Assessment of nutritional status in patients with Parkinson's disease and its relationship with severity of the disease.

Background: Malnutrition, loss of body weight, muscle and fat mass wasting are common in patients with Parkinson's disease, and are associated with disability, longer length of hospital stay, impaired immune system and increased risk of mortality. The aim of this study was to assess the nutritional status in patients with Parkinson's disease and its relation to the severity of the disease. Methods: This cross- sectional study was conducted on 130 patients with Parkinson's disease, with a mean (SD) age of 59.1 (12.9) years in disease stages of 1 to 4. In this study, the Mini Nutritional Assessment (MNA) questionnaire was used along with anthropometric measurements (Body Mass Index (BMI), Mid-arm circumference (MAC), Calf Circumference (CC)) to evaluate the nutritional status, and they were applied by a trained nutritionist. Hoehn and Yahr Scale were used to determine the severity of the disease. One-way ANOVA test was used to assess the relationship between anthropometric indices, nutritional status and severity of disease. Assessment of the relationship between age, duration of disease and nutritional status was categorized according to MNA score, and was performed, using one-way ANOVA. Chi - Square test was utilized to assess the relationship between education level and nutritional status. SPSS Version 18 was used for data analysis. Results: In this study, 30% (n=39) of the participants were diagnosed with normal nutritional status, 58.5% (n=76) were at risk of malnutrition and 11.5% (n=15) were malnourished according to MNA. Reduction of weight, and muscle mass wasting was observed in different disease stages. Muscle mass wasting and worsening nutritional status, based on MNA score, showed a significant increase as the disease progressed, MAC (p=0.009), MNA score (p<0.001). After assessing the relationship between education level, age, duration of disease with nutritional status, the results revealed a significant relationship between age (p=0.008), education level (p<0.001) with nutritional status according to MNA score. Conclusion: Reduction of BMI, depletion of muscle mass, and worsening of nutritional status according to MNA, was observed in many patients along with an increase in the severity of the disease. Assessing nutritional status in those with Parkinson's disease to provide information to identify necessary nutritional intervention is highly recommended.

The Sac1 domain of SYNJ1 identified mutated in a family with early-onset progressive Parkinsonism with generalized seizures.

This study aimed to elucidate the genetic causes underlying early-onset Parkinsonism (EOP) in a consanguineous Iranian family. To attain this, homozygosity mapping and whole-exome sequencing were performed. As a result, a homozygous mutation (c.773G>A; p.Arg258Gln) lying within the NH2 -terminal Sac1-like inositol phosphatase domain of polyphosphoinositide phosphatase synaptojanin 1 (SYNJ1), which has been implicated in the regulation of endocytic traffic at synapses, was identified as the disease-segregating mutation. This mutation impaired the phosphatase activity of SYNJ1 against its Sac1 domain substrates in vitro. We concluded that the SYNJ1 mutation identified here is responsible for the EOP phenotype seen in our patients probably due to deficiencies in its phosphatase activity and consequent impairment of its synaptic functions. Our finding not only opens new avenues of investigation in the synaptic dysfunction mechanisms associated with Parkinsonism, but also suggests phosphoinositide metabolism as a novel therapeutic target for Parkinsonism.

Identification of COL6A2 mutations in progressive myoclonus epilepsy syndrome.

In this study, a consanguineous family with progressive myoclonus epilepsy (PME) was clinically examined and molecularly investigated to determine the molecular events causing disease. Since exclusion of known genes indicated that novel genes causing PME still remained unidentified, homozygosity mapping, exome sequencing, as well as validation and disease-segregation analyses were subsequently carried out for both loci and gene identification. To further assure our results, a muscle biopsy and gene expression analyses were additionally performed. As a result, a homozygous, disease-segregating COL6A2 mutation, p.Asp215Asn, absent in a large number of control individuals, including control individuals of Iranian ancestry, was identified in both affected siblings. COL6A2 was shown to be expressed in the human cerebral cortex and muscle biopsy revealed no specific histochemical pathology. We conclude that the COL6A2 p.Asp215Asn mutation is likely to be responsible for PME in this family; however, additional studies are warranted to further establish the pathogenic role of both COL6A2 and the extracellular proteolysis system in the pathogenesis of PME.

