Antibody Prevalence in Epilepsy before Surgery (APES) in drug-resistant focal epilepsy.

OBJECTIVE: There is a growing recognition of immune-mediated causes in patients with focal drug-resistant epilepsy (DRE); however, they are not systematically assessed in the pre-surgical diagnostic workup. Early diagnosis and initiation of immunotherapy is associated with a favorable outcome in immune-mediated seizures. Patients with refractory focal epilepsy with neuronal antibodies (Abs) tend to have a worse surgical prognosis when compared to other etiologies. METHODS: We studied the prevalence of serum Abs in patients ≥18 years of age with DRE of unknown cause before surgery. We proposed and calculated a clinical APES (Antibody Prevalence in Epilepsy before Surgery) score for each subject, which was modified based on Dubey's previously published APE2 score. RESULTS`: A total of 335 patients were screened and 86 subjects were included in final analysis. The mean age at the time of recruitment was 44.84 ± 14.86 years, with age at seizure onset 30.89 ± 19.88 years. There were no significant differences among baseline clinical features between retrospective and prospective sub-cohorts. The prevalence of at least one positive Ab was 33.72%, and central nervous system (CNS)-specific Abs was 8.14%. APES score ≥4 showed slightly better overall prediction (area under the curve [AUC]: 0.84 vs 0.74) and higher sensitivity (100% vs 71.4%), with slightly lower but similar specificity (44.3% vs 49.4%), when compared to APE2 score ≥4. For subjects who had available positron emission tomography (PET) results and all components of APES score (n = 60), the sensitivity of APES score ≥4 yielded a similar prediction potential with an AUC of 0.80. SIGNIFICANCE: Our findings provide persuasive evidence that a subset of patients with focal DRE have potentially immune-mediated causes. We propose an APES score to help identify patients who may benefit from a workup for immune etiologies during the pre-surgical evaluation for focal refractory epilepsy with unknown cause.

Associations between Depressive Symptomatology and Neurocognitive Impairment in HIV/AIDS.

OBJECTIVE: Mood disorders and neurocognitive impairments are debilitating conditions among patients with HIV/AIDS. How these comorbidities interact and their relationships to systemic factors remain uncertain. Herein, we investigated factors contributing to depressive symptomatology (DS) in a prospective cohort of patients with HIV/AIDS in active care that included neuropsychological assessment. METHODS: Among patients with HIV/AIDS receiving combination antiretroviral therapy (cART) and ongoing clinical assessments including measures of sleep, health-related quality of life (HQoL), neuropsychological testing, and mood evaluation (Patient Health Questionnaire-9 [PHQ-9]) were performed. Univariate and multivariate analyses were applied to the data. RESULTS: In 265 persons, 3 categories of DS were established: minimal (PHQ-9: 0-4; n = 146), mild (PHQ-9: 5-9; n = 62), and moderate to severe (PHQ-9: 10+; n = 57). Low education, unemployment, diabetes, reduced adherence to treatment, HIV-associated neurocognitive disorders (HAND), low health-related quality of life (HQoL), reduced sleep times, and domestic violence were associated with higher PHQ-9 scores. Motor impairment was also associated with more severe DS. In a multinomial logistic regression model, only poor HQoL and shorter sleep duration were predictive of moderate to severe depression. In this multivariate model, the diagnosis of HAND and neuropsychological performance (NPz) were not predictive of DS. CONCLUSIONS: Symptoms of depression are common (45%) in patients with HIV/AIDS and represent a substantial comorbidity associated with multiple risk factors. Our results suggest that past or present immunosuppression and HAND are not linked to DS. In contrast, sleep quality and HQoL are important variables to consider in screening for mood disturbances among patients with HIV/AIDS and distinguishing them from neurocognitive impairments.

Planimetric hematoma measurement in patients with intraventricular hemorrhage: is total volume a preferred target for reliable analysis?

