Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268

Prospective Cohort Study

Objective
To present the International Parkinson and Movement Disorder Society (MDS) Clinical Diagnostic Criteria for Parkinson9s disease.
Background
Although several diagnostic criteria for Parkinson9s disease have been proposed, none have been officially adopted by an official Parkinson society. Moreover, the commonest-used criteria, the UK brain bank, were created more than 25 years ago. In recognition of the lack of standard criteria, the MDS initiated a task force to design new diagnostic criteria for clinical Parkinson9s disease.
Methods/Results
The MDS-PD Criteria are intended for use in clinical research, but may also be used to guide clinical diagnosis. The benchmark is expert clinical diagnosis; the criteria aim to systematize the diagnostic process, to make it reproducible across centers and applicable by clinicians with less expertise. Although motor abnormalities remain central, there is increasing recognition of non-motor manifestations; these are incorporated into both the current criteria and particularly into separate criteria for prodromal PD. Similar to previous criteria, the MDS-PD Criteria retain motor parkinsonism as the core disease feature, defined as bradykinesia plus rest tremor and/or rigidity. Explicit instructions for defining these cardinal features are included. After documentation of parkinsonism, determination of PD as the cause of parkinsonism relies upon three categories of diagnostic features; absolute exclusion criteria (which rule out PD), red flags (which must be counterbalanced by additional supportive criteria to allow diagnosis of PD), and supportive criteria (positive features that increase confidence of PD diagnosis). Two levels of certainty are delineated: Clinically-established PD (maximizing specificity at the expense of reduced sensitivity), and Probable PD (which balances sensitivity and specificity).
Conclusion
The MDS criteria retain elements proven valuable in previous criteria and omit aspects that are no longer justified, thereby encapsulating diagnosis according to current knowledge. As understanding of PD expands, criteria will need continuous revision to accommodate these advances. Disclosure: Dr. Postuma has received personal compensation for activities with Roche Diagnostics Corporation and Biotie Therapies. Dr. Berg has received research support from Michael J. Fox Foundation, the Bundesministerium fur Bildung und Forschung (BMBF), the German Parkinson Association and Novartis GmbH.

MDS Clinical Diagnostic Criteria for Parkinson's Disease (S19.001)

Two decades of clinical experience with immunomodulatory treatments for multiple sclerosis point to distinct immunological pathways that drive disease relapses and progression. In light of this, we discuss our current understanding of multiple sclerosis immunopathology, evaluate long-standing hypotheses regarding the role of the immune system in the disease and delineate key questions that are still unanswered. Recent and anticipated advances in the field of immunology, and the increasing recognition of inflammation as an important component of neurodegeneration, are shaping our conceptualization of disease pathophysiology, and we explore the potential implications for improved healthcare provision to patients in the future.

Immunopathology of multiple sclerosis

Several studies, including work from the Parkinson's disease (PD) non-motor group and others, have established that the non-motor symptoms of PD are common, occur across all stages of PD, are under-reported, and are a key determinant of quality of life. Research suggests that the non-motor symptoms of the disease are frequently unrecognised by clinicians and remain untreated. Even when identified, there is a common perception that many of these symptoms are untreatable. The role of dopaminergic drugs in treating the various non-motor problems of PD, although clinically recognised, has received little attention. In this Review, we investigate the dopaminergic basis of the range of non-motor symptoms that occur in PD such as depression, apathy, sleep disorders (including rapid-eye movement sleep behaviour disorder), and erectile dysfunction. We discuss the evidence that these symptoms are treatable, at least in part, with various dopaminergic strategies and, where relevant, we also refer to the use of deep-brain stimulation of appropriate targets in the brain. This Review provides a comprehensive overview of the management of this challenging aspect of PD.

https://www.thelancet.com/pdfs/journals/laneur/PIIS1474-4422%2809%2970068-7.pdf

Non-motor symptoms of Parkinson's disease: dopaminergic pathophysiology and treatment

The dementia spectrum encompasses a range of disorders with complex diagnosis, pathophysiology and limited treatment options. Positron emission tomography (PET) imaging provides insights into specific neurodegenerative processes underlying dementia disorders in vivo. Here we focus on some of the most common dementias: Alzheimer's disease, Parkinsonism dementias including Parkinson's disease with dementia, dementia with Lewy bodies, progressive supranuclear palsy and corticobasal syndrome, and frontotemporal lobe degeneration. PET tracers have been developed to target specific proteinopathies (amyloid, tau and α-synuclein), glucose metabolism, cholinergic system and neuroinflammation. Studies have shown distinct imaging abnormalities can be detected early, in some cases prior to symptom onset, allowing disease progression to be monitored and providing the potential to predict symptom onset. Furthermore, advances in PET imaging have identified potential therapeutic targets and novel methods to accurately discriminate between different types of dementias in vivo. There are promising imaging markers with a clinical application on the horizon, however, further studies are required before they can be implantation into clinical practice.

