Umeå universitets logga

umu.sePublikationer
Ändra sökning
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • 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 universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurofysiologi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
2011 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
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.

Ort, förlag, år, upplaga, sidor
Umeå: Umeå universitet , 2011. , s. 67
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 1470
Nyckelord [en]
Amyloidosis, cold thresholds, heart rate variability, method-of-limits, quantitative sensory testing, transthyretine, warm thresholds
Nationell ämneskategori
Annan klinisk medicin
Forskningsämne
klinisk neurofysiologi
Identifikatorer
URN: urn:nbn:se:umu:diva-50617ISBN: 978-91-7459-320-4 (tryckt)OAI: oai:DiVA.org:umu-50617DiVA, id: diva2:465976
Disputation
2012-01-13, Sal B (Rosa salen), by 1D, 9 tr, Norrlands Universitetssjukhus, Umeå, 09:00 (Svenska)
Opponent
Handledare
Tillgänglig från: 2011-12-22 Skapad: 2011-12-15 Senast uppdaterad: 2018-06-08Bibliografiskt granskad
Delarbeten
1. Reproducibility and influence of test modality order on thermal perception and thermal pain thresholds in quantitative sensory testing
Öppna denna publikation i ny flik eller fönster >>Reproducibility and influence of test modality order on thermal perception and thermal pain thresholds in quantitative sensory testing
2010 (Engelska)Ingår i: Clinical Neurophysiology, ISSN 1388-2457, E-ISSN 1872-8952, Vol. 121, nr 11, s. 1878-1885Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

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

Nyckelord
Method of limits; Quantitative sensory testing; Reproducibility; Thermal pain thresholds; Thermal perception thresholds
Nationell ämneskategori
Neurovetenskaper
Identifikatorer
urn:nbn:se:umu:diva-42326 (URN)10.1016/j.clinph.2010.03.055 (DOI)000282158200012 ()20478739 (PubMedID)2-s2.0-77956935650 (Scopus ID)
Tillgänglig från: 2011-04-07 Skapad: 2011-04-07 Senast uppdaterad: 2023-03-24Bibliografiskt granskad
2. Thermal perception thresholds: reference data and response characteristics
Öppna denna publikation i ny flik eller fönster >>Thermal perception thresholds: reference data and response characteristics
(Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
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.

Nyckelord
Cold perception thresholds, Method of limits, Reference data, Stimuli response characteristics, Warm perception thresholds
Nationell ämneskategori
Neurovetenskaper
Forskningsämne
klinisk neurofysiologi
Identifikatorer
urn:nbn:se:umu:diva-50586 (URN)
Tillgänglig från: 2011-12-14 Skapad: 2011-12-14 Senast uppdaterad: 2018-06-08Bibliografiskt granskad
3. Quantified sensory abnormalities in early genetically verified transthyretin amyloid polyneuropathy
Öppna denna publikation i ny flik eller fönster >>Quantified sensory abnormalities in early genetically verified transthyretin amyloid polyneuropathy
2007 (Engelska)Ingår i: Muscle and Nerve, ISSN 0148-639X, E-ISSN 1097-4598, Vol. 35, nr 2, s. 189-195Artikel i tidskrift (Refereegranskat) Published
Nyckelord
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
Nationell ämneskategori
Neurologi
Identifikatorer
urn:nbn:se:umu:diva-10680 (URN)10.1002/mus.20689 (DOI)17094098 (PubMedID)2-s2.0-33846944682 (Scopus ID)
Tillgänglig från: 2008-10-17 Skapad: 2008-10-17 Senast uppdaterad: 2023-03-23Bibliografiskt granskad
4. Comparison of quantitative sensory testing and heart rate variability in Swedish Val30Met ATTR
Öppna denna publikation i ny flik eller fönster >>Comparison of quantitative sensory testing and heart rate variability in Swedish Val30Met ATTR
Visa övriga...
2011 (Engelska)Ingår i: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 18, nr 4, s. 183-190Artikel i tidskrift (Refereegranskat) 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.

Ort, förlag, år, upplaga, sidor
Pearl River, NY: Parthenon Pub., 2011
Nyckelord
amyloid, cold perception thresholds, early-onset, FAP, heart rate variability, late-onset, quantitative, sensory testing, transthyretin, val30met, warm perception thresholds
Nationell ämneskategori
Neurovetenskaper
Identifikatorer
urn:nbn:se:umu:diva-49187 (URN)10.3109/13506129.2011.614294 (DOI)22035563 (PubMedID)2-s2.0-81255124276 (Scopus ID)
Tillgänglig från: 2011-11-02 Skapad: 2011-11-02 Senast uppdaterad: 2023-03-24Bibliografiskt granskad

Open Access i DiVA

Avhandling (Victoria H)(2188 kB)1178 nedladdningar
Filinformation
Filnamn FULLTEXT01.pdfFilstorlek 2188 kBChecksumma SHA-512
5fdc634d72016dacd89fa3025191011e880f1c24bdd32c2a6c614f2f4c464ac892077aa3a2ece19855fc9b7f2d7b1401db9e8c73fa168a9ba5fd8a52c5abe2d6
Typ fulltextMimetyp application/pdf
errata(118 kB)80 nedladdningar
Filinformation
Filnamn ERRATA02.pdfFilstorlek 118 kBChecksumma SHA-512
b0a40b110e22bc480ea912472f17101a72ec51818b91cfe2279fe13e2ddcc5162dcffb74185185b79d49d39d9c7eff2441dc31bf2a8d6c8b42bba954799bac1a
Typ errataMimetyp application/pdf

Person

Heldestad, Victoria

Sök vidare i DiVA

Av författaren/redaktören
Heldestad, Victoria
Av organisationen
Klinisk neurofysiologiMedicin
Annan klinisk medicin

Sök vidare utanför DiVA

GoogleGoogle Scholar
Totalt: 1180 nedladdningar
Antalet nedladdningar är summan av nedladdningar för alla fulltexter. Det kan inkludera t.ex tidigare versioner som nu inte längre är tillgängliga.

isbn
urn-nbn

Altmetricpoäng

isbn
urn-nbn
Totalt: 1715 träffar
RefereraExporteraLänk till posten
Permanent länk

Direktlänk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf