Edward M. Manno

Clinical Spectrum of Reversible Posterior Leukoencephalopathy Syndrome

BACKGROUND Reversible posterior leukoencephalopathy syndrome (RPLS) is characterized by neuroimaging findings of reversible vasogenic subcortical edema without infarction. The clinical syndrome of RPLS typically involves headache, encephalopathy, visual symptoms, and seizures. OBJECTIVE To retrospectively identify patients with RPLS with a characteristic clinical presentation and neuroimaging abnormalities and documented improvement on repeated neuroimaging. DESIGN Retrospective. SETTING Mayo Clinic. PATIENTS Thirty-six patients with RPLS. MAIN OUTCOME MEASURES Associated comorbid medical conditions, presenting clinical symptoms, duration of clinical symptoms, diagnostic test results (magnetic resonance imaging, electroencephalography, and lumbar puncture), and time to clinical and neuroimaging recovery. RESULTS We identified 38 episodes of RPLS in 36 patients (20 females and 16 males) with a mean age of 44.7 years. Comorbid conditions included hypertension (53%), renal disease (45%), dialysis dependency (21%), malignancy (32%), and transplantation (24%). Presenting symptoms included clinical seizures (87%), encephalopathy (92%), visual symptoms (39%), and headache (53%). Mean peak systolic blood pressure at presentation was 187 mm Hg. Clinical symptoms resolved after a mean of 5.3 days. Atypical neuroimaging features included significant frontal involvement in 22 episodes (58%), gray matter lesions in 16 (42%), unilateral lesions in 2 (5%), hemorrhage in 2 (5%), recurrent RPLS in 2 (5%), confluent lesions in 2 (5%), and foci of permanent injury in 10 (26%). Twenty-two episodes (58%) had brainstem/cerebellar involvement on neuroimaging. CONCLUSIONS This is the largest clinical series to date of RPLS with confirmed neuroimaging improvement. Clinical recovery occurred in most patients within days. The condition was rarely isolated to the parieto-occipital white matter, and atypical neuroimaging features were frequent.

Validation of a new coma scale: The FOUR score

The Glasgow Coma Scale (GCS) has been widely adopted. Failure to assess the verbal score in intubated patients and the inability to test brainstem reflexes are shortcomings. We devised a new coma score, the FOUR (Full Outline of UnResponsiveness) score. It consists of four components (eye, motor, brainstem, and respiration), and each component has a maximal score of 4. We prospectively studied the FOUR score in 120 intensive care unit patients and compared it with the GCS score using neuroscience nurses, neurology residents, and neurointensivists. We found that the interrater reliability was excellent with the FOUR score (κw = 0.82) and good to excellent for physician rater pairs. The agreement among raters was similar with the GCS (κw = 0.82). Patients with the lowest GCS score could be further distinguished using the FOUR score. We conclude that the agreement among raters was good to excellent. The FOUR score provides greater neurological detail than the GCS, recognizes a locked‐in syndrome, and is superior to the GCS due to the availability of brainstem reflexes, breathing patterns, and the ability to recognize different stages of herniation. The probability of in‐hospital mortality was higher for the lowest total FOUR score when compared with the lowest total GCS score. Ann Neurol 2005;58:585–593

Predictors of Cerebral Infarction in Aneurysmal Subarachnoid Hemorrhage

Background— Clinical and radiologic predictors of cerebral infarction occurrence and location after aneurysmal subarachnoid hemorrhage have been seldom studied. Methods— We evaluated all patients admitted to our hospital with aneurysmal subarachnoid hemorrhage between 1998 and 2000. Cerebral infarction was defined as a new hypodensity located in a vascular distribution on computed tomography (CT) scan. Results— Fifty-seven of 143 patients (40%) developed a cerebral infarction. On univariate analysis, occurrence of cerebral infarction was associated with a worse World Federation of Neurological Surgeons grade (P =0.01), use of ventriculostomy catheter (P =0.01), preoperative vasospasm (P =0.03), surgical clipping (P =0.02), symptomatic vasospasm (P <0.01), and vasospasm on transcranial Doppler ultrasonography (TCD) or repeat angiogram (P <0.01). On multivariable analysis, only presence of symptoms ascribed to vasospasm (P <0.01) and evidence of vasospasm on TCD or angiogram predicted cerebral infarction (P <0.01). TCD and angiogram agreed on the diagnosis of vasospasm in 73% of cases (95% CI, 63% to 81%), but the diagnostic accuracy of this combination of tests was suboptimal for the prediction of cerebral infarction occurrence (sensitivity, 0.72; specificity, 0.68; positive predictive value, 0.67; negative predictive value, 0.72). Location of the cerebral infarction on delayed CT was predicted by neurological symptoms in 74%, by aneurysm location in 77%, and by angiographic vasospasm in 67%. Conclusions— Evidence of vasospasm on TCD and angiogram is predictive of cerebral infarction on CT scan but sensitivity and specificity are suboptimal. Cerebral infarction location cannot be predicted in one quarter to one third of patients by any of the studied clinical or radiological variables.

