Critical illness neuropathy and myopathy. Muscle weakness in the Intensive Care
Unit.
Reinhard Dengler, M.D., Dept. of Neurology, Hannover Medical School, Hannover,
Germany
Abstract:
Critically ill patients in the intensive care unit (ICU) frequently develop severe muscle
weakness independently of whether they suffer from primary neurological diseases. This
becomes apparent, at the latest, when weaning from the ventilator proves impossible or
difficult and if physical rehabilitation is cumbersome. Essential risk factors for this condition
seem to be sepsis, systemic inflammatory response and multiple organ failure. The
weakness can be caused by critical illness polyneuropathy (CIP) or by critical illness
myopathy (CIM) which can also occur in conjunction.
Early diagnosis and diagnostic differentiation appears important to modify treatment, make
a prognosis (prognosis of CIM better than that of CIP) and to develop rehabilitation plans.
Clinical neurophysiology, especially Electromyography and Nerve Conduction Studies play
an important role in the diagnosis of these conditions. CIP and CIM have in common a
decrease of the compound muscle action potential (CMAP) after supramaximal nerve
stimulation and CIM may also show a prolongation of CMAP. Sensory nerve action
potentials (SNAP) are usually decreased in CIP and normal in CIM. Nerve conduction
velocities are normal in CIM and maybe slightly decreased in CIP. In EMG, pathological
spontaneous activity occurs in CIP after 2 to 3 weeks while it may be seen much earlier in
CIM. The extent of pathological spontaneous activity, however, may be variable in both
conditions. Evaluation of single motor unit action potentials (MUAP) can be difficult in the
acute situation as patients may be unable to cooperate, but will become important in the
course of the disease. While patients with CIP typically develop increased and polyphasic
MUAP, CIM shows normal or small MUAP occasionally of polyphasic shape. If patients
can fully cooperate the interference pattern in CIP is reduced and normal in CIM with early
recruitment. Frequently recommended although not widely distributed is the comparison of
CMAP in response to supramaximal nerve stimulation and after direct muscle stimulation.
The quotient of these two CMAP is about “1” in CIM and clearly smaller than “1” in CIP.
Although there is currently no specific treatment for CIP and CIM early recognition,
consequent antiseptic treatment and early rehabilitation can positively modulate the course
of the disease.
Introduction:
Critically ill patients on the intensive care unit (ICU) frequently reveal a severe muscle
weakness especially if they develop sepsis and systemic inflammatory response syndrome
or multi organ failure (I, 2). Bacterial toxins such as Endotoxin and proinflammatory
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proteins seem to play a crucial role in the pathophysiology (Mohammadi). If this
weakness was not the primary cause for hospitalization or does not result from an
underlying neurological condition such as GBS or Myasthenia gravis it can be caused by
critical illness polyneuropathy (CIP), first described by Bolton and colleagues (3) or by
critical illness myopathy (CIM) both typically attracted in the ICU. The muscle weakness
resulting from CIP and CIM may lead to a prolongation of the time on the respirator, to
difficulties in weaning from the ventilator and in an impairment of physical rehabilitation.
Differentiation between CIP and CIM is clinically difficult and sometimes impossible,
especially, as the two conditions can occur in combination. Early diagnosis and
differentiation between these two conditions is a challenge for the clinical
neurophysiologist and seems, however, to be worthwhile to induce timely anti-infectious
treatment and to allow for making a prognosis which seems to be better in CIM. This
article will focus on the role of clinical neurophysiology in CIP and CIM and its capability to
make an early diagnosis and to differentiate between these two conditions.
Differentiation between CIP and CIM, clinical neurophysiology.
The following chapter will deal with clinical neurophysiology in CIP and CIM, especially
with nerve conduction studies (NCS) and electromyography (EMG) while clinical aspects,
pathomechanisms and treatment options are beyond its scope.
Motor and send sensory NCS in CIP and CIM:
The most typical finding in CIP is the reduction in the amplitudes of the compound muscle
action potential (CMAP) which can occur already after a few days on the ICU. Values
decrease to 50% of the lower limit or less and this can usually be found in several nerves.
This reduction of the CMAP results from increasing inexcitability of the nerve fibers and, in
severe cases, from nerve fiber degeneration. Figure 1 illustrates the CMAP decrease in
CIP and its relationship to serum endotoxin levels as found in own investigations
(Mohammadi). These changes are usually observed within a week or two on the ICU, but
can be seen earlier. Sensory nerve conduction is mostly also involved in CIP and sensory
nerve action potential (SNAP) amplitudes may decrease. This is not the case in CIM and
may help to distinguish between these two conditions.
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Endotoxin (pg/ml)
80
Fig.1 Amplitudes of CMAP in CIP in relation to serum endotoxin levels. CMAP amplitudes
decrease as endotoxin levels rise.
.
In CIM, the CMAP is similarly decreased. Its duration may be prolonged due to impaired
excitability of the muscle fiber membrane which is usually not the case in CIP. SNAP
amplitudes should remain unchanged.
