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  • 1.
    Edmundsson, David
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Svensson, Olle
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Toolanen, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Intermittent claudication in diabetes mellitus due to chronic exertinal compartment syndrome of the leg: an observation study of 17 patients2008In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 79, no 4, p. 534-539Article in journal (Refereed)
    Abstract [en]

    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.

  • 2.
    Edmundsson, David
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Toolanen, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Chronic exertional compartment syndrome in diabetes mellitus2011In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 28, no 1, p. 81-85Article in journal (Refereed)
    Abstract [en]

    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.

  • 3.
    Edmundsson, David
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Toolanen, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Muscle changes in diabetics with chronic compartment syndromeManuscript (preprint) (Other academic)
  • 4.
    Edmundsson, David
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Toolanen, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Thornell, Lars-Eric
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Stål, Per
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Evidence for low muscle capillary supply as a pathogenic factor in chronic compartment syndrome2010In: Scandinavian Journal of Medicine and Science in Sports, ISSN 0905-7188, E-ISSN 1600-0838, Vol. 20, no 6, p. 805-813Article in journal (Refereed)
    Abstract [en]

    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.

  • 5.
    Einarsdottir, Elisabet
    et al.
    Umeå University, Faculty of Medicine, Medical Biosciences, Medical and Clinical Genetics.
    Carlsson, Anna
    Umeå University, Faculty of Medicine, Medical Biosciences, Medical and Clinical Genetics.
    Minde, Jan
    Toolanen, Göran
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Orthopaedics.
    Svensson, Olle
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Orthopaedics.
    Solders, Göran
    Holmgren, Gösta
    Umeå University, Faculty of Medicine, Medical Biosciences, Medical and Clinical Genetics.
    Holmberg, Dan
    Umeå University, Faculty of Medicine, Medical Biosciences, Medical and Clinical Genetics.
    Holmberg, Monica
    Umeå University, Faculty of Medicine, Medical Biosciences, Medical and Clinical Genetics.
    A mutation in the nerve growth factor beta gene (NGFB) causes loss of pain perception.2004In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 13, no 8, p. 799-805Article in journal (Refereed)
    Abstract [en]

    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.

  • 6.
    Guez, Michel
    et al.
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Orthopaedics.
    Brännström, Rigmor
    Umeå University, Faculty of Medicine, Pharmacology and Clinical Neuroscience, Neurology.
    Nyberg, Lars
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Toolanen, Göran
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Orthopaedics.
    Hildingsson, Christer
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Orthopaedics.
    Neuropsychological functioning and MMPI-2 profiles in chronic neck pain: a comparison of whiplash and non-traumatic groups.2005In: Journal of Clinical and Experimental Neuropsychology, ISSN 1380-3395, E-ISSN 1744-411X, Vol. 27, no 2, p. 151-163Article in journal (Refereed)
  • 7.
    Guez, Michel
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Hildingsson, Christer
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Nilsson, Marie
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Toolanen, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    The prevalence of neck pain: A population-based study from northern Sweden2002In: Acta Orthopaedica Scandinavica, ISSN 0001-6470, Vol. 73, no 4, p. 455-459Article in journal (Refereed)
    Abstract [en]

    The two northernmost counties in Sweden form together 1 of the 39 collaborating centers in the World Health Organization (WHO) MONICA (MONItoring of trends and determinants in CArdiovascular disease) project. At the last survey in 1999, we added some questions about cervical spine complaints. Persons randomly selected from the population in a geographically well-defined area completed a self-administered questionnaire. The sample included 8,356 subjects and 6,000 (72%) of them answered. 43% of the population reported neck pain, more women (48%) than men (38%). Women of working age had more neck pain than older ones, a phenomenon not seen among men. Chronic neck pain, defined as continuous pain of more than 6 months' duration, was commoner in women (22%) than men (16%).More than one fourth of the cases with chronic symptoms had a history of neck or head trauma and one third of these had sustained a whiplash type of injury. Thus, all types of neck trauma seem to be associated with chronic neck pain.

  • 8.
    Gustafsson, Patrik
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Crenshaw, Albert G.
    Edmundsson, David
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Toolanen, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Crnalic, Sead
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Muscle oxygenation in Type 1 diabetic and non-diabetic patients with and without chronic compartment syndrome2017In: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 12, no 10, article id e0186790Article in journal (Refereed)
    Abstract [en]

    Background: Type 1 diabetic patients and non-diabetic patients were referred for evaluation for chronic exertional compartment syndrome (CECS) based on clinical examination and complaints of activity-related leg pain in the region of the tibialis anterior muscle. Previous studies using near-infrared spectroscopy (NIRS) showed greater deoxygenation during exercise for CECS patients versus healthy controls; however, this comparison has not been done for diabetic CECS patients. Methods: We used NIRS to test for differences in oxygenation kinetics for Type 1 diabetic patients diagnosed with (CECS-diabetics, n = 9) versus diabetic patients without (CON-diabetics, n = 10) leg anterior chronic exertional compartment syndrome. Comparisons were also made between non-diabetic CECS patients (n = 11) and healthy controls (CON, n = 10). The experimental protocol consisted of thigh arterial cuff occlusion (AO, 1-minute duration), and treadmill running to reproduce symptoms. NIRS variables generated were resting StO(2)%, and oxygen recovery following AO. Also, during and following treadmill running the magnitude of deoxygenation and oxygen recovery, respectively, were determined. Results: There was no difference in resting StO2% between CECS-diabetics (78.2 +/- 12.6%) vs. CON-diabetics (69.1 +/- 20.8%), or between CECS (69.3 +/- 16.2) vs. CON (75.9 +/- 11.2%). However, oxygen recovery following AO was significantly slower for CECS (1.8 +/- 0.8%/sec) vs. CON (3.8 +/- 1.7%/sec) (P = 0.002); these data were not different between the diabetic groups. StO2% during exercise was lower (greater deoxygenation) for CECS-diabetics (6.3 +/- 8.6%) vs. CON-diabetics (40.4 +/- 22.0%), and for CECS (11.3 +/- 16.8%) vs. CON (34.1 +/- 21.2%) (P<0.05 for both). The rate of oxygen recovery post exercise was faster for CECS-diabetics (3.5 +/- 2.6%/sec) vs. CON-diabetics (1.4 +/- 0.8%/sec) (P = 0.04), and there was a tendency of difference for CECS (3.1 +/- 1.4%/sec) vs. CON (1.9 +/- 1.3%/sec) (P = 0.05). Conclusion: The greater deoxygenation during treadmill running for the CECS-diabetics group (vs. CON-diabetics) is in line with previous studies (and with the present study) that compared non-diabetic CECS patients with healthy controls. Our findings could suggest that NIRS may be useful as a diagnostic tool for assessing Type 1 diabetic patients suspected of CECS.

  • 9.
    Minde, Jan
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Andersson, T
    Department of Clinical Neuroscience Section of Neurophysiology, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden .
    Fulford, M
    Department of Internal Medicine, Gällivare Hospital, Gällivare, Sweden.
    Aguirre, M
    Department of Clinical Neuroscience Section of Neurophysiology, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden .
    Nennesmo, I
    Department of Pathology, Karolinska University Hospital, Stockholm, Sweden.
    Remahl, I Nilsson
    Department of Neurology, Karolinska University Hospital, Stockholm, Sweden.
    Svensson, Olle
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Holmberg, Monica
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Medical and Clinical Genetics.
    Toolanen, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
    Solders, G
    Department of Clinical Neuroscience Section of Neurophysiology, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden .
    A novel NGFB point mutation: a phenotype study of heterozygous patients2009In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 80, no 2, p. 188-195Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: A family with neurological findings similar to hereditary sensory and autonomic neuropathy type V having a point mutation in the nerve growth factor beta (NGFB) gene was recently described. The homozygous genotype gives disabling symptoms. The purpose of the present study was to evaluate the symptoms in heterozygous patients. METHODS: 26 patients heterozygous for the NGFB mutation (12 men, mean age 50 (13-90) years) were examined clinically and answered a health status questionnaire, including the Michigan Neuropathy Screening Instrument (MNSI). 28 relatives (15 men, mean age 44 (15-86) years) without the mutation served as controls in the clinical examination part. 23 of the heterozygotes were examined neurophysiologically and six heterozygous patients underwent a sural nerve biopsy. RESULTS: The heterozygous phenotype ranged from eight patients with Charcot arthropathy starting in adult age and associated with variable symptoms of neuropathy but without complete insensitivity to pain, anhidrosis or mental retardation, to 10 symptom free patients. There was no difference in MNSI between the young heterozygous cases (<55 years old) and the controls. Six of 23 heterozygous patients had impaired cutaneous thermal perception and 11 of 23 had signs of carpal tunnel syndrome. Sural nerve biopsies showed a moderate reduction of both small myelinated (Adelta) and unmyelinated (C) fibres. No apparent correlation of small fibre reduction to symptoms was found. CONCLUSIONS: The NGFB mutation in its heterozygous form results in a milder disease than in homozygotes, with a variable clinical picture, ranging from asymptomatic cases to those with Charcot arthropathy appearing in adult age. Particularly age, but perhaps lifestyle factors also, may influence the development of clinical polyneuropathy.

