Plasma cytokines profile in patients with Alzheimer's and Parkinson's Disease: a comparative study in terms of inflammation.

BACKGROUND: Neurodegenerative disorders such as Alzheimer's and Parkinson's disease inflict economic and health burdens on societies. Alzheimer's disease (AD), the most prevalent form of dementia, is accompanied by progressive degradation of memory, decision-making, and judgment. Parkinson's disease (PD) is characterized by resting tremor, rigidity, bradykinesia, and loss of balance. Extensive research has pinpointed inflammation as a cause of the onset and progression of both diseases. However, it has not been confirmed which one is more formidable in terms of inflammation. METHODS: To assess the extent of inflammation that is implicated in AD and PD and answer the question of which one is more inflammatory, serum levels of inflammatory biomarkers, including cytokines, chemokines, and prostaglandin E2 (PEG2), were measured in AD and PD patients as well as a healthy group. RESULTS: Our results showed a significant increase in IL-1α, IL-1ß, IL-4, IL-6, IL-10, IL-12p70, IP-10, MCP-1, PEG2, and TNF-α in AD and PD patients compared with the control. Interestingly, IFN-γ did not manifest any significant difference in AD or PD patients compared with the control. CONCLUSION: As a hallmark of our results, it could be inferred that inflammation, as the underlying etiological cause, plays a more crucial role in PD compared with AD. Based on our results, it is proposed that anti-inflammatory remedies would be putatively more effective in PD rather than AD.

Psychometric Properties of the Persian Version of Penn Parkinson Daily Activities Questionnaire-15.

Introduction: Appropriate information about the ability of patients with Parkinson disease (PD) to perform cognitive instrumental activities of daily living (IADL) is necessary. The present study aimed to assess the psychometric properties of the Persian version of the Penn Parkinson daily activities questionnaire-15 (PDAQ-15). Methods: A total of 165 knowledgeable informants of PD patients completed the PDAQ-15. The clinical dementia rating scale, Hoehn and Yahr staging, hospital anxiety and depression scale (HADS), and Lawton IADL scale were used in the study. Internal consistency and test-retest reliability were evaluated by the Cronbach α coefficient and intraclass correlation coefficient (ICC), respectively. To examine the dimensionality of the questionnaire, exploratory factor analysis was used. The construct validity was assessed using the Spearman rank correlation test. To assess the discriminative validity, PDAQ-15 scores were compared across cognitive stages. Results: The PDAQ-15 showed strong internal consistency (the Cronbach α=0.99) and test-retest reliability (ICC= 0.99). Only one dimension was identified for the PDAQ-15 in the factor analysis. There was a strong correlation between PDAQ-15 with the depression domain of the HADS scale and the Lawton IADL scale (rs=|0.71-0.95|). The correlation of PDAQ-15 with the anxiety domain of the HADS scale was moderate (rs=0.66). Discriminative validity analysis showed that the PDAQ-15 has significant power to discriminate between PD patients across cognitive stages. Conclusion: These results suggest that the PDAQ-15 is a valid and reliable PD-specific instrument and can be useful in clinical and research settings.

Consensus guidelines for botulinum toxin therapy: general algorithms and dosing tables for dystonia and spasticity.

Botulinum toxin (BT) therapy is a complex and highly individualised therapy defined by treatment algorithms and injection schemes describing its target muscles and their dosing. Various consensus guidelines have tried to standardise and to improve BT therapy. We wanted to update and improve consensus guidelines by: (1) Acknowledging recent advances of treatment algorithms. (2) Basing dosing tables on statistical analyses of real-life treatment data of 1831 BT injections in 36 different target muscles in 420 dystonia patients and 1593 BT injections in 31 different target muscles in 240 spasticity patients. (3) Providing more detailed dosing data including typical doses, dose variabilities, and dosing limits. (4) Including total doses and target muscle selections for typical clinical entities thus adapting dosing to different aetiologies and pathophysiologies. (5) In addition, providing a brief and concise review of the clinical entity treated together with general principles of its BT therapy. For this, we collaborated with IAB-Interdisciplinary Working Group for Movement Disorders which invited an international panel of experts for the support.

Dilemma in Parkinson's Treatment; Levodopa Monotherapy May be the Best Choice.

