Occurrence of Crohn's disease with Parkinson’s disease

We retrospectively investigated the co-occurrence of Crohn's disease in a cohort of 876 patients with Parkinson’s disease, based on the observation that LRRK2 is a shared genetic risk factor. We identified 2 patients with Crohn's disease; this number was consistent with the number of cases expected in the general population.     

How Parkinson's disease patients recognize Parkinson's disease therapeutic guideline?]

The "Parkinson's disease (PD) therapeutic guideline 2002 (PGL)" was published by Societas Neurologica Japonica in Japan. The guideline, which is based on evidence-based medicine (EBM), is a good reference for making medical decisions. Although physicians recognize the usefulness of the guideline, it is unclear whether PD patients know of the its existence. We performed a survey of 42 PD patients to evaluate their thoughts on the guideline. Sixty-seven percent of the patients had no knowledge of the existence of the PGL. However, after informing them of the existence of the PGL, 93% of the patients welcomed its publication. Forty-three percent of the patients wanted to read the PGL, although they expressed reservation that the PGL might be difficult to understand. Ninety-five percent of the patients answered that they would read the PGL if an easy-to read explanation manual were provided. However, none of the patients wanted an excessively strict obedience to the PGL. Eighty-three percent of the patients wanted a flexible application of the PGL to their own therapy. The PGL seems to have been accepted by the patients. A plain-language explanation manual of the PGL for PD patients, if published, would be helpful to the patients' understanding of PD therapy and to building cooperation between patients and physicians.     

Adeloye-Odeku disease: an African disease in the Indian child?

The "Adeloye-Odeku disease" or congenital dermoid cysts over the anterior fontanelle, is a rare congenital disorder of children initially described in Nigeria. It has been rarely reported in the Indian population (3 cases in 2 reports). These rare lesions are operated on by neurosurgeons in view of their location and differential diagnoses. We present two infants with the condition and a comprehensive review of the literature on pubmed using six common phrases used to describe this condition. The review was undertaken to analyze the reasons for the paucity of cases from the Indian sub-continent. The ethnicity, differential diagnosis, radiological features and management is discussed.     

Quantitative EEG reflects non-dopaminergic disease severity in Parkinson’s disease

Objective

In Parkinson’s Disease (PD), measures of non-dopaminergic systems involvement may reflect disease severity and therefore contribute to patient-selection for Deep Brain Stimulation (DBS). There is currently no determinant for non-dopaminergic disease severity. In this exploratory study, we investigated whether quantitative EEG reflects non-dopaminergic disease severity in PD.

Alpha-synuclein and Parkinson disease

OBJECTIVE:To review the recent progresses on the studies ofα-synuclein in the pathogenesis of Parkinson disease(PD)and look into the perspective ofα-synuclein as a new therapy target.DATA SOURCES:To search the literatures on the progresses of PD studies,especially on the structure,gene expression of α-synuclein and the pathogenesis of PD in Medline from January 1998 to February 2007.Search terms were “Parkinson's disease,α-synuclein” in English.STUDY SELECTION:Initial check the data and choose the original and review articles directly linked to the role of α-synuclein in PD pathogenesis and screening out indirectly discussing articles.Collect the full text and trace the quoting articles and the quoted articles.Only the latest reviews were chosen in Chinese articles.DATA EXTRACTION:There were 424 articles on α-synuclein and its role in the pathogenesis of PD and 43 articles directly related withα-synuclein were chosen among which 12 were reviews.DATA SYNTHESIS:α-synuclein is a kind of soluble protein expressed in pre-synapse in central nervous system encoded by gene in homologous chromosome 4q21.It has physiological function in modulating the stability of membrane and neural plasticity.There is a close relationship between gene mutation inα-synuclein and the pathogenesis of PD.Environmental and genetic factors can induce the misfolding ofα-synuclein,and secondary structural change can result in oligomer formation which induces a series of cascade reaction to damage dopaminergic system subsequently.Cell and animal transgenic and non-transgenic models are established recently and the important role of α-synuclein in the pathogenesis both of familial and sporadic PD is confirmed.Studies reveal that inhibiting the aggregation of α-synuclein can prevent its neurotoxicity;gene parkin can intercept the cell death pathway triggered by the aggregation ofα-synuclein in cytoplasm.CONCLUSION:Gene mutation ofα-synuclein and the impairment in its structure and function are importan in the pathogenesis of PD.Intervention of the gene mutations and abnormal protein aggregation ofα-synuclein may be a new strategy for preventing and treating PD.     

Controversy: is Parkinson's disease a single disease entity? Yes

Parkinson's disease (PD) is a common, and in principle, sporadic, neurodegenerative disorder that occurs in adults. Pathological studies have revealed that in PD, nerve cell loss and Lewy bodies (LB) are distributed widely in the nervous system. Moreover, molecular pathology has made remarkable advances over the last several years, after the identification of alpha-synuclein gene abnormality in familial PD. Extensive pathological findings support the idea that PD is a single disease entity and that there are no cases of PD in which neurodegeneration occurs only in the substantia nigra and in which there are no LBs.     

Is Parkinson’s disease a chronic low-grade inflammatory bowel disease?

Journal of Neurology - While the pathogenesis of Parkinson’s disease is not fully understood, there is increasing evidence that inflammatory responses in the brain are implicated in both...     

Parkinson’s disease in patients and obligate carriers of Gaucher disease

BackgroundGaucher disease is an autosomal recessive disorder caused by glucocerebrosidase gene mutations. Accumulating evidence from several Parkinson’s disease cohorts of varying ethnicities suggests that glucocerebrosidase mutations even in the heterozygous state (carriers) may be a susceptibility factor for Parkinson’s. Very few studies have analyzed the frequency of Parkinson’s in carriers and individuals with Gaucher disease.ObjectiveTo determine frequency of Parkinson’s in patients with Gaucher disease and obligate carriers of glucocerebrosidase mutations and compare it with a control group.MethodsA questionnaire was completed by 100 Ashkenazi Jewish Gaucher patients followed at our center and 109 ethnicity-matched controls with no personal or family history of Gaucher disease.ResultsFrequency of Parkinson’s was higher in Gaucher patients (8/100) than in controls (0/109; P = 0.0024). Frequency of Parkinson’s in obligate carriers (11/200) was higher than controls (6/218), but the difference was not statistically significant (P = 0.215). Average age of onset of Parkinson’s was earlier in Gaucher patients (57.2) than the general population and in obligate carriers (60) when compared with controls (76.8; P = 0.01). The L444P genotype was more frequent in Gaucher patients who reported a parent with Parkinson’s (36.40%) than those who did not (4.50%).ConclusionOur study suggests that the risk for developing Parkinson’s may be higher in affected versus carriers of glucocerebrosidase mutations and suggests that L444P may pose a higher risk of developing Parkinson’s than other mutations. It also confirms previous findings that the age of onset of Parkinson’s associated with glucocerebrosidase mutations is earlier than in the general population.     

Pathological gambling in Parkinson's disease: disease related or drug related?

Pathological gambling and other impulse-control disorders occur in susceptible Parkinson's disease patients during dopaminergic therapy, particularly in association with dopamine agonists. Additional factors such as age at onset play an important role, and predisposing personality traits have been identified both in treated patients, as well as in patients even before therapy is initiated. The contributions of specific allelic polymorphisms of the dopamine receptor and transporter genes were also tested as predictors of adverse effects of dopaminergic therapy but results are not conclusive. Recent imaging studies have shed light on the mechanism underlying pathological gambling. Resting-state brain perfusion of Parkinson's disease gamblers showed higher activity in 'limbic' areas associated with addictive processes. More importantly, severity of this behavior is associated with the impaired functioning of brain regions that are involved in 'top-down' cognitive monitoring and inhibition of inappropriate behaviors. This evidence is consistent with a significant contribution of disease-related factors.     

How do heart disease and stroke become risk factors for Alzheimer's disease?

BACKGROUND: Heart disease and stroke are two of the major leading causes of death and disability in the world. Mainly affecting the elderly population, heart disease and stroke are important risk factors for Alzheimer's disease (AD). METHODS: This review examines the evidence linking chronic brain hypoperfusion (CBH) produced by several types of heart disease and stroke on the development of AD. RESULTS: The evidence indicates a strong association between such risk factors as coronary artery bypass surgery (CABG), atrial fibrillation, aortic/mitral valve damage, hypertension, hypotension, congestive heart failure, cerebrovascular-carotid atherosclerosis, and transient ischemic attacks in producing CBH. In people whose cerebral perfusion is already diminished by their advanced age, further cerebral blood flow reductions from heart-brain vascular-related risk factors, seemingly increases the probability of AD. The evidence also suggests that a neuronal energy crisis brought on by a relentless CBH is responsible for protein synthesis defects that later result in the classic AD neurodegenerative lesions such as the formation of excess beta-amyloid plaques and neurofibrillary tangles. CONCLUSIONS: Knowledge of how heart disease and stroke can progress to AD should provide a better understanding of the physiopathology characteristic of AD and also target more precise therapy in preventing, controlling or reversing this dementia.     

Pathogenesis of motor neuron disease

OBJECTIVE: To summarize and analyze the factors and theories related to the attack of motor neuron disease, and comprehensively investigate the pathogenesis of motor neuron disease. DATA SOURCES: A search of Pubmed database was undertaken to identify articles about motor neuron disease published in English from January 1994 to June 2006 by using the keywords of "neurodegenerative diseases". Other literatures were collected by retrieving specific journals and articles. STUDY SELECTION: The data were checked primarily, articles related to the pathogenesis of motor neuron disease were involved, and those obviously irrelated to the articles were excluded. DATA EXTRACTION: Totally 54 articles were collected, 30 of them were involved, and the other 24 were excluded. DATA SYNTHESIS: The pathogenesis of motor neuron disease has multiple factors, and the present related theories included free radical oxidation, excitotoxicity, genetic and immune factors, lack of neurotrophic factor, injury of neurofilament, etc. The studies mainly come from transgenic animal models, cell culture in vitro and patients with familial motor neuron disease, but there are still many restrictions and disadvantages. CONCLUSION: It is necessary to try to find whether there is internal association among different mechanisms, comprehensively investigate the pathogenesis of motor neuron diseases, in order to provide reliable evidence for the clinical treatment.     

Sporadic Creutzfeldt–Jakob disease

To investigate a possible relationship between the severity of pathological and radiological lesions in diffusion–weighted MRI (DWI) we compared DWI findings from 6 sequential brain MRI scans with pathological features of numerous tissue blocks of different cortical and subcortical regions in a case of autopsy–proven sporadic CJD. Whereas DWI and pathological examination revealed multifocal, cortical and deep hyperintensities at corresponding localizations, no correlation between the degree of severity of radiologically visible and pathological damage was found.The characteristic focal involvement and extension of lesions of the cortex and the basal ganglia bilaterally shown by DWI may be an argument for the spreading of the disease per contiguitatem.     

Gait variability as digital biomarker of disease severity in Huntington’s disease

Journal of Neurology - Impaired gait plays an important role for quality of life in patients with Huntington’s disease (HD). Measuring objective gait parameters in HD might provide an...     

Kennedy's disease: a triplet repeat disorder or a motor neuron disease?

Two definite genetic causes of adult motor neuron degeneration have been identified to date: CAG repeat expansion in the androgen receptor gene in Kennedy's disease and point mutations in the SOD1 gene, encoding the enzyme, Cu/Zn superoxide dismutase, in some familial forms of amyotrophic lateral sclerosis. Although both have unrelated genetic causes, Kennedy's disease and SOD1-linked amyotrophic lateral sclerosis share several pathogenic features. First, expanded androgen receptor and mutant Cu/Zn superoxide dismutase have a propensity to aggregate into insoluble complexes and form inclusion bodies in affected neurons. Deposits of mutant proteins could be detrimental to neuronal viability by interfering with the normal housekeeping functions of chaperones and of the ubiquitin/proteasome system. Secondly, cytoskeletal function may be impaired in both diseases as decreased transactivational activity of expanded androgen receptor may cause an abnormal pattern of tubulin expression in motor neurons in Kennedy's disease and disruption of neurofilament organisation is a hallmark of amyotrophic lateral sclerosis. The concept of activation of overlapping cell death cascades by two distinct genetic defects could help elucidating downstream pathogenic processes and may provide novel targets for pharmacological intervention or gene therapy for the treatment of motor neuron disorders.     

Mitochondrial dysfunction and Huntington disease

Huntington disease (HD) is a chronic autosomal-dominant neurodegenerative disease. The gene coding Huntingtin has been identified, but the pathogenic mechanisms of the disease are still not fully understood. This paper reviews the involvement of mitochondrial dysfunction in pathogenesis of HD.     

Imaging Alzheimer’s disease

Prior reviews on the topic of imaging and Alzheimer’s disease have focused predominately on the technical features of imaging modalities or have summarized the results of epidemiologic studies. As brain scientists and brain practitioners, our main focus should be on the neurobiologic correlates of imaging, so we can intertwine this knowledge with our understanding of disease pathophysiology. A focus on these two features—the neurobiologic correlates of imaging and the pathophysiology of Alzheimer’s disease—has provided the organizing principle of this review.