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Biomedical subjects

A E Harding

Publications and source records attributed to A E Harding.

At least 235 records · Page 13Linked to original sources
PubMed1984

Intracerebral haemorrhage complicating dural arteriovenous fistula: a report of two cases.

Two patients presented with unilateral peri-orbital pain, proptosis, chemosis and external ophthalmoplegia. They were shown to have dural arteriovenous fistulae related to the cavernous sinus. Intracerebral haemorrhage occurred in both patients within 18 months of presentation; this gave rise to focal seizures and signs of unilateral hemisphere dysfunction. The haematomas were in the region drained by the superficial middle cerebral vein ipsilateral to the shunt and are presumed to have been the result of locally raised venous pressure.

Aged↗
PubMed1983

Chronic asymmetrical spinal muscular atrophy.

The clinical and neurophysiological features of 18 cases of chronic asymmetrical spinal muscular atrophy are described. These were patients presenting with asymmetrical neurogenic atrophy involving one or more limbs who had no evidence of pyramidal tract dysfunction after 3 or more years of symptoms. There were twice as many males as females and the mean age of onset of the disorder was about 32 years. None of the patients had bulbar involvement. The tendon reflexes tended to be depressed. The distribution of muscle weakness in the limbs was very variable, and only slowly progressive. In 5 cases symptoms and signs were confined to the hands and forearms. Motor nerve conduction velocities to wasted muscles were slightly reduced but there was no evidence of generalised neuropathy. A diagnosis of chronic asymmetrical spinal muscular atrophy, as opposed to that of classical motor neurone disease, is favoured by an age of onset under 40 years, an absence of pyramidal signs or bulbar involvement after 3 years or more of symptoms, and depressed or absent tendon reflexes. The 2 conditions appear to be clinically distinct and prognosis is considerably better in chronic asymmetrical spinal muscular atrophy. The aetiology of this condition in unknown; it may be of relevance that 2 patients in this series had close relatives with Werdnig-Hoffmann disease.

Adult↗
PubMed1983

The heart disease of Friedreich's ataxia: a clinical and electrocardiographic study of 115 patients, with an analysis of serial electrocardiographic changes in 30 cases.

One hundred and fifteen patients with carefully defined Friedreich's ataxia were assessed clinically and electrocardiographically for evidence of heart disease. Cardiac symptoms, of which dyspnoea and palpitations were the most frequent, occurred in less than 30 per cent. Abnormalities on clinical examination were present in a similar proportion; harsh systolic murmurs, ventricular hypertrophy and added heart sounds were the commonest of these. Cardiac failure and persistent arrhythmias were rare and occurred late in the evolution of the neurological disease. Two patients presented with heart disease before developing neurological symptoms. Cardiac signs and symptoms were uncommon in patients without electrocardiographic abnormalities. About two-thirds of the cases had definitely abnormal ECG recordings. The characteristic finding was of widespread T-wave inversion with ventricular hypertrophy. Serial ECGs, recorded over periods of up to 32 years, were available in 30 cases and showed that abnormalities may develop in patients with Friedreich's ataxia at any time up until 20 years after the onset of neurological symptoms. In four patients initial ECG abnormalities had either improved or disappeared subsequently.

Adolescent↗
PubMed1982

Spinocerebellar degeneration secondary to chronic intestinal malabsorption: a vitamin E deficiency syndrome.

Two adults are described who developed a progressive neurological disorder more than 20 years after the onset of chronic fat malabsorption. The clinical features included dysarthria, cerebellar ataxia, and prominent proprioceptive loss with depressed or absent tendon reflexes. Serum vitamin E was undetectable in both cases. One patient improved clinically and electrophysiologically after oral therapy with vitamin E. The findings in these patients were similar to those in others recently reported with vitamin E deficiency associated with biliary atresia. Electrophysiological observations suggested that the human deficiency state parallels that found neuropathologically in vitamin E-deficient animals.

Adult↗
PubMed1982

The clinical features and classification of the late onset autosomal dominant cerebellar ataxias. A study of 11 families, including descendants of the 'the Drew family of Walworth'.

