Impact of Donepezil and Memantine on Behavioral and Psychological Symptoms of Alzheimer Disease: Six-month Open-label Study.

BACKGROUND: Behavioral and psychological symptoms of dementia (BPSD) are common in individuals with Alzheimer disease (AD). Donepezil and memantine are both widely used for the treatment of moderate AD. OBJECTIVE: To evaluate the effects of donepezil and memantine in relieving BPSD in individuals with moderate AD. METHOD: We conducted a prospective, randomized, 6-month clinical trial involving 85 individuals with moderate AD divided into two groups: group 1 (n = 42) was treated with donepezil; group 2 (n = 43) was treated with memantine. We used the Neuropsychiatric Inventory (NPI) to assess the prevalence and severity of BPSD at baseline and after 6 months of treatment with donepezil or memantine. RESULTS: The two groups' baseline characteristics, including age, sex, mean length of education, and disease duration, were comparable, as were their baseline Mini-Mental State Examination scores. The NPI Total score improved from baseline to month 6 in both groups (P < 0.0001). Analyses of the NPI subdomains revealed that both donepezil treatment and memantine treatment produced statistically significant improvement in all of the NPI domains except euphoria and apathy, for which no improvement was observed after memantine treatment. Both treatments were well tolerated, with mostly mild and transient adverse effects. CONCLUSION: Specific drugs for AD, including donepezil and memantine, may be effective in treating BPSD in individuals with moderate AD, with a favorable safety profile.

THE VALUE OF BLINK REFLEX IN EARLY DIAGNOSIS OF MULTIPLE SCLEROSIS.

The aim was to determine differences of blink reflex in clinically definite multiple sclerosis (CDMS) and clinically isolated syndrome (CIS) in patients presented with symptoms and signs of brainstem impairment. The study included 20 patients diagnosed with CDMS, 20 with CIS, and 20 healthy controls. We recorded latencies of early (R1) and late component ipsilaterally (R2) and contralaterally (R2'), and occurrence of irritative component (R3). We analyzed data on sex, age, signs of brainstem impairment and magnetic resonance imaging (MRI) findings for the presence of brainstem demyelinating lesions. There was no statistically significant difference between patient groups according to sex, age, symptoms of brainstem involvement and MRI findings. There was no statistically significant difference in R1 component latencies and R2 latencies on the right side. Latencies of R2 on the left and R2' on the right were statistically longer in CDMS group. There was no difference in the appearance of R3 component. In conclusion, blink reflex was found to be a very sensitive and useful diagnostic tool in the assessment of brainstem structures, especially because abnormalities are seen not only in CDMS but also in CIS. Slowing of the late component as a sign of dysfunction in the efferent part of the reflex arc is not very specific but is a highly sensitive finding.

RANKL/RANK/OPG Axis Is Deregulated in the Cerebrospinal Fluid of Multiple Sclerosis Patients at Clinical Onset.

OBJECTIVES: Our study focused on the RANKL (receptor activator of nuclear factor-κB ligand)/RANK/OPG (osteoprotegerin) axis and selected proinflammatory/immunoregulatory upstream mediators in the peripheral blood (PBL) and cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients. METHODS: PBL and CSF were collected from healthy controls (n = 35) and MS patients at the clinical onset of the disease (n = 33). In addition, PBL samples were obtained from relapse-remitting (RR)-MS patients (n = 30). Patients were assessed by means of the expanded disability status scale (EDSS) and routine laboratory parameters. Soluble (s)RANKL and OPG were measured in the CSF and plasma; gene expression was detected for RANKL, RANK, OPG, and selected cytokines/chemokines (interleukin [IL]-4, IL-10, IL-17, CCL2, and CXCL12) in PBL mononuclear cells. RESULTS: The OPG level in the CSF was lower in MS patients at clinical onset than in controls. Moreover, the sRANKL/OPG ratio was higher in the CSF of MS patients at clinical onset and in the plasma of RR-MS patients than in controls. Gene expression of RANKL/RANK/OPG in PBL mononuclear cells was higher only in RR-MS patients. IL-4, CCL2, and CXCL12 were positively correlated and IL-10 was negatively correlated with RANKL/RANK expression. OPG was negatively correlated with EDSS and alkaline phosphatase level. CONCLUSION: Our study revealed that changes of RANKL/RANK/OPG axis are associated with MS, particularly the decreased OPG level in the CSF at disease onset. Therefore, these factors may serve as disease biomarkers and molecular targets of novel therapeutic approaches.

Nonmotor symptoms in de novo Parkinson disease comparing to normal aging.

OBJECTIVE: Nonmotor symptoms (NMSs) are common in Parkinson disease (PD), affecting patient's quality of life. The prevalence and domains of NMSs in untreated de novo PD remains unclear, especially comparing to normal aging. The objective was to determine NMSs in untreated de novo PD patients. PATIENTS AND METHODS: We performed a cross-sectional study to evaluate the frequency and severity of NMSs in untreated de novo PD patients (n=71) and age-matched normal controls (n=60) using the Non-Motor Symptoms Scale (NMSS). The motor section of the Unified Parkisnon Disease Rating Scale (mUPDRS) and the Hoehn and Yahr (HY) stage were also obtained in PD patients RESULTS: The number of NMSs and the NMSS scores were significantly higher in the PD patients than in controls (p<0.001). There was no correlation of the NMSS scores with age and sex in both group and additionally with mUPDRS score and HY stage in PD patients group. Mood/cognition, attention/memory and gastrointestinal domains are the most frequent in PD patients and rarely seen in controls. CONCLUSION: NMSs in untreated de novo PD patients are more prevalent and severe with different domain involvement comparing to normal aging.

