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Biomedical subjects

Spiridon Papapetropoulos

Publications and source records attributed to Spiridon Papapetropoulos.

At least 19 recordsLinked to original sources
PubMed2007

Glutathione S-transferase polymorphisms and onset age in alpha-synuclein A53T mutant Parkinson's disease.

Monogenic forms of Parkinson's disease (PD) provide an opportunity to examine mechanisms underlying phenotypic variation. Glutathione S-transferase (GST) has detoxification and antioxidative functions. To screen genetic variations in GST for an effect on the onset age (OA) of PD, we typed seven common genetic polymorphisms in five GST isoenzymes, M1, M3, P1, T1, and Z1, in 36 affected individuals of Italian or Greek origin with the alpha-synuclein A53T (PARK1) mutation. Mean OA was 45.2 years with a wide SD of 11.03 years, similar to that of idiopathic PD. Our allelic analysis showed that the subjects homozygous for the GSTP1 G-for-A nucleotide substitution at position 313 had a mean OA acceleration of 15.2 years (31.3 +/- 7.09 years, n = 3 vs. 46.5 +/- 10.50 years, n = 33, P = 0.020). The GSTP1 C341T substitution was associated with a 9.7-year acceleration of OA, but the significance was borderline (36.4 +/- 8.35 years vs. 46.7 +/- 10.85 years, P = 0.0519). After correction for the five genes examined, both results lose statistical significance. Nevertheless, our results suggest that further investigation in GSTP1 variants and PD pathogenesis is warranted in sporadic PD and that a search for toxins that accelerate PD OA should pay particular attention to GST-P1 substrates.

Adenine↗
PubMed2007

Phenotypic associations of tau and ApoE in Parkinson's disease.

Overlaps in clinical, pathological and molecular features of Parkinson's disease (PD), dementing and motor tauopathies have prompted association studies in search of common genetic risk factors that may predispose or modify this spectrum of disorders. To explore possible phenotypic implications, we studied common tau and ApoE gene polymorphisms, associated with Alzheimer's disease (AD), progressive supranuclear palsy (PSP) and PD, in a clinically and pathologically characterized cohort of PD patients and aged control subjects. Our results reveal a novel association between PD-related hallucinations and H1H1 genotype. We also report an association between PDD and the presence of the ApoE epsilon4 allele. Better determination of subsets of PD patients based upon the presence of specific phenotypic features may improve the accuracy of association studies.

Aged↗
PubMed2006

Eating dysfunction associated with oromandibular dystonia: clinical characteristics and treatment considerations.

BACKGROUND: In oromandibular dystonia (OMD) abnormal repetitive contractions of masticatory, facial, and lingual muscles as well as the presence of orobuccolingual (OBL) dyskinesias may interfere with the appropriate performance of tasks such as chewing and swallowing leading to significant dysphagia and weight loss. We present here the clinical characteristics and treatment variables of a series of patients that developed an OMD-associated eating dysfunction. METHODS: We present a series of patients diagnosed and followed-up at the Movement Disorders Clinic of the Department of Neurology of University of Miami, Miller School of Medicine over a 10-year period. Patients were treated with botulinum toxin injections according to standard methods. RESULTS: Five out of 32 (15.6%) OMD patients experienced symptoms of eating dysfunction associated with OMD. Significant weight loss was reported in 3/5 patients (ranged for 13-15 lbs). Two patients regained the lost weight after treatment and one was lost to follow-up. Tetrabenazine in combination with other antidystonic medication and/or botulinum toxin injections provided substantial benefit to the patients with dysphagia caused by OMD. CONCLUSION: Dystonic eating dysfunction may occasionally complicate OMD leading to weight loss. Its adequate characterization at the time of history taking and clinical examination should be part of outcome measurements of the anti-dystonic treatment in clinical practice.

Adult↗
PubMed2006

Insular pathology in Parkinson's disease patients with orthostatic hypotension.

Orthostatic hypotension (OH) in Parkinson's disease (PD) patients may be a significant source of morbidity and discomfort. Although peripheral ANS components have been associated with its development, central mechanisms are probably involved. The insular cortex is a central site of autonomic and limbic integration and neuropathologic studies have indicated its involvement in the neurodegenerative process of PD. To this end, we studied the neuropathology of the insular, temporal and parietal cortices in PD patients with and without OH. Our results suggest an association between the severity of PD-related neuropathology in the insular cortex and OH. Further research into the subject is warranted.

Age of Onset↗
PubMed2006

Collaborative analysis of alpha-synuclein gene promoter variability and Parkinson disease.

CONTEXT: Identification and replication of susceptibility genes for Parkinson disease at the population level have been hampered by small studies with potential biases. Alpha-synuclein (SNCA) has been one of the most promising susceptibility genes, but large-scale studies have been lacking. OBJECTIVE: To determine whether allele-length variability in the dinucleotide repeat sequence (REP1) of the SNCA gene promoter is associated with Parkinson disease susceptibility, whether SNCA promoter haplotypes are associated with Parkinson disease, and whether REP1 variability modifies age at onset. DESIGN, SETTING, AND PARTICIPANTS: We performed a collaborative analysis of individual-level data on SNCA REP1 and flanking markers in patients with Parkinson disease and controls. Study site recruitment, data collection, and analyses were performed between April 5, 2004, and December 31, 2005. Eighteen participating sites of a global genetics consortium provided clinical data. Genotyping was performed for SNCA REP1, -770, and -116 markers at individual sites; however, each site also provided 20 DNA samples for regenotyping centrally. MAIN OUTCOME MEASURES: Measures included estimations of Hardy-Weinberg equilibrium in controls; a test of heterogeneity; analyses for association of single variants or haplotypes; and survival analyses for age at onset. RESULTS: Of the 18 sites, 11 met stringent criteria for concordance with Hardy-Weinberg equilibrium and low genotyping error rate. These 11 sites provided complete data for 2692 cases and 2652 controls. There was no heterogeneity across studies (P>.60). The SNCA REP1 alleles differed in frequency for cases and controls (P<.001). Genotypes defined by the 263 base-pair allele were associated with Parkinson disease (odds ratio, 1.43; 95% confidence interval, 1.22-1.69; P<.001 for trend). Multilocus haplotypes differed in frequency for cases and controls (global score statistic, P<.001). Two-loci haplotypes were associated with Parkinson disease only when they included REP1 as one of the loci. However, genotypes defined by REP1 alleles did not modify age at onset (P = .55). CONCLUSION: This large-scale collaborative analysis demonstrates that SNCA REP1 allele-length variability is associated with an increased risk of Parkinson disease.

