Nicola Latronico

Critical illness myopathy and neuropathy

BACKGROUND Critically ill patients may develop muscle weakness or paralysis during the course of sepsis and multiple-organ failure. We studied peripheral nerve and muscle disorders (NMD) in comatose patients. METHOD Comatose patients who developed paralysis associated with absent deep-tendon reflexes had electroneuromyography (ENMG) and muscle-nerve biopsy specimens taken. Onset and duration of sepsis, multiple-organ dysfunction and failure, biochemical alterations, and drugs potentially interfering with nerve-muscle function were recorded. FINDINGS 24 patients became quadriparetic or quadriplegic; muscle changes were found in 23. Axonal neuropathy was found in eight of 22 patients examined. All patients had prolonged sepsis and multiple-organ dysfunction, but only 14 had multiple-organ failure. Drugs such as steroids, neuromuscular-blocking agents, and aminoglycosides were not responsible for paresis, and the part played by hyperglycaemia and hypoalbuminaemia is uncertain. Attending physicians predicted a fatal outcome in all cases, although six of seven survivors fully recovered within 115-210 days from the onset of paralysis. INTERPRETATION Comatose patients may become completely paralysed because of NMD. The diagnosis is important to avoid unnecessary investigations and unreasonably pessimistic prognosis. ENMG is essential for the diagnosis and for planning further clinical management. Biopsy needs to be done only when it is necessary to properly classify NMD.

Critical illness polyneuropathy and myopathy: a major cause of muscle weakness and paralysis

Critical illness polyneuropathy (CIP) and myopathy (CIM) are complications of critical illness that present with muscle weakness and failure to wean from the ventilator. In addition to prolonging mechanical ventilation and hospitalisation, CIP and CIM increase hospital mortality in patients who are critically ill and cause chronic disability in survivors of critical illness. Structural changes associated with CIP and CIM include axonal nerve degeneration, muscle myosin loss, and muscle necrosis. Functional changes can cause electrical inexcitability of nerves and muscles with reversible muscle weakness. Microvascular changes and cytopathic hypoxia might disrupt energy supply and use. An acquired sodium channelopathy causing reduced muscle membrane and nerve excitability is a possible unifying mechanism underlying CIP and CIM. The diagnosis of CIP, CIM, or combined CIP and CIM relies on clinical, electrophysiological, and muscle biopsy investigations. Control of hyperglycaemia might reduce the severity of these complications of critical illness, and early rehabilitation in the intensive care unit might improve the functional recovery and independence of patients.

Critical illness myopathy and neuropathy.

Purpose of reviewTo present the major pathophysiological and diagnostic features of critical illness myopathy (CIM) and polyneuropathy (CIP), and to discuss problems concerning the risk factors for CIM and CIP. Recent findingsThe pathophysiology of critical illness myopathy and critical illness polyneuropathy is complex, involving metabolic, inflammatory, and bioenergetic alterations. This review cites new evidence supporting several pathogenetic mechanisms. These include microvascular changes in peripheral nerves (with increased endothelial expression of E-selectin), the possible role for an altered lipid serum profile in promoting organ dysfunction (including nerve dysfunction), the damage or inhibition of complex I of the respiratory chain as a cause of muscle ATP depletion and bioenergetic failure, and the activation of specific intracellular proteolytic systems causing myofilament loss and apoptosis in CIM. The diagnostic role of direct muscle stimulation and the rapid quantification of myosin/actin ratio based on electrophoresis are also presented. SummaryBasic and clinical research is unraveling the pathophysiological mechanisms of critical illness myopathy and polyneuropathy, and methods for rapid diagnosis are actively investigated. Future studies should better define the population at risk of developing CIM and CIP. In fact, although sepsis, multi-organ failure and steroids are often cited as risk factors, uncertainty remains due to the poor methodological quality of studies, or because of inferences that are exclusively based on animal studies. New simplified diagnostic techniques and machines for electrophysiological investigations of peripheral nerves and muscles in the intensive-care unit (ICU) patient would also be welcome.

Neuromuscular sequelae of critical illness.

Purpose of reviewTo investigate the impact of critical illness polyneuropathy and critical illness myopathy on short-term and long-term patient outcome. Recent findingsIn the acute-care setting, critical illness polyneuropathy and critical illness myopathy are important causes of acute paralysis in critically ill comatose patients, and may cause inappropriately pessimistic prognoses. Duration of weaning from artificial ventilation is 2 to 7 times greater in patients with critical illness polyneuropathy than in patients without critical illness polyneuropathy. After intensive care unit and hospital discharge, many patients diagnosed with critical illness polyneuropathy or critical illness myopathy are reported to complain of profound muscle weakness. Chronic disability was a common finding among them. Complete functional recovery with patients regaining the ability to breathe spontaneously and to walk independently was reported in 180 of 263 patients (68.4%); severe disability with tetraparesis, tetraplegia, or paraplegia was reported in 74 patients (28.1%). Persisting milder disabilities were common even in patients with complete functional recovery, and included reduced or absent deep tendon reflexes, stocking and glove sensory loss, muscle atrophy, painful hyperesthesia, and foot drop. An association of critical illness polyneuropathy and critical illness myopathy with increased intensive care unit and hospital mortality has been demonstrated only in selected intensive care unit populations; data are insufficient to demonstrate any association with long-term mortality. SummaryIntensive care unit-acquired critical illness polyneuropathy and critical illness myopathy influence the evaluation of acutely ill comatose patients and may instigate unreasonably pessimistic prognosis. Critical illness polyneuropathy and critical illness myopathy are an important cause of difficult weaning of patients from the ventilator and of persisting muscle weakness and disability after intensive care unit discharge.

Cerebral Blood Flow Threshold of Ischemic Penumbra and Infarct Core in Acute Ischemic Stroke A Systematic Review

Background and Purpose— Cerebral blood flow (CBF) reduction below critical thresholds discriminates between irreversible infarct core, penumbra, and benign oligemia (penumbra that recovers spontaneously). Thresholds are based on animal studies, and their diagnostic accuracy in humans has never been established. The purpose of this study was to assess the evidence available on CBF thresholds for infarct core and penumbra in adult stroke patients. Methods— Electronic database searching using Medline, Embase and the Cochrane Library, crosschecking of references, and contact with experts and authors of primary studies was used. Studies on adult stroke patients were included if they compared CBF measurements with a diagnostic gold standard (follow-up brain CT/MRI), and reported CBF thresholds. Two reviewers independently extracted the data and assessed study quality. Results— A meta-analysis could not be carried out because of insufficient data. The optimal reported CBF thresholds varied widely, from 14.1 to 35.0 and from 4.8 to 8.4 mL/100 g per minute for penumbra and infarct core, respectively. Conclusions— The use of CBF thresholds in commercial software for imaging methods cannot be recommended without further evaluation.

Emergent decompressive craniectomy in patients with fixed dilated pupils due to cerebral venous and dural sinus thrombosis: report of three cases.

OBJECTIVE AND IMPORTANCE Cerebral venous and dural sinus thrombosis is a rare cause of stroke. Although morbidity and mortality have greatly decreased in recent years as a result of early diagnosis and timely medical treatment, when coma occurs the prognosis remains poor. We evaluated whether emergent decompressive craniectomy has a role in the treatment of patients with brain herniation from dural sinus thrombosis and hemorrhagic infarct. CLINICAL PRESENTATION Three patients developed large hemorrhagic infarct with coma and bilaterally fixed and dilated pupils resulting from aseptic dural sinus thrombosis. INTERVENTION Two patients underwent emergent surgical decompression as soon as brain herniation developed, and these patients had complete functional recovery. One underwent delayed surgical decompression and remained severely disabled. CONCLUSION Our results provide preliminary evidence that emergent decompressive craniectomy is effective in patients with brain herniation from dural sinus thrombosis, provided that the clinical onset is recent. We therefore recommend consideration of this aggressive surgical technique for such patients, who may survive with good outcomes.

Long-term outcome in patients with critical illness myopathy or neuropathy: the Italian multicentre CRIMYNE study

Background: Critical illness myopathy (CIM) and polyneuropathy (CIP), alone or in combination (CIP/CIM), are frequent complications in patients in the intensive care unit (ICU). There is no evidence that differentiating between CIP and CIM has any impact on patient prognosis. Methods: 1-year prospective cohort study of patients developing CIP, CIM or combined CIP and CIM during ICU stay. Results: 28 out of 92 (30.4%) patients developed electrophysiological signs of CIP and/or CIM during their ICU stay, which persisted in 18 patients at ICU discharge. At hospital discharge, diagnoses in the 15 survivors were CIM in six cases, CIP in four, combined CIP and CIM in three and undetermined in two uncooperative patients. During the 1-year follow-up of six patients with CIM, one patient died and five recovered completely within 3 (three patients) to 6 (two patients) months. Of three patients with CIP/CIM, one died, one recovered and one with residual CIP remained tetraplegic. Of four patients with CIP, one recovered, two had persisting muscle weakness and one remained tetraparetic. Conclusion: CIM has a better prognosis than CIP. Differential diagnosis is important to predict long-term outcome in ICU patients.

Simplified electrophysiological evaluation of peripheral nerves in critically ill patients: the Italian multi-centre CRIMYNE study

IntroductionCritical illness myopathy and/or neuropathy (CRIMYNE) is frequent in intensive care unit (ICU) patients. Although complete electrophysiological tests of peripheral nerves and muscles are essential to diagnose it, they are time-consuming, precluding extensive use in daily ICU practice. We evaluated whether a simplified electrophysiological investigation of only two nerves could be used as an alternative to complete electrophysiological tests.MethodsIn this prospective, multi-centre study, 92 ICU patients were subjected to unilateral daily measurements of the action potential amplitude of the sural and peroneal nerves (compound muscle action potential [CMAP]). After the first ten days, complete electrophysiological investigations were carried out weekly until ICU discharge or death. At hospital discharge, complete neurological and electrophysiological investigations were performed.ResultsElectrophysiological signs of CRIMYNE occurred in 28 patients (30.4%, 95% confidence interval [CI] 21.9% to 40.4%). A unilateral peroneal CMAP reduction of more than two standard deviations of normal value showed the best combination of sensitivity (100%) and specificity (67%) in diagnosing CRIMYNE. All patients developed the electrophysiological signs of CRIMYNE within 13 days of ICU admission. Median time from ICU admission to CRIMYNE was six days (95% CI five to nine days). In 10 patients, the amplitude of the nerve action potential dropped progressively over a median of 3.0 days, and in 18 patients it dropped abruptly within 24 hours. Multi-organ failure occurred in 21 patients (22.8%, 95% CI 15.4% to 32.4%) and was strongly associated with CRIMYNE (odds ratio 4.58, 95% CI 1.64 to 12.81). Six patients with CRIMYNE died: three in the ICU and three after ICU discharge. Hospital mortality was similar in patients with and without CRIMYNE (21.4% and 17.2%; p = 0.771). At ICU discharge, electrophysiological signs of CRIMYNE persisted in 18 (64.3%) of 28 patients. At hospital discharge, diagnoses in the 15 survivors were critical illness myopathy (CIM) in six cases, critical illness polyneuropathy (CIP) in four, combined CIP and CIM in three, and undetermined in two.ConclusionA peroneal CMAP reduction below two standard deviations of normal value accurately identifies patients with CRIMYNE. These should have full neurological and neurophysiological evaluations before discharge from the acute hospital.

Cerebral blood flow threshold of ischemic penumbra and infarct core in acute ischemic stroke: A systematic review

Background and Purpose— Cerebral blood flow (CBF) reduction below critical thresholds discriminates between irreversible infarct core, penumbra, and benign oligemia (penumbra that recovers spontaneously). Thresholds are based on animal studies, and their diagnostic accuracy in humans has never been established. The purpose of this study was to assess the evidence available on CBF thresholds for infarct core and penumbra in adult stroke patients. Methods— Electronic database searching using Medline, Embase and the Cochrane Library, crosschecking of references, and contact with experts and authors of primary studies was used. Studies on adult stroke patients were included if they compared CBF measurements with a diagnostic gold standard (follow-up brain CT/MRI), and reported CBF thresholds. Two reviewers independently extracted the data and assessed study quality. Results— A meta-analysis could not be carried out because of insufficient data. The optimal reported CBF thresholds varied widely, from 14.1 to 35.0 and from 4.8 to 8.4 mL/100 g per minute for penumbra and infarct core, respectively. Conclusions— The use of CBF thresholds in commercial software for imaging methods cannot be recommended without further evaluation.

An Official American Thoracic Society Clinical Practice Guideline: The Diagnosis of Intensive Care Unit–acquired Weakness in Adults

RATIONALE Profound muscle weakness during and after critical illness is termed intensive care unit-acquired weakness (ICUAW). OBJECTIVES To develop diagnostic recommendations for ICUAW. METHODS A multidisciplinary expert committee generated diagnostic questions. A systematic review was performed, and recommendations were developed using the Grading, Recommendations, Assessment, Development, and Evaluation (GRADE) approach. MEASUREMENT AND MAIN RESULTS Severe sepsis, difficult ventilator liberation, and prolonged mechanical ventilation are associated with ICUAW. Physical rehabilitation improves outcomes in heterogeneous populations of ICU patients. Because it may not be feasible to provide universal physical rehabilitation, an alternative approach is to identify patients most likely to benefit. Patients with ICUAW may be such a group. Our review identified only one case series of patients with ICUAW who received physical therapy. When compared with a case series of patients with ICUAW who did not receive structured physical therapy, evidence suggested those who receive physical rehabilitation were more frequently discharged home rather than to a rehabilitative facility, although confidence intervals included no difference. Other interventions show promise, but fewer data proving patient benefit existed, thus precluding specific comment. Additionally, prior comorbidity was insufficiently defined to determine its influence on outcome, treatment response, or patient preferences for diagnostic efforts. We recommend controlled clinical trials in patients with ICUAW that compare physical rehabilitation with usual care and further research in understanding risk and patient preferences. CONCLUSIONS Research that identifies treatments that benefit patients with ICUAW is necessary to determine whether the benefits of diagnostic testing for ICUAW outweigh its burdens.