Juvenile parkinsonism: Differential diagnosis, genetics, and treatment

Niemann, Nicki; Jankovic, Joseph

doi:10.1016/j.parkreldis.2019.06.025

Cited by 78 publications

(56 citation statements)

References 253 publications

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“…Besides levodopa, there are many other types of medications available for the treatment of PD-related motor symptoms: anticholinergics, amantadine, MAOIs, COMTIs, dopamine agonists and istradefylline. 77…”

Section: Other Drugsmentioning

confidence: 99%

Parkinson’s disease: etiopathogenesis and treatment

Jankovic

Tan

2020

J Neurol Neurosurg Psychiatry

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671

398

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The concept of ‘idiopathic’ Parkinson’s disease (PD) as a single entity has been challenged with the identification of several clinical subtypes, pathogenic genes and putative causative environmental agents. In addition to classic motor symptoms, non-motor manifestations (such as rapid eye movement sleep disorder, anosmia, constipation and depression) appear at prodromic/premotor stage and evolve, along with cognitive impairment and dysautonomia, as the disease progresses, often dominating the advanced stages of the disease. The key molecular pathogenic mechanisms include α-synuclein misfolding and aggregation, mitochondrial dysfunction, impairment of protein clearance (associated with deficient ubiquitin-proteasome and autophagy-lysosomal systems), neuroinflammation and oxidative stress. The involvement of dopaminergic as well as noradrenergic, glutamatergic, serotonergic and adenosine pathways provide insights into the rich and variable clinical phenomenology associated with PD and the possibility of alternative therapeutic approaches beyond traditional dopamine replacement therapies.One of the biggest challenges in the development of potential neuroprotective therapies has been the lack of reliable and sensitive biomarkers of progression. Immunotherapies such as the use of vaccination or monoclonal antibodies directed against aggregated, toxic α-synuclein.as well as anti-aggregation or protein clearance strategies are currently investigated in clinical trials. The application of glucagon-like peptide one receptor agonists, specific PD gene target agents (such as GBA or LRRK2 modifiers) and other potential disease modifying drugs provide cautious optimism that more effective therapies are on the horizon. Emerging therapies, such as new symptomatic drugs, innovative drug delivery systems and novel surgical interventions give hope to patients with PD about their future outcomes and prognosis.

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Section: Other Drugsmentioning

confidence: 99%

Parkinson’s disease: etiopathogenesis and treatment

Jankovic

Tan

2020

J Neurol Neurosurg Psychiatry

Self Cite

671

398

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“…This therapy consists of the combination of levodopa and carbidopa, together with close evaluation of parkinsonism. Dopamine agonists or anticholinergics can be prescribed in some cases [ 168 ].…”

Section: Autophagosome/lysosome Regulationmentioning

confidence: 99%

Mitochondrial Dysfunction, Oxidative Stress and Neuroinflammation in Neurodegeneration with Brain Iron Accumulation (NBIA)

et al. 2020

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The syndromes of neurodegeneration with brain iron accumulation (NBIA) encompass a group of invalidating and progressive rare diseases that share the abnormal accumulation of iron in the basal ganglia. The onset of NBIA disorders ranges from infancy to adulthood. Main clinical signs are related to extrapyramidal features (dystonia, parkinsonism and choreoathetosis), and neuropsychiatric abnormalities. Ten NBIA forms are widely accepted to be caused by mutations in the genes PANK2, PLA2G6, WDR45, C19ORF12, FA2H, ATP13A2, COASY, FTL1, CP, and DCAF17. Nonetheless, many patients remain without a conclusive genetic diagnosis, which shows that there must be additional as yet undiscovered NBIA genes. In line with this, isolated cases of known monogenic disorders, and also, new genetic diseases, which present with abnormal brain iron phenotypes compatible with NBIA, have been described. Several pathways are involved in NBIA syndromes: iron and lipid metabolism, mitochondrial dynamics, and autophagy. However, many neurodegenerative conditions share features such as mitochondrial dysfunction and oxidative stress, given the bioenergetics requirements of neurons. This review aims to describe the existing link between the classical ten NBIA forms by examining their connection with mitochondrial impairment as well as oxidative stress and neuroinflammation.

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“…By contrast, peak-dose dystonia tends to involve the neck, face, and upper limbs [98], whereas dystonia occurring as part of diphasic dyskinesia seems to mainly involve lower limbs. Dystonia, which typically presents after years of disease, rarely occurs in an early stage, usually related to young-onset PD and to autosomal recessive genetic parkinsonism forms, such as PARK-PARKIN (PARK2) and PARK-SNCA (PARK1) mutations [99].…”

Section: Advanced Stagementioning

confidence: 99%

A Stage-Based Approach to Therapy in Parkinson’s Disease

et al. 2019

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Parkinson’s disease (PD) is a neurodegenerative disorder that features progressive, disabling motor symptoms, such as bradykinesia, rigidity, and resting tremor. Nevertheless, some non-motor symptoms, including depression, REM sleep behavior disorder, and olfactive impairment, are even earlier features of PD. At later stages, apathy, impulse control disorder, neuropsychiatric disturbances, and cognitive impairment can present, and they often become a heavy burden for both patients and caregivers. Indeed, PD increasingly compromises activities of daily life, even though a high variability in clinical presentation can be observed among people affected. Nowadays, symptomatic drugs and non-pharmaceutical treatments represent the best therapeutic options to improve quality of life in PD patients. The aim of the present review is to provide a practical, stage-based guide to pharmacological management of both motor and non-motor symptoms of PD. Furthermore, warning about drug side effects, contraindications, as well as dosage and methods of administration, are highlighted here, to help the physician in yielding the best therapeutic strategies for each symptom and condition in patients with PD.

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Juvenile parkinsonism: Differential diagnosis, genetics, and treatment

Cited by 78 publications

References 253 publications

Parkinson’s disease: etiopathogenesis and treatment

Parkinson’s disease: etiopathogenesis and treatment

Mitochondrial Dysfunction, Oxidative Stress and Neuroinflammation in Neurodegeneration with Brain Iron Accumulation (NBIA)

A Stage-Based Approach to Therapy in Parkinson’s Disease

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