INTRODUCTION: Several treatment strategies have been claimed for Parkinson's disease (PD) so far. However, there remains controversies over the best possible treatment. The aim of this study is to compare Levodopa monotherapy versus Pramipexole in combination with Levodopa L in patients with PD with regards to the efficacy and side effects. METHODS: Patients being treated with levodopa alone and Pramipexole add-on therapy to Levodopa were enrolled in the study. Factors regarding efficacy and side effects were assessed and analyzed between both groups by appropriate tests. RESULTS: 176 Patients were enrolled in the study. Results showed significant higher total MDS-UPDRS (worse total disease severity score) among patients being treated with Pramipexole add-on therapy which was particularly higher in parts 1 (Mentation, behavior and mood), 2 (Activity of daily living) and 3 (Motor examination) (P-values < 0.05). Psychosis global score with significantly higher frequency of hallucination and depression, statistically higher in combination therapy group compared to Levodopa monotherapy group (P-value < 0.05). Patients in the Pramipexole add-on group reported lower scores of Health-related quality of life (HRQoL) (P-value < 0.05). Significant correlation was between disease duration and psychosis score among Levodopa monotherapy group (P-value < 0.05). CONCLUSIONS: Compared to Levodopa monotherapy, Add-on therapy with Pramipexole shows less efficiency yet more side effects. This indicates that single administration of Levodopa still remains the best available treatment for Parkinson's disease.

A new postural stability-indicator to predict the level of fear of falling in Parkinson's disease patients.

BACKGROUND: Fear of falling (FoF) is defined as a lasting concern about falling that causes a person to limit or even stop the daily activities that he/she is capable of. Seventy percent of Parkinson's disease (PD) patients report activity limitations due to FoF. Timely identification of FoF is critical to prevent its additional adverse effects on the quality of life. Self-report questionnaires are commonly used to evaluate the FoF, which may be prone to human error. OBJECTIVES: In this study, we attempted to identify a new postural stability-indicator to objectively predict the intensity of FoF and its related behavior(s) in PD patients. METHODS: Thirty-eight PD patients participated in the study (mean age, 61.2 years), among whom 10 (26.32%) were identified with low FoF and the rest (73.68%) with high FoF, based on Falls Efficacy Scale-International (FES-I). We used a limit of stability task calibrated to each individual and investigated the postural strategies to predict the intensity of FoF. New parameters (FTRis; functional time ratio) were extracted based on the center of pressure presence pattern in different rectangular areas (i = 1, 2, and 3). The task was performed on two heights to investigate FoF-related behavior(s). RESULTS: FTR1/2 (the ratio between FTR1 and FTR2) was strongly correlated with the FES-I (r = - 0.63, p < 0.001), Pull test (r = - 0.65, p < 0.001), Timed Up and Go test (r = - 0.57, p < 0.001), and Berg Balance Scale (r = 0.62, p < 0.001). The model of FTR1/2 was identified as a best-fitting model to predicting the intensity of FoF in PD participants (sensitivity = 96.43%, specificity = 80%), using a threshold level of ≤ 2.83. CONCLUSIONS: Using the proposed assessment technique, we can accurately predict the intensity of FoF in PD patients. Also, the FTR1/2 index can be potentially considered as a mechanical biomarker to sense the FoF-related postural instability in PD patients.

Effects of treadmill training on the balance, functional capacity and quality of life in Parkinson's disease: A randomized clinical trial.

Background There is growing evidence that exercise modalities have considerable effects on Parkinson's disease (PD). This trial aimed to provide a more detailed viewpoint of short-term and long-term treadmill training (TT) effects on some motor and non-motor features of PD. Methods In this prospective, randomized, single-blind clinical trial, 20 mild to moderate PD patients, admitted in Rasoul-e-Akram hospital in Tehran, Iran, were randomly allocated in case (11) and control (9) groups. Treadmill intervention was performed at moderate intensity with 60% of heart rate reserved (HRR) in two 30-min sessions/week for a duration of 10 weeks. Both the groups were evaluated for three times; at the baseline, 2 months later and then 2 months after the second evaluation. We assigned the Timed Up and Go test (TUG), 6-min walk test (6MW), and the SF-8 healthy questionnaire, for assessment of balance, functional capacity, and Quality of life (QoL), respectively. Results Balance and functional capacity were significantly improved in the case group after the intervention (TUG p-value: 0.003, 6MW p-value: 0.003). Moreover, the long-term analysis revealed significant results as well (TUG p-value: 0.001, 6MW p-value: 0.004). Mental condition's scores of SF-8 in cases were not statistically different in short-term follow-up (F/U). However, analysis illustrated p-value: 0.016 for long-term assessment. The intervention induced significant changes in physical condition's scores in both of the F/Us (PC p-value: 0.013). Conclusions This study provides evidence that a TT of mild to moderate intensity has significant and persistent benefits for the balance, functional capacity, and QoL in PD.

