Comparison of pramipexole versus ropinirole in the treatment of Parkinson's disease.

Background and purpose: Parkinson's disease is a progressive neurodegenerative disease characterized by motor and non-motor symptoms. Levodopa is the most effective drug in the symptomatic treatment of the disease. Dopamine receptor agonists provide sustained dopamin-ergic stimulation and have been found to delay the initiation of levodopa treatment and reduce the frequency of various motor complications due to the long-term use of levodopa. The primary aim of this study was to compare the efficacy of potent nonergoline dopamine agonists pramipexole and ropinirole in both "dopamine agonist monotherapy group" and "levodopa add-on therapy group" in Parkinson's disease. The secondary aims were to evaluate the effects of these agents on depression and the safety of pramipexole and ropinirole. Methods: A total of 44 patients aged between 36 and 80 years who were presented to the neurology clinic at Ministry of Health Diskapi Yildirim Beyazit Training and Research Hospital, Ankara, Turkey and were diagnosed with idiopathic Parkinson's disease, were included into this randomized parallel-group clinical study. Dopamine agonist monotherapy and levodopa add-on therapy patients were randomized into two groups to receive either pramipexole or ropinirole. The maximum daily dosages of pramipexole and ropinirole were 4.5 mg and 24 mg respectively. Patients were followed for 6 months and changes on Unified Parkinson's Disease Rating Scale, Clinical Global Impression-severity of illness, Clinical Global Impression-improvement, Beck Depression Inven-tory scores, and additionally in advanced stages, changes in levodopa dosages were evaluated. Drug associated side effects were noted and compared. Results: In dopamine agonist monotherapy group all of the subsections and total scores of Unified Parkinson's Disease Rating Scale and Clinical Global Impression-severity of illness of the pramipexole subgroup showed significant improvement particularly at the end of the sixth month. In the pramipexole subgroup of levodopa add-on therapy group, there were significant improvements on Clinical Global Impression-severity of illness and Beck Depression Inventory scores, but we found significant improvement on Clinical Global Impression-severity of illness score at the end of the sixth month in ropinirole subgroup too. The efficacy of pramipexole and ropinirole as antiparkinsonian drugs for monotherapy and levodopa add-on therapy in Parkinson's disease and their effects on motor complications when used with levodopa treatment for add-on therapy have been demonstrated in several previous studies. Conclusion: This study supports the effectiveness and safety of pramipexole and ropinirole in the monotherapy and levodopa add-on therapy in the treatment of Parkinson's disease.

Prospective investigation of cerebellar cognitive affective syndrome in a previously non-demented population of acute cerebellar stroke.

OBJECTIVE: In this prospective study, we aimed to investigate the presence and evolution of cerebellar cognitive affective syndrome in a cohort of isolated cerebellar stroke with no known cognitive or psychiatric impairment. We tried to distinguish the unconfounded effect of cerebellar lesions on neuropsychological processing. METHODS: After a meticulous exclusion procedure based on possible confounders, we recruited 14 patients and 13 age-matched healthy controls to the study, prospectively. All of the patients had a detailed initial neuropsychological assessment at the first week and a follow-up assessment at the 4th month after stroke. RESULTS: The prevalence of cognitive or behavioral-affective abnormalities in our cohort were 86% and 64% respectively. The patients exhibited mild and transient affective-behavioral abnormalities except for depressive symptoms that persisted in the subacute stage. They scored lower in general cognitive performance as revealed by mini mental test (p=0.001). Memory, executive functions, attention and working memory, central processing speed, and linguistic abilities were impaired (p<0.001; p=0.001; p=0.007; p=0.05; p<0.001 respectively). Improvement was evident only in memory domain of the cognitive functions in the subacute stage. Cognitive impairment was more likely with a medial or posterolateral infarct (p=0.014). Behavioral-affective abnormalities were not associated with a specific location in our cohort. Age seemed to negatively correlate with the recovery in general cognitive performance on the follow-up. CONCLUSIONS: These findings show that acute denervation of cerebellocortical projections leads to mild affective-behavioral abnormalities, and full-blown cerebellar cognitive affective syndrome is rare. However, cognition was significantly affected after an acute cerebellar infarct even in a previously healthy, non-demented pure population.

Vestibular evoked myogenic potential responses in Parkinson's disease.

