| 1. |
- Einarsdottir, Elisabet, et al.
(författare)
-
A mutation in the nerve growth factor beta gene (NGFB) causes loss of pain perception.
- 2004
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 13:8, s. 799-805
-
Tidskriftsartikel (refereegranskat)abstract
- Identification of genes associated with pain insensitivity syndromes can increase the understanding of the pathways involved in pain and contribute to the understanding of how sensory pathways relate to other neurological functions. In this report we describe the mapping and identification of the gene responsible for loss of deep pain perception in a large family from northern Sweden. The loss of pain perception in this family is characterized by impairment in the sensing of deep pain and temperature but with normal mental abilities and with most other neurological responses intact. A severe reduction of unmyelinated nerve fibers and a moderate loss of thin myelinated nerve fibers are observed in the patients. Thus the cases in this study fall into the class of patients with loss of pain perception with underlying peripheral neuropathy. Clinically they best fit into HSAN V. Using a model of recessive inheritance we identified an 8.3 Mb region on chromosome 1p11.2-p13.2 shared by the affected individuals in the family. Analysis of functional candidate genes in the disease critical region revealed a mutation in the coding region of the nerve growth-factor beta (NGFB) gene specific for the disease haplotype. This NGF mutation seems to separate the effects of NGF involved in development of central nervous system functions such as mental abilities, from those involved in peripheral pain pathways. This mutation could therefore potentially provide an important tool to study different roles of NGF, and of pain control.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Edmundsson, David, et al.
(författare)
-
Chronic exertional compartment syndrome in diabetes mellitus
- 2011
-
Ingår i: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 28:1, s. 81-85
-
Tidskriftsartikel (refereegranskat)abstract
- Aims Intermittent claudication is common in diabetes mellitus. However, a proportion of patients with diabetes have symptoms of claudication without signs of vascular disease and these patients were evaluated for chronic exertional compartment syndrome. Methods Forty-two patients with diabetes (10 men, 32 women), earlier investigated at diabetic clinics because of claudication with no explanation for the symptoms, were examined. Their median age was 48 years (18–72 years) and the median duration of diabetes was 29 years (1–45 years). Thirty-one patients had Type 1 diabetes, 11 had Type 2 diabetes and 29 had diabetic complications. All were investigated clinically, with radiography, bone scan and intramuscular pressure measurements. Results Thirty-eight of 42 patients with diabetes were diagnosed with chronic exertional compartment syndrome of the lower leg and 32 were treated surgically. Thirty-one patients were operated with fasciotomy of the anterior compartment and 18 also with fasciotomy of the posterior compartment. Additionally, one patient had only fasciotomy of the posterior compartment. Fourteen of 32 surgically treated patients (27 legs) were followed for more than 2 years and rated the post-operative outcome as excellent or good in 21 of the treated legs. The walking distance before lower leg pain increased in all but one patient and seven patients reported unrestricted walking ability. Conclusions Chronic exertional compartment syndrome should be considered as a differential diagnoses in patients with diabetes and exercise-related lower leg pain. The results after surgery are encouraging and the increased walking ability is beneficial in the treatment of diabetes.
|
|
| 5. |
- Edmundsson, David, 1956-
(författare)
-
Chronic exertional compartment syndrome of the lower leg : a novel diagnosis in diabetes mellitus: a clinical and morphological study of diabetic and non-diabetic patients
- 2010
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Chronic exertional compartment syndrome (CECS) of the lower leg, defined as a condition with exercise-induced pain due to increased intramuscular pressure (IMP), has previously mainly been described in running athletes, and etiologic factors are poorly described. CECS has not been reported to occur together with other diseases and information about consequences on muscles morphology after treatment with fasciotomy is largely unknown. We investigated etiologic and pathophysiologic aspects to CECS in a consecutive series of 63 patients with exercise-related leg pain and in 17 diabetic patients with symptoms of intermittent claudication but no circulatory insufficiency. Clinical examination, radiography, scintigraphy and IMP measurements at rest and after reproduction of symptoms were done. Patients with CECS were recommended treatment with fasciotomy. Biopsies were taken from the tibialis anterior muscle at time of fasciotomy and at follow-up 1 year later. For comparison muscle samples were taken from normal controls. Enzyme- and immunohistochemical and morphometric methods were used for analysis of muscle fiber morphology/pathology, fiber phenotype composition, mitochondrial oxidative capacity and capillary supply. Thirty-six of the 63 patients fulfilled the criteria for diagnosis of CECS in the anterior tibial compartment. The CECS patients could be divided into different etiologic groups: 18 healthy, 10 with history of trauma against the lower leg, 4 diabetic patients and 4 others. Only 5 of 36 CECS patients were athletes. The results after fasciotomy were good or excellent in 41 of 57 treated legs. Sixteen of the 17 diabetic patients were diagnosed with CECS, 11 with diabetes type 1 and 5 with type 2. The diabetic patients differed from the other groups with longer symptom-duration, shorter pain-free walking distance, firm and tender lower leg muscles and higher IMP. The postoperative outcome was good or excellent in 15 of 18 treated legs. The muscle biopsies taken at fasciotomy showed frequent histopathological changes including small and large sized fibers, fiber atrophy, internal myonuclei, split fibers, fibrosis, disorganization of mitochondria in contrast to healthy CECS subjects having low muscle capillarization as the main finding. Muscular abnormalities were generally more complex, severe and widespread in diabetic patients. After 1 year, the majority of CECS patients could return to unrestricted physical activity and the histopathological muscle changes were clearly reduced. The muscle fiber size was larger and the muscles contained signs of regeneration and repair. Remaining muscle abnormalities were present mainly in diabetic patients. CECS is a new differential-diagnosis in diabetic patients with symptoms of claudication without signs of vascular disease. A low ability for physical activity, reflected by the signs of both myopathy and neuropathy, indicates that high IMP and circulatory impairment has deleterious effects for the involved muscles. Increased physical activity and normalization of muscle morphology 1 year after treatment shows the benefit of fasciotomy. The more severe clinical and morphological findings in diabetic compared to healthy subjects with CECS indicate differences in the pathogenesis. The unrestricted physical ability after treatment is very important for diabetic patients, since physical activity is an essential part of the therapy of the disease.
|
|
| 6. |
- Edmundsson, David, 1956-, et al.
