Expert Consensus on the Use of On-Demand Treatments for OFF Episodes in Parkinson's Disease: A Modified Delphi Panel.

Background: On-demand treatments can treat OFF episodes in Parkinson's disease, however, there is limited information regarding when to prescribe them. Objective: Develop expert consensus to determine appropriate clinical factors for considering on-demand treatments. Methods: Using a RAND/UCLA modified Delphi panel method, a panel developed consensus on the use of on-demand treatments for OFF episodes. Results: The panel agreed on-demand treatments were appropriate when OFF episodes were associated with greater functional impact and interfered with basic daily activities. The panel also agreed on-demand treatment may be appropriate for patients with morning akinesia and/or delayed ON of first levodopa dose and >1 type of OFF episode (eg, early morning OFF or wearing OFF regardless of frequency). Conclusions: Experts agreed on-demand treatment is appropriate for many patients with OFF episodes. The greater the functional impact of OFF episodes, the more likely experts agreed that on-demand treatment is appropriate to prescribe.

Clinical features and ATTCT repeat expansion in spinocerebellar ataxia type 10.

BACKGROUND: Spinocerebellar ataxia type 10, an autosomal dominant disease characterized by ataxia and seizures, is caused by a large expansion of an unstable ATTCT pentanucleotide repeat. OBJECTIVES: To characterize the phenotypic expression of spinocerebellar ataxia type 10 and to examine the genotype-phenotype correlations in 2 large families. DESIGN: Clinical characterization and genotype-phenotype correlation. SETTING: Studies at 2 medical schools with private practice referral. PATIENTS: Twenty-two affected individuals from 2 large Mexican American pedigrees. RESULTS: Of the 22 individuals, ataxia was the initial symptom in 21; seizure disorders developed in 11, mostly within several years following the onset of ataxia. The seizure frequency was different in the 2 families: 3 (25%) of 12 had seizures in family 1, and 8 (80%) of 10 had seizures in family 2 (P =.01). A brain magnetic resonance imaging or computed tomographic scan showed cerebellar atrophy in all patients examined. An electroencephalogram demonstrated epileptiform discharges in 4 of 8 patients studied. Although anticipation was apparent in both families, only family 1 showed a strong inverse correlation between age of onset and repeat number (r(2) = 0.79, P =.001). In family 1, 8 transmissions, of which 7 were paternal, resulted in an average gain of 1940 repeats. In contrast, despite anticipation, 2 affected male subjects transmitted their expanded alleles to 8 progenies, with an average loss of 755 repeats, in family 2. CONCLUSIONS: Seizure is an integral part of the spinocerebellar ataxia type 10 phenotype, with documented morbidity and mortality. Family-dependent factors may alter the frequency of the seizure phenotype and the pattern of intergenerational repeat size changes, making the genotype-phenotype correlation complex.

Somatic and germline instability of the ATTCT repeat in spinocerebellar ataxia type 10.

Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant disorder characterized by ataxia, seizures, and anticipation. It is caused by an expanded ATTCT pentanucleotide repeat in intron 9 of a novel gene, designated "SCA10." The ATTCT expansion in SCA10 represents a novel class of microsatellite repeat and is one of the largest found to cause human diseases. The expanded ATTCT repeat is unstably transmitted from generation to generation, and an inverse correlation has been observed between size of repeat and age at onset. In this multifamily study, we investigated the intergenerational instability, somatic and germline mosaicism, and age-dependent repeat-size changes of the expanded ATTCT repeat. Our results showed that (1) the expanded ATTCT repeats are highly unstable when paternally transmitted, whereas maternal transmission resulted in significantly smaller changes in repeat size; (2) blood leukocytes, lymphoblastoid cells, buccal cells, and sperm have a variable degree of mosaicism in ATTCT expansion; (3) the length of the expanded repeat was not observed to change in individuals over a 5-year period; and (4) clinically determined anticipation is sometimes associated with intergenerational contraction rather than expansion of the ATTCT repeat.