Relation between Voice Handicap Index (VHI) and disease severity in Iranian patients with Parkinson's disease.

BACKGROUND: One third of patients with Parkinson's disease (PD) have mentioned "dysphonia" as their most debilitating communication deficit. Patient-based measurements, such as Voice Handicap Index (VHI) add necessary supplementary information to clinical and physiological assessment. There are a few studies about relation between VHI and disease severity in PD, although none of them showed any significant correlation. The goal of this study was to find correlation between these variables in Iranian PD patients. METHOD: This cross-sectional, analytical and non-interventional study was done on 23 PD patients who reported a voice disorder related to their disease. They were selected from attendants of movement disorders clinic of Hazrat Rasool Akram Hospital. The relationship between disease severity (according to Hoehn and Yahr/H&Y and Unified Parkinson's Disease Rating Scale-part3 /UPDRS-III) and VHI questionnaire (and its 3 domains) was investigated based on patients' sex, UPDRS-III score H&Y and VHI. RESULTS: Total VHI and its 3 domains had no relationship with disease severity (H&Y) in all patients and by sex separation. However, there was a positive correlation between VHI and disease severity (UPDRS-III) (r = 0.485). There was also a relation between physical and functional domains of VHI and UPDRS (rP=0.530, rF=0.479) while no relationship observed regarding sex differences. 9 out of 18 UPDRS-III items had strong relationship with VHI (total and 3subscales). CONCLUSION: Iranian PD patients feel handicap according to voice disorder caused by PD. Patient satisfaction of voice decreases with the disease severity and progression. A larger sample size is necessary to find relationship in genders. VHI is an important issue could be offered to be used in PD beside other assessments.

Genetic screening in two Iranian families with early-onset Alzheimer's disease identified a novel PSEN1 mutation.

A subset of early-onset Alzheimer's disease is inherited as an autosomal-dominant trait and is associated with mutations in the genes encoding ß-amyloid precursor protein, presenilin 1, or presenilin 2. In this study, we identified 2 PSEN1 mutations (1 novel and 1 known) in 2 unrelated Iranian families with autosomal-dominant Alzheimer's disease. The disease progressed rapidly with a mean age at onset of 33 and 42 years and an age at death ranging from 43 to 48 years.

Relationship Between Voice and Motor Disabilities of Parkinson's Disease.

To evaluate voice of Iranian patients with Parkinson's disease (PD) and find any relationship between motor disabilities and acoustic voice parameters as speech motor components. We evaluated 27 Farsi-speaking PD patients and 21 age- and sex-matched healthy persons as control. Motor performance was assessed by the Unified Parkinson's Disease Rating Scale part III and Hoehn and Yahr rating scale in the "on" state. Acoustic voice evaluation, including fundamental frequency (f0), standard deviation of f0, minimum of f0, maximum of f0, shimmer, jitter, and harmonic to noise ratio, was done using the Praat software via /a/ prolongation. No difference was seen between the voice of the patients and the voice of the controls. f0 and its variation had a significant correlation with the duration of the disease, but did not have any relationships with the Unified Parkinson's Disease Rating Scale part III. Only limited relationship was observed between voice and motor disabilities. Tremor is an important main feature of PD that affects motor and phonation systems. Females had an older age at onset, more prolonged disease, and more severe motor disabilities (not statistically significant), but phonation disorders were more frequent in males and showed more relationship with severity of motor disabilities. Voice is affected by PD earlier than many other motor components and is more sensitive to disease progression. Tremor is the most effective part of PD that impacts voice. PD has more effect on voice of male versus female patients.

PLA2G6-associated Dystonia-Parkinsonism: Case Report and Literature Review.

BACKGROUND: Phospholipase-associated neurodegeneration (PLAN) caused by PLA2G6 mutations is a recessively inherited disorder with three known phenotypes: the typical infantile onset neuroaxonal dystrophy (INAD); an atypical later onset form (atypical NAD); and the more recently recognized young-onset dystonia-parkinsonism (PLAN-DP). CASE REPORT: We report the clinical, radiological, and genetic findings of a young Pakistani male with PLAN-DP. We review 11 previously published case reports cited in PubMed, and summarize the demographic, clinical, genetic, and radiological data of the 23 patients described in those articles. DISCUSSION: PLAN-DP presents with diverse motor, autonomic, and neuropsychiatric features and should be considered in the differential diagnosis of patients with young-onset neurodegenerative disorders.

Biased homozygous haplotypes across the human caveolin 1 upstream purine complex in Parkinson's disease.

The alpha-synuclein-caveolin 1 axis is suggested to be of role in the pathogenesis of Parkinson's disease in cell line models. The objective of this study was to analyze the homozygous haplotype compartment of the human caveolin 1 gene upstream purine complex in patients afflicted with Parkinson's disease. This complex was screened in patients with Parkinson's disease (n = 141) and compared with a group of controls (n = 760) using polymerase chain reaction and sequencing. The expression activity of the homozygous haplotypes was then examined using luciferase Dual-Glo system in human neuronal cell line, LAN-5. Six haplotypes were found to be homozygous in the patients, and not in the control pool (Fisher exact p < 1 × 10(-6)). Three of those haplotypes were specific to Parkinson's disease (Fisher exact p < 0.002), and the remaining three overlapped with homozygous haplotypes in Alzheimer's disease and multiple sclerosis (Fisher exact p < 0.002). The disease haplotypes contained motif lengths that were nonexistent in the control homozygous haplotype pool and significantly increased gene expression (p < 9 × 10(-6)). We conclude that skew in the caveolin 1 purine complex homozygous haplotype compartment and an additive effect of those haplotypes may be linked with Parkinson's disease.

Detection of copy number changes in genes associated with Parkinson's disease in Iranian patients.

Parkinson's disease (PD) is the second most common neurodegenerative disorder, after Alzheimer's disease. Genomic rearrangements are common mutations reported in PD patients. In this study, we investigated the prevalence of genomic rearrangements in a total of 232 Iranian PD patients, out of which 102 were sporadic early-onset (age-at-onset ≤ 45 years) and 51 had a family history. We used multiplex ligation-dependent probe amplification (MLPA) method to detect exon dosage changes. Two new improved probe kits, SALSA P051 and P052, were used and altogether α-synuclein, parkin, UCHL1, PINK1, DJ-1, LRRK2, GCH1, ATP13A2, CAV1, CAV2, LPA and TNFRSF9 genes were analyzed. Exon or whole-gene rearrangements were identified in 14 (13.7%) sporadic early-onset PD patients in parkin, α-synuclein and PINK1. Of familial PD patients 46 cases from 18 families (35.3%) showed exon or whole-gene rearrangements in parkin, α-synuclein, PINK1, DJ-1, and ATP13A2 genes. All changes were verified by quantitative PCR (qPCR). Novel mutations and unusual clinical features are reported in this study. Mutations in parkin were the predominant genetic cause in both early-onset and familial PD groups. Also the mutations observed in family PD group are more in number and diversity than the sporadic early-onset PD group.

Chorea-acanthocytosis: report of three cases from Iran.

Chorea-acanthocythosis (ChAc) is an inherited neurodegenerative disorder characterized by movement disorders, neuropsychiatric disturbances, neuropathy, myopathy, seizures and acanthocytosis accompanied by an elevated serum creatine kinase (CK) level. Its causative gene (VPS13A) produces chorein which is absent in ChAc patients as evaluated by Western blot assay. We report the first three Iranian patients whose disease has been confirmed by chorein Western blot. Our cases presented with heterogeneous courses of ChAc. A high sense of clinical awareness in approaching patients with deteriorating and/or multiple abnormal movements that are accompanied by other neurological signs such as neuropathy, myopathy, seizures and high serum CK level will support an early diagnosis of this disease. We also emphasize on the presence of axial flexion/extension spasms as a good clinical sign for narrowing differential diagnosis.