Clinical Features Indicating Nigrostriatal Dopaminergic Degeneration in Drug-Induced Parkinsonism

Lee, Seung Ha; Kim, Han Kyeol; Lee, Young Gun; Lyoo, Chul Hyoung; Ahn, Sung Jun; Lee, Myung Sik

doi:10.14802/jmd.16045

Cited by 7 publications

(10 citation statements)

References 20 publications

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“…Third, blockade of Ca V 3 channels stops pathological firing patterns in DARx and DA-depleted neurons and silences them, suggesting that these channels are instrumental for both conditions (Ibáñez-Sandoval et al 2007). Fourth, blockade of nonspecific cationic currents also stopped the pathological burst firing pattern silencing SNr neurons (Lee and Tepper 2007b;Lee et al 2011;Lutas et al 2014;. Fifth, the first generation antipsychotic haloperidol produces similar pathological firing patterns as DA-receptor blockers in SNr neurons in vitro, as it was shown in vivo (Maurice et al 2015).…”

Section: Discussionmentioning

confidence: 77%

“…Also, the differences in the presence of bursting between control and tested samples detected with this method suggest that the encoding capability of SNr neurons has been severely altered by the absence of DA signaling even when dopaminergic receptor blockade was acutely produced. To conclude, it is enough to block DA receptors to induce pathological firing correlating with many drugs that are suspected to produce DA-receptor blockade as their main mechanism in DIP clinical cases (however, while DA-receptor blockade may produce DIP after hours or days of usage, other drugs may require longer time and their mechanisms of action need to be studied; Lee et al 2017;Mukilan et al 2018). However, still a more precise comparison was used in trying to observe subtle differences between DARx and DA-depleted firing patterns.…”

Section: Spontaneous Activity Ofmentioning

confidence: 99%

“…Relevant examples of drugs inducing DIP are neuroleptics, calcium channel antagonists, antidepressants, anticholinergics, anticonvulsants, and gastrointestinal prokinetics, among others (Bondon-Guitton et al 2011;López-Sendon et al 2013). These drugs may generate a Parkinsonian syndrome themselves, worsen Parkinson's disease (PD), or disclose PD ahead of time (Lee et al 2017); are the second cause of PS, or~20 -40% of the cases, reaching epidemic proportions; and are frequently overlooked (López-Sendon et al 2013;Mukilan et al 2018). This problem is a main reason for a careful differential diagnosis.…”

Section: Introductionmentioning

confidence: 99%

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Acute dopamine receptor blockade in substantia nigra pars reticulata: a possible model for drug-induced Parkinsonism

Cáceres-Chávez

Hernández-Martínez

Pérez-Ortega

et al. 2018

Journal of Neurophysiology

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Acute dopamine receptor blockade in substantia nigra pars reticulata: a possible model for drug-induced Parkinsonism. Dopamine (DA) depletion modifies the firing pattern of neurons in the substantia nigra pars reticulata (SNr), shifting their mostly tonic firing toward irregularity and bursting, traits of pathological firing underlying rigidity and postural instability in Parkinson's disease (PD) patients and animal models of Parkinsonism (PS). Drug-induced Parkinsonism (DIP) represents 20 -40% of clinical cases of PS, becoming a problem for differential diagnosis, and is still not well studied with physiological tools. It may co-occur with tardive dyskinesia. Here we use in vitro slice preparations including the SNr to observe drug-induced pathological firing by using drugs that most likely produce it, DA-receptor antagonists (SCH23390 plus sulpiride), to compare with firing patterns found in DA-depleted tissue. The hypothesis is that SNr firing would be similar under both conditions, a prerequisite to the proposal of a similar preparation to test other DIP-producing drugs. Firing was analyzed with three complementary metrics, showing similarities between DA depletion and acute DAreceptor blockade. Moreover, blockade of either nonselective cationic channels or Ca v 3 T-type calcium channels hyperpolarized the membrane and abolished bursting and irregular firing, silencing SNr neurons in both conditions. Therefore, currents generating firing in control conditions are in part responsible for pathological firing. Haloperidol, a DIP-producing drug, reproduced DA-receptor antagonist firing modifications. Since acute DA-receptor blockade induces SNr neuron firing similar to that found in the 6-hydroxydopamine model of PS, output basal ganglia neurons may play a role in generating DIP. Therefore, this study opens the way to test other DIP-producing drugs.NEW & NOTEWORTHY Dopamine (DA) depletion enhances substantia nigra pars reticulata (SNr) neuron bursting and irregular firing, hallmarks of Parkinsonism. Several drugs, including antipsychotics, antidepressants, and calcium channel antagonists, among others, produce drug-induced Parkinsonism. Here we show the first comparison between SNr neuron firing after DA depletion vs. firing found after acute blockade of DA receptors. It was found that firing in both conditions is similar, implying that pathological SNr neuron firing is also a physiological correlate of drug-induced Parkinsonism.

