Bruno Guarneri

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.

Acute neuromuscular respiratory failure after ICU discharge

Objective: To describe a syndrome of acute neuromuscular respiratory failure (NM-ARF) caused by ICU-acquired acute myopathy and neuropathy.¶Design: Case series.¶Setting: General Regional University Hospital in Brescia, Italy.¶Patients: Five adult patients with NM-ARF after prolonged ICU stay and successful weaning from the ventilator and ICU discharge.¶Interventions: None.¶Measurements: Clinical signs of NM-ARF, electroneurography and electromyography (ENMG) of peripheral nerves and muscles, and functional assessment of respiratory muscles.¶Results: NM-ARF was diagnosed at the time of (one case), or 1–3 days after, ICU discharge. Limb weakness alarmed the physicians, while the signs of the NM-ARF were initially undetected. In the first observed case the acute respiratory failure was near fatal, and necessitated ICU readmission, while in the other cases 2 weeks of aggressive chest physiotherapy permitted resolution of the respiratory failure. History, clinical course and ENMG indicated the diagnosis of critical illness myopathy and neuropathy (CRIMYNE). Three patients recovered fully, while two had persisting evidence of axonal polyneuropathy several months after the onset.¶Conclusions: Critically ill patients with prolonged ICU stay, sepsis and MOF are at great risk of developing CRIMYNE, which in turn may be responsible for NM-ARF. This latter complication may arise after resolution of the respiratory and cardiac dysfunctions and successful weaning from the ventilator. As NM-ARF may cause unplanned ICU readmission or even unexpected death, strict clinical surveillance and monitoring of respiratory muscle function is recommended after discharge to the general ward of patients with proven NM-ARF. Early intensive chest physiotherapy can resolve the condition.

Use of electrophysiologic testing.

Objective:To define the electrophysiologic tests to diagnose critical illness myopathy and critical illness polyneuropathy in intensive care unit patients. Design:Literature review. Measurements and Main Results:Critical illness myopathy and neuropathy are common complications in the critically ill patient. Myopathy and neuropathy are equally common, and often coexist. Electrophysiological alterations of peripheral nerves and muscle have an early onset in the first days of intensive care unit stay or shortly after sepsis, and precede the structural alterations. Conventional electrophysiologic evaluation can be performed easily on most intensive care unit patients, including patients with altered consciousness; in conjunction with direct muscle stimulation, it can differentiate myopathy from neuropathy, which might be important to define the long-term prognosis. However, electrophysiologic tests are not universally available; their interpretation requires special expertise; and their application is time consuming. A recently proposed simplified test of peroneal nerve stimulation could be used as a screening method to select patients who merit in-depth neurologic evaluation. Conclusions:Early identification of neuromuscular alterations by means of electrophysiologic tests may be of value for targeted treatments and to anticipate the risk of short-term disability. Complete neurologic and electrophysiological evaluation is important to define the risk of long-term disability after intensive care unit discharge.

Small Nerve Fiber Pathology in Critical Illness

Background Degeneration of intraepidermal nerve fibers (IENF) is a hallmark of small fiber neuropathy of different etiology, whose clinical picture is dominated by neuropathic pain. It is unknown if critical illness can affect IENF. Methods We enrolled 14 adult neurocritical care patients with prolonged intensive care unit (ICU) stay and artificial ventilation (≥ 3 days), and no previous history or risk factors for neuromuscular disease. All patients underwent neurological examination including evaluation of consciousness, sensory functions, muscle strength, nerve conduction study and needle electromyography, autonomic dysfunction using the finger wrinkling test, and skin biopsy for quantification of IENF and sweat gland innervation density during ICU stay and at follow-up visit. Development of infection, sepsis and multiple organ failure was recorded throughout the ICU stay. Results Of the 14 patients recruited, 13 (93%) had infections, sepsis or multiple organ failure. All had severe and non-length dependent loss of IENF. Sweat gland innervation was reduced in all except one patient. Of the 7 patients available for follow-up visit, three complained of diffuse sensory loss and burning pain, and another three showed clinical dysautonomia. Conclusions Small fiber pathology can develop in the acute phase of critical illness and may explain chronic sensory impairment and pain in neurocritical care survivors. Its impact on long term disability warrants further studies involving also non-neurologic critical care patients.

