Patterns of neurophysiological abnormality in prolonged critical illness

Objective: To describe the various patterns of neurophysiological abnormalities which may complicate prolonged critical illness and identify possible aetiological factors. Design: Prospective case series of neurophysiological studies, severity of illness scores, organ failures, drug therapy and hospital outcome. Some patients also had muscle biopsies. Setting: General intensive care unit (ICU) in a University Hospital. Patients: Forty-four patients requiring intensive care unit stay of more than 7 days. The median age was 60 (range 27–84 years), APACHE II score 19 (range 8–33), organ failures 3 (range 1–6), and mortality was 23 %. Results: Seven patients had normal neurophysiology (group I), 4 had a predominantly sensory axonal neuropathy (group II), 11 had motor syndromes characterised by markedly reduced compound muscle action potentials and sensory action potentials in the normal range (group III) and 19 had combinations of motor and sensory abnormalities (group IV). Three patients had abnormal studies but could not be classified into the above groups (group V). All patients had normal nerve conduction velocities. Electromyography revealed evidence of denervation in five patients in group III and five in group IV. There was no obvious relationship between the pattern of neurophysiological abnormality and the APACHE II score, organ failure score, the presence of sepsis or the administration of muscle relaxants and steroids. A wide range of histological abnormalities was seen in the 24 patients who had a muscle biopsy; there was no clear relationship between these changes and the neurophysiological abnormalities, although histologically normal muscle was only found in patients with normal neurophysiology. Only three of the eight patients from group III in whom muscle biopsy was performed had histological changes compatible with myopathy. Conclusions: Neurophysiological abnormalities complicating critical illness can be broadly divided into three types – sensory abnormalities alone, a pure motor syndrome and a mixed motor and sensory disturbance. The motor syndrome could be explained by an abnormality in the most distal portion of the motor axon, at the neuromuscular junction or the motor end plate and, in some cases, by inexcitable muscle membranes or extreme loss of muscle bulk. The mixed motor and sensory disturbance which is characteristic of ’critical illness polyneuropathy' could be explained by a combination of the pure motor syndrome and the mild sensory neuropathy. More precise identification of the various neurophysiological abnormalities and aetiological factors may lead to further insights into the causes of neuromuscular weakness in the critically ill and ultimately to measures for their prevention and treatment. Received: 23 January 1998 Accepted: 22 May 1998     

Functioning Adrenocortical Carcinoma

Functioning adrenal carcinoma is an unusual condition. In this case it produced Cushing's syndrome that lacked many of the usual characteristics. Hypokalemic alkalosis and associated myopathy were the most striking features. The microscopic picture of a metastatic lesion in the neck differed sufficiently from that of the primary tumor to prevent an early definitive diagnosis.     

Serial electrodiagnostic studies in West Nile virus-associated acute flaccid paralysis

A man in his 70s presented for acute rehabilitation with severe acute flaccid asymmetric weakness in both lower limbs. Cerebrospinal fluid and serum immunoglobulin M titers were positive for West Nile virus. Electrodiagnostic studies demonstrated severe diffuse motor axonopathy consistent with an anterior myelitis. Electrodiagnostic and clinical improvements were monitored. Electrodiagnostic testing at 6 and 18 mos demonstrated continuing reinnervation; nascent voluntary motor unit action potentials were first noted proximally and, at 18 mos, distally in the left lower limb, including muscles in which motor unit potentials were not initially noted. Corresponding clinical improvements, though slow, were demonstrated even at 1(1/2) yrs after onset. Thus, motoric changes after West Nile virus-associated anterior myelitis need to be monitored over a prolonged time period to allow accurate assessment of prognosis for recovery in rehabilitation programs.     

