Movement Disorders Associated with COVID-19

As neurological complications associated with COVID-19 keep unfolding, the number of cases with COVID-19-associated de novo movement disorders is rising. Although no clear pathomechanistic explanation is provided yet, the growing number of these cases is somewhat alarming. This review gathers information from 64 reports of de novo movement disorders developing after/during infection with SARS-CoV-2. Three new cases with myoclonus occurring shortly after a COVID-19 infection are also presented. Treatment resulted in partial to complete recovery in all three cases. Although the overall percentage of COVID-19 patients who develop movement disorders is marginal, explanations on a probable causal link have been suggested by numerous reports; most commonly involving immune-mediated and postinfectious and less frequently hypoxic-associated and ischemic-related pathways. The current body of evidence points myoclonus and ataxia out as the most frequent movement disorders occurring in COVID-19 patients. Some cases of tremor, chorea, and hypokinetic-rigid syndrome have also been observed in association with COVID-19. In particular, parkinsonism may be of dual concern in the setting of COVID-19; some have linked viral infections with Parkinson’s disease (PD) based on results from cerebrospinal fluid analyses, and PD is speculated to impact the outcome of COVID-19 in patients negatively. In conclusion, the present paper reviewed the demographic, clinical, and treatment-associated information on de novo movement disorders in COVID-19 patients in detail; it also underlined the higher incidence of myoclonus and ataxia associated with COVID-19 than other movement disorders.

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Unexplained worsening of parkinsonian symptoms in a patient with advanced Parkinson’s disease as the sole initial presentation of COVID-19 infection: a case report

The Egyptian Journal of Neurology Psychiatry and Neurosurgery ◽

10.1186/s41983-021-00314-3 ◽

2021 ◽

Vol 57 (1) ◽

Author(s):

Walaa A. Kamel ◽

Ismail Ibrahim Ismail ◽

Mohamed Ibrahim ◽

Jasem Y. Al-Hashel

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Viral Infections ◽

Neurological Complications ◽

Initial Presentation ◽

Nasopharyngeal Swab ◽

Initial Manifestation ◽

Advanced Parkinson’S Disease ◽

Case Presentation ◽

Dystonic Posturing

Abstract Background Parkinson’s disease (PD) is a neurodegenerative condition that has been reported following viral infections in rare occasions. Several neurological complications have emerged in association with coronavirus disease 2019 (COVID-19), since its declaration as a pandemic. Herein, we present a novel case of unexplained worsening of PD as the sole initial presentation of COVID-19, in the absence of fever or respiratory symptoms. Case presentation A 56-year-old male with advanced PD presented with severe rigidity, dystonic posturing of both feet, and confusion of 4 days duration. His condition progressed to an akinetic-rigid state and confusion during the following week, and a routine nasopharyngeal swab tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the 9th day of onset. He developed fever and dyspnea later and was intubated on the 10th day. Conclusion To our knowledge, worsening of PD symptoms as the sole initial manifestation of SARS-CoV-2 infection, in the absence of other cardinal features of COVID-19, has not been reported in the literature. We suggest testing for COVID-19 infection in patients with PD, especially advanced cases, who present with unexplained worsening of symptoms, even in the absence of COVID-19 cardinal features.

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Cerebrospinal fluid amyloid- and phenotypic heterogeneity in de novo Parkinson's disease

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2012-303808 ◽

2012 ◽

Vol 84 (5) ◽

pp. 537-543 ◽

Cited By ~ 43

Author(s):

G. Alves ◽

K. F. Pedersen ◽

B. R. Bloem ◽

K. Blennow ◽

H. Zetterberg ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cerebrospinal Fluid ◽

De Novo ◽

Phenotypic Heterogeneity

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Neurodegeneration and Inflammation—An Interesting Interplay in Parkinson’s Disease

International Journal of Molecular Sciences ◽

10.3390/ijms21228421 ◽

2020 ◽

Vol 21 (22) ◽

pp. 8421

Author(s):

