scholarly journals Network diffusion model predicts neurodegeneration in limb-onset amyotrophic lateral sclerosis

2021 ◽  
Author(s):  
Anjan Bhattarai ◽  
Zhaolin Chen ◽  
Phyllis Chua ◽  
Paul Talman ◽  
Susan Mathers ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Diffusion Model ◽  
Inferior Frontal Gyrus ◽  
Brain Atlas ◽  
Biophysical Model ◽  
Brain Connectome ◽  
Lateral Sclerosis ◽  
Limb Onset ◽  
Over Time ◽  
Network Diffusion

The trans-neural propagation of phosphorylated 43-kDa transactive response DNA-binding protein (pTDP-43) contributes to neurodegeneration in Amyotrophic Lateral Sclerosis (ALS). We investigated whether Network Diffusion Model (NDM), a biophysical model of spread of pathology via the brain connectome, could capture the severity and progression of neurodegeneration (atrophy) in ALS. We measured degeneration in limb-onset ALS patients (n=14 at baseline, 12 at 6-months, and 9 at 12 months) and controls (n=12 at baseline) using FreeSurfer analysis on the structural T1-weighted Magnetic Resonance Imaging (MRI) data. The NDM was simulated on the canonical structural connectome from the IIT Human Brain Atlas. To determine whether NDM could predict the atrophy pattern in ALS, the accumulation of pathology modelled by NDM was correlated against atrophy measured using MRI. The cross-sectional analyses revealed that the network diffusion seeded from the inferior frontal gyrus (pars triangularis and pars orbitalis) significantly predicts the atrophy pattern in ALS compared to controls. Whereas, atrophy over time with-in the ALS group was best predicted by seeding the network diffusion process from the inferior temporal gyrus at 6-month and caudal middle frontal gyrus at 12-month. Our findings suggest the involvement of extra-motor regions in seeding the spread of pathology in ALS. Importantly, NDM was able to recapitulate the dynamics of pathological progression in ALS. Understanding the spatial shifts in the seeds of degeneration over time can potentially inform further research in the design of disease modifying therapeutic interventions in ALS.

scholarly journals Longitudinal Study of Cognitive and Emotional Alterations in Amyotrophic Lateral Sclerosis: Clinical and Imaging Data

2021 ◽  
Vol 12 ◽  
Author(s):  
Soumia Benbrika ◽  
Franck Doidy ◽  
Laurence Carluer ◽  
Audrey Mondou ◽  
Alice Pélerin ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Executive Functions ◽  
Inferior Frontal Gyrus ◽  
Disease Onset ◽  
Psychological State ◽  
Imaging Data ◽  
Cortical Thinning ◽  
Lateral Sclerosis ◽  
Over Time

Objectives: Extra-motor manifestations occur in 50% of patients with amyotrophic lateral sclerosis (ALS). These mainly concern cognition, emotional processing and behavior. Depression and anxiety are less frequent. Little is known about how these manifestations change as the disease progresses. Similarly, although cortical thinning has been well-documented at disease onset, there are scant data about cortical thinning over time and how this correlates with extra-motor manifestations. The present study therefore assessed cognitive, emotional and psychological state and cortical thinning in a group of patients with ALS at baseline and after a follow-up period.Methods: We assessed executive functions, facial emotion recognition, depressive and anxious symptoms, and cortical thinning in 43 patients with ALS at baseline, comparing them with 28 healthy controls, and 21 of them 9 months later. We looked for links among the extra-motor manifestations and correlations with cortical thickness.Results: At baseline, patients had poor executive function and recognition of complex emotions from the eyes, and more anxious and depressive symptoms than controls. At follow-up, only inhibition abilities had worsened. Cortical thinning was observed in bilateral pre-central regions and other parts of the cerebral cortex at baseline. Over time, it worsened in motor and extra-motor areas. Executive functions correlated with thinning in the middle and inferior frontal gyrus and orbitofrontal cortex.Conclusions: During follow-up, there was little deterioration in extra-motor manifestations and psychological state, despite continuing cortical thinning. Patients with affective Theory of Mind (ToM) changes seemed less depressed than the others. Impaired mental flexibility was subtended by prefrontal regions with cortical thinning.

scholarly journals Patterns of Non-Invasive Ventilation in Amyotrophic Lateral Sclerosis

2018 ◽  
Vol 45 (4) ◽  
pp. 445-450
Author(s):  
Nevena Markovic ◽  
Marcus Povitz ◽  
Joanne Smith ◽  
David Leasa ◽  
Christen Shoesmith ◽  
...  
Keyword(s):  
Decision Making ◽  
Amyotrophic Lateral Sclerosis ◽  
End Of Life ◽  
Invasive Ventilation ◽  
Non Invasive ◽  
Non Invasive Ventilation ◽  
End Of Life Decision ◽  
Life Decision ◽  
Lateral Sclerosis ◽  
Over Time

AbstractBackground: Non-invasive ventilation (NIV) improves quality of life and survival in patients with amyotrophic lateral sclerosis (ALS) and respiratory symptoms. Little is known about the patterns of NIV use over time and the impact of NIV on end-of-life decision-making in ALS. Objective: This study assessed the pattern of NIV use over the course of the disease and the timing of end-of-life discussions in people living with ALS. Method: A retrospective single-center cohort study was performed at London Health Sciences Centre. Daily NIV duration of use was evaluated at 3-month intervals. The timing of diagnosis, NIV initiation, discussions relating to do-not-attempt-resuscitation (DNAR) and death were examined. Results: In total, 48 patients were included in the analysis. Duration of NIV use increased over time, and tolerance to NIV was observed to be better than expected in patients with bulbar-onset ALS. There was a high degree of variability in the timing of end-of-life discussions in patients with ALS (356±451 days from diagnosis). In this cohort, there was a strong association between the timing of discussions regarding code status and establishment of a DNAR order (r2=0.93). Conclusion: This retrospective cohort study suggests that the use of NIV in ALS increases over time and that there remains a great deal of variability in the timing of end-of-life discussions in people living with ALS. Future prospective studies exploring the use NIV over the disease trajectory and how NIV affects end-of-life decision-making in people with ALS are needed.

