Presymptomatic studies in ALS

Benatar, Michael; Wuu, Joanne

doi:10.1212/wnl.0b013e31826e9b1d

Cited by 93 publications

(91 citation statements)

References 42 publications

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“…Ultimately, such research may yield reliable biomarkers which, in turn, could enable the initiation of clinical interventions in the pre-symptomatic phase of the disease, before the bulk of neurodegeneration occurs [38]. If certain cognitive functions are found to deteriorate mainly in the pre-symptomatic phase, clinicians determining whether to randomise high-risk individuals into a clinical trial could integrate neuropsychological screenings for those functions into the decision-making process.…”

Section: Discussionmentioning

confidence: 99%

No Change in Executive Performance in ALS Patients: A Longitudinal Neuropsychological Study

et al. 2015

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Background/Aims: A substantial proportion of amyotrophic lateral sclerosis (ALS) patients develop cognitive impairments. Longitudinal investigations of cognition in ALS have shown mixed results. While some authors report that cognitive performance remains stable as the disease progresses, others have found evidence for deterioration in various domains. Our objective was to investigate cognitive performance in ALS longitudinally, using the example of executive functions. Methods: 93 ALS patients and 73 age-, sex- and education-matched healthy controls underwent up to four neuropsychological evaluations, separated by 3- to 6-month intervals. We examined whether performance declined longitudinally on seven tests assessing various sub-components of executive functioning. Furthermore, we assigned an executive-performance-based ‘cognitive status' to each participant for every evaluation, examining whether cognitive deterioration (if present) was modulated by their baseline cognitive status and whether cognitive status changed over time. Results: Regardless of their cognitive status at baseline, ALS patients showed no significant decline in the sub-components of executive functioning. Conclusion: Our findings imply that the executive deficits which develop in some ALS patients emerge before motor symptoms and remain stable after an initial decline. The discrepancy between this trajectory and the progressive decline in motor functions may result from a differential vulnerability of motor and non-motor prefrontal neurons to the pathomechanism of ALS.

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Section: Discussionmentioning

confidence: 99%

No Change in Executive Performance in ALS Patients: A Longitudinal Neuropsychological Study

et al. 2015

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“…Healthy controls, typically spouses of patients, were similar in age, handedness, and level of education. AGCs included were recruited locally, and through collaboration with the presymptomatic Familial ALS (Pre‐FALS) study (MB, JW) [Benatar and Wuu, 2012], participants in which travelled to Oxford for both MEG and MRI. Demographics for all participant groups are detailed in Table I.…”

Section: Methodsmentioning

confidence: 99%

Altered cortical beta‐band oscillations reflect motor system degeneration in amyotrophic lateral sclerosis

Proudfoot

Rohenkohl

Quinn

et al. 2016

Human Brain Mapping

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Continuous rhythmic neuronal oscillations underpin local and regional cortical communication. The impact of the motor system neurodegenerative syndrome amyotrophic lateral sclerosis (ALS) on the neuronal oscillations subserving movement might therefore serve as a sensitive marker of disease activity. Movement preparation and execution are consistently associated with modulations to neuronal oscillation beta (15–30 Hz) power. Cortical beta‐band oscillations were measured using magnetoencephalography (MEG) during preparation for, execution, and completion of a visually cued, lateralized motor task that included movement inhibition trials. Eleven “classical” ALS patients, 9 with the primary lateral sclerosis (PLS) phenotype, and 12 asymptomatic carriers of ALS‐associated gene mutations were compared with age‐similar healthy control groups. Augmented beta desynchronization was observed in both contra‐ and ipsilateral motor cortices of ALS patients during motor preparation. Movement execution coincided with excess beta desynchronization in asymptomatic mutation carriers. Movement completion was followed by a slowed rebound of beta power in all symptomatic patients, further reflected in delayed hemispheric lateralization for beta rebound in the PLS group. This may correspond to the particular involvement of interhemispheric fibers of the corpus callosum previously demonstrated in diffusion tensor imaging studies. We conclude that the ALS spectrum is characterized by intensified cortical beta desynchronization followed by delayed rebound, concordant with a broader concept of cortical hyperexcitability, possibly through loss of inhibitory interneuronal influences. MEG may potentially detect cortical dysfunction prior to the development of overt symptoms, and thus be able to contribute to the assessment of future neuroprotective strategies. Hum Brain Mapp 38:237–254, 2017. © 2016 Wiley Periodicals, Inc.

