Tarun D. Singh

The spectrum of acute encephalitis Causes, management, and predictors of outcome

Objective: To describe and analyze etiologies, clinical presentations, therapeutic management, and outcomes of patients with acute encephalitis and identify outcome predictors. Methods: We conducted a retrospective review of patients diagnosed with acute encephalitis at Mayo Clinic Rochester between January 2000 and December 2012. On the basis of the final diagnosis, the patients were categorized into 3 groups: viral encephalitis, autoimmune encephalitis, and encephalitis of unknown/other etiology. Multivariate logistic regression analysis was used to analyze factors associated with good (modified Rankin Scale scores of 0–2) or poor (scores of 3–6) outcome at hospital discharge. Results: We identified 198 patients (100 [50.5%] men and 98 [49.5%] women) 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%). Good outcome at discharge was achieved by 48 patients (50.5%) with viral encephalitis, 17 (40.5%) with autoimmune encephalitis, and 32 (54.2%) with unknown/other etiologies. Mortality rates were 8%, 12%, and 5% in each of the 3 categories, respectively. On multivariate regression analysis, the factors that were associated with poor outcome were age 65 years or older (p = 0.0307), immunocompromised state (p = 0.0153), coma (p = 0.0062), mechanical ventilation (p = 0.0124), and acute thrombocytopenia (p = 0.0329). CSF polymorphonuclear cell count was also strongly associated with poor outcome in viral encephalitis (p = 0.0027). Conclusions: Advanced age, immunocompromised state, coma, mechanical ventilation, and acute thrombocytopenia portend a worse prognosis in acute encephalitis. In contrast, the etiology of encephalitis, development of seizures or focal neurologic deficit, and MRI findings were not associated with clinical outcomes.

Long‐term risk of seizures and epilepsy in patients with posterior reversible encephalopathy syndrome

Seizures 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.

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.

18F-FDG PET in Posterior Cortical Atrophy and Dementia with Lewy Bodies

Posterior cortical atrophy (PCA) and dementia with Lewy bodies (DLB) have both been associated with occipital lobe hypometabolism on 18F-FDG PET, whereas relative sparing of posterior cingulate metabolism compared with precuneus/cuneus (i.e., cingulate island sign) is a feature of DLB. We aimed to determine whether patterns of hypometabolism or the cingulate island sign differed between PCA and DLB. Methods: Sixteen clinically diagnosed PCA and 13 probable DLB subjects underwent 18F-FDG PET. All PCA subjects showed β-amyloid deposition on PET scanning. Regional hypometabolism was assessed compared with a control cohort (n = 29) using voxel- and region-level analyses in statistical parametric mapping. A ratio of metabolism in the posterior cingulate to precuneus plus cuneus was calculated to assess the cingulate island sign. In addition, the 18F-FDG PET scans were visually assessed to determine whether the cingulate island sign was present in each subject. Results: PCA and DLB showed overlapping patterns of hypometabolism involving the lateral occipital lobe, lingual gyrus, cuneus, precuneus, posterior cingulate, inferior parietal lobe, supramarginal gyrus, striatum, and thalamus. However, DLB showed greater hypometabolism in the medial occipital lobe, orbitofrontal cortex, anterior temporal lobe, and caudate nucleus than PCA, and PCA showed more asymmetric patterns of hypometabolism than DLB. The cingulate island sign was present in both DLB and PCA, although it was more asymmetric in PCA. Conclusion: Regional hypometabolism overlaps to a large degree between PCA and DLB, although the degree of involvement of the frontal and anterior temporal lobes and the presence of asymmetry could be useful in differential diagnosis.

Postencephalitic epilepsy: Clinical characteristics and predictors

To describe the etiologies, clinical presentations, outcomes, and predictors of postencephalitic epilepsy (PE) in a large series of adult patients with acute encephalitis.

Asymptomatic Carotid Stenosis: Risk of Progression and Development of Symptoms.

