technetium-tc-99m-bicisate and Narcolepsy

To investigate the effects of modafinil on regional cerebral blood flow (rCBF) in narcolepsy, we performed 99mTc-ethylcysteinate dimer single photon emission computed tomography (SPECT) before and after modafinil or placebo medication.. Brain SPECT was performed twice during the awake state before and after modafinil or placebo administration for 4 weeks in 43 drug-naive narcoleptics with cataplexy (M/F = 23/20, 29.5 +/- 5.8 years). For SPM analysis, all SPECT images were spatially normalized to the standard SPECT template and then smoothed using a 12-mm full width at half-maximum Gaussian kernel. The paired t-test was used to compare pre- and post-modafinil or placebo SPECT images.. The mean modafinil dose used was 207.8 +/- 62.3 mg/day. Modafinil significantly reduced Epworth Sleepiness Scale scores from 20.3 +/- 2.1 to 5.2 +/- 3.1 (P < 0.01), while placebo did not. Compared to the off-modafinil condition, the on-modafinil condition showed significantly increased rCBF in the right dorsolateral and bilateral medial prefrontal cortices. Conversely, after modafinil administration, rCBF was decreased in bilateral precentral gyri, left hippocampus, left fusiform gyrus, bilateral lingual gyri, and cerebellum. There was no significant rCBF change after placebo administration.. By a chronic administration of modafinil in narcoleptic patients, rCBF increased in the bilateral prefrontal cortices, whereas it decreased in left mesio/basal, temporal, bilateral occipital areas, and cerebellum.

Topics: Adolescent; Adult; Benzhydryl Compounds; Brain; Central Nervous System Stimulants; Cerebrovascular Circulation; Cysteine; Female; Humans; Male; Middle Aged; Modafinil; Narcolepsy; Organotechnetium Compounds; Polysomnography; Radiopharmaceuticals; Severity of Illness Index; Tomography, Emission-Computed, Single-Photon

To investigate abnormal cerebral perfusion in narcoleptics with cataplexy, 25 narcoleptics with cataplexy and 25 normal controls were enrolled in this study. Cerebral perfusion was measured by brain single photon emission computed tomography (SPECT) using 99mTc-ethylcysteinate dimer. Patients and normal controls had not received any medication prior to the SPECT scan. Differences in cerebral perfusion between narcoleptics and normal controls were subjected to statistical parametric mapping (SPM) analysis. Overnight polysomnography and multiple sleep latency test (MSLT) were performed in all patients. Brain SPECT was carried out on all patients and normal controls during the waking state. Clinical symptoms and MSLT results of all patients are in accord with the International Classification of Sleep Disorders criteria for narcolepsy. MSLT showed a short mean sleep latency (1.69 +/- 1.0 min) and 2-5 sleep onset REM periods in individual patient. SPM analysis of brain SPECT showed hypoperfusion of the bilateral anterior hypothalami, caudate nuclei, and pulvinar nuclei of thalami, parts of the dorsolateral/ventromedial prefrontal cortices, parahippocampal gyri, and cingulate gyri in narcoleptics [P < 0.05 by Student's t test with false discovery rate (FDR) correction]. Significant hypoperfusion in the white matter of frontal and parietal lobes was also noted in narcoleptics. This study shows reduced cerebral perfusion in subcortical structures and cortical areas in narcoleptics. The distribution of abnormal cerebral perfusion is concordant with the pathway of the cerebral hypocretin system and may explain the characteristic features of narcolepsy, i.e., cataplexy, emotional lability, and attention deficit.

Topics: Adolescent; Adult; Brain; Brain Mapping; Cataplexy; Caudate Nucleus; Cerebrovascular Disorders; Cysteine; Data Interpretation, Statistical; Female; Humans; Hypothalamus; Image Processing, Computer-Assisted; Male; Middle Aged; Narcolepsy; Organotechnetium Compounds; Polysomnography; Radiopharmaceuticals; Sleep; Tomography, Emission-Computed, Single-Photon