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Biomedical subjects

E M Brett

Publications and source records attributed to E M Brett.

At least 19 recordsLinked to original sources
PubMed1996

A form of juvenile Batten disease with granular osmiophilic deposits.

The clinical, neurophysiological and pathological features of a patient who presented with the clinical features of juvenile Batten disease, yet who had storage of granular osmiophilic deposits (GROD) on ultrastructural examination of biopsy and postmortem tissues is described. The ultrastructural features are those usually found in the infantile form of Batten disease. The postmortem study showed marked neuronal storage of a lipofuscin-like material in an atrophic brain without loss of myelin. The cerebellum showed almost complete loss of Purkinje cells and loss of the granule cells. No accumulation of subunit c of mitochondrial ATP synthase was found. The clinical and neurophysiological findings are compared with those of the classical juvenile form and with those of the few reported cases of juvenile Batten disease with GROD. The importance of correct classification of patients with Batten disease and its impact on the molecular genetic studies is emphasised. The pathogenesis of this form of the disease is considered to be similar to that for infantile Batten disease.

Adolescent↗
PubMed1993

Peripheral neuropathy as the presenting feature of tyrosinaemia type I and effectively treated with an inhibitor of 4-hydroxyphenylpyruvate dioxygenase.

A 21 month old girl presented with a short history of frequent falls and a right sided foot drop. She went on to suffer recurrent episodes of distal weakness in her arms and legs with hyporeflexia. Electrophysiological studies were consistent with inflammatory demyelinating polyradiculoneuropathy (IDP) and treatment with corticosteroids appeared to lead to an improvement. However, the development of hypertension, evidence of tubulopathy, and hepatomegaly led to re-evaluation. A diagnosis of type I tyrosinaemia was made, based on increased urinary excretion of succinylacetone and decreased activity of fumarylacetoacetase in her cultured skin fibroblasts. A low tyrosine diet did not prevent life-threatening exacerbations of neuropathy but intravenous haemarginate appeared to aid her recovery from one exacerbation. An immediate improvement in strength was seen after starting treatment with 2-(2-nitro-4-trifluoro-methyl-benzoyl)-1,3-cyclohexanedione (NTBC), an inhibitor of 4-hydroxy-phenylpyruvate dioxygenase. A liver transplant was performed but the patient died of immediate postoperative complications. Tyrosinaemia needs to be considered in a child with recurrent peripheral neuropathy because (i) the signs of liver disease and renal tubular dysfunction may be subtle; (ii) acute exacerbations may be life threatening; (iii) specific forms of treatment are available.

4-Hydroxyphenylpyruvate Dioxygenase↗
PubMed1993

Alexander's disease: clues to diagnosis.

The clinical, radiologic, neurophysiologic, and pathologic findings in 10 children with histologically proven Alexander's disease are described, and the presence of two broad clinical subgroups is confirmed. Macrocephaly, regression, and seizures are found in the infantile form, whereas bulbar signs predominate the so-called juvenile form. None of the clinical or neurophysiologic findings is pathognomonic, and radiologic features suggesting the diagnosis are not present in all cases. However, the combination of abnormalities may suggest the diagnosis and justify histologic confirmation.

Cerebral Cortex↗
PubMed1992

Autosomal recessive microcephaly with severe psychomotor retardation.

Autosomal recessive microcephaly has long been recognized in association with normal early motor development and mild to severe mental retardation. We report three sibling pairs with microcephaly and severe neurological impairment. These cases and other sibling pairs reported in the literature illustrate that microcephaly with spasticity and severe mental retardation may also have autosomal recessive inheritance. Furthermore this severely affected group of patients forms a significant proportion of cases of genetic microcephaly. We looked for specific morphological features to identify these forms of genetic microcephaly for genetic counselling, but failed to find characteristic abnormalities among our group of patients.

Adolescent↗
PubMed1992

Progressive bulbar paralysis of childhood. A reappraisal of Fazio-Londe disease.

Fazio-Londe disease is a label sometimes applied to a degenerative disease of the motor neurons characterized by progressive bulbar paralysis in children. It is very rare with only 22 case reports describing 24 children including four sibling pairs. In two reports mothers and sons were affected. The neuropathology is described in only four cases. Previous authors have recognized that the condition is very heterogeneous. The clinical features of five children with this type of progressive bulbar paralysis, diagnosed at this hospital between 1969 and 1989, are reviewed, and in two cases neuropathological findings are detailed. Based on this experience, suggested criteria for diagnosis include clinical features of a pure motor neuronopathy affecting the bulbar nuclei, exclusion of other causes of progressive bulbar paralysis and positive support for the diagnosis from electromyography and/or pathological examination. A review of the literature, combined with the present series, suggests that there are at least three distinct subtypes: a very rare autosomal dominant form (as described by Fazio) and two variants with probable autosomal recessive inheritance either with early onset of respiratory symptoms and rapid progression to death or later onset, less prominent respiratory symptoms and protracted clinical course. There is strong concordance for each clinical pattern within families.

Bulbar Palsy, Progressive↗
PubMed1992

Eye movement tics.