/pdf/dementia-spectrum-disorders-lessons-learnt-from-decades-with-2x53yurhid.pdf

Dementia spectrum disorders: lessons learnt from decades with PET research

Objective: To assess in vivo the expression of phosphodiesterase 4 (PDE4) and its relevance to cognitive symptoms in patients with Parkinson disease (PD) using [11C]rolipram PET. Methods: We studied 12 levodopa-treated patients with PD with no concurrent diagnosis of mild cognitive impairment or dementia. Their data were compared with those from 12 healthy controls. All participants underwent neuropsychiatric and cognitive assessment using the Cambridge Neuropsychological Test Automated Battery. Parametric images of [11C]rolipram volume of distribution (VT) values were determined with the Logan plot. Results: Patients with PD performed worse than healthy controls in cognitive examinations assessing psychomotor speed, episodic memory, and spatial working memory and executive function. Patients with PD showed reductions in [11C]rolipram VT compared to healthy controls, in the caudate (28%), thalamus (23%), hypothalamus (32%), and cortex (16%). Within thalamic subregions, [11C]rolipram VT values in patients with PD were decreased by 12%–32%, with most marked decreases observed in prefrontal and temporal thalamic nuclei, whereas motor nuclei were less affected. Within the cortex, [11C]rolipram VT values in patients with PD were decreased by 11%–20%, with most marked decreases observed in posterior dorsolateral frontal cortex, medial frontal cortex, and supplementary motor area, whereas orbitofrontal cortex was less affected. Worse performance in spatial working memory correlated with lower [11C]rolipram VT values in posterior dorsolateral frontal cortex, medial frontal cortex, supplementary motor area, precentral gyrus, caudate, and prefrontal thalamic nuclei. Conclusions: Our findings demonstrate loss of PDE4 expression in the striato-thalamo-cortical circuit, which is associated with deficits of spatial working memory in patients with PD.

/pdf/loss-of-phosphodiesterase-4-in-parkinson-disease-relevance-1d9mdkupyh.pdf

Loss of phosphodiesterase 4 in Parkinson disease: Relevance to cognitive deficits

Background: Reduplicative paramnesia (RP) is a content-specific delusional misidentification syndrome (DMS) which has received little attention in the research li

/pdf/reduplicative-paramnesia-a-review-p3ylhhx6e2.pdf

Reduplicative paramnesia: a review.

Parkinson’s disease (PD) is now considered to be a multisystemic disorder consequent on multineuropeptide dysfunction including dopaminergic, serotonergic, cholinergic, and noradrenergic systems. This multipeptide dysfunction leads to expression of a range of non-motor symptoms now known to be integral to the concept of PD and preceding the diagnosis of motor PD. Some non-motor symptoms in PD may have a dopaminergic basis and in this review, we investigate the evidence for this based on imaging techniques using dopamine-based radioligands. To discuss non-motor symptoms we follow the classification as outlined by the validated PD non-motor symptoms scale.

/pdf/presynaptic-dopaminergic-terminal-imaging-and-non-motor-yeo1yrgr5g.pdf

Presynaptic dopaminergic terminal imaging and non-motor symptoms assessment of Parkinson’s disease: evidence for dopaminergic basis?

The purpose of review is to review the current status of positron emission tomography (PET) molecular imaging of serotonergic system in Parkinson's patients who experience levodopa-induced (LIDs) and graft-induced dyskinesias (GIDs). PET imaging studies have shown that Parkinson's disease is characterized by progressive loss of dopaminergic and serotonergic neurons. Parkinson's patients who experienced LIDs and GIDs have an aberrant spreading of serotonergic terminals, which lead to an increased serotonergic/dopaminergic terminals ratio within the putamen. Serotonergic terminals convert exogenous levodopa into dopamine in a non-physiological manner and release an abnormal amount of dopamine without an auto-regulatory feedback. This results in higher swings in synaptic levels of dopamine, which leads to the development of LIDs and GIDs. The modulation of serotonergic terminals with 5-HT1A and 5-HT1B receptors agonists partially reduced these motor complications. In vivo PET studies confirmed that abnormal spreading of serotonergic terminals within the putamen has a pivotal role in the development of LIDs and GIDs. However, glutamatergic, adenosinergic, opioid systems, and phosphodiesterases 10A may also play a role in the development of these motor complications. An integrative multimodal imaging approach combining PET and MRI imaging techniques is needed to fully understand the mechanisms underlying the development of LIDs and GIDs.

/pdf/the-serotonergic-system-in-parkinson-s-patients-with-4c0ki4vl0f.pdf

Marios Politis

Papers

Dementia spectrum disorders: lessons learnt from decades with PET research

Loss of phosphodiesterase 4 in Parkinson disease: Relevance to cognitive deficits

Reduplicative paramnesia: a review.

Presynaptic dopaminergic terminal imaging and non-motor symptoms assessment of Parkinson’s disease: evidence for dopaminergic basis?

The serotonergic system in Parkinson’s patients with dyskinesia: evidence from imaging studies