Compound Muscle Action Potential and Myosin-Loss Pathology in Patients With Critical Illness Myopathy: Correlation and Prognostication.

BACKGROUND AND OBJECTIVES: Prolonged compound muscle action potential (CMAP) duration and preferential loss of myosin are considered the diagnostic hallmarks of critical illness myopathy (CIM); however, their correlation and prognostic values have not been studied. We aimed to investigate the correlation between CMAP duration and myosin loss and their effect on mortality by comparing between patients with CIM with and without myosin loss. METHODS: We searched the Mayo Clinic Electromyography Laboratory databases (1986-2021) for patients diagnosed with CIM on the basis of prolonged distal CMAP durations (>15 msec in fibular motor nerve studies recording over the tibialis anterior or >8 msec in other motor nerves) and needle EMG findings compatible with myopathy. Electrodiagnostic studies were generally performed within 24 hours after weakness became noticeable. We included only patients who underwent muscle biopsy. Clinical, electrophysiologic, and myopathologic data were reviewed. We conducted myosin/actin ratio analysis when muscle tissue was available. We used the Fisher exact test for categorical data comparisons and the Mann-Whitney 2-tailed test for continuous data. We applied the Kaplan-Meier technique to analyze survival rates. RESULTS: Twenty patients (13 female patients) were identified [median age at diagnosis of 62.5 years (range: 19-80 years)]. The median onset of weakness was 24 days (range: 1-128) from the first day of intensive care unit admission. Muscle biopsy showed myosin loss in 14 patients, 9 of whom had >50% of myofibers affected (high grade). Type 2 fiber atrophy was observed in 19 patients, 13 of whom also had myosin loss. Patients with myosin loss had higher frequency of steroid exposure (14 vs 3; p = 0.004); higher median number of necrotic fibers per low-power field (2.5 vs 1, p = 0.04); and longer median CMAP duration (msec) of fibular (13.4 vs 8.75, p = 0.02), tibial (10 vs 7.8, p = 0.01), and ulnar (11.1 vs 7.95, p = 0.002) nerves compared with those without. Only patients with high-grade myosin loss had reduced myosin/actin ratios (<1.7). Ten patients died during median follow-up of 3 months. The mortality rate was similar between patients with and without myosin loss. Patients with high-grade myosin loss had a lower overall survival rate than those with low-grade or no myosin loss, but this was not statistically significant (p = 0.05). DISCUSSION: Myosin loss occurred in 70% of the patients with CIM with prolonged CMAP duration. Longer CMAP duration predicts myosin-loss pathology. The extent of myosin loss marginally correlates with the mortality rate. Our findings highlight the potential prognostic values of CMAP duration and myosin loss severity in predicting disease outcome.

Septic shock definitions and associated outcomes in blood culture positive critically ill patients.

Background: The proposed definition of septic shock in the Sepsis-3 consensus statement has been previously validated in critically ill patients. However, the subset of critically ill patients with sepsis and positive blood cultures needs further evaluation. To compare the combined (old and new septic shock) versus old definition of septic shock in sepsis patients that have positive blood cultures and are critically ill. Methods: A retrospective cohort study of adult patients (age ≥18 years), who had evidence of positive blood cultures, requiring intensive care unit (ICU) admission at a large tertiary care academic center from January 2009 through October 2015. Eligible subjects who opted out of research participation, those requiring intensive care admission after elective surgery, and those who were deemed to have a low probability of infection were excluded. Basic demographics data, clinical and laboratory parameters, and outcomes of interest were pulled from the validated institutional database/repository and contrasted between the patients who qualified the new and old definitions criteria (combined) of septic shock versus the group meeting the old septic shock criteria only. Results: We included a total of 477 patients in the final analysis who qualified for old and new septic shock definitions. For the entire cohort, median age was 65.6 (IQR, 55-75) years, with male predominance (N=258, 54%). When compared to patients in the group who only met the old definition (N=206), the patients who met the combined (new or both new and old, N=271) definition had a higher APACHE III scores, 92 (IQR, 76-112) vs. 76 (IQR, 61-95), P<0.001; a higher SOFA day-1 score of 10 (IQR, 8-13) vs. 7 (IQR, 4-10), P<0.001, but did not differ significantly in age 65.5 years (IQR, 55-74) vs. 66 years (IQR, 55-76) years, P=0.47. The patients who met the combined (new or both new and old) definition had higher chances of having conservative resuscitation preferences (DNI/DNR); 77 (28.4) vs. 22 (10.7), P<0.001. The same group also had worse outcomes in terms of hospital mortality (34.3% vs. 18%, P<0.001) and standardized mortality ratio (0.76 vs. 0.52, P<0.04). Conclusions: In patients with sepsis with positive blood cultures, the group of patients meeting the combined definition (new or both new and old) have higher severity of illness, higher mortality, and a worse standardized mortality ratio as compared to patients meeting the old definition of septic shock.