Predictors of neurologic outcome in hypothermia after cardiac arrest.

To evaluate the predictive value of neurologic prognostic indicators for patients treated with hypothermia after surviving cardiopulmonary arrest.

Mechanical ventilation for ischemic stroke and intracerebral hemorrhage: Indications, timing, and outcome

Objective: To compare the incidence, indication, and timing of intubation and outcome in patients with cerebral infarction (ISCH) and intracerebral hemorrhage(HEM) requiring mechanical ventilation (MV). Background: Poor outcomes have been reported for ISCH patients requiring MV. Because the target population, pathophysiology, and management of ISCH and HEM patients differ considerably, we compared the characteristics of patients with ISCH and HEM who required MV. Methods: A retrospective review of ISCH and HEM stroke patients who underwent MV at a tertiary care academic center from 1994 to 1997 was performed to determine age, sex, type, and location of stroke (anterior or posterior circulation); brainstem dysfunction at intubation (pupillary, corneal, and oculocephalic reflexes); indication for intubation (neurologic deterioration, cardiopulmonary deterioration, or elective intubation for surgery); timing of intubation (on presentation or later); comorbidities; and outcome (hospital disposition). Results: A total of 230 patients, 74 with ISCH and 156 with HEM (mean age, 61± 16 years; male-to-female ratio, 1.15:1), underwent MV. Intubation rates were 6% for ISCH patients and 30% for HEM patients. Two-thirds of the patients required intubation on presentation (84% were intubated for neurologic deterioration) and 131 patients (57%) died (ISCH, 55%; HEM, 58%). Signs of brainstem dysfunction predicted a higher mortality for both groups. Additionally, early intubation and older age predicted mortality for HEM, and male gender predicted mortality in ISCH. Stroke location and comorbidities did not influence outcome. Conclusions: MV in acute stroke is associated with high mortality. Mortality and outcome were similar for ISCH and HEM; however, the factors predictive of outcome may differ and influence decisions about the use of MV in such patients.

Predictors of outcome after anterior temporal lobectomy Positron emission tomography

We assessed the relationship between temporal lobe metabolism measured quantitatively and qualitatively with PET using [18F]-fluorodeoxyglucose (FDG) and postoperative seizure frequency after anterior temporal lobectomy. Forty-three patients with refractory partial epilepsy had anterior temporal lobectomy and preoperative assessment with PET-FDG. Qualitative PET analysis was performed visually by two blinded observers, and quantitative PET analysis was performed using an anatomic template for six control and six temporal lobe subregions, deriving an asymmetry index for each region. Seizure outcome was assessed 1 year after surgery; patients were classified as being seizure-free or as having persistent seizures. Qualitative data were analyzed using Fishers exact test and the t test, and quantitative data were analyzed using a repeated-measures ANOVA. Thirty-two patients (74%) were seizure-free at follow-up, and 11 had persistent seizures, although most improved. Twenty-nine of 35 patients (83%) with restricted temporal lobe hypometabolism by visual analysis were seizure-free, compared with three of eight patients (37.5%) with normal scans or multilobar hypometabolism. Quantitative analysis revealed that an asymmetry of mesial temporal lobe glucose consumption (uncal region) correlated with improved surgical outcome (p < 0.02). We developed a logistic regression model to predict individual outcome based on the asymmetry in uncal metabolism. Lateral temporal metabolism did not correlate with outcome. We conclude that both visual PET analysis and quantitative PET analysis predict outcome after temporal lobectomy, although quantitative measures offer more precise information.

