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N A Fletcher

Publications and source records attributed to N A Fletcher.

At least 19 recordsLinked to original sources
PubMed2003

Pathological heterogeneity of clinically diagnosed corticobasal degeneration.

Two patients fulfilling suggested clinical diagnostic criteria for corticobasal degeneration (CBD) are presented, who were found at postmortem to have alternative pathological diagnoses not suspected during life, namely, Alzheimer's disease and Pick's disease, respectively. The nosological position of these cases is considered in light of a literature review of previous reports of clinically diagnosed corticobasal degeneration with atypical (not corticobasal degeneration) pathology. Since such phenocopies may be common, we suggest that all clinically diagnosed cases of corticobasal degeneration should initially be labelled as "corticobasal degeneration syndrome" (CBDS) to emphasize that this is a diagnosis based on clinical phenotype, with the term corticobasal degeneration being reserved for the specific neuropathological phenotype, which itself may have a variety of clinical presentations.

Alzheimer Disease↗
PubMed1998

The role of DYT1 in primary torsion dystonia in Europe.

Primary torsion dystonia (PTD) is a clinically and genetically heterogeneous movement disorder. DYT1 on chromosome 9q34 was the first PTD gene to be mapped. A 3-bp (GAG) deletion in this gene was reported to account for almost all early limb-onset generalized PTD. No relationship has been found with DYT1 in patients with prominent craniocervical involvement. To elucidate the DYT1-associated phenotype, we analysed the DYT1 mutation in 150 PTD patients, either sporadic or index cases from small PTD families. Twenty-two patients were positive for the GAG deletion in the DYT1 gene. Fifteen of them presented with the typical DYT1 phenotype (early, limb-onset generalized dystonia without spread to craniocervical muscles), four had limb-onset dystonia with spread to craniocervical muscles, two patients had arm-onset segmental dystonia and one had focal right-arm dystonia. One-hundred and twenty-eight patients were negative for the DYT1 mutation. Forty-six of them had segmental dystonia and 59 had focal dystonia. The other 23 patients presented with generalized dystonia, either with craniocervical involvement (13 patients) or without spread to the craniocervical region (typical DYT1 phenotype-10 patients). These data confirm the importance of the GAG deletion in European cases of PTD, and indicate phenotypic and genotypic heterogeneity.

Adolescent↗
PubMed1997

New variant Creutzfeldt-Jakob disease: neurological features and diagnostic tests.

BACKGROUND: In April, 1996, ten cases of Creutzfeldt-Jakob disease (CJD) with an apparently new clinicopathological phenotype were published and it was suggested that these new variant cases (nvCJD) might be causally linked to bovine spongiform encephalopathy (BSE). There have now been 21 cases of nvCJD in the UK and one case in France. We report clinical features and diagnostic test results of the first 14 cases of nvCJD in the UK. METHODS: Case ascertainment of CJD was mainly by direct referral from neurologists and neuropathologists. Clinical and investigate details were obtained by interview with patients' relatives and by examination of case notes. Ten cases in this report were examined while alive. Prion protein (PrP) gene analysis was carried out with informed consent from the patient or from a relative. The diagnosis of nvCJD was established histologically. FINDINGS: Eight cases were women. Mean age at onset of symptoms was 29 (16-48) years and the median duration of illness was 14 (9-35) months. All patients had early psychiatric symptoms, most often depression, and 13 were seen by a psychiatrist early in the clinical course. Eight patients developed early sensory symptoms which were persistent and often painful. Neurological signs, including ataxia and involuntary movements, developed in all cases and towards the end of the illness, most had akinetic mutism. The electroencephalogram was abnormal in most patients but typical periodic complexes of CJD were not seen in any case. Cerebral imaging was usually normal or showed non-specific abnormalities; in two cases magnetic-resonance imaging scans showed high signal in the thalamus. INTERPRETATION: Clinical features in these cases are similar and relatively distinct from other forms of CJD, suggesting that this is a new clinical phenotype consistent with a single strain of infectious agent. There is, however, some overlap with atypical cases of sporadic CJD, and the diagnosis of nvCJD remains dependent on neuropathological confirmation.

