Overlooked Holmes’ clinical signs: reevaluation by recent physiological findings
© Ishikawa et al. 2015
Received: 30 October 2015
Accepted: 2 November 2015
Published: 6 November 2015
Holmes proposed not only the term ataxia, but also opposite clinical signs related to muscle recruitment, which have escaped clinical attention; (1) asthenia, representing delay in initiating muscle contraction and slowness in attaining exertion of full power, and (2) adventitiousness, representing adventitious movements. Recent physiological studies have shown that cerebellar outputs are modified by release or facilitation of Purkinje cell-mediated inhibition on dentate neurons. We believe that asthenia and adventitiousness, which correlate with deficits in the control of disinhibition and inhibition, respectively, deserve more attention in clinical examination.
KeywordsCerebellar symptoms Ataxia Asthenia Adventitious movement Cerebellar motor control
In 1917, Holmes proposed the term ataxia, which included decomposition of movement, asynergia, dysmetria, and tremor, as a clinical sign of cerebellar disorders . However, asthenia and adventitiousness, both of which were also described in the original publication, have been clinically overlooked in spite of their clinical significance. Recently, these clinical signs were reevaluated in a consensus paper by Bodranghien et al. (chapter by Steiner and Timmann) . The present letter proposes other underlying physiological mechanisms of these overlooked clinical signs.
Holmes also described other curious complaints by the patients “they have not nearly so much power in them (affected limbs)” (page 469). Then he described “a delay in initiating muscular contractions and a slowness in attaining the exertion of the full power” (page 474–5), which was defined clinically as asthenia . The concept of asthenia was originally proposed by Luciani based on animal experiments [3, 4]. Luciani described a deficit in muscular force production during voluntary movements in hemicerebellectomized dogs and primates . Thus, Holmes confirmed the occurrence of asthenia in patients and, furthermore, introduced a simple method for examination of asthenia; “when the observer’s hands are placed in the patient’s, and he is asked to grasp them firmly at a given signal; the slowness of the affected limb in starting the action and in developing full power is often unmistakable” (page 471) . In addition, adventitious movements were described in a chapter on adiadochokinesis. Holmes did not only describe inability to execute alternate movements quickly and correctly, but also stressed adventitious movements at elbow and shoulder (page 486–7), which led to failure of fixing the proximal muscles to preserve correct posture . Thus, asthenia and adventitiousness are opposite deficits of activities of a group of muscles. Asthenia represents failure of augmentation in muscles to be recruited, whereas adventitious movement is exaggerated activation of muscle to be paused. These clinical signs related to muscle recruitment could have been overlooked by clinicians, compared with ataxic symptoms; conspicuous deficits observed during multi-joint movements.
However, recent physiological findings explain well and systematically the two signs of asthenia and adventitiousness. We (TI and SK) found that during wrist movement of monkeys, a large proportion of Purkinje cells (PCs), with somatosensory receptive fields (RFs) in the distal arm, was strongly suppressed before movement onset, while the majority of dentate cells (DNs) with the same RFs showed concurrent burst of activity. In contrast, PCs with RFs in the proximal arm demonstrated marked and simultaneous increase in activity, while DNs with the same RFs were strongly suppressed . Our observation suggests that activation of DNs generated by reduced inhibition from PCs, i.e., disinhibition, facilitates the execution of wrist movement, while suppression of the DNs by increased PC activity contributes to the stabilization of proximal muscles and improves task performance. Thus, deficits of disinhibition and inhibition of DNs could be the physiological counterparts of asthenia and adventitiousness, respectively (Fig. 1).
In conclusion, it seems that asthenia and adventitiousness reflect deficits in the control of disinhibition and inhibition that determines the strength of cerebellar outputs. Thus, these Holmes’ overlooked clinical signs could be clinically utilized as elements underlying ataxia.
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- Holmes G. The symptoms of acute cerebellar injuries due to gunshot injuries. Brain. 1917;40:461–535.View ArticleGoogle Scholar
- Bodranghien F, Bastian A, Casali C, Hallet M, Louis ED, Manto M, et al. Consensus paper: Revisiting the symptoms and signs of cerebellar syndrome. Cerebellum. 2015; doi:https://doi.org/10.1007//s12311-015-0687-3.
- Luciani L. Il cervelletto: nuovi studi di fisiologia normale e pathologica. Le Monnier 1891.Google Scholar
- Ermanno M, Petrosini L. Luciani’s work on the cerebellum a century later. Trends Neurosci. 1997;20:112–6.View ArticleGoogle Scholar
- Ishikawa T, Tomatsu S, Lee J, Hoffman DS, Kakei S. Releasing dentate nucleus cells from Purkinje cell inhibition generates output from the cerebrocerebellum. PLoS One. 2014;9:e108774.PubMed CentralView ArticlePubMedGoogle Scholar