Background
A Task Force was convened by the EFNS/MDS‐ES Scientist Panel on Parkinson's disease (PD) and other movement disorders to systemically review relevant publications on the diagnosis of PD.
...Methods
Following the EFNS instruction for the preparation of neurological diagnostic guidelines, recommendation levels have been generated for diagnostic criteria and investigations.
Results
For the clinical diagnosis, we recommend the use of the Queen Square Brain Bank criteria (Level B). Genetic testing for specific mutations is recommended on an individual basis (Level B), taking into account specific features (i.e. family history and age of onset). We recommend olfactory testing to differentiate PD from other parkinsonian disorders including recessive forms (Level A). Screening for pre‐motor PD with olfactory testing requires additional tests due to limited specificity. Drug challenge tests are not recommended for the diagnosis in de novo parkinsonian patients. There is an insufficient evidence to support their role in the differential diagnosis between PD and other parkinsonian syndromes. We recommend an assessment of cognition and a screening for REM sleep behaviour disorder, psychotic manifestations and severe depression in the initial evaluation of suspected PD cases (Level A). Transcranial sonography is recommended for the differentiation of PD from atypical and secondary parkinsonian disorders (Level A), for the early diagnosis of PD and in the detection of subjects at risk for PD (Level A), although the technique is so far not universally used and requires some expertise. Because specificity of TCS for the development of PD is limited, TCS should be used in conjunction with other screening tests. Conventional magnetic resonance imaging and diffusion‐weighted imaging at 1.5 T are recommended as neuroimaging tools that can support a diagnosis of multiple system atrophy (MSA) or progressive supranuclear palsy versus PD on the basis of regional atrophy and signal change as well as diffusivity patterns (Level A). DaTscan SPECT is registered in Europe and the United States for the differential diagnosis between degenerative parkinsonisms and essential tremor (Level A). More specifically, DaTscan is indicated in the presence of significant diagnostic uncertainty such as parkinsonism associated with neuroleptic exposure and atypical tremor manifestations such as isolated unilateral postural tremor. Studies of 123IMIBG/SPECT cardiac uptake may be used to identify patients with PD versus controls and MSA patients (Level A). All other SPECT imaging studies do not fulfil registration standards and cannot be recommended for routine clinical use. At the moment, no conclusion can be drawn as to diagnostic efficacy of autonomic function tests, neurophysiological tests and positron emission tomography imaging in PD.
Conclusions
The diagnosis of PD is still largely based on the correct identification of its clinical features. Selected investigations (genetic, olfactory, and neuroimaging studies) have an ancillary role in confirming the diagnosis, and some of them could be possibly used in the near future to identify subjects in a pre‐symptomatic phase of the disease.
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ObjectiveTo assess reductions of cerebral glucose metabolism in Parkinson's disease (PD) with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET), and their associations with cognitive ...decline.MethodsFDG-PET was performed on a cohort of 79 patients with newly diagnosed PD (mean disease duration 8 months) and 20 unrelated controls. PD participants were scanned while on their usual dopaminergic medication. Cognitive testing was performed at baseline, and after 18 months using the Cognitive Drug Research (CDR) and Cambridge Neuropsychological Test Automated Battery (CANTAB) computerised batteries, the Mini-Mental State Examination (MMSE), and the Montreal Cognitive Assessment (MoCA). We used statistical parametric mapping (SPM V.12) software to compare groups and investigate voxelwise correlations between FDG metabolism and cognitive score at baseline. Linear regression was used to evaluate how levels of cortical FDG metabolism were predictive of subsequent cognitive decline rated with the MMSE and MoCA.ResultsPD participants showed reduced glucose metabolism in the occipital and inferior parietal lobes relative to controls. Low performance on memory-based tasks was associated with reduced FDG metabolism in posterior parietal and temporal regions, while attentional performance was associated with more frontal deficits. Baseline parietal to cerebellum FDG metabolism ratios predicted MMSE (β=0.38, p=0.001) and MoCA (β=0.3, p=0.002) at 18 months controlling for baseline score.ConclusionsReductions in cortical FDG metabolism were present in newly diagnosed PD, and correlated with performance on neuropsychological tests. A reduced baseline parietal metabolism is associated with risk of cognitive decline and may represent a potential biomarker for this state and the development of PD dementia.
Background and purpose
The prevalence and duration of non‐motor symptoms (NMS) in prodromal Parkinson's disease (PD) has not been extensively studied. The aim of this study was to determine the ...prevalence and duration of prodromal NMS (pNMS) in a cohort of patients with recently diagnosed PD.
