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COVID-19, lassitude, and the Bereitschaftspotential

Posted in Personal Perspective,Special Feature on 9th Jun 2021

Andrew Larner MD, PhD, Cognitive Function Clinic, Walton Centre for Neurology and Neurosurgery, Liverpool L9 7LJ   UK.
Correspondence toa.larner@thewaltoncentre.nhs.uk
Provenance and peer review: Submitted and reviewed internally
Date first submitted: 4/1/2021
Acceptance date: 4/1/2021
To cite: Larner, A. Adv Clin Neurosci Rehabil 2021; COVID-19, lassitude, and the Bereitschaftspotential. https://acnr.co.uk/2021/06/covid-19-lassitude
Published online: 9/6/2021

Published under a Creative Commons license 
https://doi.org/10.47795/LXHI2543

During my clinical training in the mid-1980s it was possible to subscribe to the British Medical Journal (it had not yet metamorphosed into “BMJ”) at student rates. This was an era when the journal was still largely devoted to clinical matters, unlike now, and hence relevant to clinical training, usually with several editorials. I recently had reason to recall one of these editorials (published 20th April 1985), entitled simply “Lassitude”.1 One of the Consultant Physicians on the firm I was then attached to, the late (great) Clinical Pharmacologist David Grahame-Smith, commented that he had seen the title but couldn’t summon the energy to read it.2

The cue for this recall came from my experience of COVID-19. Initially presenting with monosymptomatic anosmia, my self-isolation period was almost complete when systemic symptoms set in, with swinging pyrexias, non-productive cough, inability to eat, sleep disturbance, and physical and mental prostration, all presumably a consequence of pneumonia (thankfully never bad enough to necessitate hospital admission). Hardly able to do much more than transfer between bed and couch, I wondered how best to describe this sluggishness: Lethargy? Inertia? Lassitude? Even when the call to urinate was apparent, initiating movement off the couch was still difficult: I could not “get moving”. “Avolitional” might be the adjective that best captures this, and might also be relevant to the extraordinary inability to countenance eating any food. This was not indifference as I had food cravings (often for childhood treats: Smarties! Lardy cake!), nor was it a consequence of nausea (only induced by the aloe vera smell of my hand soap, suggesting my anosmia was partial rather than complete), and cognitively I knew I must eat. Nevertheless, foods passed their best before dates and, shamefully, had to be wasted. I lost about 6kg during the course of the illness.

So what explanation might be advanced for this lassitude? No doubt the interstitial fluids are a veritable soup of cytokines, interferons, and other inflammatory mediators which I have not heard of, as a consequence of the immune response to SARS-Cov-2. But is an explanation along these lines sufficient to satisfy a Neurologist’s curiosity? It may be the case that the self-styled “Coroneurologists” have already solved this particular issue, and I claim no familiarity with the mushrooming literature. In my ignorance, what came to mind was the Bereitschaftspotential.

As an undergraduate I had learned, from the first edition of the textbook by Kandel and Schwartz,3 of the work of Kornhuber and Deecke in the 1960s which, using back averaging techniques, characterised the Bereitschaftspotential,4 or “readiness potential”, or “premovement potential”, occurring in the 1000ms or more prior to voluntary movement. Different components of the Bereitschaftspotential have subsequently been characterised, an early component thought to originate in the anterior supplementary motor area (SMA) and rostral pre-SMA, and a late phase from the SMA and contralateral primary motor area.5,6 Both cortical and subcortical (basal ganglia) generators may contribute to the Bereitschaftspotential. Some evidence has subsequently accrued for the absence or diminution of the Bereitschaftspotential in involuntary movement disorders such as Parkinson’s disease, but with preservation in (so called) psychogenic movement disorders.

So, I wondered if my COVID-19-related lassitude/inertia/lethargy/avolition might possibly be a consequence of an inability to generate a Bereitschaftspotential, or a component thereof. Interestingly in this connection there was a frontal-subcortical flavour to some of my other symptoms at the time of systemic illness: stooped posture when attempting to walk, slow short-stepped gait, bradykinesia, and bradyphrenia (I couldn’t concentrate on daytime TV programmes, let alone read).

If there is any credibility to this suggestion (and it should be noted that cogent conceptual argument may be made that the temporal priority of the Bereitschaftspotential may not be equivalent to causal priority7) might it be relevant beyond the specific situation of COVID-19-related symptoms of lassitude? Could difficulties in generating a Bereitschaftspotential, or components thereof, potentially explain clinically defined syndromes such as abulia and akinetic mutism? These syndromes are often associated with frontal lobe damage or pathology.

References

1. Havard CWH. Lassitude. BMJ 1985:290:1161-1162. https://doi.org/10.1136/bmj.290.6476.1161
2. Aronson JK. David Grahame-Smith. Clinical pharmacologist 1933-2011. Br J Clin Pharmacol 2011;73:830-832. https://doi.org/10.1111/j.1365-2125.2011.04160.x
3. Kandel ER, Schwartz JH. Principles of neural science. New York: Elsevier, 1981.
4. Kornhuber HH, Deecke L. Hirnpotentialänderungen bei Willkürbewegungen und passiven Bewegungen des Menschen: Bereitschaftspotential und reafferente Potentiale. Pflügers Archiv 1965;284:1-17. https://doi.org/10.1007/BF00412364 
5. Shibasaki H, Hallett M. What is the Bereitschaftspotential? Clin Neurophysiol 2006;117:2341-2356. https://doi.org/10.1016/j.clinph.2006.04.025
6. Colebatch JG. Bereitschaftspotential and movement-related potentials: origin, significance, and application in disorders of human movement. Mov Disord 2007;22:601-610. https://doi.org/10.1002/mds.21323
7. Nachev P, Hacker P. The neural antecedents to voluntary action: a conceptual analysis. Cog Neurosci 2014;5:193-208. https://doi.org/10.1080/17588928.2014.934215