REVIEW Pract Neurol: first published as 10.1136/practneurol-2013-000557 on 24 April 2013. Downloaded from Mimics and chameleons in motor neurone disease Martin R Turner, Kevin Talbot University of Oxford Nuffield ABSTRACT It is easy to understand why the neur- Department of Clinical The progression of motor neurone disease ologist might wish to put off conveying Neurosciences, Oxford, UK (MND) is currently irreversible, and the grave the diagnosis and to undertake every Correspondence to implications of diagnosis naturally fuels concern possible investigation in the pursuit of Dr Martin Turner, Department of among neurologists over missing a potential treatable alternatives. Might we, as neu- Clinical Neurosciences, John mimic disorder. There is no diagnostic test for Radcliffe Hospital, West Wing rologists, also occasionally succumb to Level 3, Oxford OX3 9DU, UK; MND but in reality there are few plausible the fear of just not wanting to get it [email protected] mimics in routine clinical practice. In the wrong in a speciality where diagnostic presence of a progressive pure motor disorder, precision is so highly prized? Most MND signs such as florid fasciculations, bilateral mimic disorders are equally irreversible, tongue wasting, the ‘split hand’, head drop, though there are still implications for the emotionality, and cognitive or behavioural accurate counselling of patients and care- impairment carry high positive predictive value. planning, meaning it is entirely appropri- MND is clinically heterogeneous, however, with ate to pursue these vigorously where clin- some important chameleon-like presentations ically indicated. The diagnosis of MND is and considerable variation in clinical course. Lack only very rarely reversed in favour of a of confidence about the scope of such variation, treatable disorder and, in our experience, or an approach to diagnosis emphasising the reaction of the patient in this situ- investigations over clinical common sense, has ation is one of relief not hostility. the potential to exacerbate diagnostic delay in Conversely, significant distress can arise MND and impede timely planning of the care from avoidable diagnostic delay and this which is essential to maximising quality of life. may permanently erode confidence in onward management. There is no diagnostic test for MND, http://pn.bmj.com/ and the quest for biomarkers is ongoing.3 INTRODUCTION Diagnostic delay in MND due to the There can be few worse tasks facing the insidious nature of disease onset and neurologist than giving the diagnosis of referral from primary care to inappropri- motor neurone disease (MND), a condi- ate specialists are to a large extent tion which is not well understood by the on September 26, 2021 by guest. Protected copyright. beyond the influence of the neurologist general public.1 Thus, the news of relent- (figure 1). The most robust marker of lessly progressive limb weakness, likely prognosis is still the interval from involvement of speech, swallowing and symptom onset to definitive diagnosis, breathing, dramatic shortening of life the average for which has remained expectancy, but no significant disease- 4 approximately 1 year, around a third of modifying therapy, is as surprising as it is the median survival from symptom devastating for the patient and their 5 onset. More aggressive and classical family. The Oxford neurologist W Bryan MND is referred more quickly to neurol- Matthews perfectly articulated the unique 6 ogists; thus, true mimics (and also some challenge of MND for the clinician: of the chameleons) tend to be slowly pro- The best test of a physician’s suitability gressive disorders and time is often for the specialized practice of neurology the neurologist’s most valuable diagnostic is not his ability to memorize improb- tool. To cite: Turner MR, Talbot K. able syndromes but whether he can con- Pract Neurol Published Online tinue to support a case of motor THE HISTORY First: [please include Day neurone disease, and keep the patient, Month Year] doi:10.1136/ his relatives and himself in a reasonably The difficulty increased so that she practneurol-2013-000557 cheerful frame of mind.2 dragged the right leg, which felt heavy Turner MR, et al. Pract Neurol 2013;13:1–12. doi:10.1136/practneurol-2013-000557 1 REVIEW Pract Neurol: first published as 10.1136/practneurol-2013-000557 on 24 April 2013. Downloaded from Figure 1 The diagnostic pathway in motor neurone disease (MND). There is an average delay of 1 year between symptom onset and diagnosis. There is a powerful relationship between rate of progression and speed of diagnosis. ALS, amyotrophic lateral sclerosis; GP, general practitioner; UMN, upper motor neurone. and cold, and it commenced to waste. The right arm The physical