The clinical features of 11 families containing 73 individuals with dominantly inherited cerebellar ataxia of late onset are described. Many of the patients had physical signs in addition to cerebellar ataxia, which included dementia, supranuclear ophthalmoplegia, extrapyramidal dysfunction, optic atrophy, pigmentary retinal degeneration, myoclonus and deafness. These associated features were generally very variable within members of the same family. Intrafamilial correlation of age of onset and an analysis of clustering of clinical features within families using X2 tests suggested that there was little evidence of genetic heterogeneity in the eight kindreds where ophthalmoplegia, optic atrophy, dementia, or extrapyramidal signs were found in affected individuals. One of these families contained descendants of the 'Drew family of Walworth' described by Ferguson and Critchley in 1929. The three other families contained patients with clinically distinct syndromes which were: cerebellar ataxia with pigmentary retinal degeneration; a later onset (over 60 years) 'pure' cerebellar syndrome; and an ataxia disorder associated with myoclonus and deafness. A simple classification of the autosomal dominant cerebellar ataxias is proposed and discussed in relation to previous attempts to classify these disorders on clinical and pathological grounds.

Adult↗
PubMed1982

X-linked recessive bulbospinal neuronopathy: a report of ten cases.

A form of adult onset 'bulbospinal muscular atrophy' of X-linked recessive inheritance is described in 10 patients from eight families. Muscle weakness in the limbs was mainly proximal and developed in the third to fifth decades of life, often preceded by muscle cramps on exertion and tremor of the hands. Weakness and fasciculation of the facial muscles and tongue were prominent. All the patients had gynaecomastia and some were infertile. Two had diabetes mellitus. Motor nerve conduction studies were normal but most patients had small or unrecordable sensory action potentials in the absence of clinical sensory loss. Plasma creatine kinase levels were considerably elevated and muscle biopsies showed neurogenic atrophy together with secondary myopathic changes. The importance of recognising this distinctive disorder in single cases (six of the present series) is emphasised.

Biopsy↗
PubMed1981

"Idiopathic" late onset cerebellar ataxia. A clinical and genetic study of 36 cases.

The clinical features of 36 patients with late onset cerebellar ataxia of unknown cause are described. Overall, the age of onset ranged from 30 to 74 years and there was a significant excess of males. The patients were divided into 3 groups on clinical grounds. The first was composed of 12 cases in whom truncal ataxia was more marked than limb ataxia and onset was relatively late (mean 54.75 years); these correspond to the Marie-Foix-Alajouanine type of cerebellar degeneration. The second group contained 6 individuals who had prominent tremor in the upper limbs, both resting and during action. The 18 individuals in the 3rd group were clinically similar to patients previously reported as sporadic examples of olivopontocerebellar atrophy. It was this latter category which contributed to excess of males. None of the patients had similarly affected relatives. Both the 3rd groups, and all 36 cases were compared wih 37 other patients with dominantly inherited late onset cerebellar ataxia in order to establish which clinical features might indicate the presence of new dominant mutations in the "sporadic" cases. Optic atrophy ophthalmoplegia and pigmentary retinal degeneration were more frequent in the familial cases.

Adult↗
PubMed1981

Friedreich's ataxia: a clinical and genetic study of 90 families with an analysis of early diagnostic criteria and intrafamilial clustering of clinical features.

The clinical features of 115 patients from 90 families with Friedreich's ataxia are described. Onset of symptoms was before the age of 25 (mean 10.52) years in all the index cases. An analysis of early cases suggested that limb and truncal ataxia and absent tendon reflexes in the legs were the only consistent diagnostic criteria within five years of presentation. Dysarthria, signs of pyramidal tract dysfunction in the legs and loss of joint position and vibration sense are not necessarily present during the first five years of symptoms, but appear to develop eventually in all cases. Scoliosis and ECG evidence of cardiomyopathy were found in over two-thirds of the patients studied; pes cavus, distal amyotrophy, optic atrophy, nystagmus and deafness were all less frequent. The disorder was gradually progressive in all cases. The mean age of losing the ability to walk was 25 years; 95 per cent were chair-bound by the age of 44 years. About 10 per cent of the patients had diabetes mellitus which was controlled by oral hypoglycaemic drugs in one quarter. Diabetes appeared to be associated with a higher incidence of optic atrophy and deafness. Diabetes also clustered within sibships; the risk of an individual with Friedreich's ataxia developing diabetes if an affected sib has it is over 40 per cent. Similarly, cardiomyopathy ran true within affected members of the same sibship, but there were instances of discordance which suggest that the development of the non-neurological features of Friedreich's ataxia may be controlled by modifying genes rather than heterogeneity of the main gene. Segregation analysis and an increased consanguinity rate amongst parents of patients (5.55 per cent) confirmed that this disorder is of autosomal recessive inheritance. A study of 101 first degree relatives of the patients with Friedreich's ataxia failed to demonstrate any neurological or electrocardiographic abnormalities which could be ascribed to the heterozygous state.

