Gender differences in Parkinson’s disease Haaxma, Charlotte A; Bloem, Bastiaan R; Borm, George F ...
Journal of neurology, neurosurgery and psychiatry,
08/2007, Letnik:
78, Številka:
8
Journal Article
Recenzirano
Odprti dostop
Objective: To investigate gender differences in basic disease characteristics, motor deterioration and nigrostriatal degeneration in Parkinson’s disease (PD). Methods: We studied 253 consecutive PD ...patients who were not receiving levodopa or dopamine agonists (disease duration ⩽10 years). We investigated the influence of gender and oestrogen status on: (1) age at onset, (2) presenting symptom, (3) severity and progression of motor symptoms (Unified Parkinson’s Disease Rating Scale III (UPDRS-III) scores) and (4) amount and progression of nigrostriatal degeneration (123IFP-CIT single photon emission computed tomography measurements). Results: Age at onset was 2.1 years later in women (53.4 years) than in men (51.3 years). In women, age at onset correlated positively with parity, age at menopause and fertile life span. Women more often presented with tremor (67%) than men (48%). Overall, patients presenting with tremor had a 3.6 year higher age at onset and a 38% slower UPDRS-III deterioration. Mean UPDRS-III scores at disease onset were equal for both genders, as was the rate of deterioration. Women had a 16% higher striatal 123IFP-CIT binding than men at symptom onset and throughout the course of PD. Conclusions: Our results suggest that, in women, the development of symptomatic PD may be delayed by higher physiological striatal dopamine levels, possibly due to the activity of oestrogens. This could explain the epidemiological observations of a lower incidence and higher age at onset in women. Women also presented more often with tremor which, in turn, is associated with milder motor deterioration and striatal degeneration. Taken together, these findings suggest a more benign phenotype in women with PD.
To assess the prevalence, nature, and associated phenotypes of PINK1 gene mutations in a large series of patients with early-onset (<50 years) parkinsonism.
The authors studied 134 patients (116 ...sporadic and 18 familial; 77% Italian) and 90 Italian controls. The whole PINK1 coding region was sequenced from genomic DNA; cDNA was analyzed in selected cases.
Homozygous pathogenic mutations were identified in 4 of 90 Italian sporadic cases, including the novel Gln456Stop mutation; single heterozygous truncating or missense mutations were found in another 4 Italian sporadic cases, including two novel mutations, Pro196Leu and Gln456Stop. Pathogenic mutations were not identified in the familial cases. Novel (Gln115Leu) and known polymorphisms were identified with similar frequency in cases and controls. In cases carrying single heterozygous mutation, cDNA analysis detected no additional mutations, and revealed a major pathogenic effect at mRNA level for the mutant C1366T/Gln456Stop allele. All patients with homozygous mutations had very early disease onset, slow progression, and excellent response to l-dopa, including, in some, symmetric onset, dystonia at onset, and sleep benefit, resembling parkin-related disease. Phenotype in patients with single heterozygous mutation was similar, but onset was later.
PINK1 homozygous mutations are a relevant cause of disease among Italian sporadic patients with early-onset parkinsonism. The role of mutations found in single heterozygous state is difficult to interpret. Our study suggests that, at least in some patients, these mutations are disease causing, in combination with additional, still unknown factors.
Abstract The healthy brain appears to have an asymmetric dopamine distribution, with higher levels of dopamine in the left than in the right striatum. Here, we test the hypothesis that this ...neurochemical asymmetry renders the right striatum relatively more vulnerable to the effects of dopaminergic denervation in Parkinson's disease (PD). Using the pegboard dexterity test, we compared motor performance of both hands between healthy subjects ( n =48), PD patients with predominantly right-hemispheric dopamine depletion (PD-RIGHT; n =83) and PD patients with more severe left-hemispheric dopamine depletion (PD-LEFT; n =103). All subjects were right-handed. After adjusting for hand-dominance effects, we found that PD-RIGHT patients exhibited a 55% larger difference between right and left dexterity scores than PD-LEFT patients. This effect could be attributed to greater motor dysfunction of the more-affected hand in PD-RIGHT patients, while the less-affected hand performed similarly in both groups. We conclude that the side of symptom onset affects motor dysfunction in PD, and suggest that the non-dominant right hemisphere may be more susceptible to dopaminergic denervation than the dominant left hemisphere.
Background
Prehabilitation is a novel clinical strategy to optimize patients’ health in the waiting period before surgery.
