Table Of ContentFatigue in
Multiple
Sclerosis
Background, Clinic, Diagnostic,
Therapy
Iris-Katharina Penner
Editor
123
Fatigue in Multiple Sclerosis
Iris-Katharina Penner
Editor
Fatigue in Multiple
Sclerosis
Background, Clinic, Diagnostic, Therapy
Editor
Iris-Katharina Penner
Department of Neurology, Inselspital
Bern University Hospital, University of Bern
Bern, Switzerland
Translation from the German language edition: “Fatigue bei Multipler Sklerose Grundlagen –
Klinik – Diagnostik– Therapie, 2nd edition” by Iris-Katharina Penner, © Hippocampus
Verlag 2021. Published by Hippocampus Verlag. All Rights Reserved.
ISBN 978-3-031-13497-5 ISBN 978-3-031-13498-2 (eBook)
https://doi.org/10.1007/978-3-031-13498-2
© COGITO GmbH 2023
The translation was done with the help of artificial intelligence (machine translation by the
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Preface
Fatigue in the context of multiple sclerosis is one of the most relevant neuropsychi-
atric symptoms of the disease and is considered one of the most distressing ones
from the patient's perspective. Fatigue often occurs abruptly without any external
reason in everyday life and thus complicates a normal daily functioning. Often,
patients’ fatigue-associated behavior leads to stigmatization in the sense of "lazi-
ness attribution," "inability to work under pressure," or "simulating and exaggerat-
ing the symptoms." This lack of understanding in the social environment is increased
by the fact that fatigue occurs independently of the degree of disability and thus also
affects patients who do not appear to have any “obvious” disease symptoms. But
especially the group of patients with a low degree of disability have been shown to
feel fatigue forces them to reduce their workload or even to give up employment
completely, consequently resulting in social isolation and depressive episodes.
This book is the first English edition following the recently published second
German edition. It is dedicated to all those dealing with fatigue symptoms directly
or indirectly in the context of multiple sclerosis. This includes various professional
groups (e.g., doctors, psychologists, therapists, nurses a.o.) as well as the patients
themselves and their relatives. The aim of the book is to present the latest scientific
findings, from the basics to clinics and diagnostics to therapy, in order to increase
our understanding of the whole spectrum of fatigue. To achieve this, renowned col-
leagues from the clinical and scientific communities have agreed to illuminate vari-
ous aspects from their respective research and practice perspective. I would therefore
like to take this opportunity to thank my esteemed colleagues for their support and
enthusiasm in the endeavor to publish this English edition of the Fatigue book.
Bern, Switzerland Iris-Katharina Penner
April 2022
v
Contents
Part I Background
On the History of Fatigue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
J. Kesselring
Definitions, Epidemiology, and Etiological Factors . . . . . . . . . . . . . . . . . . . . 9
P. Flachenecker
Pathophysiology and Differentiation from Other Symptoms
and Diseasess . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
F. Paul
Immunopathology and Pathogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
U. K. Zettl and R. Patejdl
Part II Clinic
Motor Performance Fatigability in MS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
K.-C. Broscheid, C. Dettmers, M. Behrens, W. Wolff, A. Peters,
L. Schega, M. Vieten, and M. Jöbges
Cognitive Fatigue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 73
Iris-Katharina Penner, P. Flachenecker, and H. Meißner
Personality Factors and Motivation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
M. Filser and Iris-Katharina Penner
Fatigue and Depression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
S. M. Gold
Sleep and Wake Disturbances . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
U. Kallweit, A. Chan, and C. L. A. Bassetti
Part III Diagnostics
Clinical Assessment Tools for Fatigue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109
Iris-Katharina Penner
vii
viii Contents
Neuroimaging and Fatigue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
Daniela Pinter and Christian Enzinger
Electrophysiology and Fatigue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135
J. Liepert
Expert Opinion and Medicolegal Assessment . . . . . . . . . . . . . . . . . . . . . . . . 149
B. Widder
Part IV Therapy
Disease Modifying Immunotherapies and Fatigue . . . . . . . . . . . . . . . . . . . . 161
Iris-Katharina Penner and H. Schreiber
Symptomatic Drug Treatment of Fatigue . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179
D. Woitalla
Non-drug Treatment Approaches and Neurorehabilitation . . . . . . . . . . . . . 193
M. Sailer, C. M. Sweeney-Reed, and J. Lamprecht
Part I
Background
On the History of Fatigue
J. Kesselring
In the nineteenth century, labor, with its political and economic dimensions, repre-
sented a central interest in the sociological and medical literature. With its various
forms of organization, its significance and productive potential toward the end of the
century, attempts were made to solve the “worker question” with the help of sci-
ence: Body movements and rhythms were subjected to detailed laboratory studies,
exposed to new measuring techniques, and recorded photographically. This attempt
to replace moral disputes with science is particularly visible in the discussion of
fatigue by European physiologists after 1870. Although descriptions of this phe-
nomenon can already be found in numerous literary accounts of ennui, lassitude,
languor, and Weltschmerz, they did not find their way into the medical literature
until the end of the nineteenth century (Lepenies 1985). In 1892, for example,
Lagrange provides descriptions of lamentable French schoolchildren: “Muscles
without energy only painfully support the body, the face is pale, the body without
nerves, the posture as if under weight turned downward. All the external aspects of
the child give the impression of a plant longing for air and sunlight. All the functions
of the organism are doomed.”
