Periventricular lesions in the white matter on magnetic resonance imaging in the elderly. A morphometric correlation with arteriolosclerosis and dilated perivascular spaces.

Magnetic resonance imaging (MRI) was performed postmortem on the brains of 40 patients aged over 60 yrs who had died from causes other than brain disease. Periventricular lesions of increased signal intensity on T2-weighted images, graded as moderate or severe, were found in 10% of the patients in the age group between 60 and 69 yrs, and in 50% between 80 and 89 yrs. Macroscopic and microscopic whole-brain sections were studied in 19 brain specimens (8 with normal white matter, 4 with moderate lesions and 7 with severe lesions of the white matter on MRI). The presence or absence of periventricular lesions on MRI correlated well with the severity of demyelination and astrocytic gliosis. Demyelination was always associated with an increased ratio between wall thickness and external diameter of arterioles (up to 150 microns). A variable degree of axonal loss in Bodian-stained sections was present in the white matter of all brains with demyelination. Dilated perivascular spaces were found and studied morphometrically in 9 brain specimens; their presence correlated strongly with corrected brain weight, but incompletely with demyelination and arteriolosclerosis. Our findings suggest that arteriolosclerosis is the primary factor in the pathogenesis of diffuse white matter lesions in the elderly. This is soon followed by demyelination and loss of axons, and only later by dilatation of perivascular spaces.

The pyruvate kinase isoenzyme shift in human gliomas: a potential marker in the treatment of gliomas.

In primary human brain tumours a shift occurs in the synthesis of isoenzymes of pyruvate kinase from the M towards the K-type. In astrocytomas, oligodendrogliomas and glioblastomas, which were localised in the cerebral hemispheres of adult patients over 20 years of age, the shift correlated well with histological grading and growth rate as observed in postoperative survival. Gliomas of adults, localised in midline structures, as well as childrens gliomas were characterised too by a strong shift from M towards the K type. However, in these tumours, less correlation with histological grading and growth rate was found. The isoenzyme shift can be rapidly demonstrated with an alanine inhibition test. The application of this assay may have a diagnostic value during operation for gliomas in grading of malignancy in adults as well as demarcation of the resection of gliomas in all age groups. The test can be performed within 10-15 min and can thus fit easily into a surgical procedure. A case report is presented for illustration.

The pathogenesis of fetal hypokinesia. A neurological study of 75 cases of congenital contractures with emphasis on cerebral lesions.

A comprehensive prospective clinical study is presented of 75 cases of fetal hypokinesia and congenital contractures of various causes, with neuropathological investigation in 23 cases. With the data of medical history, neurological examination, laboratory tests and neuropathology an exact or probable nosological or syndromal diagnosis could be made in 61 cases. These cases were categorized by localisation of causal pathology in the subsequent levels of the developing motor system. In 14 of 61 cases developmental brain disorders (f.i. hydrocephalus, hydranencephaly, microcephaly) were the cause of fetal hypokinesia, often with perinatal death, whereas in 7 cases both cerebral and/or spinal cord lesions were found. Besides cerebral involvement was frequently present in cases with congenital contractures of other origin, concomitant or due to perinatal complications. In a large number of cases clinical evidence of spinal cord lesions, especially anterior horn cell degeneration was present. Myopathic disorders occurred in only four cases, whereas congenital myasthenia and congenital neuropathy were present in one case each. In cases without muscle weakness miscellaneous disorders including congenital skin anomalies and probably primary connective tissue disorders were encountered. The etiologic role of intrauterine viral infection is discussed.

The heterogeneity of the Pena-Shokeir syndrome.

There is evidence that the Pena-Shokeir syndrome is not a specific phenotype but should be regarded as a "fetal akinesia deformation sequence". A neuropathological study of six random new cases was performed to evaluate this theory. Brain pathology observed included persistent fetal meningeal vascularization (two cases), agenesis of the septum pellucidum (one case) and hydranencephaly (one case). Investigation of the spinal cord (in two cases) revealed no abnormalities. Muscle histology (in four cases) was indicative of neurogenic atrophy in two cases. These findings are compared with the data of the 28 cases previously described. It is concluded that the Pena-Shokeir syndrome is a heterogeneous syndrome in which cerebral lesions may play an important role in the pathogenesis. The cerebral malformations may also indicate the time of origin and contribute in the perinatal death of this syndrome.

Congenital hypothalamic hamartoma associated with severe midline defect: a developmental field defect. Report of a case.

We describe a median "cleft" face anomaly (MCFA) with congenital hypothalamic hamartoma in a newborn girl. The MCFA was associated with a frontal midline skull lipoma and a complex congenital heart defect. Possible pathogenetic mechanisms are discussed, and a review of the pertinent literature is given. It is concluded that probably all malformations in our patient are disturbances of a single developmental field defect, ie, the midline.