Early onset chromosome 14-linked distal myopathy (Laing).

A dominantly inherited form of distal myopathy with onset in early childhood was first reported in a 4-generation Australian family in 1995. In the present report we provide further information on the clinical phenotype and natural history of this myopathy, and on the electromyogram and magnetic resonance imaging findings in affected individuals. The pattern of muscle involvement was similar to that in the 'tibial' forms of distal myopathy such as the Finnish (Udd) and Markesbery-Griggs types, with additional involvement of the finger extensors and of some more proximal limb and neck muscles. However, the age of onset was earlier than in these other myopathies and rimmed vacuoles were not found in biopsies from two affected individuals. Evidence of possible anticipation was found in one branch of the family. The gene locus for this myopathy had been mapped to 14q11.2-q13. The linkage region has been refined to a 24 cM region between D14S283 and D14S49 and mutations have been excluded in the PABP2 gene for oculopharyngeal muscular dystrophy which lies within this region.

Brain density and cerebrospinal fluid space size: CT of normal volunteers.

This study attempted to establish normal values for cerebral white and deep gray matter density and total brain density, and to discover how much dilatation of the cerebrospinal fluid--containing spaces occurs with advancing age up to 40 years. The 53 female and 62 male healthy volunteers, 15-40 years old, had been screened to exclude individuals with neurologic disease, previous head trauma, congenital or acquired heart disease, chronic pulmonary disease and other systemic illness, and those who consumed more than small amounts of alcoholic beverages. The computed tomography scan data for the 115 subjects were scored subjectively for the severity of atrophy. It was found that in both genders there was an increasing frequency with advancing age of sulcal widening of the frontal lobes and cerebellar vermis starting in the teens. A ventriculo-internal cranial ratio was calculated for 93 subjects who had been examined on the EMI CT 1010, the mean value being 0.31 +/- 0.08 for females and 0.33 +/- 0.06 for males. The ratio did not change significantly with age up to 40 years. On the same 93 subjects, mean values and standard deviations were obtained for normal white matter (30.1 +/- 3.5 Hounsfield units (H) for females and 29.8 +/- 3.3 H for males) and for normal deep gray matter (33.0 +/- 3.3 H for females; 33.2 +/- 2.6 H for males) and for total brain density (33.9 +/- 2.7 H for females; 33.6 +/- 2.6 H for males).

Computerized tomography of brain and optic nerve in multiple sclerosis. Observations in 100 patients, including serial studies in 16.

Computerized tomography (CT) of the brain was carried out in 100 patients with established or suspected multiple sclerosis (MS). The optic nerves were also examined in 53 of these patients. Areas compatible with demyelinating lesions were found in the cerebral hemisphere white matter and less frequently in the brain stem in 47% of cases. The hemisphere lesions were commonly multiple, typically situated in the deep white matter and periventricular regions, and were often asymptomatic. Small areas with unduly low attenuation coefficients were found in one or both optic nerves in 52% of patients in whom the optic nerves were examined. While these areas may represent demyelinating lesions their significance remains uncertain in view of poor correlation with clinical and electrophysiological parameters of optic nerve damage. Cerebral cortical atrophy and/or ventricular dilatation was found in 44% of cases, the frequency and severity of atrophy increasing with age and duration of disease. Serial studies after intervals of up to 21 months were performed in 16 patients, providing the opportunity to study the natural history of the cerebral lesions. While in some cases no significant change occurred, in others white matter lesions underwent an increase or a reduction in size, and in some cases new lesions appeared. In some patients minor degrees of atrophy became apparent over the period of the study. The value of CT in the investigation of patients with suspected MS and as a means of studying the natural history of the disease is discussed.

Primary cerebral neuroblastomas. A clinicopathological study of one adolescent and five adult patients.

Neuronal differentiation was demonstrated by light microscopy, immunohistochemistry and electron microscopy in the cerebral neoplasms of one adolescent and five adult patients. The tumours exhibited a wide spectrum of cellular differentiation from low to high grade malignancy which seems to correlate well with their biological behaviour. The natural history of these 6 cerebral neuroblastomas is rather long compared to that of other malignant primary cerebral neoplasms of adulthood; however, 2 patients died, one survived about 5 yr after initial symptoms whilst an untreated patient survived more than 12 yr. It is suggested that morphological grading along the lines of Kernohan's system may be useful in determining the prognosis and postoperative management of patients with cerebral neuroblastomas.

Mathematical method to utilize a computer for diagnosis of site and type of intracerebral mass lesions.

A mathematical process has been devised which can utilize full clinical data of symptoms and signs, neuroradiological procedures, EEG and isotope scanning to predict the site and pathological process in a patient presenting with disturbance of central nervous system function. The work is a further expansion and modification of the computer program described by Du Boulay and Price (1968).

CT demonstration of the early effects of alcohol on the brain.

