Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.
  • Mimics and chameleons in motor neurone disease.

    24 October 2018

    The progression of motor neurone disease (MND) is currently irreversible, and the grave implications of diagnosis naturally fuels concern among neurologists over missing a potential mimic disorder. There is no diagnostic test for MND but in reality there are few plausible mimics in routine clinical practice. In the presence of a progressive pure motor disorder, signs such as florid fasciculations, bilateral tongue wasting, the 'split hand', head drop, emotionality, and cognitive or behavioural impairment carry high positive predictive value. MND is clinically heterogeneous, however, with some important chameleon-like presentations and considerable variation in clinical course. Lack of confidence about the scope of such variation, or an approach to diagnosis emphasising investigations over clinical common sense, has the potential to exacerbate diagnostic delay in MND and impede timely planning of the care which is essential to maximising quality of life.

  • Neuroimaging in amyotrophic lateral sclerosis.

    24 October 2018

    The catastrophic system failure in amyotrophic lateral sclerosis is characterized by progressive neurodegeneration within the corticospinal tracts, brainstem nuclei and spinal cord anterior horns, with an extra-motor pathology that has overlap with frontotemporal dementia. The development of computed tomography and, even more so, MRI has brought insights into neurological disease, previously only available through post-mortem study. Although largely research-based, radionuclide imaging has continued to provide mechanistic insights into neurodegenerative disorders. The evolution of MRI to use advanced sequences highly sensitive to cortical and white matter structure, parenchymal metabolites and blood flow, many of which are now applicable to the spinal cord as well as the brain, make it a uniquely valuable tool for the study of a multisystem disorder such as amyotrophic lateral sclerosis. This comprehensive review considers the full range of neuroimaging techniques applied to amyotrophic lateral sclerosis over the last 25 years, the biomarkers they have revealed and future developments.

  • Low index-to-ring finger length ratio in sporadic ALS supports prenatally defined motor neuronal vulnerability.

    24 October 2018

    BACKGROUND: The aetiology of apparently sporadic amyotrophic lateral sclerosis (ALS) is unknown, but prenatal factors are known to influence disease development. In both men and women, motor neurons require testosterone for survival and axonal regeneration after injury, and androgen insensitivity leads to a form of motor neuron degeneration in men. Reduction in the ratio of index to ring finger length (2D:4D ratio) is considered a surrogate marker for high prenatal testosterone levels in both men and women. The authors therefore tested the hypothesis that prenatal testosterone irrespective of gender is an independent risk factor for the development of ALS later in life, and that this would be reflected in a lower 2D:4D ratio in both men and women with ALS. METHODS: Patients and unrelated control individuals attending a specialist tertiary referral centre for ALS were studied. A digital camera was used to photograph hands. Finger lengths were measured by four independent scorers blind to case-control status, and the mean 2D:4D ratio derived. Analysis was by linear regression and receiver-operator-curve analysis. RESULTS: Controlling for differences in sex ratio between groups, the 2D:4D ratio was lower for people with ALS (n=47) than for controls (n=63) (r=-0.25, two-tailed p=0.009). CONCLUSIONS: Patients with ALS have a lower 2D:4D ratio, consistent with higher prenatal circulating levels of testosterone, and possibly a prenatal influence of testosterone on motor-neuron vulnerability in later life.

  • When to consider thyroid dysfunction in the neurology clinic.

    24 October 2018

    There are many neurological manifestations of thyroid disease, and thyroid function has taken its place in the "routine bloods" of neurology practice. However, although conditions such as carpal tunnel syndrome prompt thyroid testing despite any clear evidence for this approach, other symptoms of potential significance in terms of thyroid disease may be overlooked in the busy general neurology clinic, or abnormal thyroid tests may be assumed to be incidental. Psychiatric disorders, loss of consciousness, movement disorders and weakness may all be manifestations of primary thyroid disease. This is a symptom-based review where we will consider the evidence (or lack of it) for the association of various neurological problems with thyroid dysfunction, and also the pitfalls in interpretation of the biochemical tests.

  • What is the place of thrombolysis in acute stroke? A review of the literature and a current perspective.

