ABSTRACT
Myocardial (123)Metaiodobenzylguanidine (MIBG) enables the assessment of postganglionic sympathetic cardiac innervation. MIBG uptake is decreased in nearly all patients with Parkinson's disease (PD). Our objective was to evaluate MIBG uptake in patients with genetic PD. We investigated MIBG uptake in 14 patients with PD associated with mutations in different genes (Parkin, DJ-1, PINK1, and leucine-rich repeat kinase 2 -LRRK2), in 15 patients with idiopathic PD, and 10 control subjects. The myocardial MIGB uptake was preserved in 3 of the 4 Parkin-associated Parkinsonisms, in 1 of the 2 patients with DJ-1 mutations, in 1 of the 2 brothers with PINK1 mutations, in 3 of the 6 unrelated patients with Gly2019Ser mutation in the LRRK2 gene, whereas it was impaired in all patients with idiopathic PD. MIBG was preserved in all control subjects. Our study shows that myocardial MIGB uptake was normal in 8 of 14 patients with genetic PD, suggesting that cardiac sympathetic denervation occurs less frequently in genetic PD than in idiopathic PD. Our findings also demonstrate that MIGB uptake has a heterogeneous pattern in genetic PD, because it was differently impaired in patients with different mutations in the same gene or with the same gene mutation.
Subject(s)
3-Iodobenzylguanidine/pharmacokinetics , Myocardium/metabolism , Parkinson Disease/diagnosis , Parkinson Disease/genetics , Parkinsonian Disorders/diagnosis , Parkinsonian Disorders/genetics , Point Mutation/genetics , Radiopharmaceuticals/pharmacokinetics , Adult , DNA Mutational Analysis , Diagnosis, Differential , Female , Galvanic Skin Response/physiology , Genotype , Humans , Intracellular Signaling Peptides and Proteins/blood , Intracellular Signaling Peptides and Proteins/genetics , Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 , Male , Middle Aged , Movement Disorders/diagnosis , Movement Disorders/epidemiology , Oncogene Proteins/blood , Oncogene Proteins/genetics , Parkinson Disease/epidemiology , Parkinsonian Disorders/epidemiology , Promoter Regions, Genetic , Protein Deglycase DJ-1 , Protein Kinases/blood , Protein Kinases/genetics , Protein Serine-Threonine Kinases/blood , Protein Serine-Threonine Kinases/genetics , Severity of Illness Index , Surveys and Questionnaires , Tomography, Emission-Computed, Single-Photon/methods , Ubiquitin-Protein Ligases/blood , Ubiquitin-Protein Ligases/geneticsABSTRACT
Chronic subthalamic nucleus deep brain stimulation (STN-DBS) is an efficacious treatment for idiopathic Parkinson's disease (PD) that cannot be further improved by medical therapy. We present a case of an individual with juvenile parkinsonism caused by homozygous deletion of exon 3 in the parkin gene with disabling long-term side-effects from levodopa who underwent bilateral STN neuromodulation. Parkin-linked parkinsonism may show clinical features different from sporadic PD, yet it shares levodopa responsiveness. Because levodopa responsiveness is a predictor of STN-DBS efficacy, we argued that this kind of surgical approach might be efficacious in hereditary parkin-linked juvenile parkinsonism. We evaluated clinical and functional assessment before and 12 months after surgery. The results showed that the Unified Parkinson Disease Rating Scales Motor score improved by 84% in our patient, the levodopa equivalent daily dose medication (LEDD) was reduced by 66%, and, finally, disabling and severe dyskinesias disappeared.
