Periventricular Atrophy Research Articles

Acute encephalopathy after head trauma in a patient with a RHOBTB2 mutation.

ObjectiveDe novo missense mutations in the RHOBTB2 gene have been described as causative for developmental and epileptic encephalopathy.MethodsThe clinical phenotype of this disorder includes early-onset epilepsy, severe intellectual disability, postnatal microcephaly, and movement disorder. Three RHOBTB2 patients have been described with acute encephalopathy and febrile epileptic status. All showed severe EEG abnormalities during this episode and abnormal MRI with hemisphere swelling or reduced diffusion in various brain regions.ResultsWe describe the episode of acute encephalopathy after head trauma in a 5-year-old RHOBTB2 patient. At admission, Glasgow coma scale score was E4M4V1. EEG was severely abnormal showing a noncontinuous pattern with slow activity without epileptic activity indicating severe encephalopathy. A second EEG on day 8 was still severely slowed and showed focal delta activity frontotemporal in both hemispheres. Gradually, he recovered, and on day 11, he had regained his normal reactivity, behavior, and mood. Two months after discharge, EEG showed further decrease in slow activity and increase in normal electroencephalographic activity. After discharge, parents noted that he showed more hyperkinetic movements compared to before this period of encephalopathy. Follow-up MRI showed an increment of hippocampal atrophy. In addition, we summarize the clinical characteristics of a second RHOBTB2 patient with increase of focal periventricular atrophy and development of hemiparesis after epileptic status.ConclusionsAcute encephalopathy in RHOBTB2 patients can also be triggered by head trauma.

A severe connatal form of Pelizaeus Merzbacher disease in a Czech boy caused by a novel mutation (725C>A, Ala242Glu) at the <jimpymsd codon> in the PLP gene

Pelizaeus Merzbacher disease (PMD) is an X-linked recessive disorder of the central nervous system myelination caused by mutations involving the proteolipid protein gene (PLP). Early nystagmus and developmental delay, progressive pyramidal, cerebellar and dystonic signs as well as white matter changes in brain MRI are typical for PMD. The PLP gene can be affected by two major types of mutations. A duplication of the whole PLP gene is the most common mutation and results usually in the milder classical phenotype, whereas point mutations in PLP gene often result in the rarer and more severe connatal form of PMD. The PLP protein is a higly conserved across species and is identical in human, mouse and rat. We describe a 13-year-old Czech boy with an early and severe developmental delay. His maternal uncle died at the age of one year and was also early and severely psychomotoricly retarded. The patient was the first child of healthy unrelated parents born after an uneventful pregnancy and delivery in 1988. Hyperbilirubinemia and bronchopneumonia and early stridor complicated his neonatal period. Diffuse hypotonia, nystagmus, psychomotor retardation, visual and hearing impairment have been observed in the patient since the age of 6 weeks. White matter abnormalities, cortical and periventricular atrophy were detected by MRI at the age of 6 and 11 years, respectively. Despite these signs and results an accurate clinical diagnosis was unclear until the age of 11 years. Last neurological examination in 1999 showed no nystagmus anymore, but extremely dystrophic limbs, truncal deformation, due to severe scoliosis, tetraplegia with hyperreflexia in C5C7 and areflexia L2S2 and positive pyramidal signs. The boy had no visual or speech contact. DNA tests followed the clinical suspicion for PMD. At first, duplication of PLP gene was excluded by quantitative comparative PCR. Direct sequencing of PLP gene detected a novel mutation in exon 6, a missense mutation 725C-->A (Ala242Glu) in the patient and in his mother and later also in his maternal grandmother. The same codon, but to valine (Ala242Val) is mutated in jimpy(msd) mouse, which is the frequently used animal model for PMD. Prenatal diagnosis for the next pregnancy has been offered to the family. The patient died recently at the age of 13 years due to respiratory failure. Our results support the data on the importance of this conserved amino acid alanine at codon 242.

The anatomy of collateral venous flow from the brain and its value in aetiological interpretation of intracranial pathology.

For more than a century, available data concerning collateral venous outflow from the brain have received insufficient attention, as existing theories did not assign practical importance to them. Ideas concerning arterial blood supply and circulation of cerebrospinal fluid were considered more relevant. But available data afford a schematic model of cerebral venous outflow that does have important pathophysiological consequences. Principal outflow through the internal jugular veins can be substituted completely by the large vertebral plexuses, through communications at the cranial base. Emissary veins of the skull vault are small and few in number. Outflow from the deep venous system through the great vein of Galen can be substituted by choroidal, thalamic and striate anastomoses toward the basal vein. So-called intracerebral venous anastomoses through the centrum semiovale towards the convexity are nonexistent or negligible. Instead, a venous watershed exists separating paraventricular white matter from a layer of subcortical white matter. In most infants, the cavernous sinus is not yet connected to the cerebral veins. Once such communications have been formed, important collateral pathways exist through basal and Sylvian veins via the cavernous sinus to the pterygoid plexuses. Simultaneous hindrance of principal and collateral venous outflow will lead to elevated venous pressure and eventual insufficiency of cerebral blood flow (CBF). This will cause increased intracranial pressure, and ventricular enlargement due to periventricular atrophy. The slow phase of the two-compartment model of CBF coincides with the paraventricular white matter area of the deep venous system. In the neonate CBF was found to be still very low, and in the two compartments CBF increases at a different rate to a maximum in childhood. In hydrocephalus, measurement of CBF in the slow deep compartment, rather than the fast cortical one, will be most informative.

