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  • Inflammatory muscle diseases.

    28 January 2018

    Dermatomyositis and polymyositis are treatable disorders of skeletal muscle. Despite their clinical similarities, they appear to have fundamentally different autoimmune origins. Inclusion body myositis, from its origins 30 years ago, has emerged as the commonest acquired myopathy of the elderly. Despite inflammatory changes, it is unclear whether it should be considered a primary inflammatory myopathy, and it generally responds poorly to the same treatments that are effective in other inflammatory myopathies.

  • Six novel connexin32 (GJB1) mutations in X-linked Charcot-Marie-Tooth disease.

    15 February 2018

    X-linked Charcot-Marie-Tooth disease (CMTX) is a clinically heterogeneous hereditary motor and sensory neuropathy with X-linked transmission. Common clinical manifestations of CMTX, as in other forms of Charcot-Marie-Tooth disease (CMT), are distal muscle wasting and weakness, hyporeflexia, distal sensory disturbance, and foot deformities. Motor nerve conduction velocity is reduced. In male patients it is often less than 38 m/s in the median nerve (a value often used to distinguish between "demyelinating" and "axonal" forms of CMT), but in female patients conduction velocity may be faster than this or normal. Mutations in the connexin32 (gap junction protein beta 1 (GJB1)) gene are responsible for the majority of CMTX cases. This report describes six British CMTX families with six novel mutations (four missense, one nonsense, and one frame shift) of the GJB1 gene. Affected members in these six families had typical signs of CMT but in some affected members of three families there was additional central nervous system involvement or deafness in the absence of any other explanation other than CMT.

  • Del(18p) shown to be a cryptic translocation using a multiprobe FISH assay for subtelomeric chromosome rearrangements.

    28 January 2018

    We have previously described a fluorescence in situ hybridisation (FISH) assay for the simultaneous analysis of all human subtelomeric regions using a single microscope slide. Here we report the use of this multiprobe FISH assay in the study of a patient whose karyotype was reported by G banding analysis as 46,XX,del(18)(p11.2). Although the proband had some features suggestive of a chromosomal abnormality, relatively few of the specific features of del(18p) were present. She was a 37 year old female with mild distal spinal muscular atrophy (SMA), arthritis of the hands, an abnormal chest shape (pectus excavatum), and an unusual skin condition (keratosis pilaris). Reverse chromosome painting with degenerate oligonucleotide primer-polymerase chain reaction (DOP-PCR) amplified del(18p) chromosomes as a probe confirmed the abnormality as del(18p), with no evidence of any other chromosome involvement. Subsequently, the multiprobe FISH assay confirmed deletion of 18p subtelomeric sequence. However, the assay also showed that sequences corresponding to the 2p subtelomeric probe were present on the tip of the shortened 18p. The patient is therefore monosomic for 18p11.2-pter and trisomic for 2p25-pter, and the revised karyotype is 46,XX,der(18)t(2;18)(p25; p11.2). We believe that a proportion of all cases reported as telomeric deletions may be cryptic translocations involving other chromosome subtelomeric regions. Further studies such as this are necessary to define accurately the clinical characteristics associated with pure monosomy in chromosomal deletion syndromes.

  • Transient visual obscurations, without papilloedema.

    28 January 2018

    Two cases of frontal, space occupying tumour without papilloedema are reported. Both presented with frequent, stereotyped attacks of visual disturbance with orbital headache, neck pain and unsteadiness of gait. Intermittent occipital lobe ischaemia, related to compression of the posterior cerebral artery against the tentorium by distorted, herniating brain, seems a probable explanation.

  • Congenital muscular dystrophy with short stature, proximal contractures and distal laxity.

    12 December 2017

    We report 5 cases (2 familial and 3 sporadic) who share a diagnosis of congenital muscular dystrophy (CMD) in association with short stature, proximal contractures, rigidity of the spine and distal joint laxity as well as early respiratory failure and mild to moderate mental retardation. The expression of collagen VI was confirmed to be normal on muscle biopsies of all 5 patients and in the informative family linkage to any of the three COL6 A loci was excluded. These findings extend the phenotypes within the CMD classification.

  • Failure of postural manoeuvres to prevent lumbar puncture headache.

    21 February 2018

    Diagnostic lumbar puncture was performed on 76 neurological inpatients. They were randomly allocated to one of four bed rest positions for four hours following the procedure (supine and horizontal, prone and horizontal, supine with head-down tilt and prone with head-down tilt) after which they were allowed to get up. There was no substantial or significant difference in the incidence of headache between the four groups. Expectation of headache did not appear to be an important factor in its development.

  • Modafinil for excessive daytime sleepiness in myotonic dystrophy type 1 - The patients' perspective

    25 December 2017

    Excessive daytime sleepiness (EDS), of very similar pattern to that seen in narcolepsy syndrome, is extremely common in myotonic dystrophy type 1 (DM1). In a significant minority it has a profound disabling effect on employment, social functioning and activities of daily living. Limited published studies have shown inconsistent results from use of the psychostimulant drug modafinil. A recent European Medicines Agency (EMA) review concluded that on current evidence regarding safety and efficacy, modafinil's use should be restricted to the treatment of narcolepsy. In other conditions (although DM1 was not specifically considered) it was concluded that there was insufficient evidence of benefit to outweigh potentially serious side-effects, including severe skin reactions and cardiac arrhythmia. Clinicians with extensive experience in the management of DM1 have found modafinil to be extremely effective in appropriately selected patients with a very low incidence of serious side-effects. Given the recent EMA review, patients have expressed concern about the potential restriction of the use of modafinil in DM1. This brief review is an audit of the experience of a large group of patients and their clinicians concerning EDS and DM1 and concludes that despite the limited literature there is strong evidence to support the use of modafinil in carefully selected patients. © 2012 Elsevier B.V.