BACKGROUND AND PURPOSE: - Our objectives were to determine the differences in the vestibular evoked myogenic potential (VEMP) responses in patients diagnosed with early staged idiopathic Parkinson's disease (PD) compared to the normal population and evaluate the vestibular system disorder causing balance-posture disorders. Second aim of this study was to investigate caloric test responses particularly in early staged PD compared to normal popu-lation. METHODS: Thirty patients (14 females and 16 males; mean age, 60.6 ± 13.1 years) diagnosed with idiopathic PD and 28 healthy subjects (20 males and 8 females; mean age, 59.1 ± 6.4 years) were included. The patient and control groups were subdivided according to their age, gender and the patient group was subdivided according to onset time of the Parkinson symptoms, Hoehn-Yahr staging. The subgroups were compared for VEMP and caloric test responses. RESULTS: There were no significant differences between the study and control groups for right and left VEMP measurements. Patients over 60 years and under 60 years did not show significant differences in terms of right and left mean VEMP measurements. However, P1 amplitude was significantly lower in patients over 60 years old (P = .004). Gender, disease duration, BERG balance scale and Hoehn-Yahr stage had no effect on the VEMP amplitudes. There was no significant correlation with the side of Parkinsonian symptoms to the side of canal paresis (P = .566) and the side on which no VEMP response was obtained in caloric test. CONCLUSION: VEMP responses were not different between PD and healthy subjects. VEMP P1 amplitude was decreased with age in PD group. Canal paresis and symptoms side were not statistically correlated in caloric test.

Tracking Pain in Resting State Networks in Patients with Hereditary and Diabetic Neuropathy.

INTRODUCTION: Chronic pain is associated with maladaptive plastic changes in the brain. It is usually more prominent in acquired pathologies of nerve fibers as in diabetic neuropathy despite less severe degeneration than hereditary neuropathies. Based on clinical differences concerning pain perception, we hypothesized that functional connectivity analysis would reveal distinct patterns in resting-state networks in these groups. METHODS: Ten diabetic patients with painful neuropathy (5F/5M; mean age=50.10±6.05 years), 10 patients with hereditary neuropathy (5F/5M; mean age=37.80±14.01 years), 18 age-and gender-matched healthy controls (eight for painful diabetic neuropathy and 10 for hereditary neuropathy) and seven diabetic controls without painful neuropathy were enrolled in the study. All subjects (n=45) underwent a 5-min resting-state scan in a 3T magnetic resonance scanner. The images were analyzed with seed-based functional connectivity method. The group-level maps of the default mode network and insula-cingulate network were identified for each group. RESULTS: Patients with hereditary neuropathy displayed increased connectivity between left insula and left anterior cingulate cortex and inversely correlated activity between left insula and left inferior parietal lobule compared to their controls. In patients with painful diabetic neuropathy, the major findings were the increased connectivity between left anterior cingulate cortex and posterior cingulate cortex/precuneus, and the increased connectivity between medial prefrontal cortex and left medial temporal region compared to their controls. CONCLUSION: This study revealed that hereditary and diabetic painful neuropathy patients exhibit different patterns of functional connectivity. The clinical differences in these groups regarding the presence of neuropathic pain may relate to this difference in cortical organization.

A prospective case control questionnaire study for restless leg syndrome on 600 pregnant women.

AIM: To evaluate the clinical characteristics of pregnant women with restless leg syndrome (RLS). MATERIALS AND METHODS: A total of 600 pregnant women were asked to complete a questionnaire of RLS and medications. RESULTS: The educational and socio-economical status was significantly lower in study group. The number of patients living in joint family in the study group was statistically higher compared to control group. Hypothyroidism was more frequent in the study group. Calcium and magnesium intake were significantly higher in patients with RLS inversely iron intake was higher in patients without RLS. Lower hemoglobin levels were found to increase the risk of restless leg in pregnancy. Living in a joint family and low educational status were also independent risk factors for restless leg in pregnancy. Iron intake was found to decrease the risk of restless leg. Lower hemoglobin levels were found to be discriminative factor for the presence of RLS. Severity of RLS decreased by iron intake and increased by magnesium intake. CONCLUSION: Hemoglobin levels, iron intake, living in joint family, educational status are the independent risk factors for restless leg in pregnancy. Lower hemoglobin levels and supplementation of iron are the independent predictors for severity of RLS in pregnant women.

Pathophysiology underlying drooling in Parkinson's disease: oropharyngeal bradykinesia.

We aimed to investigate the association between drooling and possible etiological factors in Parkinson's disease (PD) and to determine its effect on the quality of life. Demographic data of the 63 patients with idiopathic PD were recorded. Radboud Oral Motor Inventory for Parkinson's disease (ROMP) test was administered to all patients to evaluate speech, swallowing functions, and saliva control. The freezing of gait questionnaire (FOGQ) was used to evaluate gait and freezing of gait. Dynamic Parkinson gait scale (DYPAGS) was administered for the objective quantification of PD gait features. Disease severity was assessed by UPDRS and modified Hoehn & Yahr Scale. PD specific health-related quality was evaluated by PDQ-39 questionnaire. Drooling was only significantly correlated to UPDRS score; a stronger association was found between drooling and UPDRS 3 motor score; and a more significant association was determined between drooling and the bradykinesia questions of the motor part of UPDRS 3. Interestingly, no significant association was found between sialorrhea score and PDQ-39 score. Based on the results of this study, we concluded that oropharyngeal bradykinesia may be responsible for drooling in PD. In contrast to a general expectation, we did not find any adverse impact of drooling on the quality of life.

