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Parkinsonism & Related Disorders Aug 2014Drug-induced parkinsonism is the second most common cause of parkinsonism after Parkinson's disease and their distinction has crucial implications in terms of management... (Review)
Review
Drug-induced parkinsonism is the second most common cause of parkinsonism after Parkinson's disease and their distinction has crucial implications in terms of management and prognosis. However, differentiating between these conditions can be challenging on a clinical ground, especially in the early stages. We therefore performed a review to ascertain whether assessment of non-motor symptoms, or use of ancillary investigations, namely dopamine transporter imaging, transcranial sonography of the substantia nigra, and scintigraphy for myocardial sympathetic innervation, can be recommended to distinguish between these conditions. Among non-motor symptoms, there is evidence that hyposmia can differentiate between patients with "pure" drug-induced parkinsonism and those with degenerative parkinsonism unmasked by an anti-dopaminergic drug. However, several issues, including smoking history and cognitive functions, can influence smell function assessment. Higher diagnostic accuracy has been demonstrated for dopamine transporter imaging. Finally, preliminary evidence exists for sympathetic cardiac scintigraphy to predict dopaminergic pathway abnormalities and to differentiate between drug-induced parkinsonism and Parkinson's disease. Imaging of the dopaminergic pathway seems to be the only, reasonably available, technique to aid the differential diagnosis between drug-induced parkinsonism and Parkinson's disease.
Topics: Diagnosis, Differential; Humans; Parkinson Disease; Parkinsonian Disorders
PubMed: 24935237
DOI: 10.1016/j.parkreldis.2014.05.011 -
Journal of the Neurological Sciences Feb 2022Ataxia is not a common feature in Parkinson's disease. Nevertheless, some rare forms of parkinsonism have ataxia as one of the main features in their clinical picture,... (Review)
Review
Ataxia is not a common feature in Parkinson's disease. Nevertheless, some rare forms of parkinsonism have ataxia as one of the main features in their clinical picture, especially those with juvenile or early-onset. On the other side, in cerebellar degenerative diseases, parkinsonism might accompany the typical symptoms and even become predominant in some cases. Many disorders involving different neurological systems present with a movement phenomenology reflecting the underlying pattern of pathological involvement, such as neurodegeneration with brain iron accumulation, neurodegeneration associated with calcium deposition, and metabolic and mitochondrial disorders. The prototype of sporadic disorders that present with a constellation of symptoms due to the involvement of multiple Central Nervous System regions is multiple system atrophy, whose motor symptoms at onset can be cerebellar ataxia or parkinsonism. Clinical syndromes encompassing both parkinsonian and cerebellar features might represent a diagnostic challenge for neurologists. Recognizing acquired and potentially treatable causes responsible for complex movement disorders is of paramount importance, since an early diagnosis is essential to prevent permanent consequences. The present review aims to provide a pragmatic overview of the most common diseases characterized by the coexistence of cerebellar and parkinsonism features and suggests a possible diagnostic approach for both inherited and sporadic disorders. This article is part of the Special Issue "Parkinsonism across the spectrum of movement disorders and beyond" edited by Joseph Jankovic, Daniel D. Truong and Matteo Bologna.
Topics: Ataxia; Cerebellar Ataxia; Humans; Multiple System Atrophy; Parkinson Disease; Parkinsonian Disorders
PubMed: 34711421
DOI: 10.1016/j.jns.2021.120020 -
Movement Disorders : Official Journal... Dec 2018Advancing conventional open-loop DBS as a therapy for PD is crucial for overcoming important issues such as the delicate balance between beneficial and adverse effects... (Review)
Review
Advancing conventional open-loop DBS as a therapy for PD is crucial for overcoming important issues such as the delicate balance between beneficial and adverse effects and limited battery longevity that are currently associated with treatment. Closed-loop or adaptive DBS aims to overcome these limitations by real-time adjustment of stimulation parameters based on continuous feedback input signals that are representative of the patient's clinical state. The focus of this update is to discuss the most recent developments regarding potential input signals and possible stimulation parameter modulation for adaptive DBS in PD. Potential input signals for adaptive DBS include basal ganglia local field potentials, cortical recordings (electrocorticography), wearable sensors, and eHealth and mHealth devices. Furthermore, adaptive DBS can be applied with different approaches of stimulation parameter modulation, the feasibility of which can be adapted depending on specific PD phenotypes. Implementation of technological developments like machine learning show potential in the design of such approaches; however, energy consumption deserves further attention. Furthermore, we discuss future considerations regarding the clinical implementation of adaptive DBS in PD. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Topics: Basal Ganglia; Deep Brain Stimulation; Economics; Humans; Parkinson Disease; Parkinsonian Disorders; Phenotype
PubMed: 30357911
DOI: 10.1002/mds.115 -
Tidsskrift For Den Norske Laegeforening... May 2023Parkinsonism can have many causes, among them cerebrovascular disease. Vascular parkinsonism can be caused by infarction or haemorrhage in the nigrostriatal pathway,...
Parkinsonism can have many causes, among them cerebrovascular disease. Vascular parkinsonism can be caused by infarction or haemorrhage in the nigrostriatal pathway, resulting in hemiparkinsonism, or by widespread small vessel disease in the white matter, leading to the gradual development of bilateral symptoms in the lower extremities. Compared to patients with Parkinson's disease, individuals with vascular parkinsonism have earlier onset of gait disturbance, are more likely to have urinary incontinence and cognitive impairment, and have poorer treatment response and prognosis; however, they are less likely to have tremor. With its unclear pathophysiology, varying clinical picture and overlap with other diseases, vascular parkinsonism remains a little known and somewhat controversial diagnosis.
Topics: Humans; Parkinson Disease; Parkinsonian Disorders; Cerebrovascular Disorders; Vascular Diseases; Tremor
PubMed: 37158514
DOI: 10.4045/tidsskr.22.0539 -
Journal of the Neurological Sciences Feb 2022The aim of the present review is to summarize literature data on dementia in parkinsonian disorders. Cognitive decline and the gradual development of dementia are... (Review)
Review
The aim of the present review is to summarize literature data on dementia in parkinsonian disorders. Cognitive decline and the gradual development of dementia are considered to be key features in the majority of parkinsonian conditions. The burden of dementia in everyday life of parkinsonian patients and their caregivers is vast and can be even more challenging to handle than the motor component of the disease. Common pathogenetic mechanisms involve the aggregation and spreading of abnormal proteins like alpha-synuclein, tau or amyloid in cortical and subcortical regions with subsequent dysregulation of multiple neurotransmitter systems. The degree of cognitive deterioration in these disorders is variable and ranges from mild cognitive impairment to severe cognitive dysfunction. There is also variation in the number and type of affected cognitive domains which can involve either a single domain like executive or visuospatial function or multiple ones. Novel genetic, biological fluid or imaging biomarkers appear promising in facilitating the diagnosis and staging of dementia in parkinsonian conditions. A significant part of current research in Parkinson's disease and other parkinsonian syndromes is targeted towards the cognitive aspects of these disorders. Stabilization or amelioration of cognitive outcomes represents a primary endpoint in many ongoing clinical trials for novel disease modifying treatments in this field. This article is part of the Special Issue "Parkinsonism across the spectrum of movement disorders and beyond" edited by Joseph Jankovic, Daniel D. Truong and Matteo Bologna.