Lee Silverman voice treatment (LSVT) mitigates voice difficulties in mild Parkinson's disease.

Background: Parkinson's disease (PD) is a progressive neurological disorder and many PD patients experience some type of voice and speech disorders during the course of illness. In this study, the aim was to investigate the effect of Lee Silverman voice treatment (LSVT) on improving voice difficulties in patients with mild PD using voice handicap index (VHI). Methods: This interventional study was conducted on 23 PD patients who were randomly divided into 2 groups: a treatment group (PD-T) (n=13) and a no-treatment group (PD-NT) (n=10). Neurologically healthy control (NNC) group consisted of 13 healthy participants who did not suffer from voice and speech problems and were matched with PD group by age (50-65 years), sex, and education. VHI questionnaire was completed a day before the start of LSVT and a day after the treatment fulfillment for the PD-T group; the same time spots were applied for the PD-NT and NNC groups. Statistical analyses were performed using SPSS Statistics 22.0 and significance level was set at 0.05. The multivariate analysis of variance and repeated measure analysis of variance were used for data analysis. Results: PD groups showed a significant weakness in VHI scores before treatment compared to NNC group (p≤ 0.001). The mean of VHI scores for PD-T, PD-NT, and NNC groups before treatment was 44.31±11.23, 43.54±6.10, and 8.15±4.27, respectively. LSVT was successful in improving VHI scores in PD-T group (17.23±5.35, p≤ 0.001). However, no improvement was observed in PD-NT group (44.00±5.88). Conclusion: Improvement in VHI score could be the result of ameliorated self-monitoring and self-regulation created by LSVT.

Effect of Parkinson Disease on Emotion Perception Using the Persian Affective Voices Test.

BACKGROUND AND OBJECTIVES: Emotion perception plays a major role in proper communication with people in different social interactions. Nonverbal affect bursts can be used to evaluate vocal emotion perception. The present study was a preliminary step to establishing the psychometric properties of the Persian version of the Montreal Affective Voices (MAV) test, as well as to investigate the effect of Parkinson disease (PD) on vocal emotion perception. METHODS: The short, emotional sound made by pronouncing the vowel "a" in Persian was recorded by 22 actors and actresses to develop the Persian version of the MAV, the Persian Affective Voices (PAV), for emotions of happiness, sadness, pleasure, pain, anger, disgust, fear, surprise, and neutrality. The results of the recordings of five of the actresses and five of the actors who obtained the highest score were used to generate the test. For convergent validity assessment, the correlation between the PAV and a speech prosody comprehension test was examined using a gender- and age-matched control group. To investigate the effect of the PD on emotion perception, the PAV test was performed on 28 patients with mild PD between ages 50 and 70 years. RESULTS: The PAV showed a high internal consistency (Cronbach's α = 0.80). A significant positive correlation was observed between the PAV and the speech prosody comprehension test. The test-retest reliability also showed the high repeatability of the PAV (intraclass correlation coefficient = 0.815, P ≤ 0.001). A significant difference was observed between the patients with PD and the controls in all subtests. CONCLUSION: The PAV test is a useful psychometric tool for examining vocal emotion perception that can be used in both behavioral and neuroimaging studies.

Treatment of Levodopainduced dyskinesia with Vitamin D: A Randomized, double-blind, placebo-controlled trial.