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Section: Discussionmentioning

confidence: 77%

Section: Spontaneous Activity Ofmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Acute dopamine receptor blockade in substantia nigra pars reticulata: a possible model for drug-induced Parkinsonism

Cáceres-Chávez

Hernández-Martínez

Pérez-Ortega

et al. 2018

Journal of Neurophysiology

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“…Unlike other movement disorders, the diagnostic criteria for DIP are not well established, and there is ongoing debate regarding the time it takes for parkinsonism to recover after discontinuing the causative drug [ 5 ]. Inaccurate patient information, along with possible pathophysiological factors, can contribute to a misdiagnosis and subsequent reclassification of PD and DIP cases [ 5 , 12 ]. The intricate interaction between the effects of the causative drugs and preexisting neurodegenerative changes in the dopamine system may contribute to the diagnostic complexities encountered in differentiating DIP from PD in clinical practice.…”

Section: Discussionmentioning

confidence: 99%

Comparative Olfactory Profiles in Parkinson’s Disease and Drug-Induced Parkinsonism

Kwak,

Kim,

Kang

et al. 2024

JMD

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Objective Drug-induced parkinsonism (DIP) is a frequently encountered diagnostic possibility when considering Parkinson’s disease (PD). While olfactory dysfunction is a common clinical feature in PD, the comparison of olfactory function between the two conditions remains insufficient. This study aimed to compare olfactory function, including threshold, discrimination, and identification (TDI) profiles, between PD and DIP.Methods Consecutive patients with drug-naïve PD (<i>n</i> = 78) or DIP (<i>n</i> = 31) confirmed through dopamine transporter imaging were enrolled in this study. The YSK olfactory function (YOF) test, composed of TDI domains culturally familiar odorants to Koreans, was administered to all patients.Results In the study population, patients with DIP were significantly older than patients with PD. Over 70% of patients in each group had hyposmia or anosmia, and there was no significant difference in the occurrence of olfactory dysfunction between the two groups. In addition, there were no differences in the total YOF score and threshold score between the two groups. Meanwhile, the PD group had a significantly lower discrimination and identification score than the DIP group after adjusting for age, sex, the existence of diabetes, disease duration, and cognitive function.Conclusion This study demonstrated that detailed olfactory profiles are different in PD and DIP, even though olfactory dysfunction can be observed in both conditions.

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“…However, because DIP is sometimes clinically indistinguishable from PD, diagnosis is challenging. 4 5 6 7 …”

Section: Introductionmentioning

confidence: 99%

Retinal Thickness and Its Interocular Asymmetry Between Parkinson’s Disease and Drug-Induced Parkinsonism

Suh

Baek

et al. 2023

J Korean Med Sci

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Background Drug-induced parkinsonism (DIP) is common, but diagnosis is challenging. Although dopamine transporter imaging is useful, the cost and inconvenience are problematic, and an easily accessible screening technique is needed. We aimed to determine whether optical coherence tomography (OCT) findings could differentiate DIP from Parkinson’s disease (PD). Methods We investigated 97 de novo PD patients and 27 DIP patients using OCT and [ 18 F] N-(3-fluoropropyl)-2b-carbon ethoxy-3b-(4-iodophenyl) nortropane (FP-CIT) positron emission tomography. We compared peripapillary retinal nerve fiber layer thickness (pRNFLT) and macular retinal thickness (mRT) between PD and DIP patients as well as interocular differences in the pRNFLT and the mRT. Asymmetric index (%) for retinal thickness (AIRT) was calculated to measure the interocular differences between pRNFLT and mRT. The correlation between AIRT and total striatal specific/non-specific binding ratio asymmetry index (SNBRAI) was investigated in PD and DIP patients. Results No significant differences in pRNFLT and mRT values were observed between PD and DIP patients (all P values > 0.090). The mean SNBRAI was significantly higher in PD than in DIP ( P = 0.008) patients; however, AIRT did not differ between PD and DIP patients in pRNFLT and mRT (all P values > 0.100). SNBRAI did not correlate with AIRT of pRNFL or mRT in PD and DIP patients (all P values > 0.060). Conclusion Our study showed no benefit of retinal thickness and interocular asymmetry measurements using OCT for distinguishing PD from DIP in the early stages. Additional investigations are needed for confirmation.

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Clinical Features Indicating Nigrostriatal Dopaminergic Degeneration in Drug-Induced Parkinsonism

Cited by 7 publications

References 20 publications

Acute dopamine receptor blockade in substantia nigra pars reticulata: a possible model for drug-induced Parkinsonism

Acute dopamine receptor blockade in substantia nigra pars reticulata: a possible model for drug-induced Parkinsonism

Comparative Olfactory Profiles in Parkinson’s Disease and Drug-Induced Parkinsonism

Retinal Thickness and Its Interocular Asymmetry Between Parkinson’s Disease and Drug-Induced Parkinsonism

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