Adolescent↗
PubMed1981

Intrafamilial correlation in Friedreich's ataxia.

The distribution of age of onset and age of losing the ability to walk independently in patients with Friedreich's ataxia from 93 sibships are presented. Intrafamilial correlation was investigated using three methods: the Pearson product-moment correlation coefficient and to estimates of correlation based on analysis of variance, one a maximum likelihood method and the other using a weighted mean family size. All three resulted in correlation coefficients (r) of around 0.5 for both disease parameters. The latter two methods yielded similar values just greater than 0.5 and it is considered that these are more reliable estimates of intraclass correlation as there were a variable number of family members in the sibships studied. Although the examination of intraclass correlation in Friedreich's ataxia was not highly suggestive of genetic heterogeneity, the observed proportion of first cousin marriages amongst the parents of the sibships studied was about twice the expected proportion. Overall, the data would be compatible with genetic heterogeneity if one genotype is more prevalent than others. An alternative hypothesis is that there are different modifying genes operating within different families in which Friedreich's ataxia occurs.

Adolescent↗
PubMed1981

'Pseudo-dominant' inheritance in Friedreich's ataxia.

A family is described in which Friedreich's ataxia occurred in two generations. It is proposed that this resulted from a homozygote-heterozygote mating. The heterozygote frequency for the Friedreich's ataxia gene is in the order of 1 in 110, so the likelihood of the disease developing in an individual child of a patient is 1 in 220. This risk is probably higher than that often assumed when counselling patients with this disorder.

Ataxia↗
PubMed1981

Genetic aspects of autosomal dominant late onset cerebellar ataxia.

The genetic features of eight families with autosomal dominant late onset cerebellar ataxia with randomly distributed associated clinical features are described. The ratio of affected to unaffected offspring of affected subjects was not significantly different from 1:1. The mutant gene was fully penetrant when cases who died before the period of risk of developing the disease were excluded. The proportion of new mutants with this disorder appears to be low. Biological fitness was not impaired. Affected females tended to have large families than affected males. The ages of onset of females and males were not significantly different, but the offspring of affected males had earlier ages of onset and death than those of affected females. A cumulative age of onset curve is presented which should aid genetic counselling of subjects at risk and their children.

Adult↗
PubMed1981

Hereditary "pure" spastic paraplegia: a clinical and genetic study of 22 families.

In 22 families with the "pure" form of hereditary spastic paraplegia inheritance was autosomal dominant in 19 and autosomal recessive in three. Examination of intrafamilial correlation of age of onset in the dominant cases suggested that the disorder is genetically heterogeneous. Two forms of dominant hereditary spastic paraplegia were identified: one with an age of onset mostly below 35 years (type I), and the other onset usually over 35 years (type II). In the type I cases, delay in walking was not infrequent and spasticity of the lower limbs was more marked than weakness. The disorder was very slowly progressive and was extremely variable in terms of severity. Sixteen per cent of the patients aged over 20 years were asymptomatic but clinically affected. In the type II group muscle weakness, urinary symptoms and sensory loss were more marked. This form of the disease evolved more rapidly. In the three families demonstrating autosomal recessive inheritance the clinical features were very similar to those of the dominant cases. Biological fitness of patients from both the dominant groups was not impaired and no definite evidence of new mutation was observed. A cumulative frequency curve of age of onset in the type I group was constructed with suggested that an asymptomatic child of an affected parent has a 20% chance of developing the disease at the age of 25 years; the risk is probably even less if the child is clinically normal.

Adult↗
PubMed1981

Early onset cerebellar ataxia with retained tendon reflexes: a clinical and genetic study of a disorder distinct from Friedreich's ataxia.

Twenty patients are described with a distinctive clinical syndrome characterised by progressive cerebellar ataxia developing within the first two decades. This is associated with dysarthria, pyramidal signs in the limbs, normal or increased knee jerks and upper limb reflexes and in some instances sensory loss. Inheritance is probably autosomal recessive in the majority, if not all, of the cases. The preservation of tendon reflexes distinguishes this disorder from Friedreich's ataxia. Other important differences from Friedreich's ataxia are absence of optic atrophy, cardiomyopathy, diabetes mellitus and severe skeletal deformity. The prognosis was better in the present series than in cases of Friedreich's ataxia; patients remained ambulant, on average, for more than 10 years longer.

Adolescent↗
PubMed1980

Distal and scapuloperoneal distributions of muscle involvement occurring within a family with type I hereditary motor and sensory neuropathy.

Davidenokow's syndrome has been defined as a hereditary disorder characterized by proximal muscle weakness and wasting in the uper limbs with distal weakness in the lower, and associated with distal sensory loss in all four limbs. It has been assumed to be genetically distinct. A family is described in which the index case displayed these features. Motor nerve conduction velocity was substantially reduced. Another member displayed distal motor and sensory involvement in both upper and lower limbs and thus conformed to the clinical pattern of the hypertrophic form of Charcot-Marie-Tooth disease (hereditary motor and sensory neuropathy type I). A third member was somewhat intermediate, with generalized upper limb and distal lower limb weakness. It is concluded that Davidenkow's syndrome is not genetically distinct and that it may occur as a phenotypic manifestation of type I hereditary motor and sensory neuropathy.

Aged↗
PubMed1980

Hereditary distal spinal muscular atrophy. A report on 34 cases and a review of the literature.

A description is given of 34 patients with the distal form of hereditary spinal muscular atrophy. This disorder constitutes one form of "peroneal muscular atrophy". It resembles types I and II hereditary motor and sensory neuropathy but differs from them in displaying less upper limb weakness, relative preservation of the tendon reflexes and an entirely normal clinical sensory examination. Motor nerve conduction velocity and sensory nerve action potentials are normal. Previous reports of this disorder are reviewed and compared with the present series.

Adolescent↗
PubMed1980

The clinical features of hereditary motor and sensory neuropathy types I and II.

Observations have been made on a series of 228 patients with hereditary motor and sensory neuropathy, comprising 120 index cases and 108 affected relatives. These could be separated into genetically distinct type I and type II categories depending upon whether motor nerve conduction velocity in the median nerve was below or above 38 m s-1. These disorders constitute separate genetic subgroups within the clinical spectrum of 'peroneal muscular atrophy'. Type I cases were more numerous. Most were of autosomal dominant inheritance, but a proportion were sporadic. Four families with probable autosomal recessive inheritance were identified; these displayed significantly slower motor conduction velocity. There was a positive correlation between motor conduction velocity in the propositi and that in their relatives in the total type I group which persisted after the autosomal recessive cases had been extracted, indicating further genetic heterogeneity amongst the autosomal dominant families. No X-linked recessive families were encountered. Type I cases had a peak age of onset of symptoms during the first decade of life. In comparison with the type II cases, they displayed a greater tendency to show weakness of the hands, upper limb tremor and ataxia, generalized tendon areflexia and more extensive distal sensory loss, sometimes with acrodystrophic changes. Foot and spinal deformities were more frequent, probably due to the earlier age of onset. Nerve thickening was confined to the type I cases. The onset of symptoms was most often in the second decade in the type II cases, but in some it was delayed, even as late as the seventh decade. Most cases were again of autosomal dominant inheritance, but two probable autosomal recessive families were detected, as well as sporadic cases. Upper limb tremor also occurred in this form but was considerably less common. In both types, males tended to be more severely affected, and asymptomatic affected family members ('formes frustes') were more commonly female.

Humans↗