scholarly journals Electrical impedance myography (EIM) in a natural history study of C9ORF72 mutation carriers

2020 ◽  
Vol 21 (5-6) ◽  
pp. 445-451
Author(s):  
Michelle B. Offit ◽  
Tianxia Wu ◽  
Mary Kay Floeter ◽  
Tanya J. Lehky
Keyword(s):  
Natural History ◽  
Electrical Impedance ◽  
Natural History Study ◽  
Mutation Carriers ◽  
C9orf72 Mutation

scholarly journals Disease progression in C9orf72 mutation carriers

Neurology ◽  
2017 ◽  
Vol 89 (3) ◽  
pp. 234-241 ◽  
Author(s):  
Mary K. Floeter ◽  
Bryan J. Traynor ◽  
Jennifer Farren ◽  
Laura E. Braun ◽  
Michael Tierney ◽  
...  
Keyword(s):  
Disease Progression ◽  
Rating Scale ◽  
Natural History Study ◽  
Mutation Carriers ◽  
Motor Tests ◽  
C9orf72 Mutation ◽  
Clinical Measures ◽  
Study Participants ◽  
Lateral Sclerosis

Objective:To assess changes in 3 clinical measures, the Revised ALS Functional Rating Scale (ALSFRS-R), letter fluency, and Frontal Behavioral Inventory (FBI), over time in C9orf72 mutation carriers (C9+) with varied clinical phenotypes.Methods:Thirty-four unrelated participants with mutations in C9orf72 were enrolled in a prospective natural history study. Participants were classified as asymptomatic, amyotrophic lateral sclerosis (ALS), ALS–familial frontotemporal dementia (FTD), or behavioral-variant FTD by clinical diagnostic criteria. Diagnostic cognitive and motor tests were repeated at 6 and 18 months. The ALSFRS-R, letter fluency, and FBI were administered at baseline and follow-up visits at 6, 12, and 18 months.Results:The clinical diagnosis of most patients did not change over the follow-up. ALSFRS-R scores correlated with measures of motor function. Letter fluency correlated with FBI and cognitive tests. ALSFRS-R, letter fluency, and FBI differed among the C9+ diagnostic subgroups at enrollment and worsened over follow-up in symptomatic patients, with different slopes among the subgroups. Most patients survived to the 6-month time point after enrollment. Survival of C9+ patients with ALS and C9+ patients with ALS-FTD declined over the 12- and 18-month follow-up.Conclusions:The pattern of scores of the ALSFRS-R, letter fluency, and FBI distinguished between ALS, ALS-FTD, and FTD presentations of C9orf72 mutation carriers and asymptomatic carriers. Longitudinal changes in these measures occurred with disease progression in a manner consistent with presenting phenotype.

scholarly journals Succinic Semialdehyde Dehydrogenase Deficiency: Review of the Natural History Study

2021 ◽  
pp. 088307382098126
Author(s):  
Phillip L. Pearl ◽  
Melissa L. DiBacco ◽  
Christos Papadelis ◽  
Thomas Opladen ◽  
Ellen Hanson ◽  
...  
Keyword(s):  
Natural History ◽  
Psychiatric Symptoms ◽  
Epileptiform Activity ◽  
Laboratory Data ◽  
Standard Of Care ◽  
Succinic Semialdehyde ◽  
Succinic Semialdehyde Dehydrogenase ◽  
Natural History Study ◽  
Semialdehyde Dehydrogenase ◽  
Verbal Score

Objective: The SSADHD Natural History Study was initiated in 2019 to define the natural course and identify biomarkers correlating with severity. Methods: The study is conducted by 4 institutions: BCH (US clinical), WSU (bioanalytical core), USF (biostatistical core), and Heidelberg (iNTD), with support from the family advocacy group (SSADH Association). Recruitment goals were to study 20 patients on-site at BCH, 10 with iNTD, and 25 as a standard-of care cohort. Results: At this half-way point of this longitudinal study, 28 subjects have been recruited (57% female, mean 9 years, range 18 months–40 years). Epilepsy is present in half and increases in incidence and severity, as do psychiatric symptoms, in adolescence and adulthood. The average Full Scale IQ (FSIQ) was 53 (Verbal score of 56, Non Verbal score of 49), and half scored as having ASD. Although there was no correlation between gene variant and phenotypic severity, there were extreme cases of lowest functioning in one individual and highest in another that may have genotype-phenotype correlation. The most common EEG finding was mild background slowing with rare epileptiform activity, whereas high-density EEG and magnetoencephalography showed reduction in the gamma frequency band consistent with GABAergic dysfunction. MR spectroscopy showed elevations in the GABA/NAA ratio in all regions studied with no crossover between subjects and controls. Conclusions: The SSADH Natural History Study is providing a unique opportunity to study the complex pathophysiology longitudinally and derive electrophysiologic, neuroimaging, and laboratory data for correlation and to serve as biomarkers for clinical trials and prognostic assessments in this ultra-rare inherited disorder of GABA metabolism.

The RETRIEVE Study: A natural history study of type 2 Gaucher disease, and GM1 and GM2 gangliosidoses with early onset, in preparation of a clinical trial

2021 ◽  
Vol 132 (2) ◽  
pp. S48-S49
Author(s):  
Benedicte Heron-Longe ◽  
Spyros Batzios ◽  
Eugen Mengel ◽  
Roberto Giugliani ◽  
Marc Patterson ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Natural History ◽  
Early Onset ◽  
Gaucher Disease ◽  
Natural History Study ◽  
Gm2 Gangliosidoses

scholarly journals Spontaneous improvement of carbohydrate-deficient transferrin in PMM2-CDG without mannose observed in CDG natural history study

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Peter Witters ◽  
Andrew C. Edmondson ◽  
Christina Lam ◽  
Christin Johnsen ◽  
Marc C. Patterson ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Natural History ◽  
Randomized Study ◽  
Short Term ◽  
Double Blind ◽  
Natural History Study ◽  
Natural History Studies ◽  
Carbohydrate Deficient Transferrin ◽  
Spontaneous Improvement

AbstractA recent report on long-term dietary mannose supplementation in phosphomannomutase 2 deficiency (PMM2-CDG) claimed improved glycosylation and called for double-blind randomized study of the dietary supplement in PMM2-CDG patients. A lack of efficacy of short-term mannose supplementation in multiple prior reports challenge this study’s conclusions. Additionally, some CDG types have previously been reported to demonstrate spontaneous improvement in glycosylated biomarkers, including transferrin. We have likewise observed improvements in transferrin glycosylation without mannose supplementation. This observation questions the reliability of transferrin as a therapeutic outcome measure in clinical trials for PMM2-CDG. We are concerned that renewed focus on mannose therapy in PMM2-CDG will detract from clinical trials of more promising therapies. Approaches to increase efficiency of clinical trials and ultimately improve patients’ lives requires prospective natural history studies and identification of reliable biomarkers linked to clinical outcomes in CDG. Collaborations with patients and families are essential to identifying meaningful study outcomes.

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