Outcomes of adult patients supported by extracorporeal membrane oxygenation (ECMO) following cardiopulmonary arrest. The Mayo Clinic experience.

INTRODUCTION: To describe our experience in use of extracorporeal life support (ECLS) as a rescue strategy in patients following cardiopulmonary resuscitation. METHODS: A retrospective analysis was performed for patients (n = 101) who received ECLS after cardiorespiratory arrest between May 2001 and December 2014. The primary outcome was survival to hospital discharge. RESULTS: In this cohort median (IQR) age was 56 (37-67) years, 53 (53%) were male, and 90 (89%) were Caucasian. Ventricular tachycardia or ventricular fibrillations were the initial cardiac rhythm in 49 (48.5%) and asystole/pulseless electrical activity in 37 (36.8%). Median (IQR) time to initiation of extracorporeal support from arrest time was 72 (43-170) min. The median (IQR) duration of support was 100 (47-157) hours. Renal failure (66%) and bleeding (66%) were the two most commonly observed complications during ECLS support. The survival to hospital discharge was seen in 47 (47%) patients, and good neurologic outcome (mRs 0-3) was seen in 29%. Acidosis, lactate and continuous renal replacement therapy were independent predictors of mortality. The median (IQR) intensive care unit stay was 14 (4-28) days and hospital stay was 17 (4-35) days. CONCLUSION: Our institutional experience with ECLS as a rescue measure following cardiac arrest is associated with improvement in mortality, and favorable neurologic status at hospital discharge.

Antiseizure Medication use in Gastric Bypass Patients and Other Post-Surgical Malabsorptive States.

Healthcare professionals are encountering an increasing number of patients who have undergone bariatric surgeries. Antiseizure medications (ASM) have a narrow therapeutic window, and patients with malabsorptive states receiving ASM present a complex situation as the pharmacokinetics of these drugs have only been studied in patients with a normal functioning gastrointestinal tract. Patients with malabsorptive states may have altered pharmacokinetics, and there is limited literature to guide drug selection and dosage adjustment in patients with malabsorptive states. This review highlights pharmacokinetic parameters of common ASM, and considerations when managing patients on them. The effect of pH, lipophilicity, absorption, and metabolism should be taken into account when selecting and managing ASMs in this patient population. Based on these parameters, levetiracetam, and topiramate have fewer issues referable to absorption related to bariatric surgery while oral formulations of phenytoin, carbamazepine, oxcarbamazepine and valproic acid have reduced absorption due to effects of bariatric surgery based on the pharmacokinetic properties of these medications. Extended formulations should be avoided and ASM serum concentrations should be checked before and after surgery. The care of patients with epilepsy who are scheduled to undergo bariatric surgery should be guided by a multidisciplinary team including a pharmacist and a neurologist who should be involved in the adjustment of the ASMs throughout the pre-surgical and post-surgical periods.

Crying with depressed affect induced by electrical stimulation of the anterior insula: A stereo EEG case study.

Stereo-EEG (sEEG) is an invasive recording technique used to localize the seizure-onset zone for epilepsy surgery in people with drug-resistant focal seizures. Pathological crying reflects disordered emotional expression and the anterior insula is known to play a role in empathy and socio-emotional processing. We describe a patient where electrical stimulation mapping (ESM) of the anterior insula during sEEG generated pathological crying and profound sadness that was time-locked to the electrical stimulus. We evaluated a 35-year-old left-handed female for repeat epilepsy surgery. The patient had drug resistant focal impaired awareness seizures despite a previous left temporal neocortical resection informed by an invasive study using subdural grid and strip electrodes seven years earlier. She was studied invasively with 10 sEEG electrodes sampling temporal, occipital, and insular targets. In the process of functional mapping, stimulation of the anterior insular cortex provoked tearful crying with sad affect, reproducible upon repeat stimulation. Our case is unique in demonstrating transitory pathological crying with profound sadness provoked by ESM of the left anterior insula. Furthermore we demonstrate repeated time-synched crying from electrical stimulation, which supports the hypothesis that the anterior insula in the brain plays an important role in the biology of emotion, as implicated by previous studies.

SMART syndrome: retrospective review of a rare delayed complication of radiation.

