussed. The material consisted of 47 patients mainly with supratentorial gliomas and a few miscellaneous tumours. Astrocytomas (Kernohan grade II) were found to have no disruption of blood tumour barrier while anaplastic astrocytomas and glioblastomas (Kernohan grade III and IV) had. PET is somewhat superior to CT in detection of disruption of the blood tumour barrier. It is concluded that the combination of CT and PET is of value in the assessment of intracranial tumours.

Positron emission tomography with ([11C]methyl)-L-methionine, [11C]D-glucose, and [68Ga]EDTA in supratentorial tumors.

Sixteen patients with supratentorial tumors were examined with positron emission tomography (PET) using [( 11C]methyl)-L-methionine, [11C]D-glucose, and [68Ga]EDTA as well as CT. There were nine astrocytomas (grade II), three oligoastrocytomas (grade II), two anaplastic astrocytomas (grade III), and two meningiomas. Six patients with low-grade astrocytomas and all three patients with oligoastrocytomas had an accumulation of [11C]methionine varying from slightly to intensely increased as compared with normal brain tissue. There was a markedly increased uptake of methionine in the anaplastic astrocytomas. Three of the low-grade astrocytomas had a decreased uptake of [11C]methionine in at least part of the tumor as compared with normal brain tissue. Contrast enhancement on CT or uptake of [68Ga]EDTA was not a prerequisite for increased accumulation of methionine. Uptake of [11C]glucose was lower than or equal to that of normal brain tissue in the low-grade tumors and also in one of the two anaplastic astrocytomas and in the bulk of the other. In each individual case the methionine uptake tended to be higher--or less decreased--than the glucose uptake. In the low-grade tumors the uptake of methionine and that of glucose were often different, occasionally markedly different, as far as the tumoral-peritumoral areas involved. These differences were even more remarkable in the two anaplastic astrocytomas. An increased uptake of methionine was often seen in areas appearing normal on CT. It appears that PET with [11C]glucose has limitations with regard to delineation of the low-grade astrocytomas, whereas PET with [11C]methionine usually better reflects the extent of these tumors and, to a lesser degree, the extent of the high-grade neoplasms. The results of PET with [68Ga]EDTA were similar to those with postcontrast CT in most patients. The two meningiomas exhibited a high uptake of all tracers used for PET as well as a marked contrast enhancement on CT. The extent of the meningiomas judged by PET with the various tracers correlated well with the extent assessed by postcontrast CT.

Right retrograde brachial cerebral angiography with simultaneous compression of the left carotid artery.

Right retrograde brachial angiography with simultaneous compression of the left common carotid artery was performed in 12 patients, invariably resulting in filling of the right vertebral and the basilar artery. In all but one patient, the right carotid artery and its branches were also filled. Retrograde filling of the left internal carotid artery occurred in 8 patients. Furthermore, retrograde filling of the intracranial part of the left vertebral artery was obtained in 5 of 12 patients. A complete four-vessel cranial angiography was thus obtained in one third of the patients. The method may be considered as a safe and valuable adjunct to other angiographic techniques.