Secondary changes in segmental neurons below a spinal cord lesion in man

The function of sensory and motor neurons below the level of a spinal cord injury (SCI) was assessed in 23 patients by recording the nerve conduction velocities and the amplitudes of evoked nerve and muscle compound action potentials for sural and posterior tibial nerves. Sensory and motor conduction velocities were generally normal when obtainable. Two patients had a unilateral reduction in the sural nerve and abductor hallucis muscle compound action potentials which may have been due to peripheral nerve compression. In 11 patients the abductor hallucis muscle compound action potential was below the normal range, while sural nerve action potentials remained within the normal range. Motor unit counts showed a reduction in the number of functioning motor units in these muscles.     

Focal myositis of unilateral leg

Focal myositis is a rare, benign inflammatory pseudotumor of the skeletal muscle of unknown etiology. In Korea, there is no case report of focal myositis, which is not combined with connective tissue disease. We present an unusual case of focal myositis with ankle contracture, involving more than two muscles. A 26-year-old man visited our clinic complaining of right ankle contracture and leg muscle pain. Physical examination revealed no muscle weakness or any other neurological abnormality. T2-weighted magnetic resonance imaging of the right leg demonstrated diffuse high signal intensity of the right gastrocnemius, flexor digitorum longus, and tibialis anterior muscles. Needle electromyography showed profuse denervation potentials with motor unit action potentials of short duration and small amplitude from the involved muscles. All these findings suggested a diagnosis of focal inflammatory myositis and the patient was put under oral prednisolone and physical therapy.     

Phrenic nerve stimulation in the evaluation of ventilator-dependent individuals with C4- and C5-level spinal cord injury

Three individuals with C4 or C5 spinal cord injuries (SCI) were seen in follow-up for management of their late complications, which included impaired ventilation. Electrodiagnostic studies were performed on all three as part of the assessment of the function of their phrenic nerves and diaphragm muscles in relation to their need for mechanical ventilator support. Each patient had evidence of lower-motor neuron injury to the phrenic nerves. Two of the patients who initially displayed small-amplitude (<0.1 mV) compound muscle action potentials (CMAP) bilaterally were later reevaluated during the course of their observation in the outpatient rehabilitation clinic. The CMAP amplitude of the diaphragm increased in these two cases during the 3-11 mos after SCI. Evidence of nerve recovery occurred in parallel with improvements in pulmonary function testing and was followed by successful weaning from the ventilator. These individuals both gained ventilator independence after the CMAP amplitude of least one hemidiaphragm was >0.4 mV. In the third case, early failure of ventilator weaning was reported to the patient as a poor prognostic sign. At the time of our first evaluation 11 mos after injury, a CMAP of 1.0 mV was seen on the right, with an absent response on the left. In case 3, the needle electromyogram demonstrated voluntary active motor unit action potentials that provided additional electrophysiologic support for phrenic nerve function. Phrenic nerve-conduction studies can provide useful measures in assessing the recovery of lower-motor neuron diaphragm function in relation to impaired ventilation in individuals with C4- or C5-level SCI.     

Single-fiber electromyography

Single-fiber EMG is a technique introduced in 1963 by St?lberg and Ekstedt for recording single muscle fiber action potentials by means of a specially constructed needle with a 25-microm recording surface. The needle is positioned in the muscle to record from two or more time-locked potentials belonging to the same motor unit. Jitter is the variability in the arrival time of action potentials to the recording electrode between consecutive discharges. This variability reflects end-plate conduction and is measured along with fiber density, which is the average number of fibers belonging to the same motor unit that is in the recording area. An abnormal test is one in which more than 10%, or the mean, of 20 fiber pairs has increased jitter when compared with normal reference values. Increased fiber density is seen with reinnervation. Single-fiber EMG is more sensitive than conventional EMG and is the most sensitive, but not specific, test for myasthenia gravis. Lambert-Eaton myasthenic syndrome, and other neuromusculasr junction pathology. It has been useful in the evaluation of some neuropathies and myopathies and has provided valuable information on the motor unit spatial arrangement, territory, microphysiology, and pathophysiology.     

