Pain and temperature processing in dementia: a clinical and neuroanatomical analysis
Phillip D. Fletcher,Laura E. Downey,Hannah L. Golden,Camilla N. Clark,Catherine F. Slattery,Ross W. Paterson,Jonathan D. Rohrer,Jonathan M. Schott,Martin N. Rossor,Jason D. Warren +9 more
TLDR
Using a semi-structured caregiver questionnaire and MRI voxel-based morphometry in patients with frontotemporal degeneration or Alzheimer’s disease, Fletcher et al. show that symptoms are underpinned by atrophy in a distributed thalamo-temporo-insular network implicated in somatosensory processing.Abstract:
Symptoms suggesting altered processing of pain and temperature have been described in dementia diseases and may contribute importantly to clinical phenotypes, particularly in the frontotemporal lobar degeneration spectrum, but the basis for these symptoms has not been characterized in detail. Here we analysed pain and temperature symptoms using a semi-structured caregiver questionnaire recording altered behavioural responsiveness to pain or temperature for a cohort of patients with frontotemporal lobar degeneration (n = 58, 25 female, aged 52-84 years, representing the major clinical syndromes and representative pathogenic mutations in the C9orf72 and MAPT genes) and a comparison cohort of patients with amnestic Alzheimer's disease (n = 20, eight female, aged 53-74 years). Neuroanatomical associations were assessed using blinded visual rating and voxel-based morphometry of patients' brain magnetic resonance images. Certain syndromic signatures were identified: pain and temperature symptoms were particularly prevalent in behavioural variant frontotemporal dementia (71% of cases) and semantic dementia (65% of cases) and in association with C9orf72 mutations (6/6 cases), but also developed in Alzheimer's disease (45% of cases) and progressive non-fluent aphasia (25% of cases). While altered temperature responsiveness was more common than altered pain responsiveness across syndromes, blunted responsiveness to pain and temperature was particularly associated with behavioural variant frontotemporal dementia (40% of symptomatic cases) and heightened responsiveness with semantic dementia (73% of symptomatic cases) and Alzheimer's disease (78% of symptomatic cases). In the voxel-based morphometry analysis of the frontotemporal lobar degeneration cohort, pain and temperature symptoms were associated with grey matter loss in a right-lateralized network including insula (P < 0.05 corrected for multiple voxel-wise comparisons within the prespecified anatomical region of interest) and anterior temporal cortex (P < 0.001 uncorrected over whole brain) previously implicated in processing homeostatic signals. Pain and temperature symptoms accompanying C9orf72 mutations were specifically associated with posterior thalamic atrophy (P < 0.05 corrected for multiple voxel-wise comparisons within the prespecified anatomical region of interest). Together the findings suggest candidate cognitive and neuroanatomical bases for these salient but under-appreciated phenotypic features of the dementias, with wider implications for the homeostatic pathophysiology and clinical management of neurodegenerative diseases.read more
Citations
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Journal ArticleDOI
Primary progressive aphasia: a clinical approach.
Charles R. Marshall,Chris J.D. Hardy,Anna Volkmer,Lucy L. Russell,Rebecca L. Bond,Phillip D. Fletcher,Camilla N. Clark,Catherine J. Mummery,Jonathan M. Schott,Martin N. Rossor,Nick C. Fox,Sebastian J. Crutch,Jonathan D. Rohrer,Jason D. Warren +13 more
TL;DR: A clinical approach to the progressive aphasias is presented, based on the experience of these disorders and directed at non-specialists, and a prospect for future progress is concluded, emphasising generic information processing deficits and novel pathophysiological biomarkers.
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The clinical spectrum of sporadic and familial forms of frontotemporal dementia.
TL;DR: This review aims to clarify the often confusing terminology of FTD, and outline the various clinical features and diagnostic criteria of sporadic and familial FTD syndromes.
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Frontotemporal lobar degeneration: Pathogenesis, pathology and pathways to phenotype
TL;DR: It is possible therefore that FTLD is a reflection of dysfunction within lysosomal/proteasomal systems resulting in failure to remove potentially neurotoxic aggregates, which ultimately overwhelm capacity to function.
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Pain in amyotrophic lateral sclerosis
TL;DR: Given the multifactorial nature of pain in patients with ALS, different treatments have been suggested, ranging from non-steroidal anti-inflammatory drugs, drugs for neuropathic pain, opioids, and cannabinoids, to physical therapy strategies and preventive assistive devices.
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Psychological and Cognitive Markers of Behavioral Variant Frontotemporal Dementia-A Clinical Neuropsychologist's View on Diagnostic Criteria and Beyond.
Andreas Johnen,Maxime Bertoux +1 more
TL;DR: A critical appraisal of common methods to access the behavioral and psychological symptoms as well as the cognitive alterations presented in the diagnostic criteria for Behavioral variant frontotemporal dementia is aimed at.
References
More filters
Journal ArticleDOI
Somatotopic organisation of the human insula to painful heat studied with high resolution functional imaging.
Jonathan C W Brooks,Jonathan C W Brooks,L. Zambreanu,L. Zambreanu,A. Godinez,A. D. (Bud) Craig,Irene Tracey,Irene Tracey +7 more
TL;DR: Examination of mixed effects group activation maps suggested a pain-related somatotopy in the contralateral posterior insula and putamen, and construction of frequency maps revealed that face activation within the posterior Insula was anterior to both hand and foot, whilst foot activation was located medially in the circular sulcus.
Journal ArticleDOI
Breathlessness in humans activates insular cortex.
Robert B. Banzett,Henrietta E. Mulnier,Kevin Murphy,Stuart D. Rosen,Richard J. S. Wise,Lewis Adams +5 more
TL;DR: In this article, the authors explored the central neural structures underlying perception of dyspnea in healthy subjects by restraining ventilation below spontaneous levels while holding arterial oxygen and carbon dioxide levels constant.
Journal ArticleDOI
Enhanced medial prefrontal-default mode network functional connectivity in chronic pain and its association with pain rumination.
Aaron Kucyi,Aaron Kucyi,Massieh Moayedi,Irit Weissman-Fogel,Irit Weissman-Fogel,Irit Weissman-Fogel,Michael B. Goldberg,Michael B. Goldberg,Bruce V. Freeman,Bruce V. Freeman,Howard C. Tenenbaum,Howard C. Tenenbaum,Howard C. Tenenbaum,Karen D. Davis +13 more
TL;DR: Testing the hypothesis that in patients with chronic pain, the medial prefrontal cortex exhibits abnormal FC related to the patient's degree of rumination about their pain found that TMD patients exhibited enhanced mPFC FC with other DMN regions, including the posterior cingulate cortex (PCC)/precuneus (PCu) and retrosplenial cortex.
Journal ArticleDOI
Issues with threshold masking in voxel-based morphometry of atrophied brains
Gerard R. Ridgway,Rohani Omar,Sebastien Ourselin,Derek L. G. Hill,Jason D. Warren,Nick C. Fox +5 more
TL;DR: It is shown that one of the most commonly used strategies for defining this mask runs a major risk of excluding from the analysis precisely those voxels where the subjects' brains were most vulnerable to atrophy.
Journal ArticleDOI
Parkinson’s disease: lesions in dorsal horn layer I, involvement of parasympathetic and sympathetic pre- and postganglionic neurons
TL;DR: Investigation of the first relay stations of the pain system as well as parasympathetic and sympathetic pre- and postganglionic nerve cells in the lower brainstem, spinal cord, and coeliac ganglion indicates that physical contacts between vulnerable regions play a key role in the pathogenesis of PD.
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