Objectives
This article aims to gather the evidence for the effectiveness of ...unimodal, non-pharmacological psychological prehabilitation interventions on preoperative anxiety and stress before surgery.
Design
This is a PRISMA-guided systematic review and narrative synthesis of randomized controlled trials.
Methods
The online databases Medline, Embase, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, PsycINFO and Google Scholar were searched on March 20th 2023. The search strategy led to 13,667 records screened and five records of randomized controlled trials included for full-text analysis. A risk-of-bias assessment was performed using the Revised Cochrane Risk of Bias 2 tool.
Results
Significant reduction in preoperative anxiety was seen in three studies comprising 337 participants. Two studies did not find that unimodal psychological prehabilitation reduces preoperative anxiety. Only one study assessed preoperative stress and reported a significant reduction. Intervention types used included guided imagery, stress management training, virtual reality experience and computer cognitive behavioral therapy.
Conclusions
There is contradictory evidence whether unimodal, non-pharmacological psychological prehabilitation can reduce preoperative anxiety. There is little evidence that non-pharmacological prehabilitation can reduce preoperative stress. Suggestions to improve the research in this field are discussed.
To assess the prevalence, nature, and associated phenotypes of ATP13A2 gene mutations among patients with juvenile parkinsonism (onset <21 years) or young onset (between 21 and 40 years) Parkinson ...disease (YOPD).
We studied 46 patients, mostly from Italy or Brazil, including 11 with juvenile parkinsonism and 35 with YOPD. Thirty-three cases were sporadic and 13 had positive family history compatible with autosomal recessive inheritance. Forty-two had only parkinsonian signs, while four (all juvenile-onset) had multisystemic involvement. The whole ATP13A2 coding region (29 exons) and exon-intron boundaries were sequenced from genomic DNA.
A novel homozygous missense mutation (Gly504Arg) was identified in one sporadic case from Brazil with juvenile parkinsonism. This patient had symptoms onset at age 12, levodopa-responsive severe akinetic-rigid parkinsonism, levodopa-induced motor fluctuations and dyskinesias, severe visual hallucinations, and supranuclear vertical gaze paresis, but no pyramidal deficit nor dementia. Brain CT scan showed moderate diffuse atrophy. Furthermore, two Italian cases with YOPD without atypical features carried a novel missense mutation (Thr12Met, Gly533Arg) in single heterozygous state.
We confirm that ATP13A2 homozygous mutations are associated with human parkinsonism, and expand the associated genotypic and clinical spectrum, by describing a homozygous missense mutation in this gene in a patient with a phenotype milder than that initially associated with ATP13A2 mutations (Kufor-Rakeb syndrome). Our data also suggest that ATP13A2 single heterozygous mutations might be etiologically relevant for patients with YOPD and further studies of this gene in Parkinson disease are warranted.
To construct an early health economic model to assess the potential added value of novel hearing therapeutics, compared with the current standard of care. We use idiopathic sudden sensorineural ...hearing loss (ISSNHL) as a case example, because it is a lead indication for several emerging hearing therapeutics.
A decision analytic model was developed to assess the costs and effects of using novel hearing therapeutics for patients with ISSNHL. This was compared to the current standard of care. Input data were derived from literature searches and expert opinion. The study adopted a healthcare perspective of the UK National Health Service. Four analyses were conducted: 1) headroom, 2) scenario, 3) threshold, 4) sensitivity.
The decision analytic model showed that novel therapeutics for ISSNHL have potential value both in terms of improved patient outcomes, as well as incremental net monetary benefit (iNMB). The base case analysis revealed an iNMB of £39,032 for novel therapeutics compared with the current standard of care. Results of the threshold and scenario analysis revealed that age of treatment and severity of ISSNHL are major determinants of iNMB for novel therapeutics.
This article describes the first health economic model for novel therapeutics for hearing loss; and shows that novel hearing therapeutics can be cost-effective under NICE's cost-effectiveness threshold, with considerable room for improvement in the current standard of care. Our model can be used to inform the development of cost-effective hearing therapeutics; and help decision makers decide which therapeutics represent value for money.