Hypoxic Corpus Callosum Lesion after Cardiac Arrest with Good Prognosis.

Hypoxic ischemic damage of the corpus callosum after cardiac arrest is a rare condition. Lesions of the splenium of the corpus callosum after hypoxia are bilateral and lead to poor prognosis. Herein, we present a case with good prognosis after cardiac arrest with bilateral lesions of the splenium of corpus callosum.

In silico approach to inhibition of tyrosinase by ascorbic acid using molecular docking simulations.

Current evidence suggests that endogenous dopamine may act as a neurotoxin following its oxidation to an oquinone and reaction with cellular thiols, which are neutoxic, which may occur spontaneously or via reaction with tyrosinase or some other enzymes. Tyrosinase (E.C. 1.14.18.1) with two cupper ions coordinated by three histidines is a bifunctional enzyme that catalyses both the hydroxylation of tyrosine to L-DOPA and the consequent oxidation of the resulting catechol-containing species to an o-quinone. Therefore, tyrosinase may play a role in neuromelanin formation in the brain and could be central to dopamine neurotoxicity by contributing to the neurodegeneration associated with Parkinson's disease. In the present study, inhibitory effect of ascorbic acid against tyrosinase has been investigated and it has shown a remarkable inhibitory effect in in vitro assays. Then, the in silico-based experiments established through molecular docking calculations and scoring, docking search algorithm, and data plotting indicated that ascorbic acid is strong inhibitor of tyrosinase by interacting with four amino acid units (histidine 263, serine 282, phenylalanine 264, and valin 283) in the active site of the enzyme. The compound also had two long distant hydrogen bindings with Cu1 and Cu2 with distances of 3.57 and 3.41 A, respectively, through its O5 atom.

Acute Motor Conduction Block Neuropathy: Another Distinct Variant of Guillain-Barre Syndrome.

We describe a patient who developed progressive weakness in all limbs without sensory symptoms 4 weeks after upper respiratory system infection. Electrophysiological findings suggested a new variant of Guillain-Barré syndrome named "acute motor conduction block neuropathy". Electrophysiological studies were performed at admission, 12th and 28th weeks. At the 28th week, the clinical examination and electrophysiological findings showed complete recovery.

The effects of lipoprotein(a) and homocysteine on prognosis and risk factors in acute ischemic stroke.

The role of atherosclerosis in ischemic stroke has been intensively investigated in recent years, and homocysteine (Hcy) and lipoprotein(a) Lp(a) were found to have roles during the process. This study aims to investigate the relationship between acute ischemic stroke and Lp(a) and Hcy levels and to determine the prognosis and functional disability. Forty-one patients with acute ischemic stroke and 33 controls were included in the study. Lp(a) and Hcy levels were examined in both groups. The modified Rankin scale (MRS) scores at discharge and in the first and third months were determined to establish the functional disability and prognosis of stroke patients. In patients with acute ischemic stroke, Hcy levels were significantly higher than the controls (p = 0.003). There was no significant difference between Lp(a) levels in patients with acute ischemic stroke and controls (p = 0.150). Because there was a significant difference in terms of Hcy levels between the groups, it will be suitable to routinely monitor the Hcy levels of individuals who are known to have risk factors for stroke. Neither Lp(a) nor Hcy levels had any correlations with functional disability; therefore, it can be concluded that the Lp(a) and Hcy levels are inexpressive in predicting the functional disability and prognosis for ischemic stroke patients.

Contemporary anticholinesterase pharmaceuticals of natural origin and their synthetic analogues for the treatment of Alzheimer's disease.

Alzheimer's disease (AD), the most common form of dementia, is a degenerative and progressive neurological disorder characterized by deficit in the cholinergic transmission and formation of senile plaques containing beta-amyloid protein in the brain. Although complete pathology of the disease has not been fully elucidated yet, there are several treatment strategies for AD treatment. The complexity of AD is also due to involvement of several enzymes through its progression. Therefore, the most important therapeutic approach has emerged as inhibition of acetylcholinesterase (AChE), which is the key enzyme in the breakdown of acetylcholine. Another very attractive approach to lower beta-amyloid protein in fibrillar form has been the alpha- and beta-secretase inhibitors. On the other hand, recently, N-methyl-D-aspartate (NMDA) receptor antagonists have become a strong alternative, which has been approved to be effective in treatment of moderate to severe type of AD. Within the past few years, some pharmaceuticals have become available for clinical use; however, none of them have been shown to possess ability to discontinue the disease up to date. Hence, there is obviously a great need for discovery of new drug candidates of natural or synthetic origins for AD treatment. This review will cover AChE-inhibiting pharmaceuticals from plants and their synthetic derivatives including relevant patent literatures which may promise a future hope for AD treatment.