Dyskinesia refers to any involuntary movement, such as chorea, dystonia, ballism that affect any part of the body. Levodopa-induced dyskinesia is a neurological disorder that afflicts many patients with Parkinson disease usually 5 years after the onset of levodopa therapy and can cause severe disability. The pathophysiology of this dyskinesia is complex and not fully understood. However, the association between vitamin D and Parkinson disease is interesting. The present study was conducted to evaluate the effect of vitamin D on levodopa induced dyskinesia in patients with Parkinson's disease .In this Double blind clinical trial, 120 patients with PD divided into two groups randomly, vitamin D and placebo group. A dose of 1000 IU/d was selected, Demographic information is registered. In the first visit, three variables have been measured which were the duration, severity of dyskinesia and unified Parkinson's disease rating scale (UPDRS). These variables were measured again after 3 months and the data was analyzed using SPSS 22. There are no differences between two groups after 3 months. This study revealed, vitamin D has no effects on improvement of levodopa induced dyskinesia.

Defining spasticity: a new approach considering current movement disorders terminology and botulinum toxin therapy.

Spasticity is a symptom occurring in many neurological conditions including stroke, multiple sclerosis, hypoxic brain damage, traumatic brain injury, tumours and heredodegenerative diseases. It affects large numbers of patients and may cause major disability. So far, spasticity has merely been described as part of the upper motor neurone syndrome or defined in a narrowed neurophysiological sense. This consensus organised by IAB-Interdisciplinary Working Group Movement Disorders wants to provide a brief and practical new definition of spasticity-for the first time-based on its various forms of muscle hyperactivity as described in the current movement disorders terminology. We propose the following new definition system: Spasticity describes involuntary muscle hyperactivity in the presence of central paresis. The involuntary muscle hyperactivity can consist of various forms of muscle hyperactivity: spasticity sensu strictu describes involuntary muscle hyperactivity triggered by rapid passive joint movements, rigidity involuntary muscle hyperactivity triggered by slow passive joint movements, dystonia spontaneous involuntary muscle hyperactivity and spasms complex involuntary movements usually triggered by sensory or acoustic stimuli. Spasticity can be described by a documentation system grouped along clinical picture (axis 1), aetiology (axis 2), localisation (axis 3) and additional central nervous system deficits (axis 4). Our new definition allows distinction of spasticity components accessible to BT therapy and those inaccessible. The documentation sheet presented provides essential information for planning of BT therapy.

A Clinical and Molecular Genetic Study of 50 Families with Autosomal Recessive Parkinsonism Revealed Known and Novel Gene Mutations.

In this study, the role of known Parkinson's disease (PD) genes was examined in families with autosomal recessive (AR) parkinsonism to assist with the differential diagnosis of PD. Some families without mutations in known genes were also subject to whole genome sequencing with the objective to identify novel parkinsonism-related genes. Families were selected from 4000 clinical files of patients with PD or parkinsonism. AR inheritance pattern, consanguinity, and a minimum of two affected individuals per family were used as inclusion criteria. For disease gene/mutation identification, multiplex ligation-dependent probe amplification, quantitative PCR, linkage, and Sanger and whole genome sequencing assays were carried out. A total of 116 patients (50 families) were examined. Fifty-four patients (46.55%; 22 families) were found to carry pathogenic mutations in known genes while a novel gene, not previously associated with parkinsonism, was found mutated in a single family (2 patients). Pathogenic mutations, including missense, nonsense, frameshift, and exon rearrangements, were found in Parkin, PINK1, DJ-1, SYNJ1, and VAC14 genes. In conclusion, variable phenotypic expressivity was seen across all families.

Outcome of subthalamic nucleus deep brain stimulation on long-term motor function of patients with advanced Parkinson disease.

