Early-onset drug-induced parkinsonism after exposure to offenders implies nigrostriatal dopaminergic dysfunction

Chung, Seok Jong; Yoo, Hyung Sik; Moon, Hwan Pyo; Oh, Jungsu S.; Kim, Jae Seung; Park, Yong‐Hee; Hong, Jin Yong; Ye, Byoung Seok; Sohn, Young H.; Lee, Phil Hyu

doi:10.1136/jnnp-2017-315873

Cited by 15 publications

(7 citation statements)

References 38 publications

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“…Only when quantitative analysis was performed it was possible to observe a statistically significant reduction in DAT availability in those who presented parkinsonism less than 6 months after initiation of neuroleptics. In contrast, no alterations where found in subjects with late-onset parkinsonism, suggesting that early-onset DIP might be in fact umPD [51]In addition, one clinico-pathological study in 7 patients with DIP did not report any relationship between presence of Lewy bodies and symptom reversal [52].…”

Section: Pathophysiology and Causal Agentsmentioning

confidence: 96%

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Current Methods for the Treatment and Prevention of Drug-Induced Parkinsonism and Tardive Dyskinesia in the Elderly

Estévez-Fraga¹,

Zeun²,

Moreno

2018

Drugs Aging

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Drug induced parkinsonism and tardive dyskinesia are iatrogenic consequences of the use of antidopaminergic drugs. Both entities share risk factors, physiopathological mechanisms and to some degree, therapeutic approaches. Here we review both entities and discuss emerging therapies including the recently approved drug deutetrabenazine and relevant aspects for clinical practice such as new diagnostic techniques. Key points:-Drug induced parkinsonism and tardive dyskinesia are iatrogenic consequences of the use of antidopaminergic drugs.-DIP is considered a direct consequence of the blockage of D2 receptors while TD has a more complex physiopathology, including enhanced sensitivity of dopamine receptors.-Both entities are more frequent in older people due to a progressive loss of dopaminergic neurons with age.-New therapies are available for TD, including deutetrabenazine. Compliance with ethical Standards:Disclosure of potential conflicts of interest: no funding was received for this study.The risks of drug-induced parkinsonism/tardive dyskinesia in the elderly and current methods to overcome it. 1.-IntroductionTardive dyskinesia (TD) and drug-induced parkinsonism (DIP) are iatrogenic disorders caused by dopamine receptor blockers (DRB) [1]. They were recognized early after the introduction of antipsychotics[2] to the clinical practice, leading to the finding that DIP caused by reserpine, a dopamine depleter, was related to dopamine deficiency [3].Elderly patients are more susceptible to these side effects, probably due to an age-related decrease in nigral neurons and dopamine [4]. Since the introduction of newer second generation antipsychotics (SGA) the frequency and intensity of these side effects has improved [5] , [6] , [7] , [8] but there is still room for concern [9], [10].TD and DIP share risk factors, pathological mechanisms and management, and might coexist in one given subject. Latest available evidence has clarified some intriguing features of TD and DIP. Meanwhile, new medications to treat TD are now available, highlighting the importance of a thorough, updated, knowledge of this pathologies.This article offers a comprehensive review of the incidence, clinical features and mechanisms behind DIP and TD. The benefits and risks of previous available drugs and those that have been recently approved by regulatory agencies are discussed. Drug induced Parkinsonism DefinitionDIP occurs when symptoms emerge after exposure to drugs, usually those that either deplete dopamine storages [11] or block dopamine receptors [12]. By definition, symptoms should be reversible, six months after the offending agent has been withdrawn[13] but actually up to 20% of patients develop persistent deficits despite drug discontinuation [14] leading to the hypothesis that these patients might have subclinical Parkinson's Disease (PD) unmasked by neuroleptic exposure (umPD), complicating the differential diagnosis [15], especially between aged patients, who are more prone to both PD and DIP. Epidemiology and risk factorsAfter PD, DI...

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Section: Pathophysiology and Causal Agentsmentioning

confidence: 96%

“…Tardive parkinsonism is a term used when parkinsonism lasts for years after drug discontinuation and DaTscan is unremarkable [120] with one report disclosing absence of PD pathology. However possibly most cases are related to slightly abnormal functional neuroimaging [51].…”

Section: Clinical Featuresmentioning

confidence: 99%

Current Methods for the Treatment and Prevention of Drug-Induced Parkinsonism and Tardive Dyskinesia in the Elderly

Estévez-Fraga¹,

Zeun²,

Moreno

2018

Drugs Aging

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“…An interesting investigation of early-onset vs late-onset DIP, in relationship to neuroleptic initiation, notes that early-onset patients were more likely to have DAT abnormalities. 72 This lends credence to the discussion that many patients diagnosed with DIP already have an underlying susceptibility to develop parkinsonism. Overall, these data suggest that some DAT-positive and DAT-negative patients undergoing workup for DIP vs PD may have distinct clinical features.…”

Section: Clinical Manifestations/diagnosismentioning

confidence: 71%

Updated Perspectives on the Management of Drug-Induced Parkinsonism (DIP): Insights from the Clinic

Feldman¹,

Marmol²,

Margolesky³

2022

TCRM

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Parkinsonism refers to the clinical combination of bradykinesia, rigidity, tremor, and postural instability. Parkinsonism is often neurodegenerative, but it can be secondary or iatrogenic, as in drug-induced parkinsonism (DIP), which is the topic of this review. We review the pathophysiology of DIP, differentiate DIP and idiopathic Parkinson’s disease (PD), list culprit medications in the development of DIP, discuss the diagnosis of DIP as well as the motor and nonmotor signs and symptoms that can help with differentiation of DIP and PD, and detail the management of DIP.

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“…In this regard, a “double hit” hypothesis has been proposed, invoking a primary neurotoxic effect of dopamine blocking agents [ 131 ] and autopsy studies have reported changes compatible with an underlying idiopathic PD [ 132 ]. Moreover, there are patients with persistent DIP but visually normal DAT imaging in which mechanisms through which the offending drugs lead to parkinsonian symptoms are yet unclear, but a relatively decreased DAT levels within normal values could be indicative of a subtle nigrostriatal dopaminergic dysfunction predicting an early development of DIP [ 133 , 134 ]. This supports the evidence that DIP diagnosis represents a risk factor for idiopathic PD, implying the existence a latent parkinsonism in several patients triggered by the causative drug [ 135 ].…”

Section: Dat Imaging As Diagnostic Biomarkermentioning

confidence: 99%

Dopamine Transporter Imaging, Current Status of a Potential Biomarker: A Comprehensive Review

Palermo

Giannoni

Bellini

et al. 2021

IJMS

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A major goal of current clinical research in Parkinson’s disease (PD) is the validation and standardization of biomarkers enabling early diagnosis, predicting outcomes, understanding PD pathophysiology, and demonstrating target engagement in clinical trials. Molecular imaging with specific dopamine-related tracers offers a practical indirect imaging biomarker of PD, serving as a powerful tool to assess the status of presynaptic nigrostriatal terminals. In this review we provide an update on the dopamine transporter (DAT) imaging in PD and translate recent findings to potentially valuable clinical practice applications. The role of DAT imaging as diagnostic, preclinical and predictive biomarker is discussed, especially in view of recent evidence questioning the incontrovertible correlation between striatal DAT binding and nigral cell or axon counts.

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Early-onset drug-induced parkinsonism after exposure to offenders implies nigrostriatal dopaminergic dysfunction

Abstract: These results suggest that a short exposure to the offending drugs before the development of parkinsonism would be associated with subtle nigrostriatal dopaminergic dysfunction in patients with DIP.

Cited by 15 publications

References 38 publications

Current Methods for the Treatment and Prevention of Drug-Induced Parkinsonism and Tardive Dyskinesia in the Elderly

Current Methods for the Treatment and Prevention of Drug-Induced Parkinsonism and Tardive Dyskinesia in the Elderly

Updated Perspectives on the Management of Drug-Induced Parkinsonism (DIP): Insights from the Clinic

Dopamine Transporter Imaging, Current Status of a Potential Biomarker: A Comprehensive Review

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