BACKGROUND AND PURPOSE: Reliable quantification of both intracerebral hemorrhage and intraventricular hemorrhage (IVH) volume is important for hemostatic trials. We evaluated the reliability of computer-assisted planimetric volume measurements of IVH. METHODS: Computer-assisted planimetry was used to quantify IVH volume. Five raters measured IVH volumes, total (intracerebral hemorrhage+IVH) volumes, and Graeb scores from 20 randomly selected computed tomography scans twice. Estimates of interrater and intrarater reliability were calculated and expressed as an intrarater correlation coefficient and an absolute minimum detectable difference. RESULTS: Planimetric IVH volume analysis had excellent intra- and interrater agreement (intrarater correlation coefficient, 0.96 and 0.92, respectively), which was superior to the Graeb score (intrarater correlation coefficient, 0.88 and 0.83). Minimum detectable differences for intra- and interrater volumes were 12.1 mL and 17.3 mL, and were dependent on the total size of the hematoma; hematomas smaller than the median 43.8 mL had lower minimum detectable differences, whereas those larger than the median had higher minimum detectable differences. Planimetric total hemorrhage volume analysis had the best intra- and interrater agreement (intrarater correlation coefficient, 0.99 and 0.97, respectively). CONCLUSIONS: Computer-assisted planimetric techniques provide a reliable measurement of ventricular hematoma volume, but are susceptible to higher absolute error when assessing larger hematomas.

CT angiographic source images predict outcome and final infarct volume better than noncontrast CT in proximal vascular occlusions.

BACKGROUND AND PURPOSE: Alberta Stroke Programme Early CT Score (ASPECTS) is widely used for assessment of early ischemic changes in acute stroke. We hypothesized that CT angiography source image (CTA-SI) ASPECTS correlates better with baseline National Institutes of Health Stroke Scale score, final ASPECTS and neurological outcomes when compared with noncontrast CT ASPECTS. METHODS: We studied patients presenting with acute ischemic stroke and identified proximal arterial occlusions (internal carotid artery, middle cerebral artery M1, and proximal middle cerebral artery M2) from the Calgary CT Angiography database. CT scans were independently read by 3 observers for baseline noncontrast CT ASPECTS, CT angiography source image ASPECTS, and follow-up ASPECTS. Details of demographics and risk factors were noted. A modified Rankin Scale score ≤2 at 3 months was considered a favorable outcome. RESULTS: We identified 261 patients with proximal occlusions for analysis. We found a better correlation between CT angiography source image ASPECTS and follow-up ASPECTS (Spearman correlation coefficient r=0.65; 95% CI, 0.58 to 0.72; P<0.001) than between noncontrast CT ASPECTS and follow-up CT ASPECTS (r=0.46; 95% CI, 0.36 to 0.55; P<0.001). CT angiography source image ASPECTS correlated better with baseline National Institutes of Health Stroke Scale and 24-hour National Institutes of Health Stroke Scale when compared with noncontrast CT ASPECTS (P<0.001). In an adjusted model including both CT angiography source image ASPECTS and noncontrast CT ASPECTS, CT angiography source image ASPECTS was associated with good outcome (OR, 2.30; 95%, CI, 1.16 to 4.53), whereas noncontrast CT ASPECTS was not (OR, 1.54; 95% CI, 0.84 to 2.82). Among imaging parameters, CT angiography source image ASPECTS was the only independent predictor of good outcome (OR, 2.29; 95% CI, 1.16 to 4.53). CONCLUSIONS: CT angiography source image ASPECTS correlates better with baseline stroke severity, is a better predictor of final infarct extension, and independently predicts neurological outcome than noncontrast CT ASPECTS.

Paraneoplastic and autoimmune encephalitis: Alterations of mood and emotion.

Autoimmune encephalitis often produces signs and symptoms that appear to be at the interface between neurology and psychiatry. Since psychiatric symptoms are often prominent, patients are often first seen in a psychiatric setting. Therefore it is important that psychiatrists, as well as neurologists, be able to recognize autoimmune encephalitis, a task that is often difficult. Early diagnosis of autoimmune encephalitis is crucial as this will usually result in a better outcome for the patient. This chapter provides an introduction to various autoimmune encephalitides and describes their pathophysiology and the possible associated neuropsychiatric, neuropsychological (cognitive), and neurological (sensory-motor) signs and symptoms. This chapter also reviews the possible treatments of these associated signs and symptoms.

Longitudinal evaluation of resting-state FMRI after acute stroke with hemiparesis.

