Search results for "Dyskinesia"

Role of adenylate kinase type 7 expression on cilia motility: possible link in primary ciliary dyskinesia.

2010

Background Adenylate kinase 7 (AK7) mediates the reaction 2ADP ↔ ATP + AMP, providing energy for the beating of cilia. A study recently showed that AK7 expression may be correlated with the primary ciliary dyskinesia (PCD) phenotype in mice. In this study, we characterized AK7 expression in vitro in an air–liquid interface (ALI) model and in middle nasal turbinate biopsy specimens from a cohort of patients with PCD to elucidate whether AK7 expression is correlated with ciliary malfunction. Methods AK7 expression was measured by real-time reverse-transcription polymerase chain reaction and Western blotting. In vitro differentiated nasal human epithelial cell siRNA experiments were performed …

RISK FACTORS FOR DYSKINESIAS IN PATIENTS WITH PARKINSON'S DISEASE

2011

Cerebellar magnetic stimulation decreases levodopa-induced dyskinesias in Parkinson disease

2009

BACKGROUND: The neural mechanisms and the circuitry involved in levodopa-induced dyskinesia (LID) are still partially obscure. LID can be considered the consequence of an abnormal pattern or code of activity that originates and is conveyed from the basal ganglia to the thalamus and the cortical motor areas. However, not only striatothalamocortical motor circuits but also other interconnected pathways could be implicated in its pathogenesis. METHODS: In a series of experiments, we applied repetitive transcranial magnetic stimulation (rTMS) over the lateral cerebellum in a group of patients with advanced Parkinson disease, to investigate whether modulation of cerebellothalamocortical circuits…

Both Short- and Long-Acting D-1/D-2 Dopamine Agonists Induce Less Dyskinesia than l-DOPA in the MPTP-Lesioned Common Marmoset (Callithrix jacchus)

2002

Abstract The current concept of dyskinesia is that pulsatile stimulation of D-1 or D-2 receptors by l -DOPA or short-acting dopamine agonists is more likely to induce dyskinesia compared to long-acting drugs producing more continuous receptor stimulation. We now investigate the ability of two mixed D-1/D-2 agonists, namely pergolide (long-acting) and apomorphine (short-acting), to induce dyskinesia in drug-naive MPTP-lesioned primates, compared to l -DOPA. Adult common marmosets ( Callithrix jacchus ) were lesioned with MPTP (2 mg/kg/day sc for 5 days) and subsequently treated with equieffective antiparkinsonian doses of l -DOPA, apomorphine, or pergolide for 28 days. l -DOPA, apomorphine, …

GDNF reverses priming for dyskinesia in MPTP-treated, L-DOPA-primed common marmosets

2001

Parkinson's disease (PD) is associated with a progressive loss of dopamine neurons in the substantia nigra and degeneration of dopaminergic terminals in the striatum. Although L-DOPA treatment provides the most effective symptomatic relief for PD it does not prevent the progression of the disease, and its long-term use is associated with the onset of dyskinesia. In rodent and primate studies, glial cell line-derived neurotrophic factor (GDNF) may prevent 6-OHDA- or MPTP-induced nigral degeneration and so may be beneficial in the treatment of PD. In this study, we investigate the effects of GDNF on the expression of dyskinesia in L-DOPA-primed MPTP-treated common marmosets, exhibiting dyskin…

Gene Therapy in Rare Respiratory Diseases: What Have We Learned So Far?

2020

Gene therapy is an alternative therapy in many respiratory diseases with genetic origin and currently without curative treatment. After five decades of progress, many different vectors and gene editing tools for genetic engineering are now available. However, we are still a long way from achieving a safe and efficient approach to gene therapy application in clinical practice. Here, we review three of the most common rare respiratory conditions—cystic fibrosis (CF), alpha-1 antitrypsin deficiency (AATD), and primary ciliary dyskinesia (PCD)—alongside attempts to develop genetic treatment for these diseases. Since the 1990s, gene augmentation therapy has been applied in multiple clinical tria…

Cognitive impairment and levodopa induced dyskinesia in Parkinson’s disease: a longitudinal study from the PACOS cohort

2021

AbstractAim of the study was to evaluate possible associations between cognitive dysfunctions and development of Levodopa Induced Dyskinesia (LID). PD patients from the Parkinson’s disease Cognitive impairment Study cohort who underwent a baseline and follow-up neuropsychological evaluations were enrolled. Mild Cognitive Impairment (PD-MCI) was diagnosed according to MDS level II criteria. The following cognitive domains were evaluated: episodic memory, attention, executive function, visuo-spatial function and language. A domain was considered as impaired when the subject scored 2 standard deviation below normality cut-off values in at least one test for each domain. Levodopa equivalent dos…

De novo loss-of-function KCNMA1 variants are associated with a new multiple malformation syndrome and a broad spectrum of developmental and neurologi…

2019

Abstract KCNMA1 encodes the large-conductance Ca2+- and voltage-activated K+ (BK) potassium channel α-subunit, and pathogenic gain-of-function variants in this gene have been associated with a dominant form of generalized epilepsy and paroxysmal dyskinesia. Here, we genetically and functionally characterize eight novel loss-of-function (LoF) variants of KCNMA1. Genome or exome sequencing and the participation in the international Matchmaker Exchange effort allowed for the identification of novel KCNMA1 variants. Patch clamping was used to assess functionality of mutant BK channels. The KCNMA1 variants p.(Ser351Tyr), p.(Gly356Arg), p.(Gly375Arg), p.(Asn449fs) and p.(Ile663Val) abolished the …

Pregabalin as add-on treatment to botulinum toxin in idiopathic hemifacial spasm

2007

Botulinum toxin (BTX) is the medical therapy of choice in hemifacial spasm (HFS). However, in some patients, its therapeutic effect is insufficient. ### Patient 1. A 64-year-old man with a 10-year history of left-sided HFS was treated with BTX over a period of 6 years with good results. However, in the last 2 years the spasms were never sufficiently relieved by BTX. The patient felt significantly impaired, but declined to undergo neurosurgical intervention. The EDB test showed a decrease in the CMAP amplitude of 60%. Without changing the BTX regime, pregabalin (initially 75 mg/day increased every 5 days by 75 mg to 150 mg twice daily) was added for a 1-month trial period in the absence of a…

rTMS of supplementary motor area modulates therapy-induced dyskinesias in Parkinson disease

2005

The neural mechanisms and circuitry involved in levodopa-induced dyskinesia are unclear. Using repetitive transcranial magnetic stimulation (rTMS) over the supplementary motor area (SMA) in a group of patients with advanced Parkinson disease, the authors investigated whether modulation of SMA excitability may result in a modification of a dyskinetic state induced by continuous apomorphine infusion. rTMS at 1 Hz was observed to markedly reduce drug-induced dyskinesias, whereas 5-Hz rTMS induced a slight but not significant increase.