umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Methodological aspects and usefulness of Quantitative Sensory Testing in early small fiber polyneuropathy: a clinical study in Swedish hereditary transthyretin amyloidosis patients
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neurophysiology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
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.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1470
Keyword [en]
Amyloidosis, cold thresholds, heart rate variability, method-of-limits, quantitative sensory testing, transthyretine, warm thresholds
National Category
Other Clinical Medicine
Research subject
Clinical Neurophysiology
Identifiers
URN: urn:nbn:se:umu:diva-50617ISBN: 978-91-7459-320-4 (print)OAI: oai:DiVA.org:umu-50617DiVA: diva2:465976
Public defence
2012-01-13, Sal B (Rosa salen), by 1D, 9 tr, Norrlands Universitetssjukhus, Umeå, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2011-12-22 Created: 2011-12-15 Last updated: 2012-02-01Bibliographically approved
List of papers
1. Reproducibility and influence of test modality order on thermal perception and thermal pain thresholds in quantitative sensory testing
Open this publication in new window or tab >>Reproducibility and influence of test modality order on thermal perception and thermal pain thresholds in quantitative sensory testing
2010 (English)In: Clinical Neurophysiology, ISSN 1388-2457, E-ISSN 1872-8952, Vol. 121, no 11, 1878-1885 p.Article in journal (Refereed) Published
Abstract [en]

The findings show that QST with the MLI is a reliable tool for indirect evaluation of human small nerve fiber function.

Keyword
Method of limits; Quantitative sensory testing; Reproducibility; Thermal pain thresholds; Thermal perception thresholds
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-42326 (URN)10.1016/j.clinph.2010.03.055 (DOI)000282158200012 ()20478739 (PubMedID)
Available from: 2011-04-07 Created: 2011-04-07 Last updated: 2017-12-11Bibliographically approved
2. Thermal perception thresholds: reference data and response characteristics
Open this publication in new window or tab >>Thermal perception thresholds: reference data and response characteristics
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Objective: To establish reference data for separate cold and warm perception thresholds at quantitative sensory testing with the method-of-limits at eight different body regions, and to evaluate the psychophysical response characteristics to consecutive cold and warm stimuli.

Methods: 75 healthy subjects were tested at the dorsum of the foot, the medial and lateral lower leg, the ventral thigh, the thenar eminence, the radial and ulnar part of the lower arm, and the anterior deltoid part of the upper arm. Thermal perception thresholds were assessed with the method of limits, and estimated from the average responses during ten consecutive cold and warm stimuli.

Results: At all tested sites, the TPT were significantly higher in the lower part of the body compared to the upper, and also the warm thresholds were significantly higher than the cold thresholds. Inconsistent correlations were noted between thermal perception thresholds and age or height, but thresholds at the dorsal foot were highly correlated with age.

Conclusions: Reference data from separate body regions in the lower and upper extremities are essential for adequate evaluation of thermal detection and perception capacity. At testing of thermal thresholds in individual subjects the thermal perception generally decreases distally in elderly and particularly in the lower extremities.

Keyword
Cold perception thresholds, Method of limits, Reference data, Stimuli response characteristics, Warm perception thresholds
National Category
Neurosciences
Research subject
Clinical Neurophysiology
Identifiers
urn:nbn:se:umu:diva-50586 (URN)
Available from: 2011-12-14 Created: 2011-12-14 Last updated: 2011-12-22Bibliographically approved
3. Quantified sensory abnormalities in early genetically verified transthyretin amyloid polyneuropathy
Open this publication in new window or tab >>Quantified sensory abnormalities in early genetically verified transthyretin amyloid polyneuropathy
2007 (English)In: Muscle and Nerve, ISSN 0148-639X, E-ISSN 1097-4598, Vol. 35, no 2, 189-195 p.Article in journal (Refereed) Published
Keyword
Adult, Age Factors, Amyloid Neuropathies/*complications/genetics, Female, Humans, Male, Methionine/genetics, Peripheral Nerves/*physiopathology, Prealbumin/genetics, Sensory Thresholds/*physiology, Somatosensory Disorders/*etiology/genetics, Temperature, Valine/genetics
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-10680 (URN)10.1002/mus.20689 (DOI)17094098 (PubMedID)
Available from: 2008-10-17 Created: 2008-10-17 Last updated: 2017-12-14Bibliographically approved
4. Comparison of quantitative sensory testing and heart rate variability in Swedish Val30Met ATTR
Open this publication in new window or tab >>Comparison of quantitative sensory testing and heart rate variability in Swedish Val30Met ATTR
Show others...
2011 (English)In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, 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
Keyword
amyloid, cold perception thresholds, early-onset, FAP, heart rate variability, late-onset, quantitative, sensory testing, transthyretin, val30met, warm perception thresholds
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-49187 (URN)10.3109/13506129.2011.614294 (DOI)22035563 (PubMedID)
Available from: 2011-11-02 Created: 2011-11-02 Last updated: 2017-12-08Bibliographically approved

Open Access in DiVA

Avhandling (Victoria H)(2188 kB)645 downloads
File information
File name FULLTEXT01.pdfFile size 2188 kBChecksum SHA-512
5fdc634d72016dacd89fa3025191011e880f1c24bdd32c2a6c614f2f4c464ac892077aa3a2ece19855fc9b7f2d7b1401db9e8c73fa168a9ba5fd8a52c5abe2d6
Type fulltextMimetype application/pdf
errata(118 kB)39 downloads
File information
File name ERRATA02.pdfFile size 118 kBChecksum SHA-512
b0a40b110e22bc480ea912472f17101a72ec51818b91cfe2279fe13e2ddcc5162dcffb74185185b79d49d39d9c7eff2441dc31bf2a8d6c8b42bba954799bac1a
Type errataMimetype application/pdf

Search in DiVA

By author/editor
Heldestad, Victoria
By organisation
Clinical NeurophysiologyMedicine
Other Clinical Medicine

Search outside of DiVA

GoogleGoogle Scholar
Total: 645 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 925 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf