Papers by David Hilton-jones
Practical neurology, 2015
Myasthenia gravis is an autoimmune disease of the neuromuscular junction for which many therapies... more Myasthenia gravis is an autoimmune disease of the neuromuscular junction for which many therapies were developed before the era of evidence based medicine. The basic principles of treatment are well known, however, patients continue to receive suboptimal treatment as a result of which a myasthenia gravis guidelines group was established under the aegis of The Association of British Neurologists. These guidelines attempt to steer a path between evidence-based practice where available, and established best practice where evidence is unavailable. Where there is insufficient evidence or a choice of options, the guidelines invite the clinician to seek the opinion of a myasthenia expert. The guidelines support clinicians not just in using the right treatments in the right order, but in optimising the use of well-known therapeutic agents. Clinical practice can be audited against these guidelines.
JAMA neurology, Jan 20, 2015
Cell-based assays (CBAs) were shown to improve detection of acetylcholine receptor (AChR) antibod... more Cell-based assays (CBAs) were shown to improve detection of acetylcholine receptor (AChR) antibodies in patients with myasthenia gravis (MG). Herein, we asked whether these assays were able to help determine the diagnosis in patients studied in routine clinical practice. To determine the diagnostic usefulness of CBAs in the diagnosis of MG and to compare the clinical features of patients with antibodies only to clustered AChRs with those of patients with seronegative MG (SNMG). All patients with clinical suspicion of MG who were seen within the Division of Clinical Neurology at the John Radcliffe Hospital in Oxford, England, between November 1, 2009, and November 30, 2013. Their serum antibodies and clinical features were studied. Radioimmunoprecipitation assay (RIPA) and CBA were used to test for standard AChR antibodies and antibodies to clustered AChRs in 138 patients. All available samples from patients with SNMG were retrospectively tested for lipoprotein receptor-related prote...
Journal of the neurological sciences, Jan 15, 2015
Rarely, inflammation can be present in genetic myopathies, such as dysferlinopathies, facioscapul... more Rarely, inflammation can be present in genetic myopathies, such as dysferlinopathies, facioscapulohumeral muscular dystrophy and GNE-myopathy (hereditary inclusion body myopathy). This may lead to erroneous initial diagnosis and unnecessary therapy which bear serious side effects. We report on an unusual case of mutations in the TTN gene presenting with inflammatory infiltrates in the muscle biopsy. Only after intensive immune-modulating therapies failed, a genetic myopathy was considered. Exome sequencing and search for mutated muscle protein-encoding genes disclosed compound heterozygous mutations in TTN: K26320T and A6135G. The parents carry one each of the mutations. Titinopathy could be considered also in patients presenting with inflammatory infiltrates resistant to therapy.
We examined the findings from single-fiber electromyography in extensor digitorum communis (EDC) ... more We examined the findings from single-fiber electromyography in extensor digitorum communis (EDC) and orbicularis oculi (OOc) in 13 myasthenia gravis (MG) patients with muscle-specific kinase antibodies (MuSK-MG) and 12 MG patients with acetylcholine receptor antibodies (AChR-MG) with similar clinical scores. More than 70% of AChR-MG patients had abnormal jitter in both EDC and OOc, but the majority of MuSK-MG patients had normal jitter in EDC despite abnormal jitter in OOc. These findings demonstrate clear differences between the neurophysiology of MuSK-MG and AChR-MG.
Practical Neurology, 2005
Brain, 1998
Summary Sporadic inclusion body myositis (s-IBM) is a chronic inflammatory myopathy of unknown pa... more Summary Sporadic inclusion body myositis (s-IBM) is a chronic inflammatory myopathy of unknown pathogenesis. The common findings of ragged red fibres, cytochrome c oxidase-negative fibres and multiple mitochondrial DNA deletions in the muscle of patients with s-IBM have suggested that a deficit of energy metabolism may be of pathogenic relevance. To test this hypothesis we used 31 P magnetic resonance
Practical Neurology, 2009
Muscle & Nerve, 1991
Serial muscle biopsies in a noncarcinomatous case of Lambert-Eaton myasthenic syndrome (LEMS) hav... more Serial muscle biopsies in a noncarcinomatous case of Lambert-Eaton myasthenic syndrome (LEMS) have shown progressive atrophy and loss of type 1 fibers, resulting in overwhelming type 2 predominance. A similar abnormality was found in a single biopsy from a second case of LEMS without associated carcinoma. Review of the literature suggests that type 2 fiber predominance has been observed in at least one other biopsied case. Interference with transmitter release caused by anti-voltage-gated calcium channel antibodies may deprive type 1 muscle fibers of the low frequency discharge necessary to maintain their metabolic properties.
Practical Neurology, 2006
How good at n you Q uestions 1. Are these statements true or false? (a) 90% of large cortical inf... more How good at n you Q uestions 1. Are these statements true or false? (a) 90% of large cortical infarcts are visible on CT within 48 h of symptom onset. (b) 40% of lacunar or small cortical infarcts are visible within 48 h after symptom onset. (c) Cerebral infarcts are most easily seen at 2-3 weeks on brain imaging. (d) The infarct is of CSF density by 3 months. (e) Fast spin echo and proton density sequences are the sequences of choice for identifying haemorrhage.
Journal of Neurology Neurosurgery and Psychiatry, 1995
The clinical features and radiological appearances of spontaneous intracranial hypotension are de... more The clinical features and radiological appearances of spontaneous intracranial hypotension are described in three patients and the medical literature is reviewed. Awareness of this condition and its differentiation from more sinister meningitic processes is important to avoid unnecessary invasive investigations and to allow prompt diagnosis and effective treatment.
Neurobiology of Aging, 2015
Sporadic inclusion body myositis sIBM APOE TOMM40 Age of onset a b s t r a c t A previous study s... more Sporadic inclusion body myositis sIBM APOE TOMM40 Age of onset a b s t r a c t A previous study showed that, in carriers of the apolipoprotein E (APOE) genotype ε3/ε3 or ε3/ε4, the presence of a very long (VL) polyT repeat allele in "translocase of outer mitochondrial membrane 40" (TOMM40) was less frequent in patients with sporadic inclusion body myositis (sIBM) compared with controls and associated with a later age of sIBM symptom onset, suggesting a protective effect of this haplotype. To further investigate the influence of these genetic factors in sIBM, we analyzed a large sIBM cohort of 158 cases as part of an International sIBM Genetics Study. No significant association was found between APOE or TOMM40 genotypes and the risk of developing sIBM. We found that the presence of at least 1 VL polyT repeat allele in TOMM40 was significantly associated with about 4 years later onset of sIBM symptoms. The age of onset was delayed by 5 years when the patients were also carriers of the APOE genotype ε3/ε3. In addition, males were likely to have a later age of onset than females. Therefore, the TOMM40 VL polyT repeat, although not influencing disease susceptibility, has a disease-modifying effect on sIBM, which can be enhanced by the APOE genotype ε3/ε3.
Neuromuscular Disorders, 2014
Journal of Neurology Neurosurgery and Psychiatry - J NEUROL NEUROSURG PSYCHIAT, 1995
Clinical Neurophysiology - CLIN NEUROPHYSIOL, 2007
Reviews in Gynaecological and Perinatal Practice, Volume 118, Issue 5, Pages 1174-1175, May 2007,... more Reviews in Gynaecological and Perinatal Practice, Volume 118, Issue 5, Pages 1174-1175, May 2007, Authors:Maria E. Farrugia; Robin P. Kennett; David Hilton-Jones; John Newsom-Davis; Angela Vincent. Journal Home, Register or Login: Password: Auto-Login [Reminder]. ...
Neuromuscular Disorders, 1995
We report a sibship in which the syndrome of congenital arthrogryposis occurred in two male and t... more We report a sibship in which the syndrome of congenital arthrogryposis occurred in two male and two female neonates, three of whom died. The mother was asymptomatic at the time of the first pregnancy and the subsequent development of muscle weakness was later confirmed to be due to myasthenia gravis. The literature on this association is briefly reviewed and the extremely high risk of recurrence of this complication in subsequent pregnancies is addressed.
Neuromuscular Disorders, 2008
Mutations in the caveolin-3 gene (CAV3) can lead to a broad spectrum of clinical phenotypes. Phen... more Mutations in the caveolin-3 gene (CAV3) can lead to a broad spectrum of clinical phenotypes. Phenotypes that have so far been associated with primary caveolin-3 deficiency include limb girdle muscular dystrophy, rippling muscle disease, distal myopathy and hyper-CKaemia. This is the first report describing the clinical, pathological and genetic features of patients with caveolinopathy from the UK. Ten patients (six families) were identified via the National Commissioning Group (NCG) service for patients with limb girdle muscle dystrophy in Newcastle. Myalgia was the most prominent symptom in our cohort of patients and for 50% it was the reason for referral. Muscle weakness was only found in 60% of the patients, whereas rippling muscle movement was present in 80%. One of the patients reported episodes of myoglobinuria and another one episodes of hypoglycaemia. Five different mutations were identified, two of which were novel and three that had previously been described. Caveolinopathy needs to be considered as a differential diagnosis in a range of clinical situations, including in patients who do not have any weakness. Indeed, rippling muscles are a more frequent symptom than weakness, and can be detected in childhood. Presentation with myalgia is common and management of it as well as of myoglobinuria and hypoglycaemia may have a major impact on the patients' quality of life.
Neuromuscular Disorders, 2003
We have recently shown that syncoilin interacts with desmin in skeletal muscle and has a role in ... more We have recently shown that syncoilin interacts with desmin in skeletal muscle and has a role in attaching and organising desmin filaments to the Z-lines. We have analysed patients with desmin accumulation and have found that syncoilin is both upregulated at the sarcolemma and aggregates with desmin indicating the presence of two distinct protein populations. Additional dystrophin-associated protein complex components also accumulate. The striking finding was that alpha-dystrobrevin-1 and neuronal nitric oxide synthase (nNOS) are almost completely lost from the membrane of these patients indicating that the myopathy may result from both the abnormal accumulation of proteins and an increase in ischaemic injury due to the loss of nNOS. We speculate that the loss of alpha-dystrobrevin from the membrane, and subsequent loss of nNOS, is due to the alpha-dystrobrevin-syncoilin-desmin interaction.
Neuromuscular Disorders, 2010
Neuromuscular Disorders, 2011
Oculopharyngodistal myopathy is an uncommon myopathy characterised clinically by cranial and dist... more Oculopharyngodistal myopathy is an uncommon myopathy characterised clinically by cranial and distal limb muscle weakness. Here we describe two siblings with autosomal dominant oculopharyngodistal myopathy apparently associated with dilated cardiomyopathy, which in one case progressed to ventricular hypertrabeculation/non-compaction. Electrocardiographic screening was normal and the cardiomyopathy was detected only with echocardiography. Our findings suggest that patients with oculopharyngodistal myopathy should be screened for cardiomyopathy (with both electrocardiography and echocardiography).
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Papers by David Hilton-jones