Several nerves should be studied depending on their accessibility in routine diagnosis on
the ICU. Most appropriate appear the median and ulnar nerves in the upper extremity and
the peroneal, tibial and sural nerves in the lower extremity. In case of subcutaneous
edema it can be difficult to record sensory NAP and particular experience may be required.
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In summary, decreased CMAP can be found in both CIP and CIM. This finding is helpful in
early diagnosis, but not in differentiation between CIP and CIM. Additional decrease of
SNAP indicates CIP while a prolongation of the CMAP may point to CIM.
Direct muscle stimulation:
The excitability of the muscle fiber membranes is reduced in CIM which can be tested by
direct muscle stimulation.Therefore, comparison between the CMAP evoked by
supramaximal nerve stimulation with that in response to direct muscle stimulation has
been recommended to distinguish between CIM and CIP (XXX). In brief, a muscle is
supramaximally stimulated by two intramuscular needle electrodes inserted near the
tendon and the corresponding muscle action potential is recorded by an intramuscular
needle electrode referenced versus a surface electrode. From the same pair of electrodes
a CMAP is recorded in response to supramaximal nerve stimulation. In CIM, the muscle
action potentials in response to supramaximal nerve stimulation and to muscle stimulation
should be similar in size and the quotient should be close to “1”, while in CIP the response
to nerve stimulation should be clearly smaller than that in response to muscle stimulation
and the quotient should be clearly smaller than “1”.
An appropriate muscle for this type of study is the M. tibialis anterior although application
to other muscles is possible. Generally, however, this method appears complex and is not
widely distributed.
Needle Electromyography:
Study at rest, pathological spontaneous activity (SPA)
Both CIP and CIM show SPA in many muscles. Fibrillation potentials and sharp positive
waves can be recorded and occasionally also repetitive discharges. The intensity is
variable and is not clearly correlated to the severity of the weakness. It appears that SPA
occurs earlier in CIM than in CIP. While in CIM SPA may be seen already within the first
week of the disease, the development of SPA in CIP may take more time, i.e. up to 2 or 3
weeks. The demonstration of SPA is helpful for early diagnosis, but does not allow to
distinguish between CIP and CIM.
Study at slight innervation, motor unit action potentials (MUAP)
Changes of MUAP occur in CIP depending on the time of the study. In early phases, i.e.
after 2 to 3 weeks, small polyphasic potentials (nascent potentials, reinnervation
potentials) may be found which increase in amplitude over time and may develop a long
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duration. Full blown changes with increased and polyphasic MUAP may be seen after
several weeks depending on the degree of axonal damage.
In CIM, MUAP may be normal in shape for some time and may rather decrease in
amplitude in the course of the disease. Polyphasicity may also be observed. These
changes can be seen in proximal as well as in distal muscles.
In general, motor unit action potential analyses can differentiate between pure CIP or pure
CIM, at least after 3 to 4 weeks. If the patients develop both conditions EMG will only be
able to show abnormalities without a clear distinction between CIP and CIM. Motor unit
action potentials will, however be helpful in long term analysis and in making a prognosis
with regard to rehabilitation outcome.
Study at maximal innervation, interference pattern
Patients in the ICU are frequently not able to cooperate and to produce an interference
pattern. In CIP, motor unit recruitment is impaired and the interference pattern is reduced
in principle. This is especially important in making a prognosis and in the evaluation of
rehabilitation progress. In CIM, motor units are quickly recruited and the interference
pattern can be dense although the average amplitude is low. Thus the evaluation of the
interference pattern may help to distinguish between CIP and CIM, at least, in later stages
of the disease.
Other tests
The clinical neurophysiologist may encounter a variety of disorders when he is asked to
study patients with weakness in the ICU.
In addition to the above described studies other tests may become necessary, e.g. to
study the function of the neuromuscular junction (low and high frequency repetitive nerve
stimulation) or of the spinal cord (somatosensory evoked potentials, transcranial magnetic
stimulation).This article, however, focuses only on CIP and CIM.
Summary:
CIP can be diagnosed if both the amplitude of the CMAP and of the SNAP are decreased.
If only the CMAP is decreased and the SNAP is normal, CIM appears more likely. Another
argument in favor of CIM is a long duration of the CMAP.
SPA indicates a neuromuscular problem, but cannot distinguish between CIP and CIM.
SAP may, however, occur earlier in CIM than in CIP.
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If the patient can cooperate, low amplitude and short duration MUAP speak in favor of CIM
while long duration MUAP with increasingly higher amplitude rather indicate CIP. A full
interference pattern points to CIM while a reduced interference pattern speaks in favour of
CIP. It has to be considered, however, that the ability of the patients to cooperate is
frequently reduced in the ICU and that MUAP analysis and the study of the interference
pattern can be difficult or impossible.
Direct muscle stimulation may be a tool to differentiate between CIP and CIM although it
appears complex and has not been widely distributed.
From a clinical point of view it is not always important to clearly differentiate between CIP
and CIM as long as the treatment of the underlying diseases is successful and the patients
start to recover. If recovery, however, is delayed differentiation should be tried to give the
patient a clear prognosis and to plan appropriate rehabilitation.
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