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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 -
Journal of Neurology, Neurosurgery, and... Jul 2020Parkinson's disease is characterised neuropathologically by α-synuclein aggregation. Currently, there is no blood test to predict the underlying pathology or...
OBJECTIVE
Parkinson's disease is characterised neuropathologically by α-synuclein aggregation. Currently, there is no blood test to predict the underlying pathology or distinguish Parkinson's from atypical parkinsonian syndromes. We assessed the clinical utility of serum neuronal exosomes as biomarkers across the spectrum of Parkinson's disease, multiple system atrophy and other proteinopathies.
METHODS
We performed a cross-sectional study of 664 serum samples from the Oxford, Kiel and Brescia cohorts consisting of individuals with rapid eye movement sleep behavioural disorder, Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, frontotemporal dementia, progressive supranuclear palsy, corticobasal syndrome and controls. Longitudinal samples were analysed from Parkinson's and control individuals. We developed poly(carboxybetaine-methacrylate) coated beads to isolate L1 cell adhesion molecule (L1CAM)-positive extracellular vesicles with characteristics of exosomes and used mass spectrometry or multiplexed electrochemiluminescence to measure exosomal proteins.
RESULTS
Mean neuron-derived exosomal α-synuclein was increased by twofold in prodromal and clinical Parkinson's disease when compared with multiple system atrophy, controls or other neurodegenerative diseases. With 314 subjects in the training group and 105 in the validation group, exosomal α-synuclein exhibited a consistent performance (AUC=0.86) in separating clinical Parkinson's disease from controls across populations. Exosomal clusterin was elevated in subjects with non-α-synuclein proteinopathies. Combined neuron-derived exosomal α-synuclein and clusterin measurement predicted Parkinson's disease from other proteinopathies with AUC=0.98 and from multiple system atrophy with AUC=0.94. Longitudinal sample analysis showed that exosomal α-synuclein remains stably elevated with Parkinson's disease progression.
CONCLUSIONS
Increased α-synuclein egress in serum neuronal exosomes precedes the diagnosis of Parkinson's disease, persists with disease progression and in combination with clusterin predicts and differentiates Parkinson's disease from atypical parkinsonism.
Topics: Aged; Aged, 80 and over; Biomarkers; Cross-Sectional Studies; Diagnosis, Differential; Exosomes; Female; Humans; Male; Middle Aged; Multiple System Atrophy; Neurons; Parkinson Disease; Parkinsonian Disorders
PubMed: 32273329
DOI: 10.1136/jnnp-2019-322588 -
Zhurnal Nevrologii I Psikhiatrii Imeni... 2023The article presents a progressive neurodegenerative disease - multisystem atrophy, characterized by a combination of autonomic failure and various motor disorders,...
The article presents a progressive neurodegenerative disease - multisystem atrophy, characterized by a combination of autonomic failure and various motor disorders, including parkinsonism and/or cerebellar ataxia; etiopathogenetic factors and variants of the clinical picture are described. We describe own clinical observation of a 59-old patient with cerebellar and bulbar syndromes, parkinsonism, pyramidal insufficiency, cognitive deficits, and autonomic dysfunction. The differential diagnosis included a whole range of neurodegenerative and hereditary diseases: Parkinson's disease, vascular parkinsonism, progressive supranuclear palsy, spinocerebellar ataxia, FXTAS, mitochondrial encephalopathies. The moderate severity of parkinsonism and the significant predominance of cerebellar symptoms and autonomic dysfunction make this clinical case difficult to diagnose. However, based on the life and disease history, clinical picture and research methods, a diagnosis of multiple system atrophy, cerebellar type (cerebellar, autonomic, bulbar syndrome, parkinsonism, pyramidal insufficiency and moderate cognitive impairment) was established. Differential search in such patients is a difficult task and includes a whole range of neurodegenerative and hereditary diseases due to the similarity of individual clinical and neuroimaging features and, unfortunately, the limited availability of molecular genetic diagnostic methods. However, earlier diagnosis is necessary to focus in time on the development of a personalized approach to the management of each such patient, taking into account the rate of symptoms development and steady progression, in order to ensure the longest possible survival time with an acceptable level of quality of life.
Topics: Humans; Multiple System Atrophy; Quality of Life; Parkinsonian Disorders; Ataxia; Parkinson Disease; Autonomic Nervous System Diseases
PubMed: 36843472
DOI: 10.17116/jnevro2023123021144 -
Journal of the Neurological Sciences Jan 2024Botulinum toxin (BoNT) was approved by the United States Food and Drug Administration (FDA) in 1989 for facial movement disorders and strabismus, but since that time its... (Review)
Review
Botulinum toxin (BoNT) was approved by the United States Food and Drug Administration (FDA) in 1989 for facial movement disorders and strabismus, but since that time its indications have been expanding beyond neurologic and ophthalmologic disorders. This article is a narrative review of the therapeutic use of BoNT in tremors, dystonia, sialorrhea, bladder and other autonomic symptoms, levodopa-induced dyskinesia and other problems occuring in the setting of parkinsonism. Though FDA approval is lacking for some of these indications, expert experiences have shown that BoNT is often beneficial in this group of patients.
Topics: United States; Humans; Botulinum Toxins; Parkinson Disease; Parkinsonian Disorders; Tremor; Dystonic Disorders; Botulinum Toxins, Type A
PubMed: 38056063
DOI: 10.1016/j.jns.2023.122810 -
Continuum (Minneapolis, Minn.) Feb 2023This article reviews commonly used imaging modalities in movement disorders, particularly parkinsonism. The review includes the diagnostic utility, role in differential... (Review)
Review
OBJECTIVE
This article reviews commonly used imaging modalities in movement disorders, particularly parkinsonism. The review includes the diagnostic utility, role in differential diagnosis, reflection of pathophysiology, and limitations of neuroimaging in the setting of movement disorders. It also introduces promising new imaging modalities and describes the current status of research.
LATEST DEVELOPMENTS
Iron-sensitive MRI sequences and neuromelanin-sensitive MRI can be used to directly assess the integrity of nigral dopaminergic neurons and thus may reflect disease pathology and progression throughout the full range of severity in Parkinson disease (PD). The striatal uptake of presynaptic radiotracers in their terminal axons as currently assessed using clinically approved positron emission tomography (PET) or single-photon emission computed tomography (SPECT) imaging correlates with nigral pathology and disease severity only in early PD. Cholinergic PET, using radiotracers that target the presynaptic vesicular acetylcholine transporter, constitutes a substantial advance and may provide crucial insights into the pathophysiology of clinical symptoms such as dementia, freezing, and falls.
ESSENTIAL POINTS
In the absence of valid, direct, objective biomarkers of intracellular misfolded α-synuclein, PD remains a clinical diagnosis. The clinical utility of PET- or SPECT-based striatal measures is currently limited given their lack of specificity and inability to reflect nigral pathology in moderate to severe PD. These scans may be more sensitive than clinical examination to detect nigrostriatal deficiency that occurs in multiple parkinsonian syndromes and may still be recommended for clinical use in the future to identify prodromal PD if and when disease-modifying treatments become available. Multimodal imaging to evaluate underlying nigral pathology and its functional consequences may hold the key to future advances.
Topics: Humans; Parkinson Disease; Positron-Emission Tomography; Parkinsonian Disorders; Tomography, Emission-Computed, Single-Photon; Substantia Nigra
PubMed: 36795878
DOI: 10.1212/CON.0000000000001210