An 8-year-old girl presented with opsoclonus-like eye movement and an 18 month history of intermittent facial tics. Investigations were all normal. Electro-oculography showed the eye movements to be of variable amplitude (10-40 degrees), with no intersaccadic interval, and with a frequency of 3-4 Hz. Saccades, smooth pursuit, optokinetic, and vestibular reflexes were all normal. These abnormal eye movements eventually disappeared. It is thought that they were a form of ocular tics.

Child↗
PubMed1991

Localized 1H NMR spectroscopy in Canavan's disease: a report of two cases.

Two children with Canavan's Disease, an autosomal recessive leukodystrophy, were studied by localized 1H spectroscopy. The N-acetylaspartate (NAA) signal intensity was high relative to other metabolite signals, and the signal intensity from choline-containing compounds was low. These findings are discussed in relation to a possible role for NAA in normal myelination.

Aspartic Acid↗
PubMed1991

Pelizaeus-Merzbacher disease: classical or connatal?

The clinical features and investigation results of 7 patients with Pelizaeus-Merzbacher disease (PMD) are described; one patient had a brain biopsy and two patients had an autopsy. This paper tries to differentiate the clinical features of the connatal and classical types of PMD. Transient stridor and nystagmus were early signs in both types of PMD. Our findings support the view that the more severe connatal form shows rapid neurological deterioration from an early age leading to death usually in the first decade. In younger patients in whom the evolution is still unclear, severe feeding problems and extrapyramidal features may suggest the connatal form. By contrast, in the classical form of PMD, cerebellar signs and cognitive deterioration are more prominent with a more slowly progressive course. Nuclear magnetic resonance imaging and brainstem auditory evoked potentials were very helpful in supporting the diagnosis of PMD either in a known affected family or in sporadic cases, but were not useful in distinguishing between the two types of PMD. Genetic counseling in this condition is difficult, particularly in the connatal form in which inheritance may be either X-linked or autosomal recessive.

Age Factors↗
PubMed1991

Severe microcephaly associated with congenital varicella infection.

A case of second-trimester congenital varicella infection, in association with isolated microcephaly and severe brain damage, is reported, and cases of classical congenital varicella syndrome are compared on a clinical and immunological basis. This case, together with others cited in the literature, suggests that congenital varicella infection may lead to microcephaly and neurological abnormalities, without the presence of skin lesions. Although first-trimester infection has been considered the most likely to produce congenital abnormalities, the second trimester may be more commonly implicated; indeed there may not be a critical period if varicella causes secondary disruption of differentiated tissues.

Atrophy↗
PubMed1991

Pearson syndrome and mitochondrial encephalomyopathy in a patient with a deletion of mtDNA.

A patient is described who has features of Pearson syndrome and who presented in the neonatal period with a hypoplastic anemia. He later developed hepatic, renal, and exocrine pancreatic dysfunction. At the age of 5 years he developed visual impairment, tremor, ataxia, proximal muscle weakness, external ophthalmoplegia, and a pigmentary retinopathy (Kearns-Sayre syndrome). Muscle biopsy confirmed the diagnosis of mitochondrial myopathy. Analysis of mtDNA from leukocytes and muscle showed mtDNA heteroplasmy in both tissues, with one population of mtDNA deleted by 4.9 kb. The deleted region was bridged by a 13-nucleotide sequence occurring as a direct repeat in normal mtDNA. Both Pearson syndrome and Kearns-Sayre syndrome have been noted to be associated with deletions of mtDNA; they have not previously been described in the same patient. These observations indicate that the two disorders have the same molecular basis; the different phenotypes are probably determined by the initial proportion of deleted mtDNAs and modified by selection against them in different tissues.

Anemia, Sideroblastic↗
PubMed1990

Megalencephaly with dysmyelination, spasticity, ataxia, seizures and distinctive neurophysiological findings in two siblings.

A progressive neurological condition characterised by megalencephaly, spasticity, ataxia and seizures in two siblings of consanguineous parents is described. The electroencephalogram showed posterior discharges and an unusual photoparoxysmal response whereas brainstem auditory evoked potential findings were consistent with a white matter disorder. Computerized tomography scans revealed diffuse hypodensity of the white matter and a brain biopsy on one sibling showed features of dysmyelination without evidence of demyelination, Rosenthal fibres or the spongy changes characteristic of Canavan's disease. There was no detectable biochemical abnormality. This combination of clinical, neurophysiological and neuropathological abnormalities has not previously been described.

Biopsy↗
PubMed1989

Neurodevelopmental delay and focal seizures as presenting symptoms of human immunodeficiency virus I infection.

Three children presenting with neurological symptoms were subsequently diagnosed as being infected with the human immunodeficiency virus I (HIV). All children showed normal development for about 12-18 months of age but later developed psychomotor and developmental regression. One child presented with generalised hypotonia, another with focal seizures, and the third with spastic quadriplegia. Two of the children showed areas of abnormal brain density on computed tomography and in one case there was calcification of the basal ganglia. In two of the children cerebrospinal fluid contained reduced amounts of total folate and elevated concentrations of neopterin. The possibility of a link between the deranged folate metabolism and the neurological symptoms in HIV infection is discussed.

Acquired Immunodeficiency Syndrome↗