The effects of mannitol on cerebral edema after large hemispheric cerebral infarct

Objective: To evaluate the effect of a single large dose of mannitol on midline tissue shifts after a large cerebral infarction. Background: Theoretically, mannitol use in the largest cerebral infarctions may preferentially shrink noninfarcted cerebral tissue, thereby aggravating midline tissue shifts and worsening neurologic status. To test this theory, we studied patients with hemispheric infarctions using continuous and sequential MRI during administration of a single dose of mannitol. Methods: Patients with neurologic deterioration from complete middle cerebral artery (MCA) infarctions and CT evidence of at least 3 mm of midline shift were studied using T1-weighted three-dimensional multiplanar rapid acquisition gradient echo image data sets acquired at 5- to 10-minute intervals before, during, and after a 1.5 gm/kg bolus infusion of mannitol. Horizontal and vertical displacements were calculated by previously described methods. Glasgow Coma Scale (GCS) and MCA Stroke Scale (MCASS) were measured before and after mannitol administration. Mean changes in tissue shifts were compared using repeated measures analysis of variance. Clinical variables were compared using paired t-tests. Results: Seven patients were enrolled. The final average change in midline shift compared with the initial displacement was 0.0 ± 1 mm for horizontal (F = 0.06, p = 0.99) and 0.25 ± 1.3 mm for vertical displacement (F = 0.06, p = 0.99). Whereas average scores for the group did not change, MCASS improved in two, GCS improved in three, and pupillary light reactivity returned in two patients. No patient worsened. Conclusions: Acute mannitol used in patients with cerebral edema after a large hemispheric infarction does not alter midline tissue shifts or worsen neurologic status.

Status epilepticus as initial manifestation of posterior reversible encephalopathy syndrome

We report 10 cases of status epilepticus (SE) in patients with posterior reversible encephalopathy syndrome (PRES). In all cases, SE brought PRES to medical attention. The majority of the cases had focal-onset complex partial SE. Complete resolution of SE was achieved after combined treatment of PRES and SE in all cases. SE in the setting of PRES carries a favorable prognosis but requires timely recognition and treatment of the course of PRES.

Predictors of outcome in warfarin-related intracerebral hemorrhage.

BACKGROUND Intracerebral hemorrhage (ICH) associated with warfarin sodium therapy is becoming more common as the use of this medication increases in the aging population. OBJECTIVE To delineate factors associated with early mortality, determine variables responsible for poor functional outcome, and evaluate possible reasons for expansion of hemorrhage and associated parenchymal edema. DESIGN Retrospective study of clinical and radiologic information for 88 patients with warfarin-associated ICH. SETTING A single hospital. Patients Eighty-eight consecutive patients with warfarin-associated ICH. METHODS Patients were included if the international normalized ratio (INR) at presentation with ICH was 1.5 or greater. Computed tomographic scans were reviewed for volumetric analysis of hematoma and perihematomal edema volume. Outcome variables included 7-day mortality, hematoma enlargement, and functional outcome based on the modified Rankin Scale score. RESULTS Seven-day mortality (39.8%) was associated with a lower Glasgow Coma Scale sum score and larger ICH volume at presentation. Univariate analysis revealed that a lower Glasgow Coma Score sum score, larger initial ICH volume, higher initial and 48-hour maximum glucose concentrations, and higher percentage of ICH expansion were significantly associated with poor functional outcome at hospital discharge. At multivariate analysis, only Glasgow Coma Score and ICH volume remained significantly associated with functional outcome measured at hospital discharge and at the last follow-up visit. Conversely, INR at presentation, time to INR correction, initial blood pressure, and enlargement of edema were not associated with functional outcome either at hospital discharge or at the last follow-up. Neither serum glucose concentration at admission nor highest level during the first 48 hours had any correlation with ICH or parenchymal edema enlargement. In addition, neither initial INR nor time to INR correction correlated with expansion of ICH or parenchymal edema. CONCLUSIONS Lower level of consciousness at presentation and larger initial ICH volume predict poor prognosis in patients with warfarin-associated ICH. In our study population, INR at presentation was not associated with functional outcome.

Subarachnoid hemorrhage: neurointensive care and aneurysm repair.

Aneurysmal subarachnoid hemorrhage (SAH) is often a neurologic catastrophe. Diagnosing SAH can be challenging, and treatment is complex, sophisticated, multidisciplinary, and rarely routine. This review emphasizes treatment in the intensive care unit, surgical and endovascular therapeutic options, and the current state of treatment of major complications such as cerebral vasospasm, acute hydrocephalus, and rebleeding. Outcome assessment in survivors of SAH and controversies in screening of family members are discussed.