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8. Limbic Network and Papez Circuit Involvement in ALS: Imaging and Clinical Profiles in GGGGCC Hexanucleotide Carriers in C9orf72 and C9orf72 -Negative Patients.

Author

Christidi, Foteini, Kleinerova, Jana, Tan, Ee Ling, Delaney, Siobhan, Tacheva, Asya, Hengeveld, Jennifer C., Doherty, Mark A., McLaughlin, Russell L., Hardiman, Orla, Siah, We Fong, Chang, Kai Ming, Lope, Jasmin, and Bede, Peter

Subjects
MOTOR neuron diseases, WHITE matter (Nerve tissue), SPINAL cord, NUCLEUS accumbens, CINGULATE cortex, AMYOTROPHIC lateral sclerosis, NEUROPSYCHOLOGICAL tests
Abstract

Simple Summary: Amyotrophic lateral sclerosis (ALS) is the most common form of Motor Neuron Disease and is traditionally associated with motor cortex, brainstem and spinal cord degeneration. Neuropsychological deficits are also increasingly recognized in ALS and have considerable clinical ramifications, but existing studies of cognitive impairment in ALS have primarily focused on cortical frontotemporal disease burden. The aim of this study is the comprehensive assessment of the grey and white matter components of limbic networks in a large cohort of patients with ALS, stratified for the C9orf72 genotype. Our MRI analyses reveal that the cortical, subcortical and white matter components of limbic circuits are not only affected in C9orf72-positive patients, but also in those who test negative for this genetic variant. Our radiological findings are consistent with previous neuropsychological observations and highlight the importance of comprehensive neuropsychological testing in ALS, irrespective of the underlying genotype. Cognitive impairment in ALS has widespread practical implications, including compliance with assistive devices, participation in clinical trials, and it has been associated with increased caregiver burden and is widely regarded as an adverse prognostic indicator. Our data provide radiological evidence of widespread limbic degeneration in ALS, which is particularly severe in C9orf72 mutation carriers. Background: While frontotemporal involvement is increasingly recognized in Amyotrophic lateral sclerosis (ALS), the degeneration of limbic networks remains poorly characterized, despite growing evidence of amnestic deficits, impaired emotional processing and deficits in social cognition. Methods: A prospective neuroimaging study was conducted with 204 individuals with ALS and 111 healthy controls. Patients were stratified for hexanucleotide expansion status in C9orf72. A deep-learning-based segmentation approach was implemented to segment the nucleus accumbens, hypothalamus, fornix, mammillary body, basal forebrain and septal nuclei. The cortical, subcortical and white matter components of the Papez circuit were also systematically evaluated. Results: Hexanucleotide repeat expansion carriers exhibited bilateral amygdala, hypothalamus and nucleus accumbens atrophy, and C9orf72 negative patients showed bilateral basal forebrain volume reductions compared to controls. Both patient groups showed left rostral anterior cingulate atrophy, left entorhinal cortex thinning and cingulum and fornix alterations, irrespective of the genotype. Fornix, cingulum, posterior cingulate, nucleus accumbens, amygdala and hypothalamus degeneration was more marked in C9orf72-positive ALS patients. Conclusions: Our results highlighted that mesial temporal and parasagittal subcortical degeneration is not unique to C9orf72 carriers. Our radiological findings were consistent with neuropsychological observations and highlighted the importance of comprehensive neuropsychological testing in ALS, irrespective of the underlying genotype. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Not a benign motor neuron disease: longitudinal imaging captures relentless motor connectome disintegration in primary lateral sclerosis

Author

Tahedl, Marlene, primary, Tan, Ee Ling, additional, Shing, Stacey Li Hi, additional, Chipika, Rangariroyashe H., additional, Siah, We Fong, additional, Hengeveld, Jennifer C., additional, Doherty, Mark A., additional, McLaughlin, Russell L., additional, Hardiman, Orla, additional, Finegan, Eoin, additional, and Bede, Peter, additional

Published
2023
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20. Validation of diagnostic criteria for early-stage primary lateral sclerosis: Disease burden in “Probable PLS” (1527)

Author

Finegan, Eoin, primary, Shing, Stacey Li Hi, additional, Siah, We Fong, additional, Chang, Kai Ming, additional, McKenna, Mary Clare, additional, Doherty, Mark A., additional, Hengeveld, Jennifer, additional, Vajda, Alice, additional, Donaghy, Colette, additional, Hutchinson, Siobhan, additional, McLaughlin, Russell L., additional, Hardiman, Orla, additional, and Bede, Peter, additional

Published
2021
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23. MRI data confirm the selective involvement of thalamic and amygdalar nuclei in amyotrophic lateral sclerosis and primary lateral sclerosis

