Neuropsychological dysfunction and neuroimaging abnormalities in neurologically intact adults with sickle cell anemia.

CONTEXT: Sickle cell anemia (SCA) is a chronic illness causing progressive deterioration in quality of life. Brain dysfunction may be the most important and least studied problem affecting individuals with this disease. OBJECTIVE: To measure neurocognitive dysfunction in neurologically asymptomatic adults with SCA vs healthy control individuals. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study comparing neuropsychological function and neuroimaging findings in neurologically asymptomatic adults with SCA and controls from 12 SCA centers, conducted between December 2004 and May 2008. Participants were patients with SCA (hemoglobin [Hb] SS and hemoglobin level < or = 10 mg/dL) aged 19 to 55 years and of African descent (n = 149) or community controls (Hb AA and normal hemoglobin level) (n = 47). Participants were stratified on age, sex, and education. MAIN OUTCOME MEASURES: The primary outcome measure was nonverbal function assessed by the Wechsler Adult Intelligence Scale, third edition (WAIS-III) Performance IQ Index. Secondary exploratory outcomes included performance on neurocognitive tests of executive function, memory, attention, and language and magnetic resonance imaging measurement of total intracranial and hippocampal volume, cortical gray and white matter, and lacunae. RESULTS: The mean WAIS-III Performance IQ score of patients with SCA was significantly lower than that of controls (adjusted mean, 86.69 for patients with SCA vs 95.19 for controls [mean difference, -5.50; 95% confidence interval {CI}, -9.55 to -1.44]; P = .008), with 33% performing more than 1 SD (<85) below the population mean. Among secondary measures, differences were observed in adjusted mean values for global cognitive function (full-scale IQ) (90.47 for patients with SCA vs 95.66 for controls [mean difference, -5.19; 95% CI, -9.24 to -1.13]; P = .01), working memory (90.75 vs 95.25 [mean difference, -4.50; 95% CI, -8.55 to -0.45]; P = .03), processing speed (86.50 vs 97.95 [mean difference, -11.46; 95% CI, -15.51 to -7.40]; P < .001), and measures of executive function. Anemia was associated with poorer neurocognitive function in older patients. No differences in total gray matter or hippocampal volume were observed. Lacunae were more frequent in patients with SCA but not independently related to neurocognitive function. CONCLUSION: Compared with healthy controls, adults with SCA had poorer cognitive performance, which was associated with anemia and age.

Gray matter perfusion correlates with disease severity in ALS.

OBJECTIVE: The goal of this study is to determine if regional brain perfusion, as measured by arterial spin labeling (ASL) MRI, is correlated with clinical measures of amyotrophic lateral sclerosis (ALS) disease severity. The presence of such a relationship would indicate a possible role for ASL perfusion as a marker of disease severity and upper motor neuron involvement in ALS. METHODS: Disease severity was assessed in 16 subjects with ALS (age 54 +/- 11) using the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) and the pulmonary function measure, forced vital capacity (FVC). Upper motor neuron involvement was assessed by testing rapid tapping of the fingers and feet. Magnetic resonance perfusion images were coregistered with structural T1-weighted MRI, corrected for partial volume effects using the structural images and normalized to a study-specific atlas. Correlations between perfusion and ALS disease severity were analyzed, using statistical parametric mapping, and including age as a factor. Analyses were adjusted for multiple clusters. RESULT: ALS severity, as measured by the ALSFRS and FVC, was correlated with gray matter perfusion. This correlation was predominantly observed in the hemisphere contralateral to the more affected limbs. ALSFRS scores correlated with perfusion in the contralateral frontal and parietal lobe (p < 0.001) and ipsilateral frontal lobe (p < 0.02). FVC scores correlated with gray matter perfusion in contralateral frontal lobe (p < 0.001). Upper motor neuron involvement, as measured by rapid finger tapping, correlated bilaterally with perfusion in the middle cingulate gyrus (p < 0.001). CONCLUSION: Amyotrophic lateral sclerosis (ALS) severity is correlated with brain perfusion as measured by arterial spin labeling (ASL) perfusion. This correlation appears to be independent of brain atrophy. ASL perfusion may be a useful tool for monitoring disease progression and assessing treatment effects in ALS.

Orbitofrontal cortex and dynamic filtering of emotional stimuli.

Event-related potentials (ER) were recorded in response to mildly aversive somatosensory and auditory stimuli. Patients with orbitofrontal lesions exhited enhanced ERPs (i.e., P3 amplitudes), as compared with control subjects. Moreover, these patients did not habituate to somatoensory stimuli across blocks of trials. The results were specific to orbitofrontal damage, since patients with damage to the dorsolateral prefontal cortex did not exhibit enhanced P3 amplitudes. These findings suggest damage to the orbitofrontal cortex impairs the ability to modulate or inhibit neural responses to aversive stimuli. The findings are couched in terms of dynamic filtering theory, which suggests that the orbitofrontal cortex is involved in the selection and active inhibition of neural circuits associated with emotional responses.