Is transcranial sonography useful to distinguish scans without evidence of dopaminergic deficit patients from Parkinson's disease?

Background:

Approximately 10% of patients clinically diagnosed with early Parkinson's disease (PD) subsequently have normal dopaminergic functional imaging. Transcranial sonography (TCS) has been shown to detect midbrain hyperechogenicity in approximately 90% of Parkinson's disease (PD) patients and 10% of the healthy population. The aim of this study was to investigate the prevalence of midbrain hyperechogenicity in patients with suspected parkinsonism and scans without evidence of dopaminergic deficit (SWEDD), in comparison to PD patients.

Methods:

TCS was performed in 14 patients with SWEDD and 19 PD patients.

Results:

There was a significantly increased area of echogenicity in the PD group (0.24 ± 0.06 cm²), compared to the group of patients with SWEDD (0.13 ± 0.06 cm²; P < 0.001). One (9.1%) of these patients, compared to 14 (82.5%) of the PD patients, was found to have hyperechogenicity (P < 0.001).

Conclusions:

We conclude that TCS is useful to distinguish PD patients from patients with suspected parkinsonism and SWEDD. © 2012 Movement Disorder Society

     

What clinical features are most useful to distinguish definite multiple system atrophy from Parkinson's disease?

OBJECTIVES: Few studies have attempted to identify what premortem features best differentiate multiple system atrophy (MSA) from Parkinson's disease (PD). These studies are limited by small sample size, clinical heterogeneity, or lack of postmortem validation. We evaluated the sensitivity and specificity of different clinical features in distinguishing pathologically established MSA from PD. METHODS: One hundred consecutive cases of pathologically confirmed PD and 38 cases of pathologically confirmed MSA in one Parkinson's disease brain bank were included. All cases had their clinical notes reviewed by one observer (AH). Clinical features were divided into two groups: those occurring up to 5 years after onset of disease and those occurring up to death. Statistical analysis comprised multivariate logistic regression analysis to choose and weight key variables for the optimum predictive model. RESULTS: The selected early features and their weightings were: autonomic features (2), poor initial levodopa response (2), early motor fluctuations (2), and initial rigidity (2). A cut off of 4 or more on the ROC curve resulted in a sensitivity of 87.1% and specificity of 70.5%. A better predictive model occurred if the following features up to death were included: poor response to levodopa (2), autonomic features (2), speech or bulbar dysfunction (3), absence of dementia (2), absence of levodopa induced confusion (4), and falls (4). The resulting ROC curve based on individual scores showed a best cut off score of at least 11 of 17 (sensitivity 90.3%, specificity 92.6%). CONCLUSIONS: Predictive models may help differentiate MSA and PD premortem. Hitherto poorly recognised features, suggestive of MSA, included preserved cognitive function and absence of psychiatric effects from antiparkinsonian medication. Diagnostic accuracy was higher in those models taking into account all clinical features occurring up to death. Further studies need to be based on new incident cohorts of parkinsonian patients with subsequent neuropathological evaluation.     

Is there a one‐way street from essential tremor to Parkinson's disease? Possible biological ramifications

There is considerable evidence for an association between essential tremor (ET) and Parkinson's disease (PD), although the topic remains somewhat controversial. An important issue, not previously addressed, is what seems to be the unidirectional nature of the relationship (ET→ET + PD and not PD→PD + ET). The aims of this review are (i) to discuss the evidence for and against a unidirectional relationship and (ii) to discuss the implications of such a unidirectional relationship, if it exists, for disease mechanisms. Evidence ‘for’ a unidirectional relationship includes (i) abundant clinical anecdotal observation and (ii) clinical and epidemiological studies. Evidence ‘against’ is theoretical rather than empirical. Overall, the evidence ‘for’ is stronger, although additional studies are needed in order to be certain; for the time being, it might be best to leave this as an open question. The biological ramifications/extensions of such a unidirectional relationship include (i) that the association is causal (i.e. some aspect of ET pathophysiology predisposes an individual to develop PD) and (ii) that some ET cases may have a circumscribed form of Lewy body disease, and the secondary development of PD may represent a spread of those Lewy bodies in the brainstem. The presence and nature of the links between ET and PD are controversial. Further primary data (epidemiological and pathological) are needed to improve understanding of the relationship and its implications for the pathogenesis of both disorders.     