Adolescent↗
PubMed1997

Trinucleotide (GAA)n repeat expansion in two families with Friedreich's ataxia with retained reflexes.

In occasional families in whom cases of classic Friedreich's ataxia (FRDA) coexist with affected cases with retained reflexes, linkage analysis has shown that both map to the FRDA locus on chromosome 9q13-21.1. A gene X25 has been identified within the critical region of the FRDA locus, and an intronic expanded GAA trinucleotide repeat has been found in most cases of FRDA. We report two further FRDA families in whom some patients with classic FRDA were areflexic whereas others had brisk reflexes. Molecular genetic analysis disclosed an abnormal trinucleotide repeat expansion within intron 1 of the FRDA gene in both phenotypes.

Adolescent↗
PubMed1997

Paraparesis due to syphilitic aortic dissection.

A patient is presented who developed an acute spinal cord infarct with paraparesis and segmental pain but no sensory or sphincter involvement. Investigations revealed an extensive dissecting thoracic aortic aneurysm and positive treponemal serologic findings consistent with tertiary cardiovascular syphilis.

Aged↗
PubMed1996

Dyskinetic cerebral palsy: a clinical and genetic study.

The clinical features and family histories of 20 adults with dyskinetic cerebral palsy from 20 families were studied. The majority of the patients showed progressive neurological deterioration in adult life. In only three did the condition stabilise by 10 years of age and in seven there was deterioration after the age of 30. Two patients developed a secondary cervical spondylotic myelopathy. Four patients had affected relatives and there were similar proportions of affected parents and siblings. The family data suggest genetic heterogeneity with autosomal recessive and dominant variants. The existence of an X-linked form cannot be excluded, and the demonstration of an increased paternal age effect among single cases suggests that some of these may arise because of fresh dominant genetic mutation.

Adolescent↗
PubMed1994

Lessons from a remarkable family with dopa-responsive dystonia.

A family is described in which dopa-responsive dystonia affected six members and segregated in an autosomal dominant fashion. Patients either presented in childhood with dystonia of the legs, going to develop parkinsonism and pseudo-pyramidal deficits, or in adult life with parkinsonian tremor and rigidity, with pseudo-pyramidal signs. Remarkably, in the three cases with childhood onset the symptoms and signs of the condition were abolished 36 to 52 years later by small doses of levodopa. No long term side effects of levodopa have appeared after 15 years of treatment.

Adult↗
PubMed1993

Linkage analysis in British and French families with idiopathic torsion dystonia.

Idiopathic torsion dystonia is most commonly caused by an autosomal dominant gene or genes with reduced penetrance. An idiopathic torsion dystonia locus has been mapped to chromosome 9q34 in one large non-Jewish and several Jewish kindreds in the USA. Linkage analysis was performed in 27 (26 British, one French) small families with idiopathic torsion dystonia, three of which were Ashkenazi Jewish, using the highly polymorphic loci argininosuccinate synthetase (ASS) and Abelson oncogene (ABL) which map to 9q34. The cumulative lod score for the more informative ASS locus at a recombination fraction of 0.001 was -6.72. A large component of this score was derived from three non-Jewish families, indistinguishable clinically from the others, in which individual lod scores excluded a disease locus tightly linked to ASS. Analysis of all the data using HOMOG showed significant heterogeneity, but evidence for linkage of an idiopathic torsion dystonia gene to 9q34 in a subset of families. The allelic association observed between ASS/ABL and idiopathic torsion dystonia in Ashkenazi families in the USA was also present in British Jewish kindreds. These data suggest genetic heterogeneity in idiopathic torsion dystonia but indicate the existence of a locus for idiopathic torsion dystonia at 9q34 in both Jewish and non-Jewish kindreds in the UK.

Argininosuccinate Synthase↗
PubMed1993

Striatal [18F]dopa uptake in familial idiopathic dystonia.