Methods
We evaluated the prevalence and duration of pNMS in patients with early PD (n = 154). NMS were screened for using the Non‐Motor Symptom Questionnaire (NMSQuest). We subtracted the duration of the presence of each individual NMS reported from the duration of the earliest motor symptom. NMS whose duration preceded the duration of motor symptoms were considered a pNMS. Individual pNMS were then grouped into relevant pNMS clusters based on the NMSQuest domains. Motor subtypes were defined as tremor dominant, postural instability gait difficulty (PIGD) and indeterminate type according to the Movement Disorder Society Unified Parkinson's Disease Rating Scale revision.
Results
Prodromal NMS were experienced by 90.3% of patients with PD and the median number experienced was 4 (interquartile range, 2–7). A gender difference existed in the pNMS experienced, with males reporting more sexual dysfunction, forgetfulness and dream re‐enactment, whereas females reported more unexplained weight change and anxiety. There was a significant association between any prodromal gastrointestinal symptoms odds ratio (OR), 2.30; 95% confidence interval (CI), 1.08–4.89, P = 0.03 and urinary symptoms (OR, 2.54; 95% CI, 1.19–5.35, P = 0.016) and the PIGD phenotype. Further analysis revealed that total pNMS were not significantly associated with the PIGD phenotype (OR, 1.10; 95% CI, 0.99–1.21, P = 0.068).
Conclusions
Prodromal NMS are common and a gender difference in pNMS experienced in prodromal PD may exist. The PIGD phenotype had a higher prevalence of prodromal gastrointestinal and urinary tract symptoms.
Nonmotor symptoms (NMS) are common in patients with established Parkinson disease (PD) but their frequency in early PD has not been extensively studied. Our aim was to determine the frequency of NMS ...in a cohort of patients with newly diagnosed PD.
A total of 159 patients with early PD and 99 healthy controls participated in this study. NMS were screened for using the nonmotor symptom questionnaire. Other assessments included measures of motor disability (Movement Disorders Society-revised unified Parkinson's disease rating scale MDS-UPDRS), disease severity (Hoehn & Yahr staging), depression (geriatric depression scale), and global cognitive function (Mini-mental state examination and Montreal cognitive assessment).
The PD group reported a significantly greater number of NMS compared with controls (8.4 4.3 vs. 2.8 2.6). In the PD group, the most commonly experienced NMS were excessive saliva, forgetfulness, urinary urgency, hyposmia, and constipation. Patients with higher MDS-UPDRS III scores and those with the postural instability gait subtype experienced a greater number of NMS.
NMS are common in early PD and reflect the multisystem nature of the disorder. Even in the earliest stages of PD, NMS may be detrimental to patients' functional status and sense of well-being.
Gait disturbance is an early feature in Parkinson's disease. Its pathophysiology is poorly understood; however, cholinergic dysfunction may be a non-dopaminergic contributor to gait. Short-latency ...afferent inhibition is a surrogate measure of cholinergic activity, allowing the contribution of cholinergic dysfunction to gait to be evaluated. We hypothesized that short-latency afferent inhibition would be an independent predictor of gait dysfunction in early Parkinson's disease. Twenty-two participants with Parkinson's disease and 22 age-matched control subjects took part in the study. Gait was measured objectively using an instrumented walkway (GAITRite), and subjects were asked to walk at their preferred speed for 2 min around a 25-m circuit. Spatiotemporal characteristics (speed, stride length, stride time and step width) and gait dynamics (variability described as the within subject standard deviation of: speed, stride time, stride length and step width) were determined. Short-latency afferent inhibition was measured by conditioning motor evoked potentials, elicited by transcranial magnetic stimulation of the motor cortex, with electrical stimuli delivered to the contralateral median nerve at intervals ranging from N20 (predetermined) to N20 + 4 ms. Short-latency afferent inhibition was determined as the percentage difference between test and conditioned response for all intervals and was described as the group mean. Participants were optimally medicated at the time of testing. Participants with Parkinson's disease had significantly reduced gait speed (P = 0.002), stride length (P = 0.008) and stride time standard deviation (P = 0.001). Short-latency afferent inhibition was also significantly reduced in participants with Parkinson's disease (P = 0.004). In participants with Parkinson's disease, but not control subjects, significant associations were found between gait speed, short-latency afferent inhibition, age and postural instability and gait disorder score (Movement Disorders Society Unified Parkinson's Disease Rating Scale) and attention, whereas global cognition and depression were marginally significant. No other gait variables were associated with short-latency afferent inhibition. A multiple hierarchical regression model explored the contribution of short-latency afferent inhibition to gait speed, controlling for age, posture and gait symptoms (Postural Instability and Gait Disorder score-Movement Disorders Society Unified Parkinson's Disease Rating Scale), attention and depression. Regression analysis in participants with Parkinson's disease showed that reduced short-latency afferent inhibition was an independent predictor of slower gait speed, explaining 37% of variability. The final model explained 72% of variability in gait speed with only short-latency afferent inhibition and attention emerging as independent determinants. The results suggest that cholinergic dysfunction may be an important and early contributor to gait dysfunction in Parkinson's disease. The findings also point to the contribution of non-motor mechanisms to gait dysfunction. Our study provides new insights into underlying mechanisms of non-dopaminergic gait dysfunction, and may help to direct future therapeutic approaches.