BACKGROUND: SMART (stroke-like migraine attacks after radiation therapy) is a rare, delayed complication of brain radiation. In this study, we wanted to review the spectrum of symptoms, neuroradiological findings, autoimmune status, and outcomes in SMART syndrome patients. METHODS: We conducted a retrospective cohort study of all consecutive adult patients (≥18 years) diagnosed with SMART syndrome at Mayo Clinic, Rochester between January 1995 and December 2018. RESULTS: We identified 25 unique patients with SMART syndrome and a total of 31 episodes and 15 (60%) patients were male. The median age at onset was 46 (interquartile range [IQR] 43-55) years and the median latency of onset after the initial radiation was 21.6 (IQR 14.4-28.2) years. Magnetic resonance imaging (MRI) showed gyral edema and enhancement in all cases with the temporal (25, 80.6%) and parietal (23, 74.2%) lobes being the most commonly affected. The median follow-up of the patients in our cohort was 10 (IQR 6-32) weeks. On univariate analysis, factors associated with an increased risk of recurrent SMART episodes were female gender (odds ratio [OR] 8.1, 95% confidence interval [95% CI] 1.1-52.6, p = 0.019) and absence of electrographic seizure discharges during initial symptoms (OR 7.4, 95% CI 1.1-45.9, p = 0.032). We could not identify an autoimmune etiology. Longer duration of symptoms (>10 weeks) correlated with an older age (p = 0.049), temporal lobe involvement (p < 0.001), and diffusion restriction (p = 0.043). CONCLUSIONS: SMART is a syndrome with characteristic imaging findings and clinical features. Incomplete recovery by 10 weeks occurred in one-third of individuals and was associated with older age, temporal lobe involvement, and restricted diffusion on MRI.

Features of Adult Hyperammonemia Not Due to Liver Failure in the ICU.

OBJECTIVES: To evaluate the epidemiology of hyperammonemia unrelated to liver failure in the critical care setting. DESIGN: Retrospective case series. SETTING: Critically ill patients admitted to ICUs at Mayo Clinic, Rochester, MN (medical ICU, two mixed medical-surgical ICUs, coronary care unit, or the cardiosurgical ICU) between July 1, 2004, and October 31, 2015. PATIENTS: Adult critically ill patients with hyperammonemia not related to acute or chronic liver failure. We excluded patients with diagnosis of moderate or severe liver disease, hyperbilirubinemia, and patients who denied the use of their medical records. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 3,908 ICU patients with hyperammonemia, 167 (4.5%) had no evidence of acute or chronic liver failure. One-hundred one patients (60.5%) were male with median age of 65.7 years (interquartile range, 50-74.5 yr) and median serum ammonia level of 68 µg/dL (interquartile range, 58-87 µg/dL). Acute encephalopathy was present in 119 patients (71%). Predisposing conditions included malnutrition 27 (16%), gastric bypass six (3.6%), total parenteral nutrition four (2.4%); exposure to valproic acid 17 (10%); status epilepticus 11 (6.6%), high tumour burden 19 (11.3%), and renal failure 82 (49.1%). Urea cycle defects were diagnosed in seven patients (4.1%). Hospital mortality was high (30%), and median ammonia level was higher among the nonsurvivors (74 vs 67 µg/dL; p = 0.05). Deaths were more likely in hyperammonemic patients who were older (p = 0.016), had greater illness severity (higher Acute Physiology and Chronic Health Evaluation III score, p < 0.01), malignancy (p < 0.01), and solid organ transplantation (p = 0.04), whereas seizure disorder was more common in survivors (p = 0.02). After adjustment, serum ammonia level was not associated with increased mortality. CONCLUSIONS: Hyperammonemia occurs in a substantial minority of critically ill patients without liver failure. These patients have a poor prognosis, although ammonia level per se is not independently associated with mortality. Serum ammonia should be measured when risk factors are present, such as nutritional deficiencies and protein refeeding, treatment with valproic acid, high tumour burden, and known or suspected urea cycle abnormalities.

Potentially Modifiable Risk Factors for Long-Term Cognitive Impairment After Critical Illness: A Systematic Review.

