Primary lateral sclerosis: a distinct entity or part of the ALS spectrum?

Finegan, Eoin; Chipika, Rangariroyashe H.; Shing, Stacey Li Hi; Hardiman, Orla; Bede, Peter

doi:10.1080/21678421.2018.1550518

Cited by 72 publications

(62 citation statements)

References 112 publications

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“…We also included patients with primary lateral sclerosis (PLS), a syndrome of pure upper motor neuron involvement that has been considered part of the motor neuron disease spectrum 22,23 . The diagnostic criteria for PLS required only UMN signs on examination at the time of baseline MRI 24 .…”

Section: Methodsmentioning

confidence: 99%

The upper cervical spinal cord in ALS assessed by cross-sectional and longitudinal 3T MRI

Wimmer

Schreiber

Hensiek

et al. 2020

Sci Rep

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the upper cervical spinal cord is measured in a large longitudinal amyotrophic lateral sclerosis (ALS) cohort to evaluate its role as a biomarker. Specifically, the cervical spinal cord´s cross-sectional area (CSA) in plane of the segments C1-C3 was measured semi-automatically with T1-weighted 3T MRI sequences in 158 ALS patients and 86 controls. Six-month longitudinal follow-up MRI scans were analyzed in 103 patients. Compared to controls, in ALS there was a significant mean spinal cord atrophy (63.8 mm² vs. 60.8 mm², p = 0.001) which showed a trend towards worsening over time (mean spinal cord CSA decrease from 61.4 mm² to 60.6 mm² after 6 months, p = 0.06). Findings were most pronounced in the caudal segments of the upper cervical spinal cord and in limb-onset ALS. Baseline CSA was related to the revised ALS functional rating scale, disease duration, precentral gyrus thickness and total brain gray matter volume. In conclusion, spinal cord atrophy as assessed in brain MRIs in ALS patients mirrors the extent of overall neurodegeneration and parallels disease severity. Spinal cord involvement is a well-known and prominent feature of amyotrophic lateral sclerosis (ALS), that reflects both anterior horn cell ("amyotrophy") and pyramidal tract degeneration/sclerosis of the lateral columns ("lateral sclerosis")-which has been highlighted since Charcot's pathology studies in 1865 1. Autopsy studies correspondingly reveal mild to marked loss of motor neurons in around 80% of the ALS patients which can affect the anterior horn of the entire spinal cord from the level of C2 to the level of its caudal sacral segments 2. Anterior horn cell loss is furthermore closely associated with large myelinated fiber degeneration of the pyramidal tract 2-4. In-vivo studies applying magnetic resonance imaging (MRI) correspondingly display a reduction of the spinal cord cross-sectional area (CSA) in ALS, i.e. showing spinal cord atrophy together with pyramidal tract integrity loss in diffusion tensor imaging (DTI) 5-7. Controversies remain, however, on the relationship of in-vivo MRI spinal cord atrophy to clinical features and biomarkers in ALS. While some studies reported an association between CSA reduction and worse motor performance or longer disease duration 8,9 , others failed to find such a clinical correlation 10,11. Conflicting or negative results might stem from small sample sizes in that most studies included less than 30 patients 8,9,12. Additionally, only a few ALS studies thus far took advantage of the capability of spinal cord in-vivo MRI to monitor CSA evolution over time 5,12,13. In consideration of these uncertainties, we conducted a retrospective analysis of the upper cervical spinal cord within brain MRIs that were acquired during a large cross-sectional (N = 158) and longitudinal (N = 103) multicenter study to understand how in-vivo spinal cord atrophy relates to clinical features, other biomarkers, and, how it evolves over time in ALS.