The aim of the study was to provide evidence‐based recommendations for the management of early (uncomplicated) Parkinson's disease (PD), based on a review of the literature. Uncomplicated PD refers ...to patients suffering from the classical motor syndrome of PD only, without treatment‐induced motor complications and without neuropsychiatric or autonomic problems. MEDLINE, Cochrane Library and International Network of Agencies for Health Technology Assessment (INAHTA) database literature searches were conducted. National guidelines were requested from all European Federation of Neurological Societies (EFNS) societies. Non‐European guidelines were searched for using MEDLINE. Part I of the guidelines deals with prevention of disease progression, symptomatic treatment of motor features (parkinsonism), and prevention of motor and neuropsychiatric complications of therapy. For each topic, a list of therapeutic interventions is provided, including classification of evidence. Following this, recommendations for management are given, alongside ratings of efficacy. Classifications of evidence and ratings of efficacy are made according to EFNS guidance. In cases where there is insufficient scientific evidence, a consensus statement (good practice point) is made.
The combination of early-onset, progressive parkinsonism with pyramidal tract signs has been known as pallido-pyramidal or parkinsonian-pyramidal syndrome since the first description by Davison in ...1954. Very recently, a locus was mapped in a single family with an overlapping phenotype, and an FBXO7 gene mutation was nominated as the likely disease cause.
We performed clinical and genetic studies in two families with early-onset, progressive parkinsonism and pyramidal tract signs.
An FBXO7 homozygous truncating mutation (Arg498Stop) was found in an Italian family, while compound heterozygous mutations (a splice-site IVS7 + 1G/T mutation and a missense Thr22Met mutation) were present in a Dutch family. We also found evidence of expression of novel normal splice-variants of FBXO7. The phenotype associated with FBXO7 mutations consisted of early-onset, progressive parkinsonism and pyramidal tract signs, thereby matching clinically the pallido-pyramidal syndrome of Davison. The parkinsonism exhibits varying degrees of levodopa responsiveness in different patients.
We conclusively show that recessive FBXO7 mutations cause progressive neurodegeneration with extrapyramidal and pyramidal system involvement, delineating a novel genetically defined entity that we propose to designate as PARK15. Understanding how FBXO7 mutations cause disease will shed further light on the molecular mechanisms of neurodegeneration, with potential implications also for more common forms of parkinsonism, such as Parkinson disease and multiple system atrophy.
To provide evidence‐based recommendations for the management of late (complicated) Parkinson's disease (PD), based on a review of the literature. Complicated PD refers to patients suffering from the ...classical motor syndrome of PD along with other motor or non‐motor complications, either disease‐related (e.g. freezing) or treatment‐related (e.g. dyskinesias or hallucinations). MEDLINE, Cochrane Library and INAHTA database literature searches were conducted. National guidelines were requested from all EFNS societies. Non‐European guidelines were searched for using MEDLINE. Part II of the guidelines deals with treatment of motor and neuropsychiatric complications and autonomic disturbances. For each topic, a list of therapeutic interventions is provided, including classification of evidence. Following this, recommendations for management are given, alongside ratings of efficacy. Classifications of evidence and ratings of efficacy are made according to EFNS guidance. In cases where there is insufficient scientific evidence, a consensus statement (‘good practice point’) is made.
OBJECTIVE
To evaluate whether visual assessment of 123I‐FP‐CIT (DaTSCAN , Nycomed Amersham, plc) single photon emission computerized tomography (SPECT) images can differentiate between parkinsonism ...and essential tremor (ET).
METHODS
123I‐FP‐CIT SPECT imaging was conducted in a six‐center study of 158 patients with a clinical diagnosis of parkinsonism compared with 27 ET cases and 35 healthy volunteers. Striatal uptake of the radioligand was graded normal or abnormal, and abnormal images were further graded to three levels of severity. An institutional read whereby each center visually assessed the images blinded to the clinical data and a consensus blinded read by a panel of five was undertaken.
RESULTS
The institutional reading scored 154 of 158 cases of parkinsonism abnormal, all 27 cases of ET as normal, and 34 of 35 healthy volunteers as normal compared with the consensus blinded read scoring 150 cases of parkinsonism as abnormal, 25 ET cases as normal, and 33 healthy volunteers as normal. Sensitivity for the clinical diagnosis of parkinsonism was 97% and specificity for ET was 100% for the institutional read, whereas sensitivity was 95% and specificity 93% for the consensus blinded read. Semiquantitative analysis of specific: nonspecific caudate and putamen uptake were consistent with the results of visual inspection.
CONCLUSION
Visual assessment of 123I‐FP‐CIT SPECT images is an easily applied diagnostic test which is helpful in the differential diagnosis of tremor disorders and in confirming a clinical diagnosis of a hypokinetic‐rigid syndrome.
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