HEMIPLEGIC CEREBRAL PALSY

Morphological findings on CT were compared with clinical features of 111 children with hemiplegic cerebral palsy. Periventricular atrophy, interpreted as periventricular leukomalacia, was the most prevalent CT finding, although this type of lesion did not indicate severity of neurological impairment. Maldevelopments were associated with arm-dominated hemiplegia and with a wider range of clinical impairments than previously described. Cortical/subcortical atrophy, less common than presumed, indicated arm-dominated hemiplegia and was associated with more severe impairment than were other CT findings. A normal CT scan indicated leg-dominated hemiplegia and mild impairment. The morphological information obtained by CT was found to be useful for predicting clinical outcome, and was considered an important adjunct to clinical history and findings in these children.

Computed Tomography as an Adjunct in Etiological Analysis of Hemiplegic Cerebral Palsy; II: Children Born at Term

CT brain scans were used to evaluate the most likely etiology of hemiplegic cerebral palsy in a group of children born at term. The population based study group comprised 83 children. The CT findings were classified to reflect the phase of brain maturation during which the injury causing hemiplegia most likely had occurred. The most common finding (37%) was periventricular atrophy considered to represent periventricular leukomalacia (PVL). PVL is a form of hypoxic-ischemic damage typical of the immature brain and most commonly seen as a complication of preterm birth. As this lesion was found in children born at term it was considered to reflect a cerebral injury that had occurred in utero. Cerebral maldevelopment, due to a very early intrauterine lesion, was detected in 17%, while cortical-/subcortical lesions, previously considered to be of major importance in hemiplegia, were seen in just 16% of the children. Altogether the CT findings indicated a prenatal origin of hemiplegia in 57%. Assessing the time of injury based on clinical records concurred with prenatal origin in 32% of the children thought to have prenatal origin of hemiplegia by CT. The objective information available from careful review of imaging information such as CT brain scans, is an important adjunct to clinical data. We propose that assessment of brain morphology, by means of imaging, should be integrated with clinical assessment when evaluating the etiology of brain lesions in children with congenital motor impairment.

Hemiplegic Cerebral Palsy: Correlation Between Ct Morphology and Clinical Findings

Morphological findings on CT were compared with clinical features of 111 children with hemiplegic cerebral palsy. Periventricular atrophy, interpreted as periventricular leukomalacia, was the most prevalent CT finding, although this type of lesion did not indicate severity of neurological impairment. Maldevelopments were associated with arm-dominated hemiplegia and with a wider range of clinical impairments than previously described. Cortical/subcortical atrophy, less common than presumed, indicated arm-dominated hemiplegia and was associated with more severe impairment than were other CT findings. A normal CT scan indicated leg-dominated hemiplegia and mild impairment. The morphological information obtained by CT was found to be useful for predicting clinical outcome, and was considered an important adjunct to clinical history and findings in these children.

Computed Tomography as an Adjunct in Etiological Analysis of Hemiplegic Cerebral Palsy - I: Children Born Preterm

Computed tomography (CT) of the brain has been used to evaluate potential etiologies of hemiplegic cerebral palsy in a population-based group of 28 children born preterm, in whom an obvious postnatal cause of hemiplegia could be excluded. The CT findings were classified according to a system so constructed to reflect the phase of brain maturation during which the insult causing hemiplegia likely had occurred. We found that 50% had evidence of periventricular leukomalacia the lesion typical of hypoxic-ischemic injury to the immature brain. However, it was not possible, neither from the CT scans nor from retrospective review of available clinical data, to date the injury more precisely to the pre- or perinatal period. Analysis of CT findings further showed that 18% of the children had cerebral maldevelopment, indicating an injury during early fetal life as the cause of hemiplegia, earlier than clinically suspected. The CT scans were normal in 25% of the children. It is concluded that the objective information obtained by studying the morphology of brain lesions using CT provides important information in addition to clinical data, and should be integrated with clinical assessment when attempts are being made to evaluate the etiology of cerebral palsy in children.

Morphology of cerebral lesions in children with congenital hemiplegia

This study has analysed the results of CT scans of the brains in children with congenital hemiplegia. The material consists of 111 out of a total of 151 children with this cerebral palsy syndrome in a population-based series. We have classified the morphological findings in five groups. The groups are designed to reflect the phase of maturation of the brain when the insult happened. The groups are: 1. Maldevelopment, 2. Periventricular atrophy, 3. Cortical-/subcortical atrophy, 4. Miscellaneous, 5. Normal. In contrast to previous reports we found a high proportion (17%) with maldevelopment. However the dominating morphological pattern was periventricular atrophy, consistent with a hypoxic-ischemic insult to the immature brain, seen in 42%. Cortical and/or subcortical atrophy was found in 12%. Three children (3%) presented with morphological patterns not possible to classify. The group with no pathology according to CT was 26%.

The Copenhagen High-Risk Project, 1962-86.

Since 1962 we have followed a sample of 207 children at high risk for schizophrenia as well as 104 control children. For these individuals, the following factors and their interaction are related to an increased risk for schizophrenic breakdown: (1) greater schizophrenia family backgrounds, (2) perinatal trauma, and (3) unstable parenting and public institutional child care. The perinatal difficulties are positively related to adult periventricular atrophy. Results of a subsequent study tentatively suggest that part of the neurological deviance in schizophrenia may be produced by disruption occurring in the second trimester of fetal development.