  • 10.
    Minde, Jan
    et al.
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Orthopaedics.
    Svensson, Olle
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Orthopaedics.
    Holmberg, Monica
    Umeå University, Faculty of Medicine, Medical Biosciences, Medical and Clinical Genetics.
    Solders, Göran
    Toolanen, Göran
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Orthopaedics.
    Orthopedic aspects of familial insensitivity to pain due to a novel nerve growth factor beta mutation.2006In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 77, no 2, p. 198-202Article in journal (Refereed)
  • 11.
    Minde, Jan
    et al.
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Orthopaedics.
    Toolanen, Göran
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Orthopaedics.
    Andersson, Thomas
    Nennesmo, Inger
    Remahl, Ingela Nilsson
    Svensson, Olle
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Orthopaedics.
    Solders, Göran
    Familial insensitivity to pain (HSAN V) and a mutation in the NGFB gene. A neurophysiological and pathological study.2004In: Muscle and Nerve, ISSN 0148-639X, E-ISSN 1097-4598, Vol. 30, no 6, p. 752-760Article in journal (Refereed)
  • 12.
    Pettersson, Kurt
    et al.
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Orthopaedics.
    Brändström, Sven
    Toolanen, Göran
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Orthopaedics.
    Hildingsson, Christer
    Umeå University, Faculty of Medicine, Surgical and Perioperative Sciences, Orthopaedics.
    Nylander, Per-Olof
    Temperament and character: prognostic factors in whiplash patients?2004In: European spine journal, ISSN 0940-6719, E-ISSN 1432-0932, Vol. 13, no 5, p. 408-14Article in journal (Refereed)
  • 13.
    Sundström, Torbjörn
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Guez, Michel
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Hildingsson, Christer
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Toolanen, Göran
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Nyberg, Lars
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Altered cerebral blood flow in chronic neck pain patients but not in whiplash patients: a 99mTc-HMPAO rCBF study2006In: European spine journal, ISSN 0940-6719, E-ISSN 1432-0932, Vol. 15, no 8, p. 1189-1195Article in journal (Refereed)
    Abstract [en]

    A cross-sectional study to investigate regional cerebral blood flow (rCBF) in patients with chronic whiplash syndrome and chronic neck pain patients without previous history of trauma along with a healthy control group. Chronic neck pain is a common disorder and a history of cervical spine injury including whiplash trauma constitute a risk factor for persistent neck pain. The aetiology of the late whiplash syndrome is unknown with no specific diagnostic criteria based on imaging, physiological, or psychological examination. Earlier studies indicate a parieto-occipital hypoperfusion but it is unclear if the hypoperfusion represents a response to chronic pain. The rCBF was monitored in 45 patients with chronic neck pain: 27 cases with chronic whiplash syndrome and 18 age and gender matched cases with non-traumatic chronic neck pain. The rCBF was estimated with single-photon emission computed tomography (SPECT) using technetium-99m hexamethylpropylene amine oxime (HMPAO). The non-traumatic patients displayed rCBF changes in comparison with the whiplash group and the healthy control group. These changes included rCBF decreases in a right temporal region close to hippocampus, and increased rCBF in left insula. The whiplash group displayed no significant differences in rCBF in comparison with the healthy controls. The present study suggests different pain mechanisms in patients with chronic neck pain of non-traumatic origin compared to those with chronic neck pain due to a whiplash trauma.

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