Author Response: Association of Age at Onset and First Symptoms With Disease Progression in Patients With Metachromatic Leukodystrophy

Neurology ◽  
2021 ◽  
Vol 97 (9) ◽  
pp. 459.1-459
Author(s):  
Samuel Groeschel ◽  
Ingeborg Krägeloh-Mann
Keyword(s):  
Disease Progression ◽  
Metachromatic Leukodystrophy ◽  
Age At Onset ◽  
Author Response

Association of age at onset and first symptoms with disease progression in patients with metachromatic leukodystrophy

Neurology ◽  
2020 ◽  
pp. 10.1212/WNL.0000000000011047 ◽  
Author(s):  
Christiane Kehrer ◽  
Saskia Elgün ◽  
Christa Raabe ◽  
Judith Böhringer ◽  
Stefanie Beck-Wödl ◽  
...  
Keyword(s):  
Disease Progression ◽  
Metachromatic Leukodystrophy ◽  
Age At Onset ◽  
Disease Onset ◽  
Tube Feeding ◽  
Motor Symptoms ◽  
Cognitive Symptoms ◽  
Adult Onset ◽  
Clinical Genetic ◽  
Language Functions

Objective:To compare disease progression between different onset forms of Metachromatic Leukodystrophy (MLD) and to investigate the influence of the type of first symptoms on the natural course and dynamic of disease progression.Methods:Clinical, genetic and biochemical parameters were analyzed within a nationwide study of patients with late-infantile (LI, onset ≤ 2.5 years), early-juvenile (EJ, onset 2.6 - < 6 years), late-juvenile (LJ, onset 6 – < 16 years), and adult (onset ≥ 16 years) forms of MLD. First symptoms were categorized as motor symptoms only, cognitive symptoms only, or both.. Standardized clinical endpoints included loss of motor and language functions, as well as dysphagia/tube feeding.Results:97 Patients with MLD were enrolled. Patients with LI (n=35) and EJ (n=18) MLD exhibited similarly rapid disease progression, all starting with motor symptoms (with or without additional cognitive symptoms). In LJ (n=38) and adult-onset (n=6) patients, the course of the disease was as rapid as in the early-onset forms, when motor symptoms were present at disease onset, while patients with only cognitive symptoms at disease onset exhibited significantly milder disease progression, independent of their age at onset. A certain genotype-phenotype correlation was observed.Conclusions:In addition to age at onset, the type of first symptoms predicts the rate of disease progression in MLD. These findings are important for counselling and therapy.Classification of Evidence:This study provides Class II evidence that in patients with MLD, age at onset and the type of first symptoms predict the rate of disease progression.

Influence of Age and Type of First Symptoms on Disease Progression in Metachromatic Leukodystrophy

2019 ◽  
Author(s):  
Saskia Elgün ◽  
Christiane Kehrer ◽  
Christa Raabe ◽  
Judith Böhringer ◽  
Andrea Bevot ◽  
...  
Keyword(s):  
Disease Progression ◽  
Metachromatic Leukodystrophy

scholarly journals Artificially Induced Pluripotent Stem Cell-Derived Whole-Brain Organoid for Modelling the Pathophysiology of Metachromatic Leukodystrophy and Drug Repurposing

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 440
Author(s):  
Sally Esmail ◽  
Wayne R. Danter
Keyword(s):  
Stem Cell ◽  
Disease Progression ◽  
Pluripotent Stem Cell ◽  
Metachromatic Leukodystrophy ◽  
Drug Repurposing ◽  
Induced Pluripotent Stem Cell ◽  
Whole Brain ◽  
Learning Platform ◽  
Brain Organoid ◽  
Induced Pluripotent

Metachromatic leukodystrophy (MLD) is a rare neurodegenerative disease that results from a deficiency of the lysosomal enzyme arylsulfatase A (ARSA). Worldwide, there are between one in 40,000 and one in 160,000 people living with the disease. While there are currently no effective treatments for MLD, induced pluripotent stem cell-derived brain organoids have the potential to provide a better understanding of MLD pathogenesis. However, developing brain organoid models is expensive, time consuming and may not accurately reflect disease progression. Using accurate and inexpensive computer simulations of human brain organoids could overcome the current limitations. Artificially induced whole-brain organoids (aiWBO) have the potential to greatly expand our ability to model MLD and guide future wet lab research. In this study, we have upgraded and validated our artificially induced whole-brain organoid platform (NEUBOrg) using our previously validated machine learning platform, DeepNEU (v6.2). Using this upgraded NEUBorg, we have generated aiWBO simulations of MLD and provided a novel approach to evaluate factors associated with MLD pathogenesis, disease progression and new potential therapeutic options.

scholarly journals Demyelination load as predictor for disease progression in juvenile metachromatic leukodystrophy

2017 ◽  
Vol 4 (6) ◽  
pp. 403-410 ◽  
Author(s):  
Manuel Strölin ◽  
Ingeborg Krägeloh-Mann ◽  
Christiane Kehrer ◽  
Marko Wilke ◽  
Samuel Groeschel
Keyword(s):  
Disease Progression ◽  
Metachromatic Leukodystrophy

Author response for "Telomere length and oxidative stress variations in a murine model of Alzheimer’s disease progression"

2020 ◽  
Author(s):  
Katia Martínez‐González ◽  
Azul Islas‐Hernández ◽  
José Darío Martínez‐Ezquerro ◽  
Federico Bermúdez‐Rattoni ◽  
Paola Garcia‐delaTorre
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Progression ◽  
Telomere Length ◽  
Murine Model ◽  
Author Response ◽  
Model Of Alzheimer’S Disease ◽  
Stress Variations ◽  
And Oxidative Stress

scholarly journals Genetic risk of Parkinson disease and progression:

2019 ◽  
Vol 5 (4) ◽  
pp. e348 ◽  
Author(s):  
Hirotaka Iwaki ◽  
Cornelis Blauwendraat ◽  
Hampton L. Leonard ◽  
Ganqiang Liu ◽  
Jodi Maple-Grødem ◽  
...  
Keyword(s):  
Parkinson Disease ◽  
Disease Progression ◽  
Disease Risk ◽  
Age At Onset ◽  
Motor Symptom ◽  
European Ancestry ◽  
Sleep Behavior ◽  
Intronic Region ◽  
Risk Variants ◽  
Faster Development

ObjectiveTo determine if any association between previously identified alleles that confer risk for Parkinson disease and variables measuring disease progression.MethodsWe evaluated the association between 31 risk variants and variables measuring disease progression. A total of 23,423 visits by 4,307 patients of European ancestry from 13 longitudinal cohorts in Europe, North America, and Australia were analyzed.ResultsWe confirmed the importance of GBA on phenotypes. GBA variants were associated with the development of daytime sleepiness (p.N370S: hazard ratio [HR] 3.28 [1.69–6.34]) and possible REM sleep behavior (p.T408M: odds ratio 6.48 [2.04–20.60]). We also replicated previously reported associations of GBA variants with motor/cognitive declines. The other genotype-phenotype associations include an intergenic variant near LRRK2 and the faster development of motor symptom (Hoehn and Yahr scale 3.0 HR 1.33 [1.16–1.52] for the C allele of rs76904798) and an intronic variant in PMVK and the development of wearing-off effects (HR 1.66 [1.19–2.31] for the C allele of rs114138760). Age at onset was associated with TMEM175 variant p.M393T (−0.72 [−1.21 to −0.23] in years), the C allele of rs199347 (intronic region of GPNMB, 0.70 [0.27–1.14]), and G allele of rs1106180 (intronic region of CCDC62, 0.62 [0.21–1.03]).ConclusionsThis study provides evidence that alleles associated with Parkinson disease risk, in particular GBA variants, also contribute to the heterogeneity of multiple motor and nonmotor aspects. Accounting for genetic variability will be a useful factor in understanding disease course and in minimizing heterogeneity in clinical trials.

scholarly journals Practice Parameter: Diagnosis and prognosis of new onset Parkinson disease (an evidence-based review)

Neurology ◽  
2006 ◽  
Vol 66 (7) ◽  
pp. 968-975 ◽  
Author(s):  
O. Suchowersky ◽  
S. Reich ◽  
J. Perlmutter ◽  
T. Zesiewicz ◽  
G. Gronseth ◽  
...  
Keyword(s):  
Parkinson Disease ◽  
Disease Progression ◽  
Clinical Features ◽  
Predictive Factors ◽  
Age At Onset ◽  
Future Research ◽  
Evidence Based ◽  
Level Of Evidence ◽  
Parkinsonian Syndromes ◽  
Olfactory Testing

Objective: To define key issues in the diagnosis of Parkinson disease (PD), to define features influencing progression, and to make evidence-based recommendations. Two clinical questions were identified: 1) Which clinical features and diagnostic modalities distinguish PD from other parkinsonian syndromes? 2) Which clinical features predict rate of disease progression?Methods: Systematic review of the literature was completed. Articles were classified according to a four-tiered level of evidence scheme. Recommendations were based on the evidence.Results and Conclusions: 1. Early falls, poor response to levodopa, symmetry of motor manifestations, lack of tremor, and early autonomic dysfunction are probably useful in distinguishing other parkinsonian syndromes from Parkinson disease (PD). 2. Levodopa or apomorphine challenge and olfactory testing are probably useful in distinguishing PD from other parkinsonian syndromes. 3. Predictive factors for more rapid motor progression, nursing home placement, and shorter survival time include older age at onset of PD, associated comorbidities, presentation with rigidity and bradykinesia, and decreased dopamine responsiveness. Future research into methods for earlier and more accurate diagnosis of the disease and identification and clarification of predictive factors of rapid disease progression is warranted.

scholarly journals The Role of SNCA Rep1 Microsatellite in Parkinson’s Disease Progression

2017 ◽  
Author(s):  
Lucia Corrado ◽  
Fabiola De Marchi ◽  
Sara Tunesi ◽  
Gaia Oggioni ◽  
Miryam Carecchio ◽  
...  
Keyword(s):  
Disease Progression ◽  
Age At Onset ◽  
Freezing Of Gait ◽  
Lewy Bodies ◽  
Alpha Synuclein ◽  
Cognitive Outcomes ◽  
Cognitive Outcome ◽  
Visual Hallucinations ◽  
Increased Risk ◽  
Wearing Off

&alpha;-synuclein is a constituent of Lewy bodies and mutations of its gene cause familial PD. A previous study showed that a variant of &alpha;-synuclein gene (SNCA), namely the 263bp allele of Rep1 was associated to faster motor progression in PD. On the contrary, a recent report failed to detect a detrimental effect of Rep1 263 on both motor and cognitive outcomes in PD. Aim of this study was to evaluate the influence of the Rep1 variants on disease progression in Parkinson&rsquo;s Disease (PD) patients. We recruited and genotyped for SNCA-Rep1 426 PD patients with age at onset &ge;40 years and disease duration &ge;4 years. We then analyzed frequency and time of occurrence of wearing-off, dyskinesia, freezing of gait, visual hallucinations and dementia. SNCA Rep1 263 carriers showed increased risk of both dementia (HR=3.03) and visual hallucinations (HR=2.69) compared to 263 non-carriers. In conclusion, SNCA Rep 1 263 allele is associated to a worst cognitive outcome in PD.

Sign in / Sign up

Export Citation Format

Share Document