Osteosclerosis associated with hepatitis C.

We describe the first Finnish case of hepatitis C associated osteosclerosis. In which the patient's bone symptoms and bone density were resolved with hepatitis C treatment. Suspecting the possibility of osteosclerosis underlying bone pains in a hepatitis C patient is well-founded, although osteoporotic fractures are a more common problem.

Decreased Aerobic Capacity in ANO5-Muscular Dystrophy.

BACKGROUND: Anoctaminopathies are muscle diseases caused by recessive mutations in the ANO5 gene. The effects of anoctaminopathy on oxidative capacity have not previously been studied in a controlled setting. OBJECTIVE: To characterize oxidative capacity in a clinically and genetically well-defined series of patients with anoctaminopathy. METHODS: We sequenced the ANO5 gene in 111 Finnish patients with suspected LGMD2. Patients with positive findings underwent close clinical examination, including electromyography, muscle MRI, and, in selected cases, muscle biopsy. Oxidative capacity was analyzed using spiroergometry and compared to age-matched healthy controls. RESULTS: We characterized 12 newly identified and 2 previously identified patients with ANO5 mutations from 11 families. Our material was genetically homogeneous with most patients homozygous for the Finnish founder variant c.2272C>T (p.Arg758Cys). In one family, we found a novel p.Met470Arg variant compound heterozygous with p.Arg758Cys. Lower limb muscle MRI revealed progressive fatty degeneration of specific posterior compartment muscles. Patients' spiroergometric profiles showed that anoctaminopathy significantly impaired oxidative capacity with increasing ventilation. CONCLUSIONS: Our findings support earlier reports that anoctaminopathy progresses slowly and demonstrate that the disease impairs the capacity for aerobic exercise.

Selective pattern of muscle involvement seen in distal muscular dystrophy associated with anoctamin 5 mutations: a follow-up muscle MRI study.

Anoctaminopathy is a new muscular dystrophy caused by mutations in the ANO5 gene. ANO5 mutations cause distal and proximal phenotypes. We report here a follow-up muscle MRI study on five patients affected by distal form of anoctaminopathy. T1 weighted scans showed subsequent involvement of gastrocnemius medialis and soleus, hip adductors, hamstrings, gastrocnemius lateralis and quadriceps muscles, and later on tensor fascia lata, gluteus minimus and biceps brachii muscles, respectively. The STIR weighted images showed in the early stages widely distributed hyperintense signals, myoedema, in the adductors, hamstrings, and quadriceps muscles, which at that time have normal T1 signals. All patients showed asymmetry of muscle involvement both clinically and on muscle imaging. The progression of muscle involvement was relatively slow. We conclude that the pattern of muscle involvement seen in patients with distal myopathy with anoctamin 5 mutations (MMD3) is typical and can thus be useful during the differential diagnosis process allowing for a more targeted molecular approach.

[Chest, skin and joint symptoms of a middle-aged man]. / Keski-ikäisen miehen rintakehä- iho- ja niveloireet.

A middle-aged male patient was examined due to chest pain. At the same time blisters appeared on his palms and soles of the foot. Radiologic examinations revealed lesions in the thoracic vertebral bodies, in the first rib and in the sternum. Inflammatory markers were elevated in the blood. The patient subsequently developed arthritis in a previously injured knee.

[Thirst and extensive bone lesions in a previously basically healthy woman]. / Aiemmin terveen naisen jano ja laaja-alaiset luustomuutokset.

A previously quite healthy 65-year-old woman sought emergency hospital care due to fatigue, weight loss and sensation of thirst appearing over a couple of months. Further analysis revealed a process affecting the neurohypophysis and extensive lytic sclerotic bone lesions. Eventually a rare generalized underlying disease was unraveled: the diagnosis included both Langerhans cell histiocytosis and Erdheim-Chester disease.

Treatment of shoulder sequelae in brachial plexus birth injury.

BACKGROUND: Many children with permanent brachial plexus birth injury (BPBI) develop shoulder problems, with subsequent joint deformity without treatment. We assessed the indications and outcome of shoulder operations for BPBI. PATIENTS AND METHODS: 31 BPBI patients who had undergone a shoulder operation in our hospital between March 2002 and December 2005 were included in the study. Relocation of the humeral head had been performed in 13 patients, external rotation osteotomy of the humerus in 5 patients, subscapular tendon lengthening in 5 patients, and teres major transposition in 8 patients. Subjective results were registered. Shoulder range of motion was measured, and function assessed according to the Mallet scale. Magnetic resonance imaging (MRI) was performed pre- and postoperatively. Glenoscapular angle (GSA) and percentage of humeral head anterior to the middle of the glenoid fossa (PHHA) were measured. Congruency of the glenohumeral joint (GHJ) was estimated. The mean follow-up time was 3.8 (1.7-6.8) years. RESULTS: At follow-up, the subjective result was satisfactory in 30 of the 31 patients. There were 4 failures, which in retrospect were due to wrong choice of surgical method in 3 of these 4 patients. Mean increase in Mallet score was 5.5 after successful relocation, 1.4 after rotation osteotomy, 2.2 after subscapular tendon lengthening, and 3.1 after teres major transposition. Congruency of the shoulder joint improved in 10 of 13 patients who had undergone a relocation operation, with mean improvement in GSA of 33º and mean increase in PHHA of 25%. There were no substantial changes in congruency of the glenohumeral joint in patients treated with other operation types. INTERPRETATION: Restriction of the range of motion and malposition of the glenohumeral joint can be improved surgically in brachial plexus birth injury. Remodeling of the joint takes place after successful relocation of the humeral head in young patients.