Ambulatory arterial stiffness index and carotid intima-media thickness in hypertensive rheumatoid patients: a comparative cross-sectional study.

AIM: Rheumatoid arthritis is associated with accelerated atherosclerosis. However, little is known about preclinical atherosclerosis in hypertensive rheumatoid arthritis patients. In this cross-sectional study we assessed the expression of preclinical atherosclerosis in hypertensive rheumatoid arthritis patients in comparison with matched hypertensive non-rheumatoid arthritis patients. METHODS: The study included 52 hypertensive rheumatoid arthritis patients and 42 hypertensive non-rheumatoid arthritis patients. The patients were extensively examined clinically and laboratory tested. The expression of preclinical atherosclerosis was estimated by assessing ambulatory arterial stiffness index and common carotid intima-media thickness. RESULTS: Arterial stiffness index and common carotid intima-media thickness were higher in hypertensive rheumatoid arthritis patients than in hypertensive non-rheumatoid arthritis patients. There was no correlation between arterial stiffness index and common carotid intima-media thickness with markers of inflammation and disease activity in hypertensive rheumatoid arthritis patients. CONCLUSION: The expression of subclinical atherosclerosis is more pronounced in hypertensive rheumatoid arthritis than in hypertensive non- rheumatoid arthritis patients.

Decreased level of sRAGE in the cerebrospinal fluid of multiple sclerosis patients at clinical onset.

OBJECTIVES: Receptor for advanced glycation end products (RAGE) ligands/RAGE interactions have been proposed to have a pathogenic role in neuroinflammatory disorders. Our study aimed to assess changes in high-mobility group box (HMGB)1 and its receptor RAGE in peripheral blood (PBL) and cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) at the disease onset compared with control subjects. METHODS: PBL and CSF were collected from control subjects (n = 30) and MS patients (n = 27) at clinical onset. Soluble RAGE (sRAGE), HMGB1, S100 calcium-binding protein A12 (S100A12), interleukin (IL)-1ß and tumor necrosis factor (TNF)-α were measured in the CSF and plasma by enzyme-linked immunosorbent assay. Gene expression in PBL mononuclear cells (PBMCs) was detected by quantitative PCR for RAGE, HMGB1, S100A12 and several proinflammatory/immunoregulatory cytokines. RESULTS: We found a significantly lower expression of IL-10 (p = 0.031) in the PBMCs of MS patients. The level of sRAGE in the CSF of MS patients was lower (p = 0.021), with the ability to discriminate between MS patients and control subjects. Moreover, PBMC gene expression for HMGB1 and S100A12 positively correlated with IL-6. CONCLUSIONS: Our study confirmed that the cytokine network is disturbed in PBL and CSF at MS clinical onset. The deregulated HMGB1/RAGE axis found in our study may present an early pathogenic event in MS, proposing sRAGE as a possible novel therapeutic strategy for MS treatment.

Normal pressure form of the spontaneous intracranial hypotension: a case report with pituitary enlargement and asymptomatic pituitary haemorrhage.

Spontaneous intracranial hypotension is a rare condition caused by spontaneous cerebrospinal fluid leak and volume depletion. It is initially misdiagnosed as a cause of an orthostatic headache, which is the most important symptom of the syndrome. It can be presented as one of four types: classic form, normal pressure form, normal pachymeninges form and acephalgic form. The diagnosis is made based on the clinical presentation, physical examination, typical cerebrospinal fluid and magnetic resonance imaging findings. We present a case of a 29-year-old woman with uncommon normal pressure form of the spontaneous intracranial hypotension, characterized by normal cerebrospinal fluid opening pressure, and typical clinical and magnetic resonance imaging findings, including the finding of pituitary gland enlargement with asymptomatic pituitary haemorrhage as an unusual complication.

Effect of educational programs on asthma control and quality of life in adult asthma patients.

This study investigated the effectiveness of different educational programs in obtaining better asthma control and asthma-related quality of life (QoL). In 60 adult patients with moderate persistent asthma we tested the benefit of individual verbal instructions (IVI), written information ("asthma booklet", B), and integrated asthma classes ("asthma school", AS). At the enrollment and at the end of the study, all participants completed the questionnaires regarding their asthma-related knowledge (ArK) and QoL. During the 12-week period all patients recorded their asthma symptoms, morning and evening peek expiratory flow rates (PEFR), and the use of rescue medication. AS and IVI groups showed a significantly greater improvement in QoL than the B group. AS group obtained the highest ArK but no difference in the level of improvement among the groups has been documented. The improved average asthma symptom score and decreased utilization of the rescue medication were documented in all groups without significant differences among them. We also found significant improvements in both morning and evening PEFR in IVI group as well as in the morning PEFR in AS group. We conclude that among tested educational interventions the AS caused the best improvement in QoL while IVI produced the best overall response in both parameters of the asthma control and QoL.