Identical patterns of cortico-efferent tract involvement in primary lateral sclerosis and amyotrophic lateral sclerosis: A tract of interest-based MRI study

Müller, Hans‐Peter; Gorges, Martin; Kassubek, Rebecca; Dorst, Johannes; Ludolph, Albert C.; Kassubek, Jan

doi:10.1016/j.nicl.2018.03.018

Cited by 26 publications

(21 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Systematic ex vivo data in patients with a PLS phenotype for the diagnostic proof as definite ALS by the neuropathological demonstration of cerebral TDP43 pathology according to the neuropathological staging concept of ALS ( Braak et al, 2013 ; Braak et al, 2017 ) are lacking yet. In order to assess this neuropathological pattern in MND patients in vivo by magnetic resonance imaging, a group of PLS patients has been subjected to the established hypothesis-guided tract-of-interest (TOI)-based diffusion tensor imaging technique of the brain ( Kassubek et al, 2014 ; Kassubek et al, 2018 ), and the results showed the same microstructural pathological patterns in PLS patients as in ALS, in support of the hypothesis that PLS is a phenotypical variant of ALS ( Müller et al, 2018 ).…”

Section: Introductionmentioning

confidence: 79%

See 1 more Smart Citation

Cortico-efferent tract involvement in primary lateral sclerosis and amyotrophic lateral sclerosis: A two-centre tract of interest-based DTI analysis

Müller

Gorges

Kassubek

et al. 2018

NeuroImage: Clinical

Self Cite

View full text Add to dashboard Cite

BackgroundAfter the demonstration of a corticoefferent propagation pattern in amyotrophic lateral sclerosis (ALS) by neuropathological studies, this concept has been used for in vivo staging of individual patients by diffusion tensor imaging (DTI) techniques, both in `classical` ALS and in restricted phenotypes such as primary lateral sclerosis (PLS).ObjectiveThe study was designed to investigate that microstructural changes according to the neuropathologically defined ALS alteration pattern in PLS patients could be confirmed to be identical to ´classical´ ALS patients. The novelty in this approach is that the results were independent of the subject samples and the data acquisition parameters (as was validated in two samples from two different centres). That way, reproducibility across (international) centres in addition to harmonisation/standardisation of data analysis has been addressed, for the possible use of MRI-based staging to stratify patients in clinical trials.MethodsTractwise analysis of fractional anisotropy (FA) maps according to the ALS-staging pattern was applied to DTI data (pooled from two ALS centres) of 88 PLS patients and 88 ALS patients with a ‘classical’ phenotype in comparison to 88 matched controls in order to identify white matter integrity alterations.ResultsIn the tract-specific analysis, alterations were identical for PLS and ALS in the tract systems corresponding to the ALS staging pattern, independent of the subject samples and the data acquisition parameters. The individual categorisation into ALS stages did not differ between PLS and ALS patients.ConclusionsThis DTI study in a two-centre setting demonstrated that the neuropathological stages can be mapped in vivo in PLS with high reproducibility and that PLS-associated cerebral propagation, although showing the same corticofugal patterns as ALS, might have a different time course of neuropathology, in analogy to its much slower clinical progression rates.

show abstract

Section: Introductionmentioning

confidence: 79%

“…in neurodegenerative diseases. The application of the TOI technique has previously been applied to show that the PLS brain alteration pattern is like in ALS ( Müller et al, 2018 ). In addition, it has been demonstrated that different DTI protocols can be pooled even in a large multi-centre study ( Müller et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Cortico-efferent tract involvement in primary lateral sclerosis and amyotrophic lateral sclerosis: A two-centre tract of interest-based DTI analysis

Müller

Gorges

Kassubek

et al. 2018

NeuroImage: Clinical

Self Cite

View full text Add to dashboard Cite

show abstract

“…It is long recognized that PLS is rarely distinguishable from ALS at the histopathological level and in diffusion-tensor imaging [16]. On the other hand, neuropathological studies in hSP have revealed pallor of the lateral corticospinal tract and, more variably, of the anterior tract within the spinal cord, besides fasciculus gracilis [17].…”