Is cerebral autoregulation impaired in Parkinson's disease? A transcranial Doppler study

Orthostatic hypotension (OH) is one of the many autonomic disturbances observed in Parkinson's disease (PD). It has been debated whether an additional impairment of cerebral autoregulation (CA) in PD patients may exacerbate the consequences of OH upon brain perfusion. We assessed CA in PD patients and the potential influence of dopaminergic agents. CA was determined by means of transcranial Doppler (TCD) monitoring of the middle cerebral artery (MCA) at rest and during a thigh cuff release test inducing a systemic blood pressure (BP) drop. Fourteen patients were investigated when taking their usual dopaminergic medication and after drug discontinuation for 12 h. A control group was composed of 11 age-matched subjects (CS). In comparison with PD patients, CS presented a significantly higher increase of the mean cerebral blood flow velocities in the MCA after the BP drop. Mean velocities were increased above the initial values in all CS, whereas a flattened curve was observed in PD patients. No significant differences could be further observed between the PD patients regarding the BP, the cerebrovascular resistance, the heart rate and the pulsatility index. These results provide evidence of an impaired cerebral autoregulation in PD patients which appears independent of dopaminergic treatment.     

Is there a need to redefine Parkinson's disease?

Parkinson's disease (PD) has initially been described as a clinical syndrome, although the exact definition has changed over the past centuries. The inclusion of the pathological changes added another level of complexity, with Lewy bodies, synuclein deposits and neuronal loss in the substantia nigra being used alternatively. A third level of complexity was added with the recognition of genetic mutations resulting in parkinsonism, sometimes with and sometimes without Lewy body deposition, and the identification of frequent additional important pre-motor manifestations. These different points of view on the definition of PD have important implications on the study of the etiology and even the therapy of PD.     

l‐DOPA‐induced dyskinesia in Parkinson's disease: Are neuroinflammation and astrocytes key elements?

Inflammation in Parkinson's disease (PD) is a new concept that has gained ground due to the potential of mitigating dopaminergic neuron death by decreasing inflammation. The solution to this question is likely to be complex. We propose here that the significance of inflammation in PD may go beyond the nigral cell death. The pathological process that underlies PD requires years to reach its full extent. A growing body of evidence has been accumulated on the presence of multiple inflammatory signs in the brain of PD patients even in very late stages of the disease. Because neuron‐microglia‐astrocyte interactions play a major role in the plasticity of neuronal response to l ‐DOPA in post‐synaptic neurons, we focused this review on our recent results of l ‐DOPA‐induced dyskinesia in rodents correlating it to significant findings regarding glial cells and neuroinflammation. We showed that in the rat model of PD/l ‐DOPA‐induced dyskinesia there was an increased expression of inflammatory markers, such as the enzymes COX2 in neurons and iNOS in glial cells, in the dopamine‐denervated striatum. The gliosis commonly seem in PD was associated with modifications in astrocytes and microglia that occur after chronic treatment with l ‐DOPA. Either as a cause, consequence, or promoter of progression of neuronal degeneration, inflammation plays a role in PD. The key aims of current PD research ought to be to elucidate (a) the time sequence in which the inflammatory factors act in PD patient brain and (b) the mechanisms by which neuroinflammatory response contributes to the collateral effects of l ‐DOPA treatment.     

Is transcranial magnetic stimulation useful in posttraumatic disorders?

<正>Dear editor,We have read with great interest the recent paper by Herrold et al.(2014)published in Neural Regeneration Research.There is evidence that approximately 20–90%of patients with mild traumatic brain injury develop posttraumatic symptoms,and 40%of these patients have persistent symptoms after trauma(Bazarian et al.,1999;Koski et al.,2015).Therefore,mild traumatic brain injury becomes an important cause of     

Is a computational model useful to understand the effect of deep brain stimulation in Parkinson's disease?

A growing number of computational models have been proposed over the last few years to help explain the therapeutic effect of deep brain stimulation (DBS) on motor disorders in Parkinson's disease (PD). However, none of these has been able to explain in a convincing manner the physiological mechanisms underlying DBS. Can these models really contribute to improving our understanding? The model by Rubin and Terman [31] represents one of the most comprehensive and biologically plausible models of DBS published recently. We examined the validity of the model, replicated its simulations and tested its robustness. While our simulations partially reproduced the results presented by Rubin and Terman [31], several issues were raised including the high complexity of the model in its non simplified form, the lack of robustness of the model with respect to small perturbations, the nonrealistic representation of the thalamus and the absence of time delays. Computational models are indeed necessary, but they may not be sufficient in their current forms to explain the effect of chronic electrical stimulation on the activity of the basal ganglia (BG) network in PD.