It is known that most cases of idiopathic torsion dystonia (ITD) are inherited in an autosomal dominant fashion. Despite clarification of the underlying genetic defect, no consistent structural lesion has been identified in ITD, and it is probable that a biochemical disturbance is the basis of the disorder. To determine whether there is impaired function of the nigro-striatal dopaminergic terminals in ITD we studied 11 subjects with generalized ITD and a positive family history using [18F]dopa and PET scanning. Of these 11 patients, eight had putamen [18F]dopa uptake within the lower half of the normal range, while three had uptake reduced by > 2 SDs below the normal mean. The lowest putamen [18F]dopa influx constants were found in the most disabled patients. As these reductions were mild it is unlikely that abnormalities of the nigro-striatal dopaminergic pathway are the primary determinant of either the nature of the severity of dystonic symptoms. In addition, we studied three presumed carriers of the ITD gene. These subjects all had normal striatal [18F]dopa influx constants suggesting that [18F]dopa PET is unsuitable as a screening tool for ITD.

Adult↗
PubMed1993

Parental age, genetic mutation, and cerebral palsy.

Parental age and birth order were studied in 251 patients with cerebral palsy. No parental age or birth order effects were observed in spastic quadriplegia or diplegia, but a paternal age effect was detected in those with athetoid/dystonic cerebral palsy and congenital hemiplegia. These observations indicate that some cases of athetoid/dystonic or hemiplegic cerebral palsy might arise by fresh dominant genetic mutation.

Adolescent↗
PubMed1993

Successful treatment of childhood onset symptomatic dystonia with levodopa.

Three patients with childhood onset symptomatic dystonia responded to levodopa. None fulfilled criteria for a diagnosis of "dopa responsive dystonia" (Segawa's disease). One may have had athetoid cerebral palsy for almost 25 years. All obtained dramatic and sustained benefit from levodopa therapy. A therapeutic trial of levodopa is advised in all patients in whom dystonia has developed in childhood or early adult life, regardless of suspected aetiology or duration of symptoms.

Adolescent↗
PubMed1993

Genomic imprinting and anticipation in idiopathic torsion dystonia.

Idiopathic torsion dystonia (ITD) is a dominantly inherited disorder with variable penetrance and expressivity. Factors affecting the penetrance of the ITD gene have not yet been identified. The present study used four published series of cases to test specific hypotheses regarding factors that could affect the expression of ITD. Among the combined 253 families, transmission of ITD did not depend on either the sex of the affected offspring or that of the transmitting parent. Furthermore, neither the specific type of dystonia manifested, the site at which clinical signs of dystonia first appeared, nor age of onset differed significantly as a function of the gender of the transmitting parent. However, in familial cases of later onset (age > or = 20 years), nearly all involved a transmitting mother. There is evidence for consistency of age of onset within the subset of Jewish families. Although anticipation effects are apparent, sampling bias cannot be ruled out.

Adolescent↗
PubMed1991

A genetic study of idiopathic focal dystonias.

A genetic study of idiopathic focal dystonias was undertaken by examining 153 first-degree relatives of 40 index patients with torticollis (14 patients), other focal cranial dystonias (16 patients), and writer's cramp (10 patients). Nine relatives with dystonia were identified in 6 families; 8 of these had symptoms such as clumsiness or tremor, but none were aware of any dystonia. A further 4 relatives, now decreased, were affected by history. Overall, 25% of index patients had relatives with dystonia. The results of segregation analysis suggested the presence of an autosomal dominant gene or genes with reduced penetrance as a common cause for focal dystonia. Segregation ratios were not significantly different from those ratios observed in generalized or segmental dystonia in the United Kingdom, and it is possible that a single autosomal dominant gene mutation is responsible for inherited dystonia in the majority of patients irrespective of distribution or severity.

Adult↗
PubMed1991

A case-control study of idiopathic torsion dystonia.

A study of 71 patients with idiopathic torsion dystonia (ITD) and 71 matched controls was performed to investigate the range of possible clinical expression of ITD and the role of environmental factors in the development of the disease. A family history of tremor and stuttering were the only factors significantly associated with ITD. No associated environmental factor was identified.

Adult↗