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“…28 The study population comprises presymptomatic individuals (English-speaking, recruited from across North America) who are carriers of any ALS-associated gene mutation (e.g., in SOD1, C9orf72, TARDBP, FUS, VCP, . ), the only population known to be at risk for ALS and in whom a study of presymptomatic disease may be considered.…”

Section: Presymptomatic Genetic Testing In Thementioning

confidence: 99%

“…The rationale for Pre-fALS and the logistics of studying a population at genetic risk for ALS have been described. 28 To appraise study participants' psychosocial readiness to undergo psGT, we have used components of the Mini International Neuropsychiatric Interview, a short structured interview, to screen for anxiety and depression, alcohol and substance abuse, and suicidality. 29 During predecision counseling (to help individuals decide whether or not to undergo psGT and whether to learn the results) and during pretest counseling, we also evaluate sources of social support.…”

Section: Presymptomatic Genetic Testing In Thementioning

confidence: 99%

Presymptomatic ALS genetic counseling and testing

Benatar¹,

Stanislaw

Reyes

et al. 2016

Neurology

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Remarkable advances in our understanding of the genetic contributions to amyotrophic lateral sclerosis (ALS) have sparked discussion and debate about whether clinical genetic testing should routinely be offered to patients with ALS. A related, but distinct, question is whether presymptomatic genetic testing should be offered to family members who may be at risk for developing ALS. Existing guidelines for presymptomatic counseling and testing are mostly based on small number of individuals, clinical judgment, and experience from other neurodegenerative disorders. Over the course of the last 8 years, we have provided testing and 317 genetic counseling sessions (including predecision, pretest, posttest, and ad hoc counseling) to 161 first-degree family members participating in the Pre-Symptomatic Familial ALS Study (Pre-fALS), as well as testing and 75 posttest counseling sessions to 63 individuals with familial ALS. Based on this experience, and the real-world challenges we have had to overcome in the process, we recommend an updated set of guidelines for providing presymptomatic genetic counseling and testing to people at high genetic risk for developing ALS. These recommendations are especially timely and relevant given the growing interest in studying presymptomatic ALS. Published guidelines for presymptomatic genetic testing (psGT) in amyotrophic lateral sclerosis (ALS) [1][2][3] have been based in part on experience in Huntington disease (HD) 4,5 and other lateonset neurodegenerative diseases such as Alzheimer disease, 6,7 and in part on experience in a small number of first-degree relatives of patients with superoxide dismutase-1 (SOD1) familial ALS.8 As the spectrum of identified genetic causes of ALS expands and the landscape of ALS genetics becomes ever more complex, 9,10 there is an increasing need to revisit the proposed guidelines. In this article, we highlight clinically relevant aspects of the genetic complexity of ALS and, drawing on the extensive experience acquired through the ongoing Pre-Symptomatic Familial ALS Study (Pre-fALS), present an approach to psGT that we have developed and refined over the last 8 years. While our experience derives from, and is most relevant to, psGT in the research arena, it may also inform the more controversial endeavor of psGT in a clinical setting.BACKGROUND AND RATIONALE "Familial," "sporadic," and "genetic" ALS. Traditionally, a distinction has been drawn between familial ALS (fALS) and sporadic ALS (sALS) based on the presence or absence of a family history of ALS, with a genetic etiology presupposed for fALS, but not for those without a family history. This distinction, however, is artificial and the inference about genetic etiology incorrect, as all the genes known to cause fALS have also been identified in patients with (seemingly) sALS.9 Some have proposed as an alternative the term hereditary ALS.11 While there are many reasons why ALS with a known genetic cause may not reveal a family history (e.g., recessive inheritance, compound heterozygosity, ...

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Presymptomatic studies in ALS

Cited by 93 publications

References 42 publications

No Change in Executive Performance in ALS Patients: A Longitudinal Neuropsychological Study

No Change in Executive Performance in ALS Patients: A Longitudinal Neuropsychological Study

Altered cortical beta‐band oscillations reflect motor system degeneration in amyotrophic lateral sclerosis

Presymptomatic ALS genetic counseling and testing

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