Electromyography interference pattern decomposition

Decomposition of an interference pattern enables examination of individual electromyography (EMG) motor units and their firing rates at more than minimal contraction forces. In this decomposition method, significant events with a constant occurrence (near motor unit action potentials) can be enhanced, and unwanted events (distant motor unit action potentials, artifacts) eliminated, by calculating the average accumulated change while sliding a fixed-width window along the digitized EMG interference pattern. Nonparametric statistical methods are then applied to these data to determine which information is significant at the .05 level. The exact duration of significant information is identified without the need for arbitrary thresholds and filters to eliminate unwanted information. Events are then classified into groups of similar events by comparing: (1) correlation coefficients, (2) point-to-point differences, (3) amplitudes, and (4) areas. The classification is further refined by the use of firing-rate information.     

Cisplatin neuropathy: a prospective clinical and electrophysiological study in Chinese patients with ovarian carcinoma

Nineteen Chinese patients with stage III or IV epithelial ovarian carcinoma by the criteria established by the International Federation of Gynaecology and Obstetrics, treated with cisplatin, 120 mg/m², every 4 weeks for a maximum of twelve courses if possible, were studied prospectively with clinical and electrophysiological evaluation before and 3, 6, 9 and 12 months during cisplatin administration. Neuropathy occurred in 12 of the 19 patients at the cumulative dose of 360 mg/m². Up to 89% of the patients assessed in their final examination developed neuropathy. Decreased vibration sensation at the ankles and depressed ankle reflexes were the early manifestations. Electrophysiological findings consisted of low amplitude sensory action potentials of median, ulnar and sural nerves, and slowing of their sensory nerve conduction velocities. Despite substantial involvement of sensory nerves, there was little change in motor nerve conduction velocities or motor unit action potentials. The progression of the neuropathy was unpredictable and could be delayed. As cisplatin is highly effective in the treatment of the tumour which is invariably fatal, if inadequately treated, patient selection with regard to neurotoxicity is unnecessary.     

Changes in Motor Unit Firing Rate in Synergist Muscles Cannot Explain the Maintenance of Force During Constant Force Painful Contractions

The firing rate of low threshold motor units is decreased in constant force contractions during experimental pain. However, as firing rate is a determinant of force, it is unclear how force is maintained. Increased synergist muscle activity may compensate. This was investigated by evaluation of motor unit firing rate in synergist ankle plantar flexor muscles (triceps surae). Single motor unit action potentials were recorded in medial gastrocnemius and soleus muscles with fine wire electrodes in 10 subjects. Gross muscle activity was estimated from surface electromyographic (EMG) recordings. Bolus injections of 5% hypertonic saline were injected into lateral gastrocnemius to induce pain (low intensity, 0.5 mL; high intensity, 1.5 mL). Subjects gently plantar-flexed the ankle to recruit 1 to 4 motor units and performed 3 20-second contractions to this target before, during, and after pain. Firing rate decreased ∼12% in synergist heads of triceps surae during pain and recovered after pain. Despite reduced firing rate, root-mean-square surface EMG amplitude did not change. The effect of nociceptor stimulation is not restricted to painful muscles but reduces motor unit firing in synergist muscles. Changes in synergist muscles cannot explain the maintenance of muscle force. Maintenance of surface EMG amplitude suggests recruitment of additional motor units.PerspectiveThis study showed that activity of synergist muscles can be affected by muscle pain. However, the changes in activity of synergist muscles may not compensate for changes in the painful muscle. This finding provides evidence of more widespread effects of pain on muscle control.     

Maladies musculaires en réanimation. Quand les évoquer ? Comment orienter la recherche diagnostique ?

Muscular and neuromuscular junction diseases include several hundreds entities. Some are acquired like inflammatory myopathy, drug-induced myopathy, and myasthenia gravis; others are inborn like muscular dystrophy, congenital myopathy, metabolic myopathy, and channelopathy. Even if scarce, they can be encountered in the intensive care unit (ICU), mainly in three situations: (1) severe worsening or complication of a known muscular disease; (2) suspicion of muscular disease in a patient presenting with acute motor weakness, severe bulbar dysfunction, rhabdomyolysis, acute respiratory distress or cardiac dysfunction (altered systolic function, impaired heart conduction or arrhythmia); (3) occurrence of muscle disease acquired while the patient is hospitalized in the ICU, that can be responsible for prolonged mechanical ventilation and increased mortality. Some muscular diseases should be suspected when patients present with encephalopathy, epilepsy, metabolic or ionic disturbance (acidosis, hypo- or hyperkaliemia) even in the absence of muscular symptoms. We will successively discuss which circumstances may suggest an underlying muscular or neuromuscular junction disease, how diagnosis can be assessed, and finally which are the main muscular or neuromuscular diseases according to their clinical presentation in the ICU.     

Motor unit synchronization of the vasti muscles in closed and open chain tasks

OBJECTIVES: To investigate motor unit synchronization between medial and lateral vasti and whether such synchronization differs in closed and open chain tasks. DESIGN: Electromyographic recordings of single motor unit action potentials were made from the vastus medialis obliquus (VMO) and multiunit recordings from vastus lateralis during isometric contractions at 30 degrees of knee flexion in closed and open chain conditions. SETTING: Laboratory. PARTICIPANTS: Five volunteers with no history of knee pain (age, 30+/-3.32 y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The degree of synchronization between motor unit firing was evaluated by identifying peaks in the electromyographic averages of the vastus lateralis, triggered from motor unit action potentials in the VMO, and the proportion of power in the power spectral density of the triggered average at the firing frequency of the reference motor unit. The proportion of cases in which there was significant power and peaks in the triggered averages was calculated. RESULTS: The proportion of trials with peaks in the triggered averages of the vastus lateralis electromyographic activity was greater than 61.5% in all tasks, and there was a significantly greater proportion of cases where power in the spectrum was greater than 7.5% ( P =.01) for the closed chain condition. CONCLUSIONS: There was a high proportion of synchronized motor units between the 2 muscles during isometric contractions, with evidence for greater common drive between the VMO and vastus lateralis in closed chain tasks. This has implications for rehabilitation because it suggests that closed chain tasks may generate better coordination between the vasti muscles.     

Corticomotor Facilitation in Vegetative State: Results of a Pilot Study

Objective

To investigate whether corticomotor facilitation induced by transcranial magnetic stimulation (TMS-CF) could evoke a simple purposeful motor behavior in patients with a diagnosis of vegetative state.

Design

Cross-sectional survey.

Setting

Post-coma and rehabilitation care unit.

Participants

Patients (N=6) with a diagnosis of vegetative state.

Interventions

A cascade of consecutive motor-evoked potentials (MEPs) was elicited under 3 different conditions: in the first condition, patients were at rest (Rest); in the second, they were asked to open and close the right hand (Execution); in the third, the examiner modeled a movement of abduction of the thumb in front of the patient who was encouraged in advance to imitate the action (Observation to Imitate).

Main Outcome Measures

Changes in MEP values from the abductor pollicis brevis muscle and improvement in scores on the Coma Recovery Scale-Revised.

Results

TMS-CF alone or combined with verbal instructions did not yield any change; only the combination with imitation caused changes in MEPs (shorter latency and increased amplitude) associated with behavioral improvement in 4 patients.

Conclusions

Encouraging observation to imitate may favor the transformation of some perceived actions into motor images and performances, probably depending on the activation of mirror motor neurons. In our opinion, combining visual input with TMS-CF might have reinforced the coupling between movement planning and execution, promoting the recovery of elementary motor activities in some patients. The proposed protocol may contribute to unmasking signs of preserved consciousness in patients with latent capacities for recovery.     

Monitoring des potentiels évoqués moteurs neurogènes lors de la chirurgie correctrice de la scoliose

Neurogenic motor evoked potentials in association with somatosensory evoked potentials were used to assess the functional integrity of spinal cord during scoliosis surgery. They were elicited by a spinal electrical stimulation and recorded from peripheral nerves in 23 patients. Reproductible responses were obtained in every patient under anesthesia. In three patients a modification of neurogenic motor evoked responses occurred: in one case, loss of potentials associated with a postoperative tetraplegia; in two cases, transient amplitude decrease without major neurological complications. Although the real origin of these potentials remains to be determined (possible involvement of antidromic sensory pathway conduction), this technique seems to be easy to perform, reproductible, fast and sensible for assessment of spinal cord during scoliosis surgery.     

Behaviour of motor unit action potential rate, estimated from surface EMG, as a measure of muscle activation level

Background  

Surface electromyography (EMG) parameters such as root-mean-square value (RMS) are commonly used to assess the muscle activation level that is imposed by the central nervous system (CNS). However, RMS is influenced not only by motor control aspects, but also by peripheral properties of the muscle and recording setup. To assess motor control separately, the number of motor unit action potentials (MUAPs) per second, or MUAP Rate (MR) is a potentially useful measure. MR is the sum of the firing rates of the contributing MUs and as such reflects the two parameters that the CNS uses for motor control: number of MUs and firing rate.     

Suction cup ground and reference electrodes in electrodiagnosis

An alternative to the taped-disc surface electrodes typically used during monopolar and concentric needle electromyographic studies has been investigated. The use of suction cup surface electrodes in place of the taped metal disc surface electrodes increases patient and operator safety and enhances patient comfort and operator efficiency. A two-channel EMG, with a single active needle and two reference electrodes, was done on patients routinely referred for electromyographic studies. The motor units were stored and compared. Similarly, baseline noise was stored and compared. This study shows that no distortion of motor unit potentials in typically measured parameters, nor alteration in baseline "noise" occurs when using the suction cup electrode in place of the taped metal discs. The safer, more comfortable suction cup surface electrodes do not distort the motor unit potentials that electromyographers are accustomed to interpreting.     

糖尿病腰骶神经根神经丛神经病临床与神经电生理学特点分析

目的 探讨糖尿病腰骶神经根神经丛神经病(DLRPN)的临床和神经电生理学特点.方法 收集并分析15例DLRPN患者的临床资料和神经电生理学及神经影像学检查结果.结果 13例患者主要表现为单侧或非对称性双侧下肢局灶性疼痛,随疾病进展出现肌无力、肌萎缩,下肢近端较远端易受累.15例患者下肢感觉、运动周围神经传导动作电位波幅明显降低或消失,伴神经传导速度轻度减慢;F波、H反射未引出波形或潜伏期延长.针极肌电图显示下肢多个肌节失神经-神经再支配性改变,伴腰段脊旁肌受累.结论 DLRPN临床表现具有阶段性、致残性,完善的神经电生理检查对明确诊断、病变范围、程度及鉴别诊断具有十分重要的作用.     

Critical illness polyneuromyopathy: the electrophysiological components of a complex entity

Objective To evaluate the spectrum and time profile of electrophysiological parameters in the detection of neuromuscular involvement in critically ill patients and establish their correlation with biopsy findings.Design Prospective clinical and neurophysiological study.Setting One general and one neurological intensive care unit in a university hospital.Patients Forty-six critically ill patients with failure of at least two organ systems were enrolled and completed the 1-month follow up.Interventions Detailed clinical and electrophysiological evaluation including direct muscle stimulation was performed in all cases on entry and at the end of the follow-up. Muscle biopsy was performed in 11, and sural nerve biopsy in 5, cases.Measurements and results Electrophysiological signs of new or progressing neuromuscular involvement at the end of the first month were detected in 26 patients (56%) and could be classified into three groups: "pure motor syndrome" (12 cases), combined motor syndrome and sensory polyneuropathy (13 cases) and isolated sensory polyneuropathy (1 case). Direct muscle stimulation showed decreased muscle membrane excitability in 11 of these abnormal cases. Muscle biopsy disclosed various myopathic abnormalities in all 11 cases examined with motor syndrome, in 7 of them in association with denervation/re-innervation changes.Conclusions Electrophysiological and histological examinations showed significant overlapping of several pathogenic components of neuromuscular involvement in critically ill patients, namely decreased muscle excitability, myopathy, axonal motor neuropathy and sensory neuropathy. The characterisation of the electrophysiological components of a complex polyneuromyopathy is preferred to the strict categorisation of abnormalities into critical illness myopathy and polyneuropathy.The study was supported by the Internal Grant Agency of the Ministry of Health of The Czech Republic-Grant No NF/5980-3An editorial regarding this article can be found in the same issue ()     

A clinicopathological study of the paraneoplastic neuromuscular syndromes associated with lung cancer

The highest incidence of remote neuromuscular disorders in cancer has previously been reported in lung carcinoma. The clinical incidence of neuromuscular disorder was estimated and correlated with muscle histology and the histological type of lung tumour in 100 patients with lung carcinoma who were studied prospectively. Thirty-five patients had small cell carcinoma and 65 patients non-small cell lung cancer. Clinically, 33 patients had a polymyopathy, of whom 18 had a cachectic myopathy and 15 had a proximal myopathy (two patients had Lambert-Eaton myasthenic syndrome, one presented with dermatomyositis and one had evidence of ectopic ACTH production). Cachexia was more common in non-small cell cancer; proximal myopathy was more common in small cell cancer. Ninety-nine patients had abnormal muscle histology; 74 had type II atrophy, 12 had type I and II atrophy, one had type I atrophy and 12 had necrosis. The majority of patients were affected sub-clinically and the clinical entities of cachectic and proximal myopathy did not correspond to previous pathological classifications. Atrophy was not related to the duration of tumour symptoms, ageing, clinical type of myopathy or histological type of lung tumour, and was statistically different from that seen in controls. Qualitatively, the presence of weight loss, muscle wasting and metastatic disease were not factors in the development of atrophy. Similarly, necrosis was not related to the type of lung tumour, the presence of metastases, ageing, weight loss, muscle wasting, duration of tumour symptoms or the clinical form of myopathy. This study demonstrates that lung carcinoma has a direct effect on the motor unit, including atrophy, a necrobiotic myopathy and Lambert-Eaton myasthenic syndrome. Clinical assessment does not accurately assess the 'remote' neuromuscular effects of cancer on the motor unit.     

A sodium channel knockin mutant (NaV1.4-R669H) mouse model of hypokalemic periodic paralysis

Hypokalemic periodic paralysis (HypoPP) is an ion channelopathy of skeletal muscle characterized by attacks of muscle weakness associated with low serum K+. HypoPP results from a transient failure of muscle fiber excitability. Mutations in the genes encoding a calcium channel (CaV1.1) and a sodium channel (NaV1.4) have been identified in HypoPP families. Mutations of NaV1.4 give rise to a heterogeneous group of muscle disorders, with gain-of-function defects causing myotonia or hyperkalemic periodic paralysis. To address the question of specificity for the allele encoding the NaV1.4-R669H variant as a cause of HypoPP and to produce a model system in which to characterize functional defects of the mutant channel and susceptibility to paralysis, we generated knockin mice carrying the ortholog of the gene encoding the NaV1.4-R669H variant (referred to herein as R669H mice). Homozygous R669H mice had a robust HypoPP phenotype, with transient loss of muscle excitability and weakness in low-K+ challenge, insensitivity to high-K+ challenge, dominant inheritance, and absence of myotonia. Recovery was sensitive to the Na+/K+-ATPase pump inhibitor ouabain. Affected fibers had an anomalous inward current at hyperpolarized potentials, consistent with the proposal that a leaky gating pore in R669H channels triggers attacks, whereas a reduction in the amplitude of action potentials implies additional loss-of-function changes for the mutant NaV1.4 channels.