Re: Estim Mp3 Files.epub
Towanda Tuning
In sepsis-associated critical illness neuromyopathy (CIPNM) serial electrical stimulation of motor nerves induces a short-lived temporary recovery of compound muscle action potentials (CMAPs) termed facilitation phenomenon (FP). This technique is different from other stimulation techniques published. The identification of FP suggests a major functional component in acute CIPNM.
In all six patients a striking variability in the magnitude and pattern of FP could be observed at each examination in the same and in different motor nerves over time. With the first stimulus most CMAPs were below 0.1 mV or absent. With slow serial pulses CMAPs could gradually recover with normal shape and near normal amplitudes. With facilitated CMAPs NCV measurements revealed low normal values. With improvement of muscle weakness subsequent tests revealed larger first CMAP amplitudes and smaller magnitudes of FP. Needle EMG showed occasional spontaneous activity in the tibialis anterior muscle.
In this pilot study striking variability and magnitude of FP during follow-up was a reproducible feature indicating major fluctuations of neuromuscular excitability that may improve during follow-up. FP can be assessed by generally available electrophysiological techniques, even before patients could be tested for muscle strength. Large scale prospective studies of the facilitation phenomenon in CIPNM with or without sepsis are needed to define diagnostic specificity and to better understand the still enigmatic pathophysiology.
Critical illness polyneuromyopathy (CIPNM or CIP/CIM) is a common neuromuscular complication in sepsis patients on intensive care units (ICU). CIPNM leads to mechanical ventilation and prolonged weaning [1, 2]. Over some decades critical illness polyneuropathy (CIP) and critical illness myopathy (CIM) have been maintained as separate entities and investigated as such [3,4,5]. Others proposed a mix of both in the majority of cases and some proposed a dominant role of CIM [2, 6,7,8,9]. The pathogenesis of CIPNM remains incompletely understood [2, 8, 10]. Electrodiagnostic nerve conduction studies (NCS) in CIPNM revealed small or absent compound muscle action potentials (CMAPs) in the acute phase and sensory nerve action potentials alike (SNAPs). With absent CMAPs and SNAPs nerve conduction velocities could not be measured [6, 11]. Spontaneous activity was found in muscles on electromyography in some patients [10]. However, all standard NCS showed unspecific abnormalities in patients with CIPNM. Moreover, they could not differentiate CIPNM from other axonal or mixed neuropathies, nor from other types of myopathies [6, 10,11,12]. Ultrasound may discover nerve swellings in CIPNM but again, this is not specific for CIPNM [13]. Muscle biopsies are not generally accepted as a diagnostic tool in these severely ill patients with sepsis and may not be widely available in contrast to standard NCS [8]. In another study in patients [14], and in a rat model [7], peripheral nerve and muscle fibers both showed a reduced excitability with inactivation of sodium channels and this was proposed as the principal cause of the weakness in CIPNM. In a more recent study on ICU patients defined as CIP inactivation of voltage-gated sodium channels was proposed as a prime disease mechanism [15]. In another study the dominant role of the myopathic contribution in CIPNM patients was identified by quantitative electromyography, direct muscle stimulation and NCS [9].
Here we report about six patients from that published cohort, in whom we were able to do repeated motor nerve stimulation tests for up to 6 weeks, allowing us to investigate variability of FP and to perform a new variant of NCS utilizing facilitated CMAPs.
Awake and cooperative patients were informed about indication and technique of the procedures and gave their consent. If patients were not able to give informed consent, the next of kin or a custodian was asked for permission, according to the approved protocol of the Ethics Committee at the University Medical Center at Leipzig. In the four surviving patients informed individual consent was confirmed by the patients when becoming cooperative. No patient had a nerve or muscle biopsy. Patients had daily laboratory investigations. In case of electrolyte imbalances these were corrected before the examination. All examinations were done at the bedside utilizing a Windows 10-based laptop digital EMG machine (Neurosoft NET-Omega software, Evidence 3201, Schreiber&Tholen, Stade, Germany). Filter settings were 5 Hz and 10,000 Hz, 50 Hz notch filter, and the post-stimulus artifact suppression was set at 0.6 ms.
Because of the absent or very small 1st CMAPs we could not estimate distal motor latencies in 5/6 patients for the peroneal and in 4/6 for the tibial nerve. Only facilitated CMAPs allowed us using the new technical variant of NCS in this pilot study. This procedure had not yet been done in the reported study (16). With maximal CMAPs (FP -max in Table 1a and b) we could analyze the shape of the CMAPs and measure distal latencies and NCVs in the peroneal, tibial or ulnar nerve (Table 1a and b), as it is done in standard nerve conduction testing. As described before the eight neuropathy control patients showed no FP (16).
