Singh, Tarun D.

Objectives: Persistent cognitive impairment after critical illness is an important healthcare problem forecasted to worsen in the near future. However, the epidemiology is insufficiently explored. We aimed to determine potentially modifiable risk factors during ICU hospitalization that play a significant role in developing persistent cognitive impairment. Design: An observational case-control study. Settings: Mayo Clinic ICUs between July 1, 2004, and November 20, 2015. Patients: We conducted a study nested in a large cohort of 98,227 adult critically ill patients. Using previously validated computable phenotypes for dementia and cognitive impairment, we determined the onset of cognitive impairment relative to ICU hospitalization and associated risk factors. The primary endpoint of the study was new and persistent cognitive impairment documented between 3 and 24 months after ICU discharge. Interventions: Unadjusted and adjusted analyses were performed to identify potentially modifiable risk factors during ICU hospitalization. Measurements and Main Results: Among 21,923 unique patients identified as cognitively impaired (22% of the entire ICU cohort), 2,428 (2.5%) developed incident new and persistent cognitive dysfunction after the index ICU admission. Compared with age- and sex-matched ICU controls (2,401 pairs), cases had higher chronic illness burden (Charlson Comorbidity Index, 6.2 vs 5.1; p < 0.01), and were more likely to have multiple ICU stays (22% vs 14%; p < 0.01). After adjustment for baseline differences, new and persistent cognitive dysfunction was associated with higher frequency of acute brain failure in the ICU, a higher exposure to severe hypotension, hypoxemia, hyperthermia, fluctuations in serum glucose, and treatment with quinolones or vancomycin. Association with sepsis observed in univariate analysis did not persist after adjustment. Conclusions: Cognitive dysfunction is highly prevalent in ICU patients. Incident new and persistent cognitive impairment is less common but important, potentially preventable problem after critical illness. Chronic comorbidities and number of ICU stays increase the risk of post-ICU cognitive dysfunction irrespective of age. Modifiable ICU exposures were identified as potential targets for future prevention trials.

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.

Objective To report a case series of a novel migraine subtype, which we term as episodic status migrainosus (ESM), characterized by attacks of migraine exclusively lasting more than 72 hours. We hypothesized that this would represent a novel nosologic entity, possibly an unstable migraine phenotype with a high conversion rate to chronic migraine (CM). Methods We conducted a retrospective review of patients diagnosed with status migrainosus at the Mayo Clinic, Rochester, between January 2005 and December 2015. All the records were then manually reviewed for patients with migraine headaches exclusively lasting more than 72 hours. Results We identified 18 patients with ESM, with a female predominance (15(83.3%)) and a median age of onset of 16.5 (IQR 13–19) years. The median monthly attack frequency was two (IQR 1–3), with each attack lasting a median duration of seven (IQR 4–12.5) days. Stress was the most commonly reported precipitant (11 (61.1%)). Migraine with aura was common (10 (55.6%)), as was comorbid depression (10 (55.6%)). Fifteen (83.3%) patients developed CM at a median of 7.8 (IQR 2.6–21.9) years from their first attack. There was no significant association between the time to the development of chronic migraine with either attack frequency or duration. Conclusions and relevance We report the existence of a novel migraine subtype, episodic status migrainosus. This migraine subtype appears to have similar clinical characteristics to episodic migraine with or without aura, except for a notably high tendency to progress to chronic migraine.

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.

SummaryObjectiveSeizures are common in patients with posterior reversible encephalopathy syndrome (PRES), which is reported in up to 70% of cases, and antiepileptic drugs (AEDs) are commonly prescribed. There is a paucity of data regarding the risk of subsequent seizures following resolution of PRES, and therefore the optimal duration of treatment with AEDs is currently unknown. The objective of this study was to identify the frequency of recurrent seizures and epilepsy following recovery from PRES.MethodsWe performed a retrospective review of consecutive adults diagnosed with PRES between 2000 and 2010.ResultsOne hundred twenty‐seven patients, median age 53 years (interquartile range [IQR] 37–64), were included in the analysis. The most common causes of PRES were hypertension (72%) and immunosuppression (20%). Renal failure was present in 47%. Eighty‐four patients (66%) had seizures at presentation (39 focal, 45 generalized), and 13 (15%) of them presented with status epilepticus. Median duration of follow‐up was 3.2 years (IQR 4 months to 6.9 years). Patients with seizures were treated with AEDs for a median of 3 months (IQR 2–7). Fifteen patients (12%) had provoked seizures during the follow‐up period; in eight (53%) patients seizures were caused by recurrent PRES. Only three patients had subsequent unprovoked seizures, one of whom was considered to have developed epilepsy.SignificanceWe conclude that unprovoked seizures and epilepsy are uncommon in patients who have recovered from PRES. Discontinuation of AEDs following resolution of PRES should be considered, provided there is adequate control of risk factors, and absence of factors that could substantially lower the seizure threshold.

Summary Objective To describe the etiologies, clinical presentations, outcomes, and predictors of postencephalitic epilepsy ( PE ) in a large series of adult patients with acute encephalitis. Methods We conducted a retrospective review of patients diagnosed with acute encephalitis at Mayo Clinic, Rochester, between January 2000 and December 2012. The patients were categorized into two groups based on the presence or absence of PE at last follow‐up. Multivariate logistic regression analysis was used to analyze factors associated with PE . Results We identified 198 consecutive patients (100 [50.5%] male and 98 [49.5%] female) with a median age of 58 years (range 41.8–69). Etiologies included viral infection (n = 95, 48%), autoimmune (n = 44, 22%), and unknown/others (n = 59, 30%). During hospitalization, seizures were seen in patients with autoimmune encephalitis (n = 24, 54.5%), unknown/others (n = 20, 33.9%), and viral encephalitis (n = 23, 24.2%). Interictal epileptiform discharges on electroencephalography (EEG) were present in 34 (54%), whereas periodic lateralized epileptiform discharges (PLEDs) and generalized periodic discharges (GPDs) were seen in 14 (41.2%) and 2 (5.9%) patients. Forty‐six patients with seizures (70.8%) had fluid‐attenuated inversion recovery ( FLAIR )/T 2 abnormalities, 20 (31.3%) diffusion abnormalities, and 43 (66.2%) cortical involvement. Good outcome at discharge among patients with seizures was seen in 8/23 patients with viral etiology (34.8%), 10/24 patients with autoimmune encephalitis (45.5%), and 12/20 patients with unknown cause (60%). PE was present in 43 patients (29.9%). On multivariate regression analysis, the factors associated with PE were generalized seizures during hospitalization (p = 0.03), focal seizures (p ≤ 0.001), and the presence of FLAIR /T 2 abnormalities on brain magnetic resonance imaging ( MRI ) (p = 0.003). Significance The presence of seizures during hospitalization and an abnormal brain MRI are the strongest predictors of the development of PE . The etiology of encephalitis, presence of focal neurologic deficits, and interictal EEG abnormalities did not influence the development of PE .