CT evidence of brain damage has been sought in subjects consuming alcohol between 10 g/day to over 200 g/day. Dietary contributing factors have been evaluated. The level of atrophy (shrinkage) has been correlated with intellectual performance. To establish a relationship between alcohol intake and brain structure and function, re-examination of subjects over a 6- to 12-month period of abstinence has been undertaken to examine any reversibility features. A record of liver function showed that brain damage always precedes liver damage. Subjects were re-examined a second time, who had initially abstained for six months and then had returned either to their original level of consumption or to one that was somewhat reduced. A regression in initial improvement was considered evidence of reversible brain damage that had originally been related to alcohol. The threshold consumption for CT damage was 40 g/day, but the level of CT atrophy at which cognitive dysfunction appeared has still to be established.

Is CT scan a valid indicator of brain atrophy in alcoholism?

The effect of ingesting varying quantities of alcohol upon the structure and function of the brain was studied using CT scan and psychometric testing. Nutritional status was also assessed. Alcoholics, heavy, moderate and light social drinkers were examined and their results compared with a normal control series. It was concluded that a daily consumption of more than 40 grams alcohol per day, "the safe level" results in brain damage. The latter may partially reverse with abstinence and having reversed maintain improvement, even though patients then resume drinking at the "safe level". The role of thiamin in brain function is still unclear.

Ataxic cerebral palsy--clinico-radiologic correlations.

Clinico-radiologic correlations, using CT, were studied in 29 patients with ataxic cerebral palsy. The scans were normal or only slightly abnormal in 38%, posterior fossa abnormalities occurred in 28%, and 55% had obvious cerebral abnormalities which always involved the parietal lobes. There were only two cases where the changes were confined to the posterior fossa. Hydrocephalus was present in four, and there was one case of a Dandy-Walker malformation. An absolute association with any clinical subtype was unusual. All cases of simple ataxia had an obviously abnormal scan, but the changes were widespread. Where dysequilibrium was present the scans were either normal or showed widespread change. Only 25% involved the vermis. Although there was some association between hydrocephalus and ataxic diplegia, the majority of this subtype had a normal or only slightly abnormal scan. Most were hypotonic docile infants with delayed speech and motor skills, particularly those with posterior fossa abnormality. Although CT did not predict development well, those with lower IQ's were more likely to have obvious CT change. Where obvious supratentorial change was present, 75% had a history of epilepsy. In ataxic cerebral palsy CT findings are common, but variable. CT change correlates better with IQ and epilepsy than clinical subtype.

Computerized axial tomography findings in a group of patients with migrainous headaches.

Computerized axial tomography of the cranium has been carried out in 46 patients referred because recurring migrainous headaches. Increasing frequency or severity of headaches or a change in headache pattern were the usual reasons for referral. Abnormalities were found in 37 cases and fell into 4 categories. The most frequent (21 cases) consisted of a mild degree of oedema in the white matter of one or both cerebral hemispheres. This was usually bi-frontal (15 patients) but was more extensive in 2 patients. Varying degrees of cerebral atrophy, as determined by widening of the Sylvian, brain-stem and interhemispheric cisterns, and/or widening of the third and lateral ventricles as compared to a group of normal scans, was found in 8 cases. Areas of occipital infarction were found in 4 patients with permanent visual field defects. Unexpected small areas of infarction were found in the temporal lobe in 2 other cases. Cerebral tumours were found in 2 cases. The significance of these findings is discussed, as well as the possible role of migrainous vaso-spasm with consequent changes in cerebral blood flow in the pathogenesis of oedema and atrophy in migraine subjects.

Computerised tomography findings in multiple sclerosis and Schilder's disease.

Computerised tomography of the brain was performed in 95 patients with multiple sclerosis and in a single patient with Schilder's disease. CT of the orbits was also carried out in 53 of these cases to examine the optic nerves. In 51% of the multiple sclerosis cases low density areas compatible with plaques of demyelination were found in the white matter of the cerebral hemispheres, and less frequently in the brain-stem. A much larger area of reduced intensity was found in the occipital white matter in the patient with Schilder's disease. Varying degrees of central and/or cortical cerebral atrophy were found in 45% of the multiple sclerosis patients, the more severe degrees being found in patients with long-standing disease. Serial observations in 15 patients who were examined on more than one occasion are also presented. Small low density areas were identified in one or both optic nerves in 52% of the multiple sclerosis cases. While these may represent demyelinating lesions their significance is uncertain.

Computerized axial tomography in the detection of brain damage: 1. Alcohol, nutritional deficiency and drugs of addiction.

The severity and extent of cerebral atrophy was assessed on cranial computerized axial tomographic (CAT) scans in 240 alcoholics in whom this investigation had been performed for diagnostic purposes, and in a group of 59 male heavy social drinkers who were studied prospectively. Findings were compared with those in a group of 115 normal volunteers who were either total abstainers or light infrequent drinkers. Only 12 (5%) of the 240 alcoholics and 20 (33%) of the 59 social drinkers had a normal CAT scan. The remainder all showed a degree of cerebral and/or cerebellar atrophy in excess of that found in the normal subjects in a comparable age bracket. Atrophy was most frequent and most severe in the frontal lobes and superior vermis of the cerebellum, but, in most cases, there was more widespread cerebral and cerebellar cortical atrophy. The CAT scans of four patients with anorexia nervosa, two of whom showed an excessive degree of cerebral cortical atrophy for the patient's age, and of eight young people addicted to heroin, cannabis, lysergic acid or barbiturates, six of whom showed varying degrees of premature cerebral atrophy, were also studied.