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Section: Methodsmentioning

confidence: 99%

The upper cervical spinal cord in ALS assessed by cross-sectional and longitudinal 3T MRI

Wimmer

Schreiber

Hensiek

et al. 2020

Sci Rep

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“…Functional imaging studies of ALS suggest that a number of compensatory processes take place in the face of progressive motor cortex degeneration and activation patterns shift from the precentral gyrus to supplementary motor, pre‐motor and cerebellar regions during movement execution . Despite the plethora of imaging studies in ALS , most studies admix heterogeneous patient cohorts without stratifying them based on their genotype, cognitive profile or upper motor neuron (UMN) versus lower motor neuron (LMN) predominance . Existing studies highlight increased cortical disease burden in UMN predominant (UMNp) cohorts compared to LMN predominant (LMNp) patients .…”

Section: Introductionmentioning

confidence: 99%

Adaptive functional reorganization in amyotrophic lateral sclerosis: coexisting degenerative and compensatory changes

Abidi

Marco

Couillandre

et al. 2019

Euro J of Neurology

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Background and purpose Considerable functional reorganization takes place in amyotrophic lateral sclerosis (ALS) in face of relentless structural degeneration. This study evaluates functional adaptation in ALS patients with lower motor neuron predominant (LMNp) and upper motor neuron predominant (UMNp) dysfunction. Methods Seventeen LMNp ALS patients, 14 UMNp ALS patients and 14 controls participated in a functional magnetic resonance imaging study. Study‐group‐specific activation patterns were evaluated during preparation for a motor task. Connectivity analyses were carried out using the supplementary motor area (SMA), cerebellum and striatum as seed regions and correlations were explored with clinical measures. Results Increased cerebellar, decreased dorsolateral prefrontal cortex and decreased SMA activation were detected in UMNp patients compared to controls. Increased cerebellar activation was also detected in UMNp patients compared to LMNp patients. UMNp patients exhibit increased effective connectivity between the cerebellum and caudate, and decreased connectivity between the SMA and caudate and between the SMA and cerebellum when performing self‐initiated movement. In UMNp patients, a positive correlation was detected between clinical variables and striato‐cerebellar connectivity. Conclusions Our findings indicate that, despite the dysfunction of SMA–striatal and SMA–cerebellar networks, cerebello‐striatal connectivity increases in ALS indicative of compensatory processes. The coexistence of circuits with decreased and increased connectivity suggests concomitant neurodegenerative and adaptive changes in ALS.

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“…Furthermore, patients with PLS have never been included in any clinical trials of ALS primarily due to the condition's rarity and slow progression. It remains unsettled whether PLS is a part of the ALS spectrum or an independent disease . No studies to date have addressed how to measure disease progression in PLS.…”

Section: Introductionmentioning

confidence: 99%

Primary lateral sclerosis (PLS) functional rating scale: PLS‐specific clinimetric scale

et al. 2019

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Introduction Our research aim was to develop a novel clinimetric scale sensitive enough to detect disease progression in primary lateral sclerosis (PLS). Methods A prototype of the PLS Functional Rating Scale (PLSFRS) was generated. Seventy‐seven participants with PLS were enrolled and evaluated at 21 sites that comprised the PLSFRS study group. Participants were assessed using the PLSFRS, Neuro‐Quality of Life (QoL), Schwab‐England Activities of Daily Living (ADL), and the Clinical Global Impression of Change scales. Participants completed telephone assessments at 12, 24, and 48 weeks after enrollment. Results The PLSFRS demonstrated internal consistency as well as intrarater, interrater, telephone test‐retest reliability, and construct validity. Significant changes in disease progression were detected at 6 and 12 months; changes measured by the PLSFRS vs the ALSFRS‐R were significantly higher. Discussion The PLSFRS is a valid tool to assess the natural history of PLS in a shorter study period.

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Primary lateral sclerosis: a distinct entity or part of the ALS spectrum?

Cited by 72 publications

References 112 publications

The upper cervical spinal cord in ALS assessed by cross-sectional and longitudinal 3T MRI

The upper cervical spinal cord in ALS assessed by cross-sectional and longitudinal 3T MRI

Adaptive functional reorganization in amyotrophic lateral sclerosis: coexisting degenerative and compensatory changes

Primary lateral sclerosis (PLS) functional rating scale: PLS‐specific clinimetric scale

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