Validation of the peroneal nerve test to diagnose critical illness polyneuropathy and myopathy in the intensive care unit: the multicentre Italian CRIMYNE-2 diagnostic accuracy study

Objectives: To evaluate the accuracy of the peroneal nerve test (PENT) in the diagnosis of critical illness polyneuropathy (CIP) and myopathy (CIM) in the intensive care unit (ICU). We hypothesised that abnormal reduction of peroneal compound muscle action potential (CMAP) amplitude predicts CIP/CIM diagnosed using a complete nerve conduction study and electromyography (NCS-EMG) as a reference diagnostic standard. Design: prospective observational study. Setting: Nine Italian ICUs. Patients: One-hundred and twenty-one adult (≥18 years) neurologic (106) and non-neurologic (15) critically ill patients with an ICU stay of at least 3 days. Interventions: None. Measurements and main results: Patients underwent PENT and NCS-EMG testing on the same day conducted by two independent clinicians who were blind to the results of the other test. Cases were considered as true negative if both NCS-EMG and PENT measurements were normal. Cases were considered as true positive if the PENT result was abnormal and NCS-EMG showed symmetric abnormal findings, independently from the specific diagnosis by NCS-EMG (CIP, CIM, or combined CIP and CIM). All data were centrally reviewed and diagnoses were evaluated for consistency with predefined electrophysiological diagnostic criteria for CIP/CIM. During the study period, 342 patients were evaluated, 124 (36.3%) were enrolled and 121 individuals with no protocol violation were studied. Sensitivity and specificity of PENT were 100% (95% CI 96.1-100.0) and 85.2% (95% CI 66.3-95.8). Of 23 patients with normal results, all presented normal values on both tests with no false negative results. Of 97 patients with abnormal results, 93 had abnormal values on both tests (true positive), whereas four with abnormal findings with PENT had only single peroneal nerve neuropathy at complete NCS-EMG (false positive). Conclusions: PENT has 100% sensitivity and high specificity, and can be used as a screening test to diagnose CIP/CIM in the ICU.OBJECTIVES To evaluate the accuracy of the peroneal nerve test (PENT) in the diagnosis of critical illness polyneuropathy (CIP) and myopathy (CIM) in the intensive care unit (ICU). We hypothesised that abnormal reduction of peroneal compound muscle action potential (CMAP) amplitude predicts CIP/CIM diagnosed using a complete nerve conduction study and electromyography (NCS-EMG) as a reference diagnostic standard. DESIGN prospective observational study. SETTING Nine Italian ICUs. PATIENTS One-hundred and twenty-one adult (≥18 years) neurologic (106) and non-neurologic (15) critically ill patients with an ICU stay of at least 3 days. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS PATIENTS underwent PENT and NCS-EMG testing on the same day conducted by two independent clinicians who were blind to the results of the other test. Cases were considered as true negative if both NCS-EMG and PENT measurements were normal. Cases were considered as true positive if the PENT result was abnormal and NCS-EMG showed symmetric abnormal findings, independently from the specific diagnosis by NCS-EMG (CIP, CIM, or combined CIP and CIM). All data were centrally reviewed and diagnoses were evaluated for consistency with predefined electrophysiological diagnostic criteria for CIP/CIM. During the study period, 342 patients were evaluated, 124 (36.3%) were enrolled and 121 individuals with no protocol violation were studied. Sensitivity and specificity of PENT were 100% (95% CI 96.1-100.0) and 85.2% (95% CI 66.3-95.8). Of 23 patients with normal results, all presented normal values on both tests with no false negative results. Of 97 patients with abnormal results, 93 had abnormal values on both tests (true positive), whereas four with abnormal findings with PENT had only single peroneal nerve neuropathy at complete NCS-EMG (false positive). CONCLUSIONS PENT has 100% sensitivity and high specificity, and can be used as a screening test to diagnose CIP/CIM in the ICU.

Long-term neurological morbidity following endoscopic transnasal resection of juvenile angiofibroma: Morbidity Following JA Resection

Although transnasal endoscopic resection (TER) of juvenile angiofibroma (JA) is unquestionably less invasive than traditional external approaches, several endonasal and neurovascular structures are sacrificed during the procedure. The aim of this study was to evaluate long‐term neurological morbidity and related quality of life following TER of JA.