Topics: Biomarkers; Cognition Disorders; Humans; Lewy Body Disease; Parkinson Disease; Parkinsonian Disorders
PubMed: 34642023
DOI: 10.1016/j.jns.2021.120015 -
Journal of the Neurological Sciences Feb 2022The relationship between cerebrovascular disease and parkinsonism is commonly seen in everyday clinical practice but remains ill-defined and under-recognised with little... (Review)
Review
The relationship between cerebrovascular disease and parkinsonism is commonly seen in everyday clinical practice but remains ill-defined and under-recognised with little guidance for the practising neurologist. We attempt to define this association and to illustrate key clinical, radiological and pathological features of the syndrome of Vascular Parkinsonism (VaP). VaP is a major cause of morbidity in the elderly associated with falls, hip fractures and cognitive impairment. Although acute parkinsonism is reported in the context of an acute cerebrovascular event, the vast majority of VaP presents as an insidious syndrome usually in the context of vascular risk factors and radiological evidence of small vessel disease. There may be an anatomic impact on basal ganglia neuronal networks, however the effect of small vessel disease (SVD) on these pathways is not clear. There are now established reporting standards for radiological features of SVD on MRI. White matter hyperintensities and lacunes have been thought to be the representative radiological features of SVD but other features such as the perivascular space are gaining more importance, especially in context of the glymphatic system. It is important to consider VaP in the differential diagnosis of Parkinson disease (PD) and in these situations, neuroimaging may offer diagnostic benefit especially in those patients with atypical presentations or refractoriness to levodopa. Proactive management of vascular risk factors, monitoring of bone density and an exercise program may offer easily attainable therapeutic targets in PD and VaP. Levodopa therapy should be considered in patients with VaP, however the dose and effect may be different from use in PD. This article is part of the Special Issue "Parkinsonism across the spectrum of movement disorders and beyond" edited by Joseph Jankovic, Daniel D. Truong and Matteo Bologna.
Topics: Aged; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Cognitive Dysfunction; Humans; Magnetic Resonance Imaging; Parkinson Disease; Parkinsonian Disorders
PubMed: 34686356
DOI: 10.1016/j.jns.2021.120011 -
Innere Medizin (Heidelberg, Germany) Feb 2023Parkinson's disease (PD) is an unparalleled example of a neurodegenerative disorder that can be effectively managed leading to sustained symptom control and quality of... (Review)
Review
Parkinson's disease (PD) is an unparalleled example of a neurodegenerative disorder that can be effectively managed leading to sustained symptom control and quality of life. The cooperation of neurologists with general practitioners, gastroenterologists, and geriatricians is of increasing importance for an optimized management of PD. New diagnostic criteria for PD and for atypical Parkinsonism, which should be considered in the differential diagnostics, include non-motor symptoms and aim to diagnose these disorders as early as possible. Recent research has shown that there are highly complex and clinically relevant interactions with PD at all levels of the gastrointestinal tract, which have been increasingly better understood and have direct clinical relevance. Novel dopaminergic treatment approaches focus on circumvention of the impaired gastrointestinal tract of PD patients. The management of geriatric PD patients and PD dementia requires specific clinical knowledge. Worldwide, PD has emerged as a model disease for the development of network structures for the treatment of chronic neurological diseases.
Topics: Humans; Aged; Parkinson Disease; Quality of Life; Parkinsonian Disorders; Neurodegenerative Diseases; Dopamine
PubMed: 36480073
DOI: 10.1007/s00108-022-01444-3 -
Turkish Journal of Medical Sciences Apr 2021The dopamine transporter (DAT) imaging provides an objective tool for the assessment of dopaminergic function of presynaptic terminals which is valuable for the... (Review)
Review
The dopamine transporter (DAT) imaging provides an objective tool for the assessment of dopaminergic function of presynaptic terminals which is valuable for the differential diagnosis of parkinsonian disorders related to a striatal dopaminergic deficiency from movement disorders not related a striatal dopaminergic deficiency. DAT imaging with single-photon emission computed tomography (SPECT) can be used to confirm or exclude a diagnosis of dopamine deficient parkinsonism in cases where the diagnosis is unclear. It can also detect the dopaminergic dysfunction in presymptomatic subjects at risk for Parkinson’s disease (PD) since the reduced radiotracer binding to DATs in striatum is already present in the prodromal stage of PD. This review covers the rationale of using DAT SPECT imaging in the diagnosis of PD and other parkinsonian disorders, specifically focusing on the practical aspects of imaging and routine clinical indications.
Topics: Corpus Striatum; Diagnosis, Differential; Dopamine; Dopamine Plasma Membrane Transport Proteins; Female; Humans; Male; Movement Disorders; Parkinson Disease; Parkinsonian Disorders; Prodromal Symptoms; Protein Binding; Radioisotopes; Tomography, Emission-Computed, Single-Photon
PubMed: 33237660
DOI: 10.3906/sag-2008-253 -
Practical Neurology Jan 2024Gait disorders are a common feature of neurological disease. The gait examination is an essential part of the neurological clinical assessment, providing valuable clues... (Review)
Review
Gait disorders are a common feature of neurological disease. The gait examination is an essential part of the neurological clinical assessment, providing valuable clues to a myriad of causes. Understanding how to examine gait is not only essential for neurological diagnosis but also for treatment and prognosis. Here, we review aspects of the clinical history and examination of neurological gait to help guide gait disorder assessment. We focus particularly on how to differentiate between common gait abnormalities and highlight the characteristic features of the more prevalent neurological gait patterns such as ataxia, waddling, steppage, spastic gait, Parkinson's disease and functional gait disorders. We also offer diagnostic clues for some unusual gait presentations, such as dystonic, stiff-person and choreiform gait, along with red flags that help differentiate atypical parkinsonism from Parkinson's disease.
Topics: Humans; Parkinson Disease; Parkinsonian Disorders; Gait; Cerebellar Ataxia; Ataxia; Gait Disorders, Neurologic
PubMed: 38135498
DOI: 10.1136/pn-2023-003917 -
Brain : a Journal of Neurology Feb 2024While Parkinson's disease remains clinically defined by cardinal motor symptoms resulting from nigrostriatal degeneration, it is now appreciated that the disease...
While Parkinson's disease remains clinically defined by cardinal motor symptoms resulting from nigrostriatal degeneration, it is now appreciated that the disease commonly consists of multiple pathologies, but it is unclear where these co-pathologies occur early in disease and whether they are responsible for the nigrostriatal degeneration. For the past number of years, we have been studying a well-characterized cohort of subjects with motor impairment that we have termed mild motor deficits. Motor deficits were determined on a modified and validated Unified Parkinson's Disease Rating Scale III but were insufficient in degree to diagnose Parkinson's disease. However, in our past studies, cases in this cohort had a selection bias, as both a clinical syndrome in between no motor deficits and Parkinson's disease, plus nigral Lewy pathology as defined post-mortem, were required for inclusion. Therefore, in the current study, we only based inclusion on the presence of a clinical phenotype with mild motor impairment insufficient to diagnose Parkinson's disease. Then, we divided this group further based upon whether or not subjects had a synucleinopathy in the nigrostriatal system. Here we demonstrate that loss of nigral dopaminergic neurons, loss of putamenal dopaminergic innervation and loss of the tyrosine hydroxylase-phenotype in the substantia nigra and putamen occur equally in mild motor deficit groups with and without nigral alpha-synuclein aggregates. Indeed, the common feature of these two groups is that both have similar degrees of AT8 positive phosphorylated tau, a pathology not seen in the nigrostriatal system of age-matched controls. These findings were confirmed with early (tau Ser208 phosphorylation) and late (tau Ser396/Ser404 phosphorylation) tau markers. This suggests that the initiation of nigrostriatal dopaminergic neurodegeneration occurs independently of alpha-synuclein aggregation and can be tau mediated.
Topics: Humans; Parkinson Disease; alpha-Synuclein; Parkinsonian Disorders; Synucleinopathies; Putamen; Substantia Nigra; Dopamine
PubMed: 38006313
DOI: 10.1093/brain/awad388