Section: Discussionmentioning

confidence: 99%

Cerebrospinal Fluid Neurofilaments May Discriminate Upper Motor Neuron Syndromes: A Pilot Study

et al. 2018

View full text Add to dashboard Cite

Background: Patients presenting with upper motor neuron (UMN) signs may widely diverge in prognosis, ranging from amyotrophic lateral sclerosis (ALS) to primary lateral sclerosis (PLS) and hereditary spastic paraplegia (hSP). Neurofilaments are emerging as potential diagnostic and prognostic biomarkers for ALS, but the diagnosis of UMN syndromes still relies mostly on clinical long-term observation and on familiarity or genetic confirmation. Objectives: To test whether phosphorylated neurofilament heavy chain (pNfH) may discriminate different UMN syndromes at diagnosis and to test their prognostic role among these diseases. Methods: We measured the cerebrospinal fluid (CSF) and serum pNfH of 30 patients presenting with UMN signs and diagnosed with ALS, hSP, and PLS, plus 9 healthy controls (HC). Results: ALS patients had higher levels of pNfH in CSF and serum compared to HC (p < 0.001 and p < 0.001 in CSF and serum, respectively) and PLS (p = 0.015 and p = 0.038) and hSP (p = 0.003 and p = 0.001) patients. PLS and hSP patients had similar CSF and serum pNfH concentrations, but a higher CSF pNfH concentration, compared to HC (p = 0.002 and p = 0.003 for PLS and hSP, respectively). Receiver operating characteristic curves for discriminating ALS from PLS and hSP showed an area under the curve of 0.79 for CSF and 0.81 for serum. In multivariable survival analysis including relevant clinical factors CSF pNfH represented the strongest variable predicting survival (HR 40.43; 95% CI 3.49–467.79, p = 0.003) independently of clinical group. Conclusions: Despite some statistical instability of the results due to limitations in sample size, our study supports the role of CSF pNfH as a prognostic biomarker for motor neuron diseases presenting with UMN signs. A potential power to discriminate between ALS and other UMN syndromes at presentation, and between all of the examined MND and HC, has been detected for both CSF and serum pNfH.

show abstract

“…In the revision of the El Escorial criteria, PLS is described as a restricted phenotype that evolves into ALS in the majority of patients ( Ludolph et al, 2015 ). In vivo , the analysis of WM integrity by regional FA reductions in 50 PLS patients vs. 50 controls showed the alterations along the CST and additionally in frontal and prefrontal brain areas in PLS and ALS patients ( Müller et al, 2018b ). The ALS-staging-related tract-specific analysis demonstrated identical alterations of ALS-related tract systems for PLS and ALS when compared with controls and showed no differences for the comparison between ALS and PLS ( Müller et al, 2018b ).…”

Section: Application Of the In Vivo Staging Approamentioning

confidence: 99%

MRI-Based Mapping of Cerebral Propagation in Amyotrophic Lateral Sclerosis

Müller

Kassubek

2018

Front. Neurosci.

Self Cite

View full text Add to dashboard Cite

Neuropathological studies revealed the propagation of amyotrophic lateral sclerosis (ALS) in a sequence of four separate disease-related regional patterns. Diffusion tensor imaging (DTI)-based analysis was established for the individual mapping of sequential disease spreading in ALS as the in vivo transfer to neuroimaging. The aim of this review is to summarize cross-sectional and longitudinal results of these technical approaches in ALS as an in vivo tool to image ALS propagation stages. This concept was also applied to restricted phenotypes of ALS, e.g., lower motor neuron disease (LMND) or primary lateral sclerosis (PLS). In summary, the regional disease patterns in the course of ALS have been successfully mapped by DTI in vivo both cross-sectionally and longitudinally so that this technique might have the potential as a read-out in clinical trials.

show abstract

Identical patterns of cortico-efferent tract involvement in primary lateral sclerosis and amyotrophic lateral sclerosis: A tract of interest-based MRI study

Cited by 26 publications

References 34 publications

Cortico-efferent tract involvement in primary lateral sclerosis and amyotrophic lateral sclerosis: A two-centre tract of interest-based DTI analysis

Cortico-efferent tract involvement in primary lateral sclerosis and amyotrophic lateral sclerosis: A two-centre tract of interest-based DTI analysis

Cerebrospinal Fluid Neurofilaments May Discriminate Upper Motor Neuron Syndromes: A Pilot Study

MRI-Based Mapping of Cerebral Propagation in Amyotrophic Lateral Sclerosis

Contact Info

Product

Resources

About