Activation of N-methyl-D-aspartate receptor glycine site temporally ameliorates neuropsychiatric symptoms of Parkinson's disease with dementia.

AIM: We have previously found that sarcosine, a glycine transporter I inhibitor, can improve the psychiatric symptoms of schizophrenia. In this study, we aimed to investigate whether the agent can also ameliorate neuropsychiatric symptoms of Parkinson's disease (PD) patients with dementia. METHODS: An 8-week, double-blind, placebo-controlled trial was conducted in patients who had PD with dementia (PD-D). Neuropsychiatric manifestations were measured before and at week 2 (V1), week 4 (V2) and week 8 (V3) after treatment. Linear regression with the generalized estimating equations was applied for data analysis. RESULTS: Fifteen patients were randomized into a sarcosine group; the other 15 into a placebo group. The generalized estimating equations model revealed significant differences in Hamilton Depression Rating Scale score (P = 0.049) at V1 and Neuropsychiatry Inventory (P = 0.039) at V2 between the treatment and placebo groups. By excluding the advanced patients from analysis, there were significant differences in Unified Parkinson's Disease Rating Scale V2 (P = 0.004) and V3 (P = 0.040), Hamilton Depression Rating Scale V1 (P = 0.014) and V2 (P = 0.047), Neuropsychiatry Inventory V1 (P = 0.002) and V2 (P < 0.001) and Behavior Pathology in Alzheimer's Disease Rating Scale V2 (P = 0.025) in favor of sarcosine. CONCLUSION: Sarcosine temporally improved depression and neuropsychiatric symptoms in PD-D patients without exacerbating the motor or cognitive features; the beneficial effects were more prominent in patients with mild-moderate severity. Enhancement of N-methyl-D-aspartate receptor-glycine cascade may lead to a novel path for the management of PD-D.

Zolpidem improves neuropsychiatric symptoms and motor dysfunction in a patient with Parkinson's disease after deep brain stimulation.

PURPOSE: To illustrate the beneficial effect of zolpidem on the neuropsychiatric and motor symptoms in a patient with Parkinson disease (PD) after bilateral subthalamic nucleus deep brain stimulation. CASE REPORT: The 61-year-old housewife was diagnosed to have PD for 12 years with initial presentation of clumsiness and rest tremor of right limbs. She was referred to our hospital in March 2009 due to shortening of drug beneficial period since 3 years ago and on-phase dyskinesia in recent 2 years. Bilateral STN DBS was conducted on 18 June, 2009. Fluctuating spells of mental confusion were developed on the next day after surgery. Electric stimuli via DBS electrodes were delivered with parameters of 2 volts, 60 µs, 130 Hz on bilateral STN 32 days after DBS. The incoherent behaviors and motor fluctuation remained to occur. The beneficial effect of zolpidem on her neuropsychiatric and motor symptoms was detected incidentally in early July 2009. She could chat normally with her caregiver and walk with assistance after taking zolpidem. The beneficial period may last for 2 hours. Zolpidem was then given in dosage of 10 mg three times per day. The neuropsychiatric inventory was scored 56 during zolpidem 'off' and 30 during zolpidem 'on'. To understand the intriguing feature, we conducted FDG-PET during 'off' and 'on' zolpidem conditions. The results revealed that the metabolism was decreased in the right frontal, parietal cortex and caudate nucleus during zolpidem 'off'. These cool spots can be partially restored by zolpidem. CONCLUSION: Zolpidem ameliorated the neuropsychiatric and parkinsonian motor symptom in the PD patient. Since GABAA benzodiazepine receptors are widely distributed throughout the central nervous system, zolpidem probably acts via modulating structures lying within the cortico-subcortical loop or by direct effect on these cortical regions.

Efficacy of infantile hepatic hemangioma with propranolol treatment: A case report.

RATIONALE: Hepatic hemangioma is rarely discovered during the infantile period. Although most of the cases are asymptomatic, some of them may suffer life-threatening situations. In this regard, early detection is mandatory for preventing the ominous consequences that might be culminated from the disease. PATIENT CONCERNS: A 2-month-14-day-old female infant was found incidentally to have multiple hepatic lesions during a newborn ultrasound screen. She was born smoothly at term after a non-eventful pregnancy course. Physical examination was completely normal and postnatal vital signs were stable. DIAGNOSIS: Infantile multiple hepatic hemangiomas. INTERVENTION: High-resolution ultrasound and abdominal computer tomogram were conducted to confirm the diagnosis. Propranolol was started at the age of 3 months and 7 days old with an initial dosage of 1.5 mg/kg per day and increased gradually to 2.5 mg/kg per day. No obvious adverse effects were noted during the treatment course. Rapid clinical improvement with decreasing size was observed by ultrasound 10 days after the treatment. Eventually, hepatic lesions totally disappeared 4.5 months later. Propranolol in dosage of 2.5 mg/kg per day was continued until 6 months after the initial prescription. OUTCOMES: A period of 11-month follow-up revealed no evidence of recurrence of hemangiomas. LESSONS: Early diagnosis and intervention are mandatory for infantile hepatic hemangiomas to prevent possible ominous consequences. Though the propranolol therapy protocol for the disease is still under developing, the current report strengthens the recommendation to use propranolol as the first-line medication for treating infantile hepatic hemangiomas.

The effects of macrolides in children with reactive airway disease: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Childhood reactive airway diseases (RADs) are concerning problems in children's airways and may be preceded by bronchiolitis and may progress to childhood asthma. The severity of the disease is indicated by deterioration in pulmonary functions, increased usage of rescue medications, and recurrent wheezing episodes. Macrolides have both antimicrobial and anti-inflammatory functions and have been used as adjunctive therapy in childhood RADs. PATIENTS AND METHODS: We conducted a meta-analysis to evaluate the effect of macrolides in children with RAD. Literature searches were systematically conducted using an electronic database from inception to August 2018. The Cochrane review risk of bias assessment tool was used to assess the quality of each randomized controlled trial. RESULTS: Sixteen randomized controlled trials comprising 1,415 participants were investigated in this meta-analysis. Children treated with macrolide therapy showed significantly better pulmonary functions in both forced expiratory volume in one second (% predicted) (difference in means=-9.77, 95% CI=-14.18 to -5.35, P<0.001; I 2=0%) and forced expiratory flow 25-75 (% predicted) (difference in means=-14.14, 95% CI=-26.11 to -2.18, P=0.02; I 2=29.56%). In addition, the short-acting ß-agonist usage days and recurrent wheezing risk were significantly lowered in children with macrolide treatment (standardized difference in means=-0.34, 95% CI=-0.59 to -0.09, P=0.007, I 2=27.05% and standardized difference in means=-0.53, 95% CI=-0.81 to -0.26, P<0.001, I 2=0%, respectively). Furthermore, the growth of Moraxella catarrhalis from nasal swabs was less in children treated with macrolides (odds ratio=0.19, 95% CI=0.11-0.35, P<0.001). Children who took macrolides had a lower risk of adverse events (risk ratio=0.83, 95% CI=0.70-0.98, P=0.024, I 2=0%). CONCLUSION: This current meta-analysis suggested that adjunctive therapy with macrolides is safe and effective for achieving better outcomes in childhood RAD.

Effects of Macrolide Treatment during the Hospitalization of Children with Childhood Wheezing Disease: A Systematic Review and Meta-Analysis.

Children are susceptible to a variety of respiratory infections. Wheezing is a common sign presented by children with respiratory infections. Asthma, bronchiolitis, and bronchitis are common causes of childhood wheezing disease (CWD) and are regarded as overlapping disease spectra. Macrolides are common antimicrobial agents with anti-inflammatory effects. We conducted a comprehensive literature search and a systematic review of studies that investigated the influences of macrolide treatment on CWD. The primary outcomes were the impact of macrolides on hospitalization courses of patients with CWD. Data pertaining to the study population, macrolide treatment, hospital courses, and recurrences were analyzed. Twenty-three studies with a combined study population of 2210 patients were included in the systematic review. Any kind of benefit from macrolide treatment was observed in approximately two-thirds of the studies (15/23). Eight studies were included in the meta-analysis to investigate the influence of macrolides on the length of stay (LOS), duration of oxygen demand (DOD), symptoms and signs of respiratory distress, and re-admission rates. Although the benefits of macrolide treatment were reported in several of the studies, no significant differences in LOS, DOD, symptoms and signs of respiratory distress, or re-admission rates were observed in patients undergoing macrolide treatment. In conclusion, any kind of benefit of macrolide treatment was observed in approximately two-thirds of the studies; however, no obvious benefits of macrolide treatment were observed in the hospitalization courses of children with CWD. The routine use of macrolides to improve the hospitalization course of children with CWD is not suggested.