Background: The objective of our study was to assess Unified Parkinson Disease Rating Scale (UPDRS) score in Parkinson disease (PD) patients who underwent subthalamic nucleus (STN) deep brain stimulation (DBS) 6 years after their surgery and to compare their UPDRS score 6 years after DBS with their score before surgery and 6 months after their operation. Methods: In this cross sectional study which was carried out at Neurology Department of Rasool-e Akram Hospital, Tehran, Iran, affiliated to Iran University of Medical Sciences between 2008 and 2014, 37 patients with advanced PD were enrolled using non-randomized sampling method. All of the patients underwent STN DBS surgery and one patient died before being discharged, therefore; we started our study with 36 patients. The UPDRS III total score at preoperative state, 6-month follow-up and 6-year follow-up state were compared using repeated-measure analysis of variance. Results: Thirty-seven patients (26 men and 10 women) with mean age of 50 ± 3 ranging from 32 to 72 years underwent STN DBS surgery. All patients were suffering from advanced PD with mean period of 11.3 ± 1.9 years. All patients except one were followed up for six months. And 14 patients (8 men and 6 women) were included in a six-year follow-up. The UPDRS score measurements before surgery, at 6-month follow-up and 6-year follow-up were 18.22 ± 2.88, 12.80 ± 3.14, 25.0 ± 11.8, respectively. Significant increase in UPDRS score was observed between the preoperative and six-year follow-up period (P < 0.001). Conclusion: In conclusion, this study suggests that total UPDRS score will increase at 5 years following STN DBS and also showed that resting tremor, one of UPDRS sub-scores, will improve over time and the benefit of DBS will be persistent even after 6 years.

Sexual dimorphism in Parkinson's disease: differences in clinical manifestations, quality of life and psychosocial functioning between males and females.

INTRODUCTION: Sex-related differences in clinical manifestations and consequences of Parkinson's disease (PD) have been poorly explored. Better understanding of sexual dimorphism in neurologic diseases such as PD has been announced as a research priority. The aim of our study was to determine independent sex differences in clinical manifestations and subtypes, psychosocial functioning, quality of life (QoL) and its domains between male and female individuals with PD. PATIENTS AND METHODS: A comprehensive list of demographics, motor symptoms and subtypes, nonmotor features, health-related quality of life (HRQoL), psychosocial functioning and general aspects of daily life was assessed in 157 individuals (108 males and 49 females) with idiopathic PD. In order to control for potential confounding variables, we applied Orthogonal Partial Least Squares - Discriminant Analysis (OPLS-DA) to explore the strength of each feature to discriminate male and female patients with PD. RESULTS: While no sex difference was found in the total Unified Parkinson's Disease Rating Scale (UPDRS) score and cumulative daily dose of levodopa, females had significantly more severe anxiety (mean difference =2.2 [95% confidence interval, CI: 0.5-4.0], P=0.011), worse nutritional status (23.8 [standard deviation, SD =4.2] vs 25.8 [SD =2.6], P=0.003) and poorer QoL (28.3 [SD =15.7] vs 17.9 [SD =14.2], P<0.001). Based on multivariate discriminant analysis, emotional well-being, bodily discomfort, social support, mobility and communication domains of HRQoL, together with anxiety, depression and psychosocial functioning, were the strongest features with more severe/worse status in females after adjustment for potential statistical confounders. CONCLUSION: Our study provides a comprehensive understanding of sexual dimorphism in PD. Anxiety, depression, specific domains of HRQoL (mobility, emotional well-being, social support and bodily discomfort) and psychosocial functioning were significantly worse in female individuals with PD. Sexual dimorphism in PD highlights the features that are more likely to be affected in each sex and should be specifically targeted when managing male and female individuals with PD.

A pilot trial of deferiprone in pantothenate kinase-associated neurodegeneration patients.

Pantothenate kinase-associated neurodegeneration (PKAN) is the most common form of neurodegeneration with brain iron accumulation, it is an autosomal recessive disease due to mutation in PANK 2 on chromosome 20, which causes the accumulation of iron in basal ganglia and production of free radicals that cause degeneration of the cells. Deferiprone is an iron chelator that was used in treatment of thalassemia patients, it can cross the blood-brain barrier and reverse the iron deposition in the brain. Five patients with genetically confirmed PKAN received 15 mg/kg deferiprone twice daily. All patients were examined at baseline, 12 and 18 months and magnetic resonance imaging (MRI) was done at the baseline and after 18 months. In our study qualitative evaluation of MRI showed that deferiprone was able to reduce the iron load in globus pallidus of all the patients and the results of clinical rating scales show that in four patients, there is an improvement in the first 12 months. The results of our paper show that deferiprone can prevent the progression of the disease.

RIT2 Polymorphisms: Is There a Differential Association?