scholarly journals Relative preservation of triceps over biceps strength in upper limb-onset ALS: the ‘split elbow’

2019 ◽  
Vol 90 (7) ◽  
pp. 730-733 ◽  
Author(s):  
Roaya Khalaf ◽  
Sarah Martin ◽  
Cathy Ellis ◽  
Rachel Burman ◽  
Jemeen Sreedharan ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Upper Limb ◽  
Selective Vulnerability ◽  
Relative Strength ◽  
Rank Test ◽  
Cortical Representation ◽  
Signed Rank Test ◽  
South East England ◽  
Lateral Sclerosis ◽  
Limb Onset

ObjectiveAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of the motor system. The split hand sign in ALS refers to observed preferential weakness of the lateral hand muscles, which is unexplained. One possibility is larger cortical representation of the lateral hand compared with the medial. Biceps strength is usually preserved relative to triceps in neurological conditions, but biceps has a larger cortical representation and might be expected to show preferential weakness in ALS.MethodsUsing the South-East England Register for Amyotrophic Lateral Sclerosis, we performed a retrospective longitudinal cohort study and extracted the modified Medical Research Council (MRC) muscle strength score for biceps and triceps in patients with a diagnosis of upper limb-onset ALS in the 19-year period 1996–2015. A Wilcoxon signed-rank test was used to assess the relative strength of the muscles within the total sum of the upper limbs involved in the study.ResultsThere were 659 people with upper limb onset of weakness. In 215 there were insufficient data to perform the analysis, and a further 33 were excluded for other reasons, leaving 411 for analysis. Biceps was stronger than triceps in 87 limbs, and triceps was stronger than biceps in 258 limbs, with no difference seen in the remaining 477. Triceps strength scores (mean rank=186.1) were higher than ipsilateral biceps strength scores (mean rank=134.2), Z=−10.1, p<0.001 (two-tailed).ConclusionTriceps strength is relatively preserved compared with biceps in ALS. This is consistent with a broadly corticofugal hypothesis of selective vulnerability, in which susceptibility might be associated with larger cortical representation.

Vocal Fold Diadochokinetic Function of Individuals With Amyotrophic Lateral Sclerosis

1995 ◽  
Vol 4 (1) ◽  
pp. 73-80 ◽  
Author(s):  
Karen A. Renout ◽  
Herbert A. Leeper ◽  
Donna L. Bandur ◽  
Arthur J. Hudson
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Vocal Fold ◽  
Group Discussion ◽  
Vocal Folds ◽  
Laryngeal Function ◽  
Analysis System ◽  
Reduced Rate ◽  
Opening And Closing ◽  
Lateral Sclerosis ◽  
Over Time

This study relates over time the changes in voluntary opening and closing of the vocal folds (vocal fold diadochokinesis, or VFDDK) of patients with amyotrophic lateral sclerosis (ALS). The rate, pattern, and periodicity of VFDDK were examined for 12 ALS subjects with bulbar and 14 subjects with nonbulbar signs of the disease. The acoustical data were analyzed with a commercially available computer-based speech analysis system. ALS patients with bulbar and nonbulbar symptoms demonstrate reduced rate and aperiodic VFDDK as the symptomatology of the neuromotor system progresses. Individuals with bulbar signs show a greater change in vocal fold activity than do the nonbulbar group. Discussion of the clinical implications for initial diagnosis and monitoring of changes over time in motor control of laryngeal function is presented.

Correlations in health status between estimates of families of people with amyotrophic lateral sclerosis and estimates of staff

2012 ◽  
Vol 11 (3) ◽  
pp. 183-189 ◽  
Author(s):  
Anneli G. Ozanne ◽  
Lennart I. Persson
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Analogue Scale ◽  
Rating Scale ◽  
Well Being ◽  
Life Situation ◽  
Next Of Kin ◽  
Holistic View ◽  
The Family ◽  
Lateral Sclerosis ◽  
Over Time

AbstractObjective:The aim of this study was to compare self-estimates of the physical, psychological, and general well-being of patients with amyotrophic lateral sclerosis (ALS) and their next of kin with the assessment of the nurses and physician of these participants.Method:The well-being of 35 pairs of patients and their next of kin was rated by themselves, and by a physician and nurses. The well-being was examined over time, using a visual analogue scale (VAS). Patients' physical function was estimated at the same time with the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised and the Norris scale.Results:The correlations between the staff's estimates of the well-being of patients and next of kin were similar to their own estimates, even though staff to a higher degree estimated a decrease in well-being over time among the patients. The estimates by the nurses correlated better to that of the patients and next of kin in psychological and general well-being than the physicians' estimates did.Significance of results:Even though the staff's estimates of participants were roughly equivalent to their self-estimates, there were some differences. This result calls attention to the importance of working in teams in which different professional roles are combined and integrated, making it possible to form a holistic view of the situation of each family. A concern overlooked by one member of staff might be covered by another, and different focuses on the family may give a better composite picture of their life situation, which could lead to better support to the family.

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