Adult↗
PubMed2006

A case of painless arms/moving fingers responsive to botulinum toxin a injections.

Painless arms/moving fingers is a rare variant of the painful limbs/moving extremities syndrome (PLME) characterized by slow involuntary movements of the toes or fingers. Its typical form is associated with limb pain. We report the first case of painless arms/moving fingers and describe its favorable response to botulinum toxin A injections. The presence of dystonic symptoms in our case argues in favor of a possible implication of a dystonic mechanism in at least some cases of PLME.

Adult↗
PubMed2006

A randomized controlled trial evaluating the efficacy and safety of vitamin E supplementation for protection against cisplatin-induced peripheral neuropathy: final results.

AIM: A randomized, open label with blind assessment, controlled trial was performed to assess efficacy and adverse-event profile of vitamin E, given as supplementation for prophylaxis against cisplatin-induced peripheral neuropathy (CIPN). PATIENTS AND METHODS: A total of 30 patients scheduled to receive six courses of cumulative cisplatin-based regimens were randomly allocated to treatment and control groups and were then studied by means of neurological examination and electrophysiological study. Patients assigned to group I (n=14) orally received vitamin E at a daily dose of 600 mg/day during chemotherapy and 3 months after its cessation were compared to patients of group II (n=16), who received no vitamin E supplementation and served as controls. The severity of neurotoxicity was summarized by means of a modified Peripheral Neuropathy (PNP) score. RESULTS: The incidence of neurotoxicity differed significantly between groups, occurring in 3/14 (21.4%) of patients assigned to the vitamin E supplementation group and in 11/16 (68.5%) of controls (p=0.026). The relative risk (RR) of developing neurotoxicity was significantly higher in case of controls, RR=2.51, 95% C.I.=1.16-5.47. Mean PNP scores were 4.99+/-1.33 for patients of group I and 10.47+/-10.62 for controls, (p=0.023). None of the adverse events or deaths occurred, were judged as likely to be related to the vitamin E supplementation. CONCLUSION: Vitamin E effectively and safely protects patients with cancer from occurrence of cisplatin neurotoxicity.

Action Potentials↗
PubMed2006

Wilson's disease and benign epilepsy of childhood with centrotemporal (rolandic) spikes.

Cases with a clinical and electroencephalographic phenotype of benign epilepsy of childhood with centrotemporal spikes (BECTS) in association with a proven organic brain lesion have rarely been reported. To our knowledge, we herein describe for the first time a patient with Wilson's disease who subsequently manifested BECTS. Our case bolsters the argument that in at least some cases, BECTS is associated with organic brain disease.

Anticonvulsants↗
PubMed2006

Clinical heterogeneity of the LRRK2 G2019S mutation.

BACKGROUND: Several pathogenic mutations have been reported in the leucine-rich repeat kinase 2 gene (LRRK2) that cause parkinsonism. The "common" LRRK2 G2019S kinase domain substitution has been reported to account for approximately 5% of familial and 1% of sporadic Parkinson disease. OBJECTIVE: To observe the clinical heterogeneity presented by LRRK2 kinase mutation carriers. DESIGN, SETTING, AND PARTICIPANTS: We screened 130 patients with pathologically confirmed Parkinson disease and 85 controls for 3 LRRK2 kinase domain pathogenic substitutions: I2012T, G2019S, and I2020T. MAIN OUTCOME MEASURES: Detailed clinical phenotypes for individuals who screened positive for LRRK2 mutations. RESULTS: Five LRRK2 G2019S carriers were identified, of whom 4 had Parkinson disease (clinically and pathologically confirmed), and the fifth was a control subject who died at age 68 years after an acute myocardial infarction with no evidence of neurodegenerative abnormalities. There was no evidence of the I2012T or I2020T mutation in these participants. CONCLUSIONS: The underlying disease mechanisms of LRRK2 G2019S-associated parkinsonism are similar to those of typical Parkinson disease. The identification of a control subject raises important questions concerning genetic diagnosis and counseling.

Aged↗
PubMed2006

Lrrk2 and Lewy body disease.

OBJECTIVE: The Lrrk2 kinase domain G2019S substitution is the most common genetic basis of familial and sporadic parkinsonism. Patients harboring the G2019S substitution usually present with clinical Parkinson's disease. METHODS: Herein, we report that the most common neuropathology of G2019S-associated Parkinson's disease is Lewy body disease. RESULTS: Lrrk2 G2019S was observed in approximately 2% (n = 8) of our Parkinson's disease/Lewy body disease cases (n = 405). The mutation was also found in one control subject and one Alzheimer's disease patient, reflecting reduced penetrance. INTERPRETATION: Therapeutic strategies targeted at modulating Lrrk2 kinase activity may be important to treat patients with genetically defined familial or typical sporadic Parkinson's disease.

Aged↗