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[Background] Niemann-Pick disease Type C (NPC) is a genetic, incurable, neurodegenerative disorder. This orphan disease is most frequently caused by mutations in the NPC1 protein, resulting in intralysossomal cholesterol accumulation. NPC1 is found in neuronal cell bodies, axon terminals and synaptosomes, suggesting it plays a role in lysosomal degradation pathway and in synaptic transmission. Neuronal function is especially vulnerable to NPC1 deficiency and synaptic changes seem a key element in disease development. Currently, Miglustat (Zavesca®) is the only approved treatment for NPC. However, preclinical evidence showed that low-dose Efavirenz reverted synaptic defects through pharmacological activation of the enzyme CYP46., [Methods] This is a single-center, phase II clinical trial to evaluate the efficacy and safety of Efavirenz in addition to standard of care in patients diagnosed with adult or late juvenile-onset NPC with cognitive impairment. All enrolled patients will be treated orally with 25 mg/d of Efavirenz for 52 weeks (1 year). Secondary objectives include evaluating clinical (neurological and neuropsychological questionnaires) and biological (imaging and biochemical biomarkers) parameters., [Discussion] NPC is still an unmet medical need. Although different therapeutic approaches are under study, this is the first clinical trial (to the best of our knowledge) studying the effects of Efavirenz in adult- and late-juvenile-onset NPC. Despite the small sample size and the single-arm design, we expect the results to show Efavirenz’s capacity of activating the CYP46 enzyme to compensate for NPC1 deficiency and correct synaptic changes, therefore compensating cognitive and psychiatric changes in these patients. This study may provide direct benefit to enrolled patients in terms of slowing down the disease progression., We thank the Spanish Niemann-Pick Foundation for providing financial support. We also thank the Bellvitge University Hospital, IDIBELL and CERCA Program/Generalitat de Catalunya for institutional support.

Objective: To investigate the factors associated with discrepancies between patient and caregiver reports of the quality of life of patients (QoLp) with Alzheimer"s disease (AD). Methods: Cross-sectional analytic study of 141 patients and their caregivers. The instruments used were the Quality of Life in AD (QoL-AD), the Global Deterioration Scale (GDS), the Geriatric Depression Scale (GDS-d) and the Anosognosia Questionnaire Dementia (AQ-D). Differences were analyzed according to GDS stage. A linear regression analysis was conducted using the difference between the absolute QoLp scores of patients and caregivers. A cluster analysis involving the patient variables was then performed. Results: The discrepancy between patient and caregiver QoLp ratings increased in line with GDS stages (χ2 (2) = 8.7, p = 0.013). In the regression model (F [7,133] = 16.6, p

Background: Sleep-disordered breathing (SDB) is a disease of increasing importance and it is frequent in stroke patients. SDB is being recognized as an independent risk factor for several clinical consequences, including cardiovascular and cerebrovascular disease. Methods: The present review summarizes the current evidence for an independent association between SDB and stroke, defining SDB subgroups, mechanisms, confounding factors and other epidemiological aspects. We analyze stroke outcome and prognosis in SDB patients. A search for recent data on this issue was made in several population-based studies and reference lists of articles. Results: Many recent studies have shown an association between SDB and stroke. Moreover, there is a high prevalence of sleep apnea in patients with stroke. The pathogenesis of stroke in obstructive sleep apnea syndrome is not completely understood and likely to be multifactorial. Several mechanisms like hemodynamic disturbances and inflammatory or endothelial dysfunction could be involved. The presence of SDB in stroke patients may lead to a poor outcome and recurrence. Noninvasive treatments such as continuous positive airway pressure may decrease the risk of stroke in terms of secondary, and possibly, primary prevention. Conclusions: SDB is associated with cerebrovascular morbidity and an unfavorable clinical course. The presence of SDB should be systematically screened in patients with acute stroke. Further studies are needed to determine whether continuous positive airway pressure treatment ameliorates stroke outcome and prognosis.