Fatigue thus became the most obvious sign of the external limitations of body
and mind, the most reliable indicator of the need to preserve the forces and prevent
their abuse. The paradigm shift consisted in the replacement of the earlier concep-
tion of laziness as a reason for resistance to work with fatigue.
Physiologists and discoverers such as Etienne-Jules Marey or Angelo Mosso
(1891) from Turin, whose classic La Fatica in 1891 was enormously influential,
attempted to describe for the body in work what Helmholz, Lord Kelvin, or Clausius
had achieved for the universe: to establish dynamic laws of energy conservation and
thus of fatigue through rigorous experiments and new measuring techniques.
J. Kesselring (*)
Rehabilitation Center, Clinics Valens Taminaplatz, Valenz, Switzerland
© The Author(s), under exclusive license to Springer Nature 3
Switzerland AG 2023
I.-K. Penner (ed.), Fatigue in Multiple Sclerosis,
https://doi.org/10.1007/978-3-031-13498-2_1
4 J. Kesselring
In the 1890s, there was an international avant-garde of fatigue experts, laboratory
specialists, and social hygienists who used fatigue to create a new field of experi-
ence in which science and politics met. The body without fatigue became a nine-
teenth century utopia. Toward its end, fatigue and exhaustion were the constant
threats and challenges to the idea of progress, the great fear of the age. Nietzsche,
for example, equated fatigue with modernity: his time was characterized by disinte-
gration and, accordingly, by uncertainty (Nietzsche 1938); Balzac planned to write
a pathology of social life to show how people wasted their energies by overexerting
themselves. Accordingly, doomsday fantasies were also in vogue in the fin de siècle.
Before 1860, there were hardly any medical or scientific studies on fatigue, but
around the turn of the century afterward there were already hundreds of studies on
muscle fatigue as well as “nervous exhaustion,” “neurasthenia,” etc., which were
understood as “maladie de l’énergie.” In 1875, George Poore (1875) published an
article in the Lancet in which he distinguished between general and local, acute and
chronic symptoms of fatigue. In France, Carrieu (1878) in his pioneering work “De
la fatigue et de son influence pathogénique” in 1878, complained that the term
fatigue did not appear in any of the major medical dictionaries of his time and that
all attempts at definition remained purely subjective, offering the following defini-
tion: “Un trouble dans l’activité des éléments anatomiques, causé par un fonc-
tionnement exagéré au point que la réparation y est momentanément impossible”
(“A disturbance in the activity of anatomical elements, caused by exaggeration of
functions until recovery is no longer possible”).
Fatigue was seen as both a physical and a moral disorder, a sign of weakness and
lack of will (see discussion in Rabinbach 1990). Reflecting a breakdown in physical
and mental functioning, fatigue was increasingly seen as a “modern” disorder with
overwhelming social and physical consequences.
The experiments of the chemist and physiologist Wilhelm Weichardt at the
University of Erlangen in Germany “on fatigue substances” caused a great stir. He
announced in 1904 that he had invented a vaccination against fatigue. He was con-
vinced that accumulated fatigue substances accumulated in the body could lead to
stupor and death. Mosso was also convinced in 1891 that by transferring blood from
one fatigued and exhausted animal to another, the latter would also succumb to
fatigue. Even in World War I, soldiers were experimented on with substances that
were supposed to be directed against fatigue toxins. In time, however, all these
experiments turned out to be artifacts. At least they led to other “nerve stimulants”
such as tea, coffee, and cocaine being studied more closely. In the following years,
there were many publications on physical and mental fatigue, new apparatuses were
introduced that would allow these symptoms to be quantified more precisely. In
1901, the psychiatrist Kraepelin introduced a distinction between “fatigue” and
“tiredness.” Based on this, he also proposed very specific measures for timetabling
in schools in order to prevent the collapse of the child’s working capacity.
The term “neurasthenia,” which had been introduced by the New York physician
Georg Miller Beard in the 1860s and was intended to express “all forms and kinds
of nervous exhaustion in the brain and spinal cord,” later became particularly popu-
lar. He attributed the cause to “excess pressure in the higher nervous centers” and