BACKGROUND: Functional magnetic resonance imaging (fMRI) of motor impairment after stroke strongly depends on patient effort and capacity to make a movement. Hence fMRI has had limited use in clinical management. Alternatively, resting-state fMRI (ie, with no task) can elucidate the brain's functional connections by determining temporal synchrony between brain regions. OBJECTIVE: The authors examined whether resting-state fMRI can elucidate the disruption of functional connections within hours of ischemic stroke as well as during recovery. METHODS: A total of 51 ischemic stroke patients--31 with mild-to-moderate hand deficits (National Institutes of Health Stroke Scale [NIHSS] motor score ≥1) and 20 with NIHSS score of 0--underwent resting-state fMRI at <24 hours, 7 days, and 90 days poststroke; 15 age-matched healthy individuals participated in 1 session. Using the resting-state fMRI signal from the ipsilesional motor cortex, the strength of functional connections with the contralesional motor cortex was computed. Whole-brain maps of the resting-state motor network were also generated and compared between groups and sessions. RESULTS: Within hours poststroke, patients with motor deficits exhibited significantly lower connectivity than controls (P = .02) and patients with no motor impairment (P = .03). Connectivity was reestablished after 7 days in recovered (ie, NIHSS score = 0) participants. After 90 days, recovered patients exhibited normal motor connectivity; however, reduced connectivity with subcortical regions associated with effort and cognitive processing remained. CONCLUSION: Resting-state fMRI within hours of ischemic stroke can demonstrate the impact of stroke on functional connections throughout the brain. This tool has the potential to help select appropriate stroke therapies in an acute imaging setting and to monitor the efficacy of rehabilitation.

Prediction of haematoma growth and outcome in patients with intracerebral haemorrhage using the CT-angiography spot sign (PREDICT): a prospective observational study.

BACKGROUND: In patients with intracerebral haemorrhage (ICH), early haemorrhage expansion affects clinical outcome. Haemostatic treatment reduces haematoma expansion, but fails to improve clinical outcomes in many patients. Proper selection of patients at high risk for haematoma expansion seems crucial to improve outcomes. In this study, we aimed to prospectively validate the CT-angiography (CTA) spot sign for prediction of haematoma expansion. METHODS: PREDICT (predicting haematoma growth and outcome in intracerebral haemorrhage using contrast bolus CT) was a multicentre prospective observational cohort study. We recruited patients aged 18 years or older, with ICH smaller than 100 mL, and presenting at less than 6 h from symptom onset. Using two independent core laboratories, one neuroradiologist determined CTA spot-sign status, whereas another neurologist masked for clinical outcomes and imaging measured haematoma volumes by computerised planimetry. The primary outcome was haematoma expansion defined as absolute growth greater than 6 mL or a relative growth of more than 33% from initial CT to follow-up CT. We reported data using standard descriptive statistics stratified by the CTA spot sign. Mortality was assessed with Kaplan-Meier survival analysis. FINDINGS: We enrolled 268 patients. Median time from symptom onset to baseline CT was 135 min (range 22-470), and time from onset to CTA was 159 min (32-475). 81 (30%) patients were spot-sign positive. The primary analysis included 228 patients, who had a follow-up CT before surgery or death. Median baseline ICH volume was 19·9 mL (1·5-80·9) in spot-sign-positive patients versus 10·0 mL (0·1-102·7) in spot-sign negative patients (p<0·001). Median ICH expansion was 8·6 mL (-9·3 to 121·7) for spot-sign positive patients and 0·4 mL (-11·7 to 98·3) for spot-negative patients (p<0·001). In those with haematoma expansion, the positive predictive value for the spot sign was61% (95% CI 47­73) for the positive predictive value and 78% (71­84) for the negative predictive value, with 51% (39­63) sensitivity and 85% (78­90) specificity[corrected]. Median 3-month modified Rankin Scale (mRS) was 5 in CTA spot-sign-positive patients, and 3 in spot-sign-negative patients (p<0·001). Mortality at 3 months was 43·4% (23 of 53) in CTA spot-sign positive versus 19·6% (31 of 158) in CTA spot-sign-negative patients (HR 2·4, 95% CI 1·4-4·0, p=0·002). INTERPRETATION: These findings confirm previous single-centre studies showing that the CTA spot sign is a predictor of haematoma expansion. The spot sign is recommended as an entry criterion for future trials of haemostatic therapy in patients with acute ICH. FUNDING: Canadian Stroke Consortium and NovoNordisk Canada.

Outcomes in acute ischemic strokes presenting with disabling neurologic deficits without intracranial vascular occlusion.

BACKGROUND: Patients with moderate to severe acute ischemic stroke without intracranial vessel occlusion are an intriguing subset of stroke patients. They pose diagnostic and therapeutic challenges to the physician. We sought to study these patients with an emphasis on their radiological and clinical outcomes. METHODS: This is a retrospective cohort study of ischemic stroke patients (NIHSS≥6), with no intracranial vessel occlusion on computed tomography angiography within six-hours of symptom onset. Follow-up imaging - either computed tomography brain or magnetic resonance imaging - was performed within one- to seven-days. The primary outcome was modified Rankin Scale score≤2 at three-months. RESULTS: In a database of 1308 patients, we identified 99 (7·6%) patients with NIHSS≥6 and no intracranial vessel occlusion on computed tomography angiography. The mean age was 67·8 ± 15·4 years and 60 (60·6%) were men. The median baseline NIHSS was nine (6-28). The initial computed tomography head was normal in 79 (79·8%) patients. Dramatic early clinical improvement at 24 h (NIHSS score ≤2 at 24 h or change between baseline and 24 h NIHSS score ≥15 points) was seen in 38 (38·4%) patients. Follow-up scans showed infarcts in 66 (66·7%) patients. Fifty (50·5%) patients received tissue plasminogen activator; one (2%) tissue plasminogen activator-treated patient developed symptomatic intracranial hemorrhage. At three-months; 59 (59·6%) patients were independent (modified Rankin Scale≤2), 34 (34·3%) patients were dependent (modified Rankin Scale 3-5), and six (6·1%) were dead. The factors associated with the unlikelihood of good outcome were higher initial NIHSS (odds ratio 0·86 per additional point, 95% confidence interval 0·77-0·95, P=0·003), and older age (odds ratio 0·95 per additional year, 95% confidence interval 0·92-0·98, P=0·004). CONCLUSION: Stroke without intracranial occlusions are not a benign entity. Factors that are independently associated with decreased likelihood of a good outcome are higher baseline NIHSS, and older age. Treatment with tissue plasminogen activator is not a predictor of outcome.

Quantomo: validation of a computer-assisted methodology for the volumetric analysis of intracerebral haemorrhage.

BACKGROUND: Volume measurements of intracerebral haemorrhage are prognostically important and are increasingly used in clinical trials to measure the effects of potential interventions. The purpose of this work is to establish the reliability of haematoma volume measurements obtained using a computer-assisted method called Quantomo (for quantitative tomography) and the ABC/2 method. Hypothesis Quantomo reliably detects smaller changes in intracerebral haemorrhage volume as compared with the ABC/2 method because computer-assisted volume measurements are tailored to measure the geometry of individual haematoma volumes whereas the ABC/2 method approximates all haematoma volumes as ellipsoids. METHODS: Thirty randomly selected computed tomography scans with intracerebral haemorrhage were measured by four raters a total of four times each (two sessions using Quantomo and two using the ABC/2 method). Interrater and intrarater reliability for both techniques were calculated simultaneously using a two-way random-effects analysis of variance model. The precision of intracerebral haemorrhage volume measurement was quantified as the minimum detectable difference with 95% confidence intervals. RESULTS: The median (first quartile and third quartile) intracerebral haemorrhage volume measurements of all rater and sessions for Quantomo were 32.7 ml (6.2 and 54.4 ml) and for ABC/2 40.7 ml (8.6 and 76.0 ml). Quantomo intracerebral haemorrhage volume measurements were more precise, having an inter- and intrarater minimum detectable difference of 8.1 and 5.3 ml, while the inter- and intrarater minimum detectable difference for ABC/2 were 37.0 and 15.7 ml. CONCLUSIONS: Quantomo is a computer-assisted methodology that is more reliable for quantifying intracerebral haemorrhage volume as compared with the ABC/2 method.