Long-term cognitive impairment is common in survivors of critical illness. Little is known about the etiology of this serious complication. We sought to summarize current scientific knowledge about potentially modifiable risk factors during intensive care unit (ICU) treatment that may play a substantial role in the development of long-term cognitive impairment. All searches were run on October 1, 2017. The search strategy included Ovid MEDLINE, Ovid Embase, Ovid CDR, Cochrane Central Register of Controlled Trials and Database of Abstracts of Reviews of Effect, Scopus, and Web of Science, and included MeSH headings and keywords related to intensive care, critical care, and cognitive disorders. Searches were restricted to adult subjects. Inclusion required follow-up cognitive evaluation at least 2 months after ICU discharge. Studies assessing patients with cardiac arrest, traumatic brain injury, and cardiac surgery history were excluded. The search strategy resulted in 3180 studies. Of these, 28 studies (.88%) met our inclusion criteria and were analyzed. Delirium and duration of delirium were associated with long-term cognitive impairment after ICU admission in 6 of 9 studies in which this factor was analyzed. Weaker and more inconsistent associations have been reported with hypoglycemia, hyperglycemia, fluctuations in serum glucose levels, and in-hospital acute stress symptoms. Instead, most of the studies did not find significant associations between long-term cognitive impairment and mechanical ventilation; use of sedatives, vasopressors, or analgesic medications; enteral feeding; hypoxia; extracorporeal membrane oxygenation; systolic blood pressure; pulse rate; or length of ICU stay. Prolonged delirium may be a risk factor for long-term cognitive impairment after critical illness, though this association has not been entirely consistent across studies. Other potentially preventable factors have not been shown to have strong or consistent associations with long-term cognitive dysfunction in survivors of critical illness.

Risk factors and outcomes of critically ill patients with acute brain failure: A novel end point.

OBJECTIVE: To determine the incidence, risk factors and outcomes of acute brain failure (ABF) in a mixed medical and surgical cohort of critically ill patients and its effect on ICU & hospital mortality. DESIGN: Observational electronic medical record (EMR) based retrospective cohort study of critically ill patients admitted to the ICU between 2006 and 2013. SETTING: Tertiary academic medical center. PATIENTS: Consecutive adult (>18years) critically ill patients admitted to medical and surgical ICUs. Patients admitted to the Neuroscience, Pediatric and Neonatal ICUs were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: ABF was defined by the presence of delirium (positive CAM-ICU) or depressed level of consciousness (by abnormal GCS and FOUR scores) in the absence of deep sedation (RASS<-3). Severity of ABF was categorized as grade I if there was delirium with GCS consistently >8 and grade II if the GCS was ≤8 with or without delirium during the ICU hospitalization. ABF duration was not used for this study. Univariate and multivariable analyses were used to access the factors associated with the development of ABF and its effect on short and long term mortality. Of 67,333 ICU patients included in the analysis, ABF was present in 30,610 (44.6%). Patients with ABF had an isolated delirium in 1985 (6.5%) patients, isolated depressed consciousness in 18,323 (59.9%), and both delirium and depressed consciousness in 10,302 (33.6%) patients. When adjusted for comorbidities and severity of illness ABF was associated with increased hospital (OR 3.47; 95% CI 3.19-3.79), and at one year (OR 2.36; 95% CI 2.24-2.50) mortality. Both hospital and one year mortality correlated with the increased severity of ABF. The factors most strongly associated with ABF were pre-admission dementia (OR 7.86; 95% CI 6.15-10.19) and invasive ventilation (OR 2.32; 95% CI 2.24-2.40) but older age, female sex, presence of liver disease, renal failure, diabetes mellitus, malignancy and COPD were also associated with increased risk of ABF. CONCLUSIONS: ABF is a common complication of critical illness and is associated with increased short and long term mortality. The risk of ABF was particularly high in older patients with baseline dementia, COPD, diabetes, liver and renal disease and those treated with invasive mechanical ventilation.

Predictors of Extubation Success in Patients with Posterior Fossa Strokes.

OBJECTIVE: Posterior fossa stroke is unique in its presentation and outcomes, and mechanical ventilation is commonly used in the management of these patients. We aimed to identify predictors of extubation success in patients with posterior fossa stroke, who require mechanical ventilation. DESIGN: We included consecutive adult patients admitted to the neurosciences ICU from January 2003 to December 2012. Extubation failure was defined as re-intubation within 7 days of extubation. A modified Rankin Scale score of 0-3 was considered a good outcome. MEASUREMENTS AND MAIN RESULTS: We identified 150 patients with mean age of 65 ± 15.7 years with posterior fossa strokes; 77 (51 %) were hemorrhagic, and 73 (49 %) were ischemic. The most common reason for intubation was depressed consciousness (54 %). Fifty-two (35 %) were successfully extubated, 18 (12 %) failed extubation, 17 (11 %) patients had tracheostomy without attempted extubation, and 63 (42 %) were transitioned to palliative care prior to extubation. In the logistic regression analysis, controlling for transition to palliative care, Glasgow Coma Score (GCS) score >6 at the time of intubation (p = 0.020), mechanical ventilation for less than 7 days (p = 0.004), and surgical evacuation of a hematoma (p = 0.058) were independently associated with successful extubation. The presence of cough, gag reflex, and absence of pneumonia/atelectasis were not associated with successful extubation. Success of extubation predicted a good outcome at hospital discharge. CONCLUSIONS: In posterior fossa stroke patients with a GCS ≤ 6 at the time of intubation and who remain intubated for more than 1 week, extubation is less likely to be successful, and tracheostomy should be considered.