Needle EMG tests were performed once during the follow-up in the tibialis anterior muscle with standard coaxial needle electrodes: in 4/6 about 14 days after the presumed CIPNM onset and in 2/6 at an earlier time point (Table 1a and b). The examination was restricted to identifying spontaneous activity (SpA) as a marker of nerve or muscle fiber degeneration. Quantitative EMG could not be done, due to lack of patient cooperation.
The 58 years old male was found comatose with generalized convulsions and hypothermia. After cardiopulmonary resuscitation circulation was restored. Septic shock ensued with multiple organ failure and pneumonia requiring invasive ventilation. Continuous dialysis was needed. The patient developed severe disseminated coagulopathy with ischemic defects in brain stem and lower legs. Weaning from the respirator remained unsuccessful. Vigilance remained poor and formal MRC muscle testing was impossible. Involuntary and induced reflex movements were all weak. The clinical diagnosis of CIPNM was made 7 days after onset of septic shock. The patient deceased 2 weeks later.
The 50 years old male was admitted to the ICU with severe respiratory insufficiency, in need of continuous invasive ventilation. He had a COVID-19 infection 1 month before and pulmonary fibrosis, and the PCR-test became negative. Septic shock, renal failure requiring dialysis, and transient delirium were diagnosed. Pulmonary gas exchange remained insufficient requiring oxygenation. Weaning attempts were unsuccessful. The approximated MRC sum score was 30/60 confirming CIPNM. The patient deceased after 42 days.
The 42 years old male suffered from cardiopulmonary arrest during a severe asthma attack and was successfully resuscitated within 10 min. On admission at the ICU sepsis was diagnosed with multiple organ failure, pneumonia, and urinary tract infection with preserved kidney function. EEG showed a non-convulsive status epilepticus which was stopped by treatment with propofol, and this treatment was continued until the EEG did not show further epileptic discharges. The patient improved gradually in vigilance and cognition with no further seizures, and muscle strength could be formally tested with a MRC sum score of 32/60 clinically confirming CIPNM. Weaning was possible after 29 days. During follow-up muscle strength slowly improved.
The 79 years old male was admitted to the ICU with pneumonia, encephalopathy, septic shock, and renal failure requiring short term dialysis treatment. Invasive ventilation was not needed. On day 3 the MRC sum score revealed 48/60 clinically confirming CIPNM. He improved and signs of sepsis remitted. On day 8 the MRC sum score was 56/60.
The 66 years old female had a chronic obstructive pulmonary disorder and rheumatoid arthritis treated with low dose prednisolone (up to 10 mg/d). She acquired acute pneumonia with sepsis, global respiratory and cardiac failure, and with encephalopathy requiring invasive ventilation, for a total of 6 days. The MRC sum score was 48/60 at day 4 after sepsis onset clinically confirming CIPNM. The patient improved rapidly and could be discharged within 16 days with a MRC sum score of 58/60.
The severe excitability defects that could be reversed temporarily through serial stimulation were reproduced at each follow-up examination, but at a highly variable degree. The magnitude and types of variability changed over minutes, an hour, or a couple of days. The stimulation of the distal or proximal segments of the identical peroneal nerve could elicit variable patterns and magnitudes of FP. The same was also observed in the tibial nerve, where only distal segments were tested in 5/6 patients. Representative examples illustrating variability patterns are shown (Figs. 1, 2, 3, 4). We named these patterns using categorial terms (Table 2). During follow-up most of these patterns could be seen in any of the examinations but often in different combinations. All these features corroborate our interpretation of the findings as indicating highly fluctuating functional defects in CIPNM.
Variability of peroneal motor nerve induced excitability with early serial stimulation. Patient 1: day 2 after sepsis onset: on left: original recordings. a distal: 1st CMAP with the 4th stimulus; moderate FP, low maximal CMAP amplitudes b 45 min later: delayed 1st CMAP from distal and proximal stimulation followed by FP. Vertical scale: sequence of stimuli; on right: bargraphs showing CMAP amplitudes at the vertical scale; horizontal scale: sequence of stimuli applied; note that facilitated maximal CMAP amplitudes remain abnormally low
Long-term variability of tibial motor nerve induced excitability with serial stimulation. Patient 6: days 2 and 36 after sepsis onset- serial distal stimulation of the left (upper panel) and right (lower panel) tibial nerves: day 2: a left tibial: 6 stimuli induce isoelectric lines, 1st CMAP appears with 7th pulse and FP is shown reaching normal CMAP amplitude; b right tibial: immediate small 1st CMAP is evoked, FP ensues with higher maximal CMAP amplitudes than in a; day 36: major clinical improvement: c left tibial: FP is still present with much higher initial and higher maximal CMAP amplitudes; d right tibial: no more FP, normal 1st CMAP amplitude. Bargraphs illustrate gain in amplitudes; Vertical scale: amplitudes of the original recordings. Horizontal scale: sequence of stimuli applied
7fc3f7cf58