Parathyroid hormone treatment improves pain and fracture healing in adult hypophosphatasia.

INTRODUCTION: Adult hypophosphatasia (HPP) is characterized by low serum alkaline phosphatase (S-ALP) and poorly healing fractures due to ALPL gene mutations. Increased S-ALP and fracture repair were reported in two patients treated with teriparatide, PTH 1-34. The effects of full-length PTH 1-84 have not been studied. METHODS: Two 56- and 64-yr-old sisters (patients 1 and 2) with HPP and with long-standing, painful femur fractures received PTH 1-84 (Preotact, 100 µg/d sc) for 7 and 18 months, respectively. Patient 1 had another treatment 8 months later because of new femur fractures. We characterized the underlying mutation(s) and treatment effects according to S-ALP, bone markers, serum ionized calcium, plasma phosphate (P-Pi), pain, mobility, and fracture healing. RESULTS: Both patients were compound heterozygotes for a p.G339R and p.E191K ALPL mutation. S-ALP increased significantly, 4.9- and 6.8-fold in patient 1 and 2.7-fold in patient 2. Responses decreased at 6 months but remained higher than basal activity. Serum N-terminal propeptide of type I procollagen and urinary N-telopeptide of type I collagen increased 14- to 19-fold and 9-5-fold in patient 1, respectively, and 9- and 3-fold in patient 2. P-Pi fluctuated in patient 1 and increased in patient 2. Pain and mobility improved promptly. Fractures healed after 7-8 months of treatment in patient 1 and at 15 months in patient 2. CONCLUSION: PTH 1-84 improves pain, mobility, and fracture repair in adult HPP, even after repeat treatment. Residual activity of the p.E191K ALPL gene mutation could explain why PTH can stimulate S-ALP. P-Pi concentrations may modulate the response.

A new distal myopathy with mutation in anoctamin 5.

We have been following clinically and with muscle MRI for the past 3-decades a Finnish family with two patients with distal muscular dystrophy. Previously we demonstrated the cellular defect in these patients to be defective membrane repair and more recently have identified the causative gene to be anoctamin 5 (ANO5). The disorder seen in these patients is characterized by onset in the third decade. First symptoms were burning sensation on the calves and later on calf tightness during running. Muscle weakness and wasting were asymmetric and early involving the calf muscles, later spread to the thigh muscles. Biceps brachi was later manifestation. Clinical course was slow. CK levels were high. Muscle biopsy showed dystrophic pattern and multifocal disruption of the sarcolemmal membrane but no subsarcolemmal vesicle accumulation nor active inflammation. We conclude that the disease seen in our cases is a new separate clinical, genetic and histopathologic entity to include within the classification of autosomal recessive distal muscular dystrophies.

Brachial plexus birth injury: US screening for glenohumeral joint instability.

PURPOSE: To prospectively evaluate the use and optimal timing of ultrasonographic (US) screening for posterior shoulder subluxation in infantswith brachial plexus birth injury (BPBI). MATERIALS AND METHODS: Approval of the ethics committee and informed consent of guardians was obtained. This population-based prospective study included neonates with BPBI who were born in Helsinki from January 1, 2003 through December 31, 2006, and in whom BPBI was verified with sequential clinical examinations. US was performed at 1, 3, 6, and 12 months. Size (width and height) of the humeral head and its ossification center and congruency of the shoulder (alpha angle) were measured. Frequency of BPBI and permanent changes were evaluated. This study also included patients who were referred from the tertiary catchment area. For statistical analysis, 95% confidence intervals were calculated, and analysis of variance was performed. RESULTS: BPBI was seen in 132 of 41980 neonates (3.1 per 1000). In 27 cases (0.64 per 1000), BPBI did not heal during the 1st year of life and was considered permanent. The humeral head and its ossification center were smaller on the affected side in permanent BPBI. Nine patients with permanent palsy had posterior subluxation of the humeral head depicted with US (alpha angle, >30 degrees ). In five patients, posterior subluxation [corrected] was detected at 3 months. Nineteen of 21 patients with BPBI from the tertiary catchment area had permanent palsy. Ten of 19 patients developed posterior subluxation of the shoulder, which was verified with US. Altogether, three of these cases were not detected by surgeons. Posterior subluxation of the humeral head developed during the 1st year of life in one-third of patients with permanent BPBI. In more than one-half (55% [five of nine]) of the patients, posterior subluxation [corrected] was detected with US at 3 months, and in 89% (eight of nine), it was detected at 6 months. CONCLUSION: US is a fast and useful tool for diagnosis of posterior subluxation of the humeral head, and examination of the glenohumeral joint should be performed at 3 and 6 months of age in infants with BPBI if symptoms persist.