Author

Chipika, Rangariroyashe H., primary, Siah, We Fong, additional, Shing, Stacey Li Hi, additional, Finegan, Eoin, additional, McKenna, Mary Clare, additional, Christidi, Foteini, additional, Chang, Kai Ming, additional, Karavasilis, Efstratios, additional, Vajda, Alice, additional, Hengeveld, Jennifer C., additional, Doherty, Mark A., additional, Donaghy, Colette, additional, Hutchinson, Siobhan, additional, McLaughlin, Russell L., additional, Hardiman, Orla, additional, and Bede, Peter, additional

Published
2020
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24. Imaging and clinical data indicate considerable disease burden in ‘probable’ PLS: Patients with UMN symptoms for 2–4 years

Author

Finegan, Eoin, primary, Siah, We Fong, additional, Shing, Stacey Li Hi, additional, Chipika, Rangariroyashe H., additional, Chang, Kai Ming, additional, McKenna, Mary Clare, additional, Doherty, Mark A., additional, Hengeveld, Jennifer C., additional, Vajda, Alice, additional, Donaghy, Colette, additional, Hutchinson, Siobhan, additional, McLaughlin, Russel L., additional, Hardiman, Orla, additional, and Bede, Peter, additional

Published
2020
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33. Reply

Author

Siah, We Fong, primary, Loughman, James, additional, and O'Brien, Colm, additional

Published
2016
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37. Macular pigment is associated with glare-affected visual function and central visual field loss in glaucoma

Author

Siah, We Fong, O’Brien, Colm, and Loughman, James J

Abstract

AimTo evaluate the relationship between macular pigment optical density (MPOD) and glare disability in open-angle glaucoma.MethodsA cross-sectional analysis of baseline data (88 subjects; median age, 67 (range 36–84) years) collected during the Macular Pigment and Glaucoma Trial (ISRCTN registry number: 56985060). MPOD at 0.25°, 0.5° and 1° of retinal eccentricity was measured using customised heterochromatic flicker photometry. Mesopic contrast sensitivity with glare (mCSg), photostress recovery time (PRT) and self-reported glare symptoms were evaluated. Fourier-domain optical coherence tomography was used to analyse ganglion cell complex (GCC) and identify foveal involvement.ResultsLow spatial frequency (f) mCSg was significantly correlated with MPOD at 0.25°(3 cycles per degree (cpd): r=0.25, p=0.04) and 0.5° (3 cpd: r=0.23, p=0.04) of retinal eccentricity. Those with foveal GCC loss exhibited lower MPOD, had worse low spatial fmCSg (1.5 cpd and 3 cpd, p=0.02 each) and prolonged PRT (p=0.02) in comparison with those without foveal involvement. The depth of central 10° field loss was related to MPOD at all eccentricities (p<0.01 for all). Those who reported glare symptoms had a significantly lower MPOD at all retinal eccentricities (0.25° and 1°: p=0.05 each; 0.5°: p=0.04), including those with foveal involvement (0.25°: p=0.05; 0.5°: p<0.01; 1°: p=0.01).ConclusionsMacular pigment level may be an important consideration among those experiencing disability glare in glaucoma, including those with foveal involvement.Trial registration numberISRCTN56985060, Post-results.

Published
2018
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38. Late outcomes of gold weights and platinum chains for upper eyelid loading

Author

Siah, We Fong, Nagendran, Sonali, Tan, Petrina, Ali Ahmad, Syed Mustafa, Litwin, Andre S, and Malhotra, Raman

Abstract

AimTo identify late outcomes of gold weights (GWs) and platinum chains (PCs) for upper eyelid loading in the management of lagophthalmos.MethodsA retrospective case series of upper eyelid GWs and PCs at a single centre over a 10-year period (2004–2013). Two independent, blinded assessors graded standard photographs for any weight-related morbidity (poor upper eyelid contour, weight prominence and migration).ResultsPrimary upper eyelid loading (high-tarsal technique) was performed in 154 eyelids of 136 patients (facial nerve palsy, n=99; non-paralytic, n=37). A total of 127 eyelids of 110 patients had primary GW insertion. Of these, 40.9% (52/127) had revision surgery: exchange of GW for PC (58%), GW repositioning (25%) and removal of GW (17%). Only 22.2% (6/27 eyelids) with primary PCs required revision surgery. In those not requiring revision surgery, photograph grading showed that both GWs and PCs had weight-related morbidity at late follow-up (median=37.5 months, range 12–110 vs median=33.5 month, range 15–106). GWs had significantly higher rate of weight prominence (p=0.001) and migration (p<0.001) compared with PCs. All PC revisions required one procedure only compared with 10% of GWs revisions requiring two or more procedures. Incidence of gold allergy was 7% (8/110 patients). There was no association between the choice of weight material, physical weight or suture material and eyelid morbidities.ConclusionGWs were found to be associated with higher complications and twice more likely to require long-term revision surgery compared with PCs. Despite weight fixation at a high-tarsal location, prominence of PCs can still occur.

Published
2018
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