signature of ‘classical’ MND is captured began to fail…gradually progressive weakness came once again, but importantly only in the context of a on, just like the leg, but especially in the thumb and prior history of progressive weakness. The core fea- forefingers, and she experienced a difficulty in holding tures here are: things. Sensation in no way affected... The wasting 1. Upper motor neurone (UMN) and lower motor neurone progressed daily until she became a living skeleton (LMN) signs in the same territory unable to move, and the breathing was mostly 7 2. Florid fasciculations. abdominal. http://pn.bmj.com/ There are a handful of key signs on examination Sir Frederick Walker Mott’s 19th century case report that, in the presence of a history of progressive weak- history is inescapably that of MND, even down to the ness in someone aged over 50 years, should immedi- now recognised patterns of spread of symptoms to ately prompt consideration of the diagnosis of MND contiguous body regions.89The ‘core’ features of the (table 1). However, the great challenge of MND is history are: that it is evidently a syndrome, and the relative degree on September 26, 2021 by guest. Protected copyright. 1. Steadily progressive initially typically asymmetric weak- of UMN and LMN predominance is highly variable ness (first affecting the lower limb in 35%, upper limb and influences prognosis. At least 10% survive into a in 30%, and speech and swallowing in 30%) second decade, over-represented by those with either 2. Absence of significant sensory symptoms. ‘pure’ LMN or UMN involvement.12 By definition, The common perception that MND patients are classical amyotrophic lateral sclerosis (ALS) displays premorbidly ‘fitter’ or more athletic remains attractive evidence of both UMN and LMN involvement, but unproven.10 There is currently no convincing evi- accounting for 85% of cases of MND, so that the dence for an MND premorbid personality type.11 terms are largely synonymous. Furthermore, many of those with apparent LMN-only disease, sometimes termed progressive muscular atrophy, have subclinical evidence of UMN pathology,13 so the distinction is THE EXAMINATION not particularly meaningful. The very rare (<2%) patients with a pure UMN syndrome, termed primary There is great wasting of the muscles of the upper and lateral sclerosis, are characterised by slow progres- lower limbs and trunks, especially the small muscles of 14 the hands. Fibrillary contraction may be observed in sion, but may be difficult to distinguish from the 15 the limbs and trunk. Elbow tap exaggerated on left so-called UMN-predominant forms of ALS (see side, and also on right, but much less marked. below). Within this taxonomy, the site of symptom Knee-jerk exaggerated on both sides.7 onset also varies. There is also a clear 2 Turner MR, et al. Pract Neurol 2013;13:1–12. doi:10.1136/practneurol-2013-000557 REVIEW Pract Neurol: first published as 10.1136/practneurol-2013-000557 on 24 April 2013. Downloaded from Table 1 Signs with a high positive predictive value* for motor grouped into those presenting with LMN- or neurone disease where there is a history of progressive motor-only UMN-only signs and those with mixed signs. LMN weakness presentations represent the greatest diagnostic chal- Sign Notes lenge. Mimics are listed below in estimated order of frequency in our tertiary referral clinic setting. Key Fasciculations If generalised (easily missed over the anterior shoulders) ‘red flags’ can be identified for each of these (table 2). Bilateral wasting of the Lateral borders, particularly where there are Conditions with sensory involvement as a core feature, tongue also fasciculations (best observed without for example, syringobulbia, are not considered. protrusion) and a brisk jaw jerk or orbicularis oris reflexes The ‘split hand’73 Preferential wasting of the lateral border of LMN-ONLY SIGNS the hand, that is, first dorsal interosseous and Benign fasciculations abductor pollicis brevis. This is thought The anxious medical student, qualified clinician18 or possibly to reflect cortical organisation other individuals (typically under 40 years of age) pre- Head drop Weakness of neck extensors. Myasthenia senting with fasciculations is a common clinical gravis is a consideration but this sign should ‘ ’ not be attributed to cervical spondylosis encounter. While muscle twitching was the most sen- Emotionality Exaggerated response to emotional stimuli, sitive symptom-based keyword for internet search 19 usually crying, typically with bulbar weakness engines to suggest MND as a diagnosis, it is part of and often with an abnormal response to normal physiology. Exercise, anxiety, caffeine and glabellar tap alcohol may all provoke fasciculations, and approxi- Cognitive