Neurological disorders include a wide variety of mostly multifactorial diseases related to the development, survival, and function of the neuron cells. Single-nucleotide polymorphisms (SNPs) have been extensively studied in neurological disorders, and in a number of instances have been reproducibly linked to disease as risk factors. The RIT2 gene has been recently shown to be associated with a number of neurological disorders, such as Parkinson's disease (PD) and autism. In the study reported here, we investigated the association of the rs12456492 and rs16976358 SNPs of the RIT2 gene with PD, essential tremor (ET), autism, schizophrenia (SCZ), and bipolar disorder (BPD; total of 2290 patients), and 1000 controls, by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Significant association was observed between rs12456492 and two disorders, PD and ET, whereas rs16976358 was found to be associated with autism, SCZ, and BPD. Our findings are indicative of differential association between the RIT2 SNPs and different neurological disorders.

Reliability and validity of the Persian translation of Berg Balance Scale in Parkinson disease.

PURPOSE: Parkinson disease (PD) is one of the common causes of imbalance, and the balance assessment is necessary for treatment and rehabilitation of these patients. The Berg Balance Scale (BBS) has been the main instrument used to evaluate balance impairment. The purpose of this study is to investigate reliability and validity of the Persian translation of BBS in Parkinson disease. METHODS: One hundred PD patients (with mean age of 56.8 ± 15.13 years) were included. Interrater reliability was measured with the Kappa statistics and interclass correlation coefficients. RESULTS: The mean values of the BBS scored by the two evaluators were 47/85 ± 11/09 and 48/03 ± 10/90, respectively. The mean of Kappa coefficient between two examiners was 0.76, which was between 0.38 and 0.93 for various items. The total score recorded by both examiners, interclass correlation coefficient, was 0.99, which is excellent. Cronbach's alpha for Iranian version of BBS was 0.92, which shows the excellent reliability of the questionnaire (0.62-0.9 for all items). CONCLUSION: The Persian version of the BBS has excellent interrater reliability and internal consistency for the assessment of PD patients.

PTRHD1 (C2orf79) mutations lead to autosomal-recessive intellectual disability and parkinsonism.

INTRODUCTION: Atypical parkinsonism is a neurodegenerative disease that includes diverse neurological and psychiatric manifestations. OBJECTIVES: We aimed to identify the disease-cauisng mutations in a consanguineous family featuring intellectual disability and parkinsonism. METHODS: Full phenotypic characterization, followed by genome-wide single-nucleotide polymorphism genotyping and whole-genome sequencing, was carried out in all available family members. RESULTS: The chromosome, 2p23.3, was identified as the disease-associated locus, and a homozygous PTRHD1 mutation (c.157C>T) was then established as the disease-causing mutation. The pathogenicity of this PTRHD1 mutation was supported by its segregation with the disease status, its location in a functional domain of the encoding protein, as well as its absence in public databases and ethnicity-matched control chromosomes. CONCLUSION: Given the role of 2p23 locus in patients with intellectual disability and the previously reported PTRHD1 mutation (c.155G>A) in patients with parkinsonism and cognitive dysfunction, we concluded that the PTRHD1 mutation identified in this study is likely to be responsible for the phenotypic features of the family under consideration. © 2016 International Parkinson and Movement Disorder Society.

Botulinum toxin therapy for treatment of spasticity in multiple sclerosis: review and recommendations of the IAB-Interdisciplinary Working Group for Movement Disorders task force.

Botulinum toxin (BT) therapy is an established treatment of spasticity due to stroke. For multiple sclerosis (MS) spasticity this is not the case. IAB-Interdisciplinary Working Group for Movement Disorders formed a task force to explore the use of BT therapy for treatment of MS spasticity. A formalised PubMed literature search produced 55 publications (3 randomised controlled trials, 3 interventional studies, 11 observational studies, 2 case studies, 35 reviews, 1 guideline) all unanimously favouring the use of BT therapy for MS spasticity. There is no reason to believe that BT should be less effective and safe in MS spasticity than it is in stroke spasticity. Recommendations include an update of the current prevalence of MS spasticity and its clinical features according to classifications used in movement disorders. Immunological data on MS patients already treated should be analysed with respect to frequencies of MS relapses and BT antibody formation. Registration authorities should expand registration of BT therapy for spasticity regardless of its aetiology. MS specialists should consider BT therapy for symptomatic treatment of spasticity.