@article{3032568,
    title = "Genotype-associated cerebellar profiles in ALS: focal cerebellar
pathology and cerebro-cerebellar connectivity alterations",
    author = "Bede, Peter and Chipika, Rangariroyashe H. and Christidi, Foteini and and Hengeveld, Jennifer C. and Karavasilis, Efstratios and Argyropoulos, and Georgios D. and Lope, Jasmin and Li Hi Shing, Stacey and Velonakis, and Georgios and Dupuis, Leonie and Doherty, Mark A. and Vajda, Alice and and McLaughlin, Russell L. and Hardiman, Orla",
    journal = "JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY",
    year = "2021",
    volume = "92",
    number = "11",
    pages = "1197-1205",
    publisher = "BMJ Publishing Group",
    doi = "10.1136/jnnp-2021-326854",
    abstract = "Objective Cerebellar disease burden and cerebro-cerebellar connectivity
alterations are poorly characterised in amyotrophic lateral sclerosis
(ALS) despite the likely contribution of cerebellar pathology to the
clinical heterogeneity of the condition. Methods A prospective imaging
study has been undertaken with 271 participants to systematically
evaluate cerebellar grey and white matter alterations, cerebellar
peduncle integrity and cerebro-cerebellar connectivity in ALS.
Participants were stratified into four groups: (1) patients testing
positive for GGGGCC repeat expansions in C9orf72, (2) patients carrying
an intermediate-length repeat expansion in ATXN2, (3) patients without
established ALS-associated mutations and (4) healthy controls.
Additionally, the cerebellar profile of a single patient with ALS who
had an ATXN2 allele length of 62 was evaluated. Cortical thickness, grey
matter and white matter volumes were calculated in each cerebellar
lobule complemented by morphometric analyses to characterise
genotype-associated atrophy patterns. A Bayesian segmentation algorithm
was used for superior cerebellar peduncle volumetry. White matter
diffusivity parameters were appraised both within the cerebellum and in
the cerebellar peduncles. Cerebro-cerebellar connectivity was assessed
using deterministic tractography. Results Cerebellar pathology was
confined to lobules I-V of the anterior lobe in patients with sporadic
ALS in contrast to the considerable posterior lobe and vermis disease
burden identified in C9orf72 mutation carriers. Patients with
intermediate ATXN2 expansions did not exhibit significant cerebellar
pathology. Conclusions Focal rather than global cerebellar degeneration
characterises ALS. Pathognomonic ALS symptoms which are typically
attributed to other anatomical regions, such as dysarthria, dysphagia,
pseudobulbar affect, eye movement abnormalities and cognitive deficits,
may be modulated, exacerbated or partially driven by cerebellar changes
in ALS."
}