(författare)
-
Evidence for low muscle capillary supply as a pathogenic factor in chronic compartment syndrome
- 2010
-
Ingår i: Scandinavian Journal of Medicine and Science in Sports. - Copenhagen : Munksgaard. - 0905-7188 .- 1600-0838. ; 20:6, s. 805-813
-
Tidskriftsartikel (refereegranskat)abstract
- There is a paucity of data regarding the pathogenesis of chronic exertional compartment syndrome (CECS), its consequences for the muscles and the effects of treatment with fasciotomy. We analyzed biopsies from the tibialis anterior muscle, from nine patients, obtained during a decompressing fasciotomy and during follow-up 1 year later. Control biopsies were obtained from nine normal subjects. Muscle capillarity, fiber-type composition and fiber area were analyzed with enzyme- and immunohistochemistry and morphometry. At baseline, CECS patients had lower capillary density (273 vs 378 capillaries/mm(2), P=0.008), lower number of capillaries around muscle fibers (4.5 vs 5.7, P=0.004) and lower number of capillaries in relation to the muscle fiber area (1.1 vs 1.5, P=0.01) compared with normal controls. The fiber-type composition and fiber area did not differ, but focal signs of neuromuscular damage were observed in the CECS samples. At 1-year follow-up after fasciotomy, the fiber area and the number of fibers containing developmental myosin heavy chains were increased, but no enhancement of the capillary network was detected. Thus, morphologically, patients with CECS seemed to have reduced microcirculation capacity. Fasciotomy appeared to trigger a regenerative response in the muscle, however, without any increase in the capillary bed.
|
|
| 7. |
- Edmundsson, David, 1956-, et al.
(författare)
-
Intermittent claudication in diabetes mellitus due to chronic exertinal compartment syndrome of the leg : an observation study of 17 patients
- 2008
-
Ingår i: Acta Orthopaedica. - Basingstoke : Taylor & Francis. - 1745-3674 .- 1745-3682. ; 79:4, s. 534-539
-
Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Intermittent claudication in diabetes mellitus is commonly associated with arterial disease but may occur without obvious signs of peripheral circulatory impairment. We investigated whether this could be due to chronic exertional compartment syndrome (CECS). Patients and methods: We report on 17 patients (3 men), mean age 39 (18–72) years, with diabetes mellitus—12 of which were type 1—and leg pain during walking (which was relieved at rest), without clinical signs of peripheral arterial disease. The duration of diabetes was 22 (1–41) years and 12 patients had peripheral neuropathy, retinopathy, or nephropathy. The leg muscles were tender and firm on palpation. Radiography, scintigraphy, and intramuscular pressure measurements were done during exercises to reproduce their symptoms. Results: 16 of the 17 patients were diagnosed as having CECS. The intramuscular pressures in leg compartments were statistically significantly higher in diabetics than in physically active non‐diabetics with CECS (p < 0.05). 15 of the 16 diabetics with CECS were treated with fasciotomy. At surgery, the fascia was whitish, thickened, and had a rubber‐like consistency. After 1 year, 9 patients rated themselves as excellent or good in 15 of the 18 treated compartments. The walking time until stop due to leg pain increased after surgery from less than 10 min to unlimited time in 8 of 9 patients who were followed up. Interpretation: Intermittent claudication in diabetics may be caused by CECS of the leg. The intramuscular pressures were considerably elevated in diabetics. One pathomechanism may be fascial thickening. The results after fasciotomy are good, and the increased pain‐free walking time is especially beneficial for diabetics.
|
|
| 8. |
|
|
| 9. |
- Edmundsson, David S., et al.
(författare)
-
Muscle changes in patients with diabetes and chronic exertional compartment syndrome before and after treatment with fasciotomy
- 2018
-
Ingår i: Muscle and Nerve. - : John Wiley & Sons. - 0148-639X .- 1097-4598. ; 57:2, s. 229-239
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Muscle changes in patients with diabetes and lower leg pain due to chronic exertional compartment syndrome (CECS) were investigated before and after fasciotomy.Methods: The tibialis anterior muscle was analyzed with histochemical and morphological techniques in 7 patients with diabetes and CECS before fasciotomy and in 5 of them 1 year after fasciotomy. Nondiabetic patients with CECS and healthy participants served as references.Results: Before treatment, walking distance until occurrence of pain was limited (<0.2 km). Intramuscular pressure was significantly higher than in reference participants. Muscle analysis showed changes pathognomonic for neuropathy and myopathy and a restricted capillary network, with significantly more severe changes in the muscles of patients with diabetes than in the muscles of nondiabetic patients. Treatment with fasciotomy improved clinical signs, increased walking ability, and reduced muscle abnormalities, but muscle capillarization remained low.Discussion: Patients with diabetes and CECS have distinct pathological changes in affected muscles. Pressure-relieving fasciotomy triggers a regenerative response in the muscle tissue but not in the capillary bed.
|
|
| 10. |
|
|
