Comparison of environmental and genetic factors for Parkinson's disease between Chinese and Caucasians

This review paper compares the differences in prevalence, and environmental and genetic risk factors for Parkinson's disease between Chinese and Caucasian subjects. Comparison of age-specific prevalence between Chinese people and Caucasians suggests that the prevalence is lower in the Chinese ( at least in the past), although the prevalence rate in China appears to be rising. Distinctions in environmental risk factors and genetic factors are discussed. The difference in prevalence may be due to distinctions in environmental and genetic risk factors as well as the complex interaction between these environmental and genetic factors, although discrepancies in methodology for prevalence surveys can also be an explanation. Copyright (C) 2004 S. Karger AG, Basel.

Polymorphic CAG repeat length in the androgen receptor gene and association with neurodegeneration in a heterozygous female carrier of Kennedy's disease

Kennedy's disease (spinobulbar muscular atrophy) is an X-linked form of motor neuron disease affecting adult males carrying a CAG trinucleotide repeat expansion within the androgen receptor gene. While expression of Kennedy's disease is thought to be confined to males carrying the causative mutation, subclinical manifestations have been reported in a few female carriers of the disease. The reasons that females are protected from the disease are not clear, especially given that all other diseases caused by CAG expansions display dominant expression. In the current study, we report the identification of a heterozygote female carrying the Kennedy's disease mutation who was clinically diagnosed with motor neuron disease. We describe analysis of CAG repeat number in this individual as well as 33 relatives within the pedigree, including two male carriers of the Kennedy's mutation. The female heterozygote carried one expanded allele of the androgen receptor gene with CAG repeats numbering in the Kennedy's disease range (44 CAGs), with the normal allele numbering in the upper-normal range (28 CAGs). The subject has two sons, one of whom carries the mutant allele of the gene and has been clinically diagnosed with Kennedy's disease, whilst the other son carries the second allele of the gene with CAGs numbering in the upper normal range and displays a normal phenotype. This coexistence of motor neuron disease and the presence of one expanded allele and one allele at the upper limit of the normal range may be a coincidence. However, we hypothesize that the expression of the Kennedy's disease mutation combined with a second allele with a large but normal CAG repeat sequence may have contributed to the motor neuron degeneration displayed in the heterozygote female and discuss the possible reasons for phenotypic expression in particular individuals.

Australian data and meta-analysis lend support for alpha-synuclein (NACP-Rep1) as a risk factor for Parkinson's disease

It remains unclear whether genetic variants in SNCA (the alpha-synuclein gene) alter risk for sporadic Parkinson's disease (PD). The polymorphic mixed sequence repeat (NACP-Rep I) in the promoter region of SNCA has been previously examined as a potential susceptibility factor for PD with conflicting results. We report genotype and allele distributions at this locus from 369 PD cases and 370 control subjects of European Australian ancestry, with alleles designated as -1, 0, +1, +2, and +3 as previously described. Allele frequencies designated (0) were less common in Australian cases compared to controls (OR = 0.80, 95% CI 0.62-1.03). Combined analysis including all previously published ancestral European Rep1 data yielded a highly significant association between the 0 allele and a reduced risk for PD (OR = 0.79, 95% CI 0.70-0.89, p = 0.0001). Further study must now proceed to examine in detail this interesting and biologically plausible genetic association. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

Assessment of disease progression in motor neuron disease

Motor neuron disease (MND) is characterised by progressive deterioration of the corticospinal tract, brainstem, and anterior horn cells of the spinal cord. There is no pathognomonic test for the diagnosis of MND, and physicians rely on clinical criteria-upper and lower motor neuron signs-for diagnosis. The presentations, clinical phenotypes, and outcomes of MND are diverse and have not been combined into a marker of disease progression. No single algorithm combines the findings of functional assessments and rating scales, such as those that assess quality of life, with biological markers of disease activity and findings from imaging and neurophysiological assessments. Here, we critically appraise developments in each of these areas and discuss the potential of such measures to be included in the future assessment of disease progression in patients with MND.

The influence of natural body sway on neuromuscular responses to an unpredictable surface translation

Previous research has shown that the postural configuration adopted by a subject, such as active leaning, influences the postural response to an unpredictable support surface translation. While those studies have examined large differences in postural conditions, it is of additional interest to examine the effects of naturally occurring changes in standing posture. Thus, it was hypothesized that the normal postural sway observed during quiet standing would affect the responses to an unpredictable support surface translation. Seventeen young adults stood quietly on a moveable platform and were perturbed in either the forward or backward direction when the location of the center of pressure (COP) was either 1.5 standard deviations anterior or posterior to the mean baseline COP signal. Postural responses, in the form of electromyographic (EMG) latencies and amplitudes, were recorded from lower limb and trunk muscles. When the location of the COP at the time of the translation was in the opposite, as compared to the same, direction as the upcoming translation, there was a significantly earlier onset of the antagonists (10-23%, i.e. 15-45 ms) and a greater EMG amplitude (14-39%) in four of the six recorded muscles. Stepping responses were most frequently observed during trials where the position of the COP was opposite to the direction of the translation. The results support the hypothesis that postural responses to unpredictable support surface translations are influenced by the normal movements of postural sway. The results may help to explain the large variability of postural responses found between past studies.

Do Psychosocial Interventions Improve Quality of Life and Wellbeing in Adults with Neuromuscular Disorders? A Systematic Review and Narrative Synthesis

Background: Quality of life and well-being are frequently restricted in adults with neuromuscular disorders. As such, identification of appropriate interventions is imperative. Objective: The objective of this paper was to systematically review and critically appraise quantitative studies (RCTs, controlled trials and cohort studies) of psychosocial interventions designed to improve quality of life and well-being in adults with neuromuscular disorders. Method: A systematic review of the published and unpublished literature was conducted. Studies meeting inclusion criteria were appraised using a validated quality assessment tool and results presented in a narrative synthesis. Results: Out of 3,136 studies identified, ten studies met criteria for inclusion within the review. Included studies comprised a range of interventions including: cognitive behavioural therapy, dignity therapy, hypnosis, expressive disclosure, gratitude lists, group psychoeducation and psychologically informed rehabilitation. Five of the interventions were for patients with Amyotrophic Lateral Sclerosis (ALS). The remainder were for patients with post-polio syndrome, muscular dystrophies and mixed disorders, such as Charcot-Marie-Tooth disease, myasthenia gravis and myotonic dystrophy. Across varied interventions and neuromuscular disorders, seven studies reported a short-term beneficial effect of intervention on quality of life and well-being. Whilst such findings are encouraging, widespread issues with the methodological quality of these studies significantly compromised the results. Conclusion: There is no strong evidence that psychosocial interventions improve quality of life and well-being in adults with neuromuscular disorders, due to a paucity of high quality research in this field. Multi-site, randomised controlled trials with active controls, standardised outcome measurement and longer term follow-ups are urgently required.

Gait analysis of the hind limb in Labrador Retrievers with and without cranial cruciate ligament disease

Cranial cruciate ligament (CCL) deficiency is the leading cause of lameness affecting the stifle joints of large breed dogs, especially Labrador Retrievers. Although CCL disease has been studied extensively, its exact pathogenesis and the primary cause leading to CCL rupture remain controversial. However, weakening secondary to repetitive microtrauma is currently believed to cause the majority of CCL instabilities diagnosed in dogs. Techniques of gait analysis have become the most productive tools to investigate normal and pathological gait in human and veterinary subjects. The inverse dynamics analysis approach models the limb as a series of connected linkages and integrates morphometric data to yield information about the net joint moment, patterns of muscle power and joint reaction forces. The results of these studies have greatly advanced our understanding of the pathogenesis of joint diseases in humans. A muscular imbalance between the hamstring and quadriceps muscles has been suggested as a cause for anterior cruciate ligament rupture in female athletes. Based on these findings, neuromuscular training programs leading to a relative risk reduction of up to 80% has been designed. In spite of the cost and morbidity associated with CCL disease and its management, very few studies have focused on the inverse dynamics gait analysis of this condition in dogs. The general goals of this research were (1) to further define gait mechanism in Labrador Retrievers with and without CCL-deficiency, (2) to identify individual dogs that are susceptible to CCL disease, and (3) to characterize their gait. The mass, location of the center of mass (COM), and mass moment of inertia of hind limb segments were calculated using a noninvasive method based on computerized tomography of normal and CCL-deficient Labrador Retrievers. Regression models were developed to determine predictive equations to estimate body segment parameters on the basis of simple morphometric measurements, providing a basis for nonterminal studies of inverse dynamics of the hind limbs in Labrador Retrievers. Kinematic, ground reaction forces (GRF) and morphometric data were combined in an inverse dynamics approach to compute hock, stifle and hip net moments, powers and joint reaction forces (JRF) while trotting in normal, CCL-deficient or sound contralateral limbs. Reductions in joint moment, power, and loads observed in CCL-deficient limbs were interpreted as modifications adopted to reduce or avoid painful mobilization of the injured stifle joint. Lameness resulting from CCL disease affected predominantly reaction forces during the braking phase and the extension during push-off. Kinetics also identified a greater joint moment and power of the contralateral limbs compared with normal, particularly of the stifle extensor muscles group, which may correlate with the lameness observed, but also with the predisposition of contralateral limbs to CCL deficiency in dogs. For the first time, surface EMG patterns of major hind limb muscles during trotting gait of healthy Labrador Retrievers were characterized and compared with kinetic and kinematic data of the stifle joint. The use of surface EMG highlighted the co-contraction patterns of the muscles around the stifle joint, which were documented during transition periods between flexion and extension of the joint, but also during the flexion observed in the weight bearing phase. Identification of possible differences in EMG activation characteristics between healthy patients and dogs with or predisposed to orthopedic and neurological disease may help understanding the neuromuscular abnormality and gait mechanics of such disorders in the future. Conformation parameters, obtained from femoral and tibial radiographs, hind limb CT images, and dual-energy X-ray absorptiometry, of hind limbs predisposed to CCL deficiency were compared with the conformation parameters from hind limbs at low risk. A combination of tibial plateau angle and femoral anteversion angle measured on radiographs was determined optimal for discriminating predisposed and non-predisposed limbs for CCL disease in Labrador Retrievers using a receiver operating characteristic curve analysis method. In the future, the tibial plateau angle (TPA) and femoral anteversion angle (FAA) may be used to screen dogs suspected of being susceptible to CCL disease. Last, kinematics and kinetics across the hock, stifle and hip joints in Labrador Retrievers presumed to be at low risk based on their radiographic TPA and FAA were compared to gait data from dogs presumed to be predisposed to CCL disease for overground and treadmill trotting gait. For overground trials, extensor moment at the hock and energy generated around the hock and stifle joints were increased in predisposed limbs compared to non predisposed limbs. For treadmill trials, dogs qualified as predisposed to CCL disease held their stifle at a greater degree of flexion, extended their hock less, and generated more energy around the stifle joints while trotting on a treadmill compared with dogs at low risk. This characterization of the gait mechanics of Labrador Retrievers at low risk or predisposed to CCL disease may help developing and monitoring preventive exercise programs to decrease gastrocnemius dominance and strengthened the hamstring muscle group.