Recently described neuronal intermediate filament inclusion disease (NIFID) shows considerable clinical heterogeneity.
To assess the spectrum of the clinical and neuropathological features in 10 ...NIFID cases.
Retrospective chart and comprehensive neuropathological review of these NIFID cases was conducted.
The mean age at onset was 40.8 (range 23 to 56) years, mean disease duration was 4.5 (range 2.7 to 13) years, and mean age at death was 45.3 (range 28 to 61) years. The most common presenting symptoms were behavioral and personality changes in 7 of 10 cases and, less often, memory loss, cognitive impairment, language deficits, and motor weakness. Extrapyramidal features were present in 8 of 10 patients. Language impairment, perseveration, executive dysfunction, hyperreflexia, and primitive reflexes were frequent signs, whereas a minority had buccofacial apraxia, supranuclear ophthalmoplegia, upper motor neuron disease (MND), and limb dystonia. Frontotemporal and caudate atrophy were common. Histologic changes were extensive in many cortical areas, deep gray matter, cerebellum, and spinal cord. The hallmark lesions of NIFID were unique neuronal IF inclusions detected most robustly by antibodies to neurofilament triplet proteins and alpha-internexin.
NIFID is a neuropathologically distinct, clinically heterogeneous variant of frontotemporal dementia (FTD) that may include parkinsonism or MND. Neuronal IF inclusions are the neuropathological signatures of NIFID that distinguish it from all other FTD variants including FTD with MND and FTD tauopathies.
Background: A previous cross sectional study found over-representation of a postural instability gait difficulty (PIGD) motor subtype in Parkinson’s disease patients with dementia (PDD) and dementia ...with Lewy bodies (DLB), compared with Parkinson’s disease (PD). Aims: (1) To examine rates of cognitive and motor decline over two years in PD (n = 40), PDD (n = 42) and DLB (n = 41) subjects, compared with age matched controls (n = 41), (2) to record whether motor phenotypes of PD, PDD, and DLB subjects changed during the study, (3) to find out if cognitive and motor decline in PD was associated with baseline motor subtype, and (4) to report the incidence of dementia in PD patients in relation to baseline motor subtype. Results: Most of PDD and DLB participants were PIGD subtype at baseline assessment. In the non-demented PD group, tremor dominant (TD) and PIGD subtypes were more evenly represented. Cognitive decline over two years was greater in PDD and DLB groups (mean decline in MMSE −4.5 and −3.9, respectively), compared with PD (−0.2) and controls (−0.3). There was an association between PIGD subtype and increased rate of cognitive decline within the PD group. Of 40 PD patients, 25% of the 16 PIGD subtype developed dementia over two years, compared with none of the 18 TD or six indeterminate phenotype cases (χ2 = 6.7, Fisher’s exact test p<0.05). Conclusion: A PIGD motor subtype is associated with a faster rate of cognitive decline in PD and may be considered a risk factor for incident dementia in PD.
Background:Changes to the efficiency and integrity of swallowing mechanisms are inevitable in Parkinson disease (PD); however, it remains unclear how many people with PD are at risk of dysphagia. The ...aim of this study was to establish the frequency of impaired swallowing in people with PD and the relationship between swallowing performance and indicators of disease progression.Methods:A community-based and hospital-based cohort of 137 individuals with PD were asked to drink 150 ml of water as quickly as possible while in an ‘off drug’ state.Results:Thirty-one (23%) patients could not completely drink the full 150 ml. Swallowing rate (ml/sec) fell to more than 1SD below published norms for 115 (84%) patients and to more than 2SD below for 44 (32%) individuals. There were moderate correlations between rate of swallowing and disease severity, depression and cognition, but not between swallowing speed and disease duration. There was poor correlation between subjective reports of dysphagia and performance on the water swallow test.Conclusions:Swallowing problems are frequent in PD. Self-report of ’no difficulty’ is not a reliable indicator of swallowing ability. Studies employing more-objective assessment of aspiration risk to compare with water swallow test performance are advocated.
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