    24 October 2018

    The global burden of stroke, the undisputed success of intravenous thrombolysis in the management of myocardial infarction and subsequent evidence from animal models of cerebral infarction have all fuelled intense interest in the potential role for thrombolytic agents in the acute management of stroke in clinical practice. Before any clinical treatment is introduced universally its safety and efficacy must be demonstrated in the routine clinical environment and not just within the ideal conditions of controlled clinical trials. Similarly, the cost effectiveness of a new treatment modality is an essential consideration before its use is promulgated. This paper reviews the current scientific evidence for thrombolysis in stroke with reference to issues of safety, efficacy and cost effectiveness.

  • Mills' and other isolated upper motor neurone syndromes: in vivo study with 11C-(R)-PK11195 PET.

    24 October 2018

    (11)C-(R)-PK11195 positron emission tomography (PET) was used to explore and delineate in vivo the cortical lesion in three clinically isolated upper motor neurone syndromes of similar presentation, with reference to the syndrome of progressive spastic hemiparesis first described by Mills. Three patients with isolated UMN syndromes underwent (11)C-(R)-PK11195 PET of the brain. One patient fulfilled criteria for PLS. Two others had clinical features similar to the cases described by Mills; one of these had a high cervical cord inflammatory lesion previously noted on magnetic resonance imaging. The patient with PLS showed focal increase in the binding of (11)C-(R)-PK11195, indicating microglial activation, in the motor cortex contralateral to the predominantly affected limbs. Of the other two patients, one demonstrated marked increases in binding in the superior frontal region (supplementary motor region) contralateral to the affected limbs. In contrast, no focal areas of increased binding were seen in the cerebral cortex of the third patient, who had a high cervical cord lesion and was presumed to have extra-cerebral inflammatory disease. (11)C-(R)-PK11195 PET demonstrates in vivo that active pathology may be detectable many years after the onset of symptoms, and that it can occur in disparate sites with clinically similar presentations. We conclude that Mills' syndrome is a purely clinical description that should be reserved for patients with a progressive spastic hemiparesis for which no other explanation can be found.

  • Distinct cerebral lesions in sporadic and 'D90A' SOD1 ALS: studies with [11C]flumazenil PET.

    24 October 2018

    Five to ten percent of amyotrophic lateral sclerosis (ALS) cases are associated with mutations of the superoxide dismutase-1 (SOD1) gene, and the 'D90A' mutation is associated with a unique phenotype and markedly slower disease progression (mean survival time 14 years). Relative sparing of inhibitory cortical neuronal circuits might be one mechanism contributing to the slower progression in patients homozygous for the D90A mutation (homD90A). The GABA(A) receptor PET ligand [11C]flumazenil has demonstrated motor and extra-motor cortical changes in sporadic ALS. In this study, we used [11C]flumazenil PET to explore differences in the pattern of cortical involvement between sporadic and genetically homogeneous ALS groups. Twenty-four sporadic ALS (sALS) and 10 homD90A patients underwent [11C]flumazenil PET of the brain. In addition, two subjects homozygous for the D90A mutation, but without symptoms or signs ('pre-symptomatic', psD90A), also underwent imaging. Results for each group were compared with those for 24 healthy controls of similar age. Decreases in the binding of [11C]flumazenil in the sALS group were found within premotor regions, motor cortex and posterior motor association areas. In the homD90A group of ALS patients, however, decreases were concentrated in the left fronto-temporal junction and anterior cingulate gyrus. In the two psD90A subjects, a small focus of reduced [11C]flumazenil binding at the left fronto-temporal junction was seen, similar to the pattern seen in the clinically affected patients. Within the sALS group, there was no statistically significant association between decreases in cortical [11C]flumazenil binding and revised ALS functional rating scale (ALSFRS-R score), whereas the upper motor neuron (UMN) score correlated with widespread and marked cortical decreases over the dominant hemisphere. In the homD90A group, there was a stronger statistical association between reduced cortical [11C]flumazenil binding and the ALSFRS-R, rather than the UMN, score, and also with disease duration. This study provides evidence for differences in the distribution of reduced cortical [11C]flumazenil binding in homD90A compared with sALS patients. We hypothesize that this might reflect differences in cortical neuronal vulnerability.