SSRI/SNRI Use is Not Associated with Increased Risk of Delayed Cerebral Ischemia After aSAH.

BACKGROUND: To determine the effect of selective serotonin reuptake inhibitor (SSRI)/selective norepinephrine reuptake inhibitor (SNRI) use on the risk of symptomatic vasospasm and delayed cerebral ischemia (DCI) in patients hospitalized with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: Retrospective review of consecutive patients with aSAH at Mayo Clinic, Rochester from January 2001 to December 2013. The variables collected and analyzed included age, sex, SSRI/SNRI use, active smoking, transfusion, modified Fisher score, WFNS grade, and outcome at discharge. Multivariate logistic regression analysis was used to evaluate factors associated with DCI, symptomatic vasospasm, and poor outcome (modified Rankin score 3-6) within 1 year. RESULTS: 579 [females 363 (62.7%)] patients with a median age of 55 (IQR 47-65) years were admitted with aSAH during the study period. WFNS at nadir was IV-V in 240 (41.5%), and modified Fisher score was 3-4 in 434 (75.0%). 81 (13.9%) patients had been prescribed an SSRI or SNRI prior to admission and all continued to receive these medications during hospitalization. Symptomatic vasospasm was present in 154 (26.4%), radiological infarction in 172 (29.5%), and DCI in 250 (42.9%) patients. SSRI/SNRI use was not associated with the occurrence of DCI (p = 0.458), symptomatic vasospasm (p = 0.097), radiological infarction (p = 0.972), or poor functional outcome at 3 months (p = 0.376). CONCLUSIONS: The use of SSRI/SNRI prior to and during hospitalization is not associated with DCI or functional outcome in patients with aSAH.

Management and outcomes of pituitary apoplexy.

OBJECT: This study was undertaken to analyze the predisposing factors, clinical presentation, therapeutic management, and clinical recovery in patients with pituitary apoplexy, with an emphasis on the long-term visual, endocrine, and functional outcomes. METHODS: The authors performed a retrospective analysis of consecutive cases involving patients treated at Mayo Clinic between 1992 and 2013. Patients were included in the study only if they had 1) abrupt onset of severe headache or visual disturbance in the presence of a pituitary adenoma and 2) radiological or surgical confirmation of a pituitary mass. The primary endpoints of analysis were the visual (ocular motility, visual fields, and visual acuity), endocrine, and functional outcomes (using the modified Rankin Scale). RESULTS: Eighty-seven patients were identified (57 males and 30 females, mean age 50.9 years, range 15-91 years). Twenty-two patients (25.3%) had a known pituitary adenoma. Hypertension was the most common associated factor (39%). Headache was the most frequent presenting symptom (89.7%), followed by visual abnormalities (47.1%). Cranial nerve palsies were present in 39% and visual field defects in 34.1%. MRI detected hemorrhage in 89% patients, as compared with 42% detected by CT scan. Sixty-one patients (70.1%) underwent surgery during acute hospitalization (median time from apoplexy 5 days, IQR 3-10 days), 8 (9.2%) had delayed surgery, and 18 (20.7%) were treated conservatively. Histopathological examination revealed adenoma with pure necrosis in 18 (30%), pure hemorrhage in 4 (6.7%), and both in 6 (10%) patients. Four patients died during hospitalization. The average duration of follow-up was 44.2 ± 43.8 months. All survivors were independent and had complete resolution or substantial improvement in eye movements and visual fields at the last follow-up. Many patients needed long-term hormonal replacement with levothyroxine (62.7%) and cortisol (60%). Daily desmopressin was needed in 23% of all surgical patients at 3 months (versus none of the medically treated) and this requirement decreased slightly over time. Regrowth of pituitary adenoma was seen in 7 patients (8.6%). There were no statistically significant differences in any of the outcome measures across the treatment groups. CONCLUSIONS: The outcome of most patients with pituitary apoplexy is excellent. Selected patients can be managed conservatively, and patients with severe neuro-ophthalmological deficits treated with early surgery can achieve an excellent recovery.