The effects of atomoxetine on emotional control in adults with ADHD: An integrated analysis of multicenter studies.

PURPOSE: To investigate the effects of atomoxetine on emotional control in adults with ADHD. METHODS: We performed an integrated analysis using individual patient data pooled from three Eli Lilly-sponsored studies. An integrated analysis can be viewed as a meta-analysis of individual patient-level data, rather than study-level summary data. RESULTS: Two populations were identified: a large sample of patients with pre-treatment baseline data (the "overall population"; n=2846); and a subset of these patients with placebo-controlled efficacy data from baseline to 10 or 12 weeks after initiating treatment (the "placebo-controlled population"; n=829). At baseline, in the overall population, ∼50% of ADHD patients had BRIEF-AS (Behavior Rating Inventory of Executive Function-Adult Version Self-Report) Emotional control subscores between 21 and 30, compared with ∼10% of normative subjects in the BRIEF-A manual. At endpoint, in the placebo-controlled population, atomoxetine led to a small (effect size 0.19) but significant (P=0.013) treatment effect for emotional control. The effect size was 0.32 in patients with BRIEF-AS Emotional control scores>20 at baseline. Improvements in emotional control correlated with improvements in the core ADHD symptoms and quality-of-life. DISCUSSION: As deficient emotional control is associated with impaired social, educational and occupational functioning over and above that explained by core ADHD symptoms alone, improvements in emotional control may be clinically relevant. CONCLUSION: At baseline, adults with ADHD were more likely to have impaired emotional control than normative subjects. In the adult ADHD patients, atomoxetine treatment was associated with improvements in emotional control, as well as in core ADHD symptoms and quality-of-life.

Fatal neurogenic pulmonary edema in a patient with progressive multiple sclerosis.

We report a case of fatal neurogenic pulmonary edema in progressive multiple sclerosis (MS). The patient had one isolated relapse-like episode. Six years later progressive disease began, lasting 5 years until unexpected death during sleep. Medico-legal autopsy revealed pulmonary edema and neuropathological examination showed infiltrations with lymphocytes and microglia in the respiratory centers of the medulla. More classical demyelinated lesions were found in the white matter of spinal cord and in the gray matter of the brain along with disseminated perivascular lymphocytic infiltrates. Medullary inflammation in progressive MS may result in sudden fatal respiratory failure.

Cognitive function and fMRI in patients with multiple sclerosis: evidence for compensatory cortical activation during an attention task.

Mild cognitive impairment has frequently been reported for patients in the early stages of multiple sclerosis. The aim of the present study was to measure whether altered cortical activation during a sustained attention task occurs along with limited extent of neuropsychological problems. Expanded brain activation of multiple sclerosis patients with normal motor function compared with healthy controls during a finger tapping paradigm has previously been reported. Compensatory brain activation in patients with multiple sclerosis compared with normal controls may also be observed when the subjects are performing cognitive functions. In 21 patients with clinically definite relapsing-remitting multiple sclerosis, a psychometric assessment was performed using the Wechsler Memory Scale (WMS) and the Multiple Sclerosis Functional Composite Score (MSFC). In addition, functional MRI was performed during a Paced Visual Serial Addition Task (PVSAT), a visual analogue of the Paced Auditory Serial Addition Task (PASAT). All patients were within 3 years of diagnosis and were not suffering from a relapse at the time of investigation. The multiple sclerosis patients were compared with a control group of 21 healthy volunteers matched for handedness, age, years of education and sex. With regard to psychometric results, the WMS general memory score showed statistically significant differences between patients and controls. We did not find differences for either the MSFC or the PASAT scores. A group analysis of the functional imaging data during the PVSAT revealed different activation patterns for patients compared with control subjects. In healthy volunteers, the main activation was found in the frontal part of the right gyrus cinguli (Brodmann area 32). In patients, the main activation was detected at the right hemispheric frontal cortex (Brodmann areas 6, 8 and 9). In addition, the left hemispheric Brodmann area 39 was activated. We interpret the different patterns of activation, accompanied with intact performance in a sustained attention task of our multiple sclerosis sample compared with healthy controls, as the consequence of compensatory mechanisms. This is an expression of neuronal plasticity during early stages of a chronic disease.