Chrysoula Marogianni ◽

Maria Sokratous ◽

Efthimios Dardiotis ◽

Georgios M. Hadjigeorgiou ◽

Dimitrios Bogdanos ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Dopaminergic Neurons ◽

Viral Infections ◽

Neurodegenerative Disorder ◽

Epidemiological Studies ◽

In Vitro Models ◽

Immune Mediated

Parkinson’s disease (PD) is a neurodegenerative disorder, caused by, so far, unknown pathogenetic mechanisms. There is no doubt that pro-inflammatory immune-mediated mechanisms are pivotal to the pathogenicity and progression of the disease. In this review, we highlight the binary role of microglia activation in the pathophysiology of the disorder, both neuroprotective and neuromodulatory. We present how the expression of several cytokines implicated in dopaminergic neurons (DA) degeneration could be used as biomarkers for PD. Viral infections have been studied and correlated to the disease progression, usually operating as trigger factors for the inflammatory process. The gut–brain axis and the possible contribution of the peripheral bowel inflammation to neuronal death, mainly dopaminergic neurons, seems to be a main contributor of brain neuroinflammation. The role of the immune system has also been analyzed implicating a-synuclein in the activation of innate and adaptive immunity. We also discuss therapeutic approaches concerning PD and neuroinflammation, which have been studied in experimental and in vitro models and data stemming from epidemiological studies.

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Interactions between SARS-CoV-2 N-protein and α-synuclein accelerate amyloid formation

10.1101/2021.04.12.439549 ◽

2021 ◽

Author(s):

Slav Semerdzhiev ◽

Mohammad Amin Abolghassemi Fakhree ◽

Ine Segers-Nolten ◽

Christian Blum ◽

Mireille M.A.E. Claessens

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Molecular Basis ◽

Amyloid Fibrils ◽

Viral Infections ◽

Protein Complexes ◽

Causal Link ◽

Test Tube ◽

Amyloid Formation ◽

N Protein

First cases that point at a correlation between SARS-CoV-2 infections and the development of Parkinson's disease have been reported. Currently it is unclear if there also is a direct causal link between these diseases. To obtain first insights into a possible molecular relation between viral infections and the aggregation of α-synuclein protein into amyloid fibrils characteristic for Parkinson's disease, we investigated the effect of the presence of SARS-CoV-2 proteins on α synuclein aggregation. We show, in test tube experiments, that SARS-CoV-2 S-protein has no effect on α-synuclein aggregation while SARS-CoV-2 N-protein considerably speeds up the aggregation process. We observe the formation of multi-protein complexes, and eventually amyloid fibrils. Microinjection of N-protein in SHSY-5Y cells disturbed the α-synuclein proteostasis and increased cell death. Our results point toward direct interactions between the N-protein of SARS-CoV-2 and α-synuclein as molecular basis for the observed coincidence between SARS-CoV-2 infections and Parkinsonism.

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Interleukin-1β and interleukin-6 are elevated in the cerebrospinal fluid of Alzheimer's and de novo Parkinson's disease patients

Neuroscience Letters ◽

10.1016/0304-3940(95)12192-7 ◽

1995 ◽

Vol 202 (1-2) ◽

pp. 17-20 ◽

Cited By ~ 477

Author(s):

Doris Blum-Degena ◽

Thomas Müller ◽

Wilfried Kuhn ◽

Manfred Gerlach ◽

Horst Przuntek ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cerebrospinal Fluid ◽

Interleukin 6 ◽

De Novo ◽

Interleukin 1Β

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Glucosylceramide in cerebrospinal fluid of patients with GBA-associated and idiopathic Parkinson’s disease enrolled in PPMI

npj Parkinson s Disease ◽

10.1038/s41531-021-00241-3 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Young Eun Huh ◽

Hyejung Park ◽

Ming Sum Ruby Chiang ◽

Idil Tuncali ◽

Ganqiang Liu ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cerebrospinal Fluid ◽

De Novo ◽

Early Stage ◽

Rapid Decline ◽

Healthy Controls ◽

Protein Coding ◽

Assessment Scores ◽

Liquid Chromatography Tandem Mass

AbstractProtein-coding variants in the GBA gene modulate susceptibility and progression in ~10% of patients with Parkinson’s disease (PD). GBA encodes the β-glucocerebrosidase enzyme that hydrolyzes glucosylceramide. We hypothesized that GBA mutations will lead to glucosylceramide accumulation in cerebrospinal fluid (CSF). Glucosylceramide, ceramide, sphingomyelin, and lactosylceramide levels were measured by liquid chromatography-tandem mass spectrometry in CSF of 411 participants from the Parkinson’s Progression Markers Initiative (PPMI) cohort, including early stage, de novo PD patients with abnormal dopamine transporter neuroimaging and healthy controls. Forty-four PD patients carried protein-coding GBA variants (GBA-PD) and 227 carried wild-type alleles (idiopathic PD). The glucosylceramide fraction was increased (P = 0.0001), and the sphingomyelin fraction (a downstream metabolite) was reduced (P = 0.0001) in CSF of GBA-PD patients compared to healthy controls. The ceramide fraction was unchanged, and lactosylceramide was below detection limits. We then used the ratio of glucosylceramide to sphingomyelin (the GlcCer/SM ratio) to explore whether these two sphingolipid fractions altered in GBA-PD were useful for stratifying idiopathic PD patients. Idiopathic PD patients in the top quartile of GlcCer/SM ratios at baseline showed a more rapid decline in Montreal Cognitive Assessment scores during longitudinal follow-up compared to those in the lowest quartile with a P-value of 0.036. The GlcCer/SM ratio was negatively associated with α-synuclein levels in CSF of PD patients. This study highlights glucosylceramide as a pathway biomarker for GBA-PD patients and the GlcCer/SM ratio as a potential stratification tool for clinical trials of idiopathic PD patients. Our sphingolipids data together with the clinical, imaging, omics, and genetic characterization of PPMI will contribute a useful resource for multi-modal biomarkers development.

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Association of the Non-Motor Burden with Patterns of Striatal Dopamine Loss in de novo Parkinson’s Disease

Journal of Parkinson s Disease ◽

10.3233/jpd-202127 ◽

2020 ◽

Vol 10 (4) ◽

pp. 1541-1549

Author(s):

Seok Jong Chung ◽

Sangwon Lee ◽

Han Soo Yoo ◽

Yang Hyun Lee ◽

Hye Sun Lee ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

De Novo ◽

Early Stage ◽

Striatal Dopamine ◽

Motor Deficits ◽

Dopamine Depletion ◽

Severe Motor ◽

Severe Group ◽

Striatal Dopamine Depletion

Background: Striatal dopamine deficits play a key role in the pathogenesis of Parkinson’s disease (PD), and several non-motor symptoms (NMSs) have a dopaminergic component. Objective: To investigate the association between early NMS burden and the patterns of striatal dopamine depletion in patients with de novo PD. Methods: We consecutively recruited 255 patients with drug-naïve early-stage PD who underwent 18F-FP-CIT PET scans. The NMS burden of each patient was assessed using the NMS Questionnaire (NMSQuest), and patients were divided into the mild NMS burden (PDNMS-mild) (NMSQuest score <6; n = 91) and severe NMS burden groups (PDNMS-severe) (NMSQuest score >9; n = 90). We compared the striatal dopamine transporter (DAT) activity between the groups. Results: Patients in the PDNMS-severe group had more severe parkinsonian motor signs than those in the PDNMS-mild group, despite comparable DAT activity in the posterior putamen. DAT activity was more severely depleted in the PDNMS-severe group in the caudate and anterior putamen compared to that in the PDMNS-mild group. The inter-sub-regional ratio of the associative/limbic striatum to the sensorimotor striatum was lower in the PDNMS-severe group, although this value itself lacked fair accuracy for distinguishing between the patients with different NMS burdens. Conclusion: This study demonstrated that PD patients with severe NMS burden exhibited severe motor deficits and relatively diffuse dopamine depletion throughout the striatum. These findings suggest that the level of NMS burden could be associated with distinct patterns of striatal dopamine depletion, which could possibly indicate the overall pathological burden in PD.

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