Computerized axial tomography in the detection of brain damage. 2. Epilepsy, migraine, and general medical disorders.

The cranial computerized axial tomography (CAT) findings in groups of patients with epilepsy, migraine, hypertension, and other general medical disorders have been reviewed to assess the frequency and patterns of focal and diffuse brain damage. In addition to demonstrating focal lesions in a proportion of patients with seizures and in patients presenting with a stroke, the CAT scan showed a premature degree of cerebral atrophy in an appreciable proportion of patients with long-standing epilepsy, hypertension and diabetes, and in some patients with migraine, valvular and ischaemic, heart disease, chronic obstructive airways disease, and chronic renal failure. The value of CAT as a means of screening for brain damage in groups of individuals at risk is discussed.

Posterior fossa, aqueduct and fourth ventricle of the living mouse studied by positive contrast and plain radiography.

Radiographic techniques have been applied to the measure the size, volume and relationships of the posterior fossa, aqueduct and fourth ventricle in two strains of laboratory mice. Significant differences in the size of posterior fossae between strains were observed. Using ventriculography in the living mouse, the outflow tract of the fourth ventricle was demonstrated, together with a communication that exists between the third ventricle and the subarachnoid space.

Computerised tomography of the cranium in patients with epilepsy: a preliminary report.

The findings are presented in 366 patients with seizures who were studied by computerised tomography of the cranium. The relative frequency of normal scans, cerebral tumours, atrophy and other pathological lesions is indicated. A more detailed analysis of the group of patients with atrophy was carried out. The frequency and severity of atrophy correlated significantly with age but not with length of seizure history. However, the more marked degrees of atrophy were found among patients with long-standing or poorly controlled epilepsy, an observation which has important implications with regard to the adequacy of seizure control in epileptic patients.

Electrophysiological and computerised tomography findings in multiple sclerosis: a comparative study.

102 patients with multiple sclerosis (MS) have been investigated by one or more of the following techniques: visual evoked potentials, cervical and cortical somatosensory evoked potentials, horizontal saccadic eye movement velocities, and computerised axial tomography of the cranium and orbits. It has been found that with each technique it is possible to detect abnormalities, which may be subclinical, in a significant proportion of patients. The proportion with abnormal results was greater in patients studied by more than 1 technique and was greatest in those patients who were studied by each of the 5 techniques. It is concluded that the techniques used have a complementary role in the investigation of patients suspected of having MS.

Evoked potentials, saccadic velocities, and computerized tomography in diagnosis of multiple sclerosis.

One hundred and two patients with suspected or established multiple sclerosis (MS) were investigated by one or more of the following techniques: measurement of visual evoked potentials (VEP); measurement of cervical and cortical somatosensory evoked potentials (SEP); measurement of horizontal saccadic eye movement velocities (SV); and computerised axial tomography of the cranium and orbits (CT). Each of the techniques was valuable in detecting abnormalities, some of which were subclinical, in many patients. More abnormalities were found in patients studied by more than one technique, the most being detected in patients who were studied by all five techniques. We conclude that the techniques have a complementary role in investigating suspected MS.

Brain atrophy and intellectual impairment in heavy drinkers--a clinical, psychometric and computerized tomography study.

The frequency of cerebral and cerebellar atrophy was assessed by computerized tomography (CT) in 26 heavy drinkers. Findings were correlated with clinical deficits, with the results of psychometric testing using the Wechsler Adult Intelligence Scale (WAIS), and with the alcoholic history and nutritional status. Cerebral atrophy was present in 19 cases (73%), 16 of whom also had cerebellar atrophy. There was a good correlation between the degree of cerebral hemisphere atrophy and age and length of drinking history, but a poor correlation between neurological deficits and atrophy. Impairment of visuo-spatial and visuo-motor functions with sparing of other non-dominant hemisphere functions and of verbal skills was the characteristic pattern found with the WAIS in 18 subjects; four showed a more global depression of intellectual function. The degree of cerebral hemisphere atrophy correlated significantly with the impairment of non-dominant hemisphere functions but not with total IQ.

Multifocal progressive neurological disorder caused by neoplastic angioendotheliosis.

The case of a 46-year-old woman who suffered a multifocal neurological illness, which rapidly progressed to dementia, is reported; the clinical signs were suggestive of multiple sclerosis. At necropsy, polyfocal cerebral white-matter lesions, associated with intravascular plugs of neoplastic cells which appeared to arise from the vascular endothelium, were found. The findings were typical of a rare form of malignant disease of the vascular endothelium known as neoplastic angioendotheliosis, which shows a striking predilection for the central nervous system.