Abnormal cortical facilitation and L-dopa-induced dyskinesia in Parkinson's disease

Guerra, Andrea; Suppa, Antonio; D'Onofrio, Valentina; Stasio, Flavio Di; Asci, Francesco; Fabbrini, Giovanni; Berardelli, Alfredo

doi:10.1016/j.brs.2019.06.012

Cited by 58 publications

(56 citation statements)

References 48 publications

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“…In contrast, exaggerated SICF peaks were reported in Parkinson's disease (Ni et al 2013;Shirota et al 2019), in particular in those with levodopa-induced dyskinesias (Guerra et al 2019), and in amyotrophic lateral sclerosis directly related to upper motoneuron signs and disease severity (Van den Bos et al 2018a), an abnormality that was interpreted as an abnormally hypersynchronized and/or hyperexcitable state of excitatory interneurons in M1.…”

Section: Clinical and Biological Relevance Of I-wavesmentioning

confidence: 99%

“…These results are directly compatible with the view that glutamate is the neurotransmitter in the proposed chains of excitatory interneurons responsible for the generation of I-waves. Similarly, in addition to its inhibitory effect on monoamine oxidase-type B, the anti-parkinsonian drug safinamide inhibits presynaptic glutamate release through blockage of voltage-gated sodium channels and results in significant suppression of SICF in patients with Parkinson’s disease and levodopa-induced dyskinesias (Guerra et al 2019 ).…”

Section: Physiology Of I-wavesmentioning

confidence: 99%

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I-waves in motor cortex revisited

Ziemann

2020

Exp Brain Res

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I-waves represent high-frequency (~ 600 Hz) repetitive discharge of corticospinal fibers elicited by single-pulse stimulation of motor cortex. First detected and examined in animal preparations, this multiple discharge can also be recorded in humans from the corticospinal tract with epidural spinal electrodes. The exact underpinning neurophysiology of I-waves is still unclear, but there is converging evidence that they originate at the cortical level through synaptic input from specific excitatory interneuronal circuitries onto corticomotoneuronal cells, controlled by GABAAergic interneurons. In contrast, there is at present no supportive evidence for the alternative hypothesis that I-waves are generated by high-frequency oscillations of the membrane potential of corticomotoneuronal cells upon initial strong depolarization. Understanding I-wave physiology is essential for understanding how TMS activates the motor cortex.

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Section: Clinical and Biological Relevance Of I-wavesmentioning

confidence: 99%

Section: Physiology Of I-wavesmentioning

confidence: 99%

I-waves in motor cortex revisited

Ziemann

2020

Exp Brain Res

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“…Classically, LIDs are attributable to the degree of nigrostriatal neurodegeneration and striatal alternation related to chronic levodopa therapy, which may induce plastic synaptic abnormalities in striatal medium spiny neurons and further have an impact on alternation of neuronal activity in striato-pallidal circuits 16 . With more and more studies focused on LIDs, the pathophysiological mechanisms have been modified from striato-motor circuitry to a broader cortico-cortical network, involving frontal cortex (including pre-SMA and IFC) 6 , 17 – 19 . As is generally known that IFC is critical for response inhibition through sending a stop command to primary motor cortex (PMC) (M1) 20 .…”

Section: Discussionmentioning

confidence: 99%

Altered interhemispheric synchrony in Parkinson’s disease patients with levodopa-induced dyskinesias

Gan

Wang

et al. 2020

npj Parkinsons Dis.

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Levodopa-induced dyskinesias are common motor complication of Parkinson’s disease after 4–6 years of treatment. The hallmarks of dyskinesias include unilateral onset and the tendency to appear on the more affected body sides. There is a growing literature documenting the lateralization abnormalities are associated with the emergence of dyskinesias. Our investigation aimed to explore interhemispheric functional and its corresponding morphological asymmetry. A total of 22 dyskinetic patients, 23 nondyskinetic patients, and 26 controls were enrolled. Resting-state functional magnetic resonance imaging scans were performed twice before and after dopaminergic medication. Voxel-mirrored Homotopic Connectivity (VMHC) and Freesurfer were employed to assess the synchronicity of functional connectivity and structural alternations between hemispheres. During OFF state, dyskinetic patients showed desynchronization of inferior frontal cortex (IFC) when compared to nondyskinetic patients. And during ON state, dyskinetic patients showed desynchronization of IFC and pre-supplementary motor area (pre-SMA) when compared to nondyskinetic patients. However, there was no corresponding significant asymmetries in cortical thickness. Moreover, the degree of desynchronization of IFC and pre-SMA in dyskinetic pateients during ON state were negatively correlated with the Abnormal Involuntary Movement Scale (AIMS) scores. Notably, among patients who showed asymmetrical dyskinesias, there was a significant negative correlation between VMHC values of IFC and dyskinesias symptom asymmetry. Our findings suggested that uncoordinated inhibitory control over motor circuits may underlie the neural mechanisms of dyskinesias in Parkinson’s disease and be related to its severity and lateralization.

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“…Effective gene therapy, including in vivo and ex vivo gene therapy (Figure 1), represents a novel and promising approach for disease treatment, particularly for neurological diseases, autoimmunity and cancer, where treatment options are currently focused on symptomatic relief instead of disease modification. [10,61] Gene therapy was first conceived in 1972, [62] and the first gene therapy trial was approved by the US Food and Drug Administration (FDA) in 1990 for adenosine deaminase (ADA) deficiency, [63] with much optimism surrounding its ability to treat or cure genetic diseases induced by defective genes. Since then, hundreds of clinical trials have been devoted to exploring the potential of gene therapy for the treatment of a variety of diseases, most trials focusing on neurodegenerative diseases, [64] autoimmune disorders, [65] and cancer.…”

Section: Gene Delivery For Gene Therapymentioning

confidence: 99%

Is Viral Vector Gene Delivery More Effective Using Biomaterials?

Wang

Bruggeman

Franks

et al. 2020

Adv Healthcare Materials

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Gene delivery has been extensively investigated for introducing foreign genetic material into cells to promote expression of therapeutic proteins or to silence relevant genes. This approach can regulate genetic or epigenetic disorders, offering an attractive alternative to pharmacological therapy or invasive protein delivery options. However, the exciting potential of viral gene therapy has yet to be fully realized, with a number of clinical trials failing to deliver optimal therapeutic outcomes. Reasons for this include difficulty in achieving localized delivery, and subsequently lower efficacy at the target site, as well as poor or inconsistent transduction efficiency. Thus, ongoing efforts are focused on improving local viral delivery and enhancing its efficiency. Recently, biomaterials have been exploited as an option for more controlled, targeted and programmable gene delivery. There is a growing body of literature demonstrating the efficacy of biomaterials and their potential advantages over other delivery strategies. This review explores current limitations of gene delivery and the progress of biomaterial‐mediated gene delivery. The combination of biomaterials and gene vectors holds the potential to surmount major challenges, including the uncontrolled release of viral vectors with random delivery duration, poorly localized viral delivery with associated off‐target effects, limited viral tropism, and immune safety concerns.

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Abnormal cortical facilitation and L-dopa-induced dyskinesia in Parkinson's disease

Cited by 58 publications

References 48 publications

I-waves in motor cortex revisited

I-waves in motor cortex revisited

Altered interhemispheric synchrony in Parkinson’s disease patients with levodopa-induced dyskinesias

Is Viral Vector Gene Delivery More Effective Using Biomaterials?

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