A case report comparing clinical, imaging and neuropsychological assessment findings in twins discordant for the VCP p.R155C mutation

Surampalli, Abhilasha; Gold, Brian T.; Smith, Charles D.; Castellani, Rudy J.; Khare, Manaswitha; Yu, Hua; Nguyen, Celeste; Lan, Mary L.; Wencel, Marie; Wigal, Sharon B.; Caiozzo, Vince; Kimonis, Virginia

doi:10.1016/j.nmd.2014.10.003

Cited by 6 publications

(10 citation statements)

References 39 publications

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“…Gomori trichrome staining showed rimmed vacuoles in muscle cells and small angulated fibers (Figure 1L), which were compatible with the pathological findings of IBMPFD during the first hospitalization. DNA analysis revealed a cytosine (C) to thymine (T) (C→T * ) mutation, resulting in an amino acid exchange of arginine to cysteine (p.R155C) ( Figure 1M) as previously described (2,3,(9)(10)(11)(12)(13)(14). The neurological finding of this case revealed general muscle weakness and atrophy, especially, proximal muscles of lower extremities, progressive cognitive decline, speech disturbance, and character change.…”

Section: Case Presentationsupporting

confidence: 71%

Section: Case Presentationsupporting

confidence: 69%

“…IBMPFD is clinically characterized by adult-onset muscle weakness and atrophy, early-onset PDB, and frontotemporal dementia (FTD) (1,2,15). VCP is identified as the most predominant causative gene among IBMPFD patients, and the R155C mutation has been reported including Japanese ethnic background (2,3,(9)(10)(11)(12)(13)(14). VCP-related IBMPFD represents a unique class D subtype of the neurodegenerative diseases named TDP-43 proteinopathies with numerous ubiquitinpositive neuronal intranuclear inclusions and dystrophic neurites (31)(32)(33).…”

Section: Discussionmentioning

confidence: 99%

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Increased Neurofilament Light Chain and YKL-40 CSF Levels in One Japanese IBMPFD Patient With VCP R155C Mutation: A Clinical Case Report With CSF Biomarker Analyses

et al. 2020

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Inclusion body myopathy (IBM) with Paget's disease of bone (PDB) and frontotemporal dementia (IBMPFD) presents with multiple symptoms and an unknown etiology. Valosin-containing protein (VCP) has been identified as the main causative gene of IBMPFD. However, no studies on neurofilament light chain (NFL) as a cerebrospinal fluid (CSF) marker of axonal neurodegeneration or on YKL-40 as a CSF marker of glial neuroinflammation have been conducted in IBMPFD patients with VCP mutations. A 65-year-old man presented with progressive muscle atrophy and weakness of all limbs, non-fluent aphasia, and changes in personality and behavior. Cerebral MRI revealed bilateral frontal and temporal atrophy. 99m Tc-HMDP bone scintigraphy and pelvic CT revealed remodeling changes and active osteoblastic accumulations in the right medial iliac bone. Muscle biopsy demonstrated multiple rimmed vacuoles in muscle cells with myogenic and neurogenic pathological alterations. After the patient was clinically diagnosed with IBMPFD, DNA analysis of the VCP gene revealed a cytosine (C) to thymine (T) (C→T) mutation, resulting in an amino acid exchange of arginine to cysteine (p.R155C mutation). The CSF levels of NFL at two time points (12 years apart) were higher than those in non-dementia controls (CTR) and Alzheimer's disease (AD); lower than those in frontotemporal dementia with motor neuron disease (FTD-MND); and comparable to those in patients with behavioral variant frontotemporal dementia (bvFTD), progressive supranuclear palsy (PSP), and corticobasal syndrome (CBS). The CSF levels of YKL-40 were comparable at both time points and higher than those in CTR; lower than those in FTD-MND; and comparable to those in bvFTD, PSP, CBS, and AD. The CSF levels of phosphorylated tau 181 (P-Tau) and total tau (T-Tau) were not significantly different from those in CTR and other neurodegenerative diseases, except those in AD, which were significantly elevated. This is the first report that demonstrates increased NFL Ikeda et al. CSF in Mutant VCP IBMPFD and YKL-40 CSF levels in an IBMPFD patient with a VCP mutation (p.R155C); NFL and YKL-40 levels were comparable to those in bvFTD, PSP, CBS, and AD and higher than those in CTR. Our results suggest that IBMPFD neuropathology may involve both axonal neurodegeneration and glial neuroinflammation.

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Section: Case Presentationsupporting

confidence: 71%

Section: Case Presentationsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

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Increased Neurofilament Light Chain and YKL-40 CSF Levels in One Japanese IBMPFD Patient With VCP R155C Mutation: A Clinical Case Report With CSF Biomarker Analyses

et al. 2020

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“…TDP-D is by far the rarest variant and associated with mutations in the valosin-containing protein gene. Preliminary MRI findings have been inconsistent and failed to demonstrate a clear pattern (Stojkovic et al 2009;Kim et al 2011;Surampalli et al 2015).…”

Section: Pathologically Defined Formsmentioning

confidence: 99%

Advances in neuroimaging in frontotemporal dementia

Gordón

Rohrer

Fox

2016

Journal of Neurochemistry

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Frontotemporal dementia (FTD) is a clinically and neuroanatomically heterogeneous neurodegenerative disorder with multiple underlying genetic and pathological causes. Whilst initial neuroimaging studies highlighted the presence of frontal and temporal lobe atrophy or hypometabolism as the unifying feature in patients with FTD, more detailed studies have revealed diverse patterns across individuals, with variable frontal or temporal predominance, differing degrees of asymmetry, and the involvement of other cortical areas including the insula and cingulate, as well as subcortical structures such as the basal ganglia and thalamus. Recent advances in novel imaging modalities including diffusion tensor imaging, resting-state functional magnetic resonance imaging and molecular positron emission tomography imaging allow the possibility of investigating alterations in structural and functional connectivity and the visualisation of pathological protein deposition. This review will cover the major imaging modalities currently used in research and clinical practice, focusing on the key insights they have provided into FTD, including the onset and evolution of pathological changes and also importantly their utility as biomarkers for disease detection and staging, differential diagnosis and measurement of disease progression. Validating neuroimaging biomarkers that are able to accomplish these tasks will be crucial for the ultimate goal of powering upcoming clinical trials by correctly stratifying patient enrolment and providing sensitive markers for evaluating the effects and efficacy of diseasemodifying therapies.

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“…MRI findings range widely, from cases showing no signs of frontal lobe atrophy to patients with prominent, asymmetric, focal atrophy in the anterior and temporal lobes (Gidaro et al, 2008 ; Djamshidian et al, 2009 ; Stojkovic et al, 2009 ; Kim et al, 2011 ; Surampalli et al, 2015 ). FDG-PET imaging has revealed severe glucose hypometabolism in the bilateral frontotemporoparietal areas (Guyant-Marechal et al, 2006 ; Stojkovic et al, 2009 ; Kim et al, 2011 ).…”

Section: Vcp Mutationsmentioning

confidence: 99%

Phenotypic Heterogeneity of Monogenic Frontotemporal Dementia

Benussi

Padovani

Borroni

2015

Front. Aging Neurosci.

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Frontotemporal dementia (FTD) is a genetically and pathologically heterogeneous disorder characterized by personality changes, language impairment, and deficits of executive functions associated with frontal and temporal lobe degeneration. Different phenotypes have been defined on the basis of presenting clinical symptoms, i.e., the behavioral variant of FTD, the agrammatic variant of primary progressive aphasia, and the semantic variant of PPA. Some patients have an associated movement disorder, either parkinsonism, as in progressive supranuclear palsy and corticobasal syndrome, or motor neuron disease (FTD–MND). A family history of dementia is found in 40% of cases of FTD and about 10% have a clear autosomal-dominant inheritance. Genetic studies have identified several genes associated with monogenic FTD: microtubule-associated protein tau, progranulin, TAR DNA-binding protein 43, valosin-containing protein, charged multivesicular body protein 2B, fused in sarcoma, and the hexanucleotide repeat expansion in intron 1 of the chromosome 9 open reading frame 72. Patients often present with an extensive phenotypic variability, even among different members of the same kindred carrying an identical disease mutation. The objective of the present work is to review and evaluate available literature data in order to highlight recent advances in clinical, biological, and neuroimaging features of monogenic frontotemporal lobar degeneration and try to identify different mechanisms underlying the extreme phenotypic heterogeneity that characterizes this disease.

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A case report comparing clinical, imaging and neuropsychological assessment findings in twins discordant for the VCP p.R155C mutation

Cited by 6 publications

References 39 publications

Increased Neurofilament Light Chain and YKL-40 CSF Levels in One Japanese IBMPFD Patient With VCP R155C Mutation: A Clinical Case Report With CSF Biomarker Analyses

Increased Neurofilament Light Chain and YKL-40 CSF Levels in One Japanese IBMPFD Patient With VCP R155C Mutation: A Clinical Case Report With CSF Biomarker Analyses

Advances in neuroimaging in frontotemporal dementia

Phenotypic Heterogeneity of Monogenic Frontotemporal Dementia

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