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Comparison of quantitative sensory testing and heart rate variability in Swedish Val30Met ATTR
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
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2011 (English)In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, Vol. 18, no 4, 183-190 p.Article in journal (Refereed) Published
Abstract [en]

Patients with transthyretin amyloidosis (ATTR) polyneuropathy, a hereditary fatal disease, often report defects in both thermal perception and autonomic nervous system function as their first clinical symptoms. While elevated thermal perception thresholds (TPT) for cold and warmth only recently have been shown as an early marker of small nerve fiber dysfunction in these patients, heart rate variability (HRV) has frequently been used to quantify autonomic neuropathy. The main purpose with this report was to elucidate a possible relationship between estimates of HRV and TPT in a selected group of early and late-onset Swedish Val30Met ATTR patients. The results show significantly more pronounced elevation of TPT in early compared to late-onset patients. Significant correlations between HRV and TPT were found among late-onset cases, indicating a possible relationship between loss of thin nerve fibers in somatic and autonomic nerves, while generally no such relationships were found among early-onset cases. This observation emphasizes the importance of testing both HRV and TPT to ensure optimal early detection of neuropathic changes in an as wide as possible range of small nerve fibers in suspected ATTR patients. This is of particular importance as the phenotype of the ATTR disease varies between groups with different age of onset.

Place, publisher, year, edition, pages
Pearl River, NY: Parthenon Pub. , 2011. Vol. 18, no 4, 183-190 p.
Keyword [en]
amyloid, cold perception thresholds, early-onset, FAP, heart rate variability, late-onset, quantitative, sensory testing, transthyretin, val30met, warm perception thresholds
National Category
URN: urn:nbn:se:umu:diva-49187DOI: 10.3109/13506129.2011.614294PubMedID: 22035563OAI: diva2:453419
Available from: 2011-11-02 Created: 2011-11-02 Last updated: 2012-06-29Bibliographically approved
In thesis
1. Methodological aspects and usefulness of Quantitative Sensory Testing in early small fiber polyneuropathy: a clinical study in Swedish hereditary transthyretin amyloidosis patients
Open this publication in new window or tab >>Methodological aspects and usefulness of Quantitative Sensory Testing in early small fiber polyneuropathy: a clinical study in Swedish hereditary transthyretin amyloidosis patients
2011 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Generalised polyneuropathy (PNP) is a common cause to neurological impairment, and may be an early symptom of a severe systemic disease. One such illness is hereditary transthyretin (TTR) amyloidosis (ATTR), a progressive fatal disorder caused by a mutation on the TTR gene. More than 100 such mutations have been found worldwide, of which Val30Met is the most common neuropathic variant with initial clinical manifestations indicating small fiber impairment. Differences in onset age, penetrance and phenotypes are present between endemic areas. Liver transplantation generally slows the progress of the symptom development, especially in patients with short disease duration. Ongoing research has also shown promising results with drug interventions. In any event, early diagnosis of PNP onset in ATTR patients is crucial to ensure early therapeutic interventions. Nerve conduction studies (NCS) and electromyography (EMG) provide the basis for evaluation of the functional state of the thick myelinated nerve fibres in patients with symptoms of PNP, but no such quantitative methods are available for the thin myelinated or unmyelinated fibers. Instead, a psychophysical method with thermal quantitative sensory testing (QST) can provide indirect information about the overall function in the afferent small fiber systems. The purpose of thesis was to evaluate the applicability of QST by the Method-of-limits (MLI) for early detection of PNP in Swedish ATTR patients with the Val30Met mutation.

In healthy subjects the repeatability of the MLI was assessed, and reference values for thermal perception thresholds (TPT) in several body regions were determined. No significant differences in TPT or pain thresholds were found at repeated testing with MLI, indicating that the MLI is a reliable method. However, the results show that the arrangement of the testing order is of importance, as cold (CT) and warm (WT) perception thresholds were significantly elevated when tested after thermal pain assessments, instead of before. I general, the TPT was more elevated at lower parts of the body compared to the upper part, and with higher WT than CT, fully in accordance with the underlying anatomical and physiological prerequisites for QST. In biopsy verified ATTR patients lacking EMG and NCS abnormalities, significantly elevated TPT were found compared to controls. Furthermore, significantly more increased TPT were observed in patients with an early onset of the disease, compared those with a late onset. Finally, a combined detailed evaluation of QST and heart rate variability (HRV) analyses demonstrated correlations between QST and HRV abnormalities in patients with late onset, but not in those with early onset.

The present thesis emphasizes the importance of incorporating QST early in the clinical evaluation of ATTR patients with a Val30Met mutation and with symptoms of thin fiber PNP. This is particularly indicated when patients report symptoms, or show signs, of neuropathic small fiber affection, but simultaneously exhibit normal EMG and NCS findings. The results furthermore underline the importance of performing both QST and HRV for a complete evaluation of both the thin somatic and autonomic nerve fibers, as both types of nerves may be affected early in the ATTR disease.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2011. 67 p.
Umeå University medical dissertations, ISSN 0346-6612 ; 1470
Amyloidosis, cold thresholds, heart rate variability, method-of-limits, quantitative sensory testing, transthyretine, warm thresholds
National Category
Other Clinical Medicine
Research subject
Clinical Neurophysiology
urn:nbn:se:umu:diva-50617 (URN)978-91-7459-320-4 (ISBN)
Public defence
2012-01-13, Sal B (Rosa salen), by 1D, 9 tr, Norrlands Universitetssjukhus, Umeå, 09:00 (Swedish)
Available from: 2011-12-22 Created: 2011-12-15 Last updated: 2012-02-01Bibliographically approved

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