Background: The aim of this study is to evaluate the rate of progression of stenosis and development of symptoms in patients with asymptomatic carotid artery stenosis (aCAS) treated with contemporary medical therapy over a prolonged time interval. Methods: This study is a retrospective review of consecutive patients diagnosed with moderate or severe aCAS at our institution between 2000 and 2001. Data were gathered from both carotid arteries for each patient excluding vessels operated within 1 year of diagnosis and occlusions. Multivariate analysis was performed to analyze factors associated with ipsilateral transient ischemic attack (TIA)/stroke. Results: We identified 214 patients (58.8% men; median age 70 years) and collected data on 349 vessels. Degree of stenosis was severe (>70%) upon diagnosis in 92 (26.4%) vessels. Median length of follow-up was 13 years (interquartile range 10-14), and mean number of time points for follow-up imaging were 8.1 ± 3.9. Progression of stenosis was observed in 237 (67.9%) vessels, and 72 (20.6%) patients developed symptoms ipsilateral to the stenosis (TIA in 14.4%, non-disabling stroke in 4%, disabling stroke in 2.2%). Median time to appearance of first symptom was 6 years (range 1-13). On multivariate analysis, degree of baseline stenosis, intracranial stenosis >50%, plaque ulceration, silent infarction and previous history of TIA/stroke were associated with ipsilateral TIA/stroke, but progression of stenosis was not. Conclusions: There was a substantial rate of progression of stenosis in patients with aCAS over time despite adequate medical therapy, but progression of stenosis did not increase the risk of ipsilateral TIA/stroke. Over long-term follow-up, 1 in 5 patients with aCAS developed ipsilateral TIA/stroke, though most events were either transient or non-disabling.

Albuminocytologic Dissociation in Posterior Reversible Encephalopathy Syndrome

OBJECTIVES To describe cerebrospinal fluid (CSF) findings in patients with posterior reversible encephalopathy syndrome (PRES) and to study its association with vasogenic edema. PATIENTS AND METHODS Retrospective review of 73 consecutive prospectively collected adults diagnosed with PRES from January 1, 2000, through December 31, 2014, who underwent lumbar puncture. RESULTS Seventy-three patients (mean age, 51±17 years), were included in the analysis; of these, 50 (69%) were women. The most common causes for PRES were hypertension (n=61 [84%]) and immunosuppression (n=22 [30%]). Renal failure was present in 42 (58%) patients. The median interval between clinical onset of PRES and CSF analysis was 1 day (interquartile range [IQR], 0-2 days). The median opening pressure was 23 cm H2O or 17 mm Hg (IQR, 18-28 cm H2O or 13-21 mm Hg), although it was available in only 27 patients. The median CSF protein level was 58 mg/dL (IQR, 44-81 mg/dL; normal value, <35 mg/dL). The median CSF protein level was higher in patients with more extensive vasogenic edema. The median white blood cell count was 1 cell/μL (IQR, 1-2 cells/μL). CONCLUSION Elevated CSF protein level without CSF pleocytosis commonly occurs in patients with PRES and is directly associated with the extent and topographical distribution of cerebral edema. Although mild CSF pleocytosis can also occur, it is an uncommon finding and may prompt consideration for further diagnostic testing.

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

&NA; 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.

Neuropsychiatric symptoms in primary progressive aphasia and apraxia of speech.

Aim: To conduct a prospective analysis of the neuropsychiatric symptoms (NPS) across the three categories of primary progressive aphasia (PPA) and progressive apraxia of speech (PAOS), compare the prevalence and nature of the symptoms, and look at which symptoms could be helpful to better differentiate these PPA and PAOS categories. Methods: A total of 106 consecutive patients with a diagnosis of semantic variant (n = 13), logopenic variant (n = 37), agrammatic variant (n = 15) or PAOS (n = 41) were included in this prospective study. The NPS were measured by the Neuropsychiatric Inventory Questionnaire. Results: There were 65 patients with PPA and 41 with PAOS diagnosis. The most distinguishing features between the two groups were anxiety, apathy, aberrant motor behavior and appetite, while among the subtypes of PPA they were disinhibition and appetite changes. PPA and PAOS patients initially exhibited depression, but with increased disease duration, PAOS patients showed apathy (55.5%) while PPA patients showed disinhibition (28.6%) and aberrant motor behavior (14.3%). Conclusion: Mood symptoms like anxiety and appetite changes are more likely to be present at initial stages of PPA, whereas behavioral symptoms like aberrant motor behavior and apathy are likely to occur early in PAOS. The NPS seem to evolve with the progression of the disease in both PPA and PAOS.

Episodic status migrainosus: A novel migraine subtype.

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.