Behavioural alterations are independent of sickness behaviour in chronic experimental Chagas disease

The existence of the nervous form of Chagas disease is a matter of discussion since Carlos Chagas described neurological disorders, learning and behavioural alterations in Trypanosoma cruzi-infected individuals. In most patients, the clinical manifestations of the acute phase, including neurological abnormalities, resolve spontaneously without apparent consequence in the chronic phase of infection. However, chronic Chagas disease patients have behavioural changes such as psychomotor alterations, attention and memory deficits, and depression. In the present study, we tested whether or not behavioural alterations are reproducible in experimental models. We show that C57BL/6 mice chronically infected with the Colombian strain of T. cruzi (150 days post-infection) exhibit behavioural changes as (i) depression in the tail suspension and forced swim tests, (ii) anxiety analysed by elevated plus maze and open field test sand and (iii) motor coordination in the rotarod test. These alterations are neither associated with neuromuscular disorders assessed by the grip strength test nor with sickness behaviour analysed by temperature variation sand weight loss. Therefore, chronically T. cruzi-infected mice replicate behavioural alterations (depression and anxiety) detected in Chagas disease patients opening an opportunity to study the interconnection and the physiopathology of these two biological processes in an infectious scenario.

The Outcome of Infantile Onset Pompe Disease in South of Iran

Background: Infantile Onset Pompe Disease (IOPD) is a rare autosomal recessive neuromuscular disorder. It is associated with cardiomegaly, hypotonia, paresis, and death in the first year of life. Since 2006, following the use of Alglucosidase alfa as Enzyme Replacement Therapy (ERT), the patients’ survival is improved to a noticeable extent. Objectives: The purpose of this study is to examine the outcome of IOPD patients in South of Iran and the degree of responsiveness to ERT. Patients and Methods: All patients who were diagnosed with IOPD on the bases of clinical symptoms, and enzyme assay on dried blood spot, were included in the study; and were followed up regarding cardiac function, locomotor activity, and cognition. Results: Six patients with IOPD were identified. All these six patients suffered from Hypertrophic Cardiomyopathy (HCM). Four (67%) of them also had generalized hypotonia. Three patients expired during the first weeks due to severe respiratory infection. One of them also got involved with Acute Cardiopulmonary Failure while receiving the fifth dose of ERT; and expired. However, the remaining two patients had a significant improvement after the maximum of 117 weeks of following up both cardiac and locomotor findings. These two patients were the same patients who showed cardiac symptoms from the beginning but did not have generalized hypotonia. Conclusions: Although ERT has a significant effect on enhancing the survival of IOPD patients, it should be associated with meticulous heart-respiratory cares during the first months of treatment and preventing infection especially nosocomial infections.

Adapting The Sniffin' Sticks Olfactory Test To Diagnose Parkinson's Disease In Estonia.

The aim of the study was to develop a culturally adapted translation of the 12-item smell identification test from Sniffin' Sticks (SS-12) for the Estonian population in order to help diagnose Parkinson's disease (PD). A standard translation of the SS-12 was created and 150 healthy Estonians were questioned about the smells used as response options in the test. Unfamiliar smells were replaced by culturally familiar options. The adapted SS-12 was applied to 70 controls in all age groups, and thereafter to 50 PD patients and 50 age- and sex-matched controls. 14 response options from 48 used in the SS-12 were replaced with familiar smells in an adapted version, in which the mean rate of correct response was 87% (range 73-99) compared to 83% with the literal translation (range 50-98). In PD patients, the average adapted SS-12 score (5.4/12) was significantly lower than in controls (average score 8.9/12), p < 0.0001. A multiple linear regression using the score in the SS-12 as the outcome measure showed that diagnosis and age independently influenced the result of the SS-12. A logistic regression using the SS-12 and age as covariates showed that the SS-12 (but not age) correctly classified 79.0% of subjects into the PD and control category, using a cut-off of <7 gave a sensitivity of 76% and specificity of 86% for the diagnosis of PD. The developed SS-12 cultural adaption is appropriate for testing olfaction in Estonia for the purpose of PD diagnosis.