Arthroscopic resection of medial plica of the knee in young adults.

The purpose of this study was to evaluate the long-term results of arthroscopic resection of a medial plica and to describe the usefulness of the clinical findings and MRI for preoperative diagnostics. From the baseline population of 172,777 military conscripts, thirty-three consecutive young adult patients with normal preoperative MRIs of the knee and a sole postoperative diagnosis of medial plica were treated with arthroscopic plica resection. Functional outcome was evaluated at a final follow-up in 25 patients with 34 knees with Kujala, Lysholm and visual analog scale (VAS) scores. Functional results were excellent to good in 17 patients, fair in three patients, and poor in 3 patients. The median Kujala score was 92 (25-100), the median Lysholm score 89 (26-100), and the median VAS 1.4 (0-8.8). Median follow-up time was 6.6 years (3.6-8.7 years). Most patients had no history of direct knee trauma preceding the symptoms. No statistically significant correlation was seen between MRI classification of the plica size or clinical findings compared to arthroscopic classification. Resection of the medial plica in a symptomatic knee has good to excellent functional long-term outcome in the majority of cases, and the procedure is not associated with postoperative complications. MRI and preoperative clinical examination seem to be unreliable in detecting medial plicae.

Severe ataxia with neuropathy in hereditary gelsolin amyloidosis.

Hereditary gelsolin amyloidosis (AGel amyloidosis) is a systemic disorder caused by a G654A or G654T gelsolin mutation, reported from Europe, North America, and Japan. Principal clinical signs are corneal lattice dystrophy, cutis laxa and cranial neuropathy, often deleterious at advanced age. Peripheral neuropathy, if present, is usually mild. We report a 78- year old male Finnish patient who presented with ataxia and mainly sensory peripheral polyneuropathy (PNP) signs, causing severe disability and ambulation loss. Electrophysiological studies showed severe generalized chronic mainly axonal sensorimotor PNP with facial paralysis. In magnetic resonance imaging proximal lower limb and axial muscle atrophy with fatty degeneration as well as moderate spinal cord atrophy were seen. A G654A gelsolin mutation was demonstrated but no other possible causes of his disability were found. At age 79 he became bedridden and died of pulmonary embolism. Neuropathological examination revealed marked gelsolin amyloid deposition at vascular and connective tissue sites along the entire length of the peripheral nerves extending to the spinal nerve roots, associated with severe degeneration of nerve fibers and posterior columns. Our report shows that advanced AGel amyloidosis due to degeneration of central and distal sensory nerve projections results in deleterious ataxia with fatal outcome. Severe posterior column atrophy may reflect radicular AGel deposition, although even altered gelsolin - actin interactions in neural cells possibly contribute to neurodegeneration with successive ataxia in carriers of a G654A gelsolin mutation.

A novel mutation of the GAA gene in a Finnish late-onset Pompe disease patient: clinical phenotype and follow-up with enzyme replacement therapy.

Pompe disease is a rare, progressive disease leading to skeletal muscle weakness due to deficiency of the acid alpha-glucosidase (GAA) enzyme. Herein we report the first diagnosed Finnish patient with a phenotype compatible with the late-onset form of Pompe disease. Molecular genetic analysis of the GAA gene revealed a novel missense mutation, 1725C>A (Y575X), combined with a previously reported mutation, 1634C>T (P545L). Human recombinant alpha-glucosidase enzyme (alglucosidase-alpha) treatment was initiated for this patient at age 20 years. After 12 months she was no longer fully wheelchair-bound, and muscle strength had improved. No disease progression was visible on muscle magnetic resonance imaging of the lower limbs, and the energy state of the muscle cells increased by 46% on phosphorus magnetic resonance spectroscopy. Overall, our findings suggest that enzyme replacement therapy is indicated, even in patients with late-onset Pompe disease, to halt disease progression and improve the quality of daily life.

Magnetic resonance imaging in occupational chronic solvent encephalopathy.

PURPOSE: The aim of this study was to characterize the magnetic resonance imaging (MRI) findings in chronic solvent encephalopathy (CSE) patients and to study whether the findings are associated with solvent exposure indices. METHODS: The brain MRI scans of 71 CSE patients were independently re-evaluated and rated by two experienced neuroradiologists. All the work tasks were analyzed and the chemical composition of lifetime exposure was categorized. RESULTS: The MRI scans of 27/71 CSE patients (38%) were classified as abnormal. Brain atrophy in any brain area was found in 17/71 CSE patients (24%). Abnormal white matter hyperintensities (WMH) were found in 20/71 CSE patients (28%). Cerebral and cerebellar brain atrophy was associated with the duration of exposure in years, and vermian atrophy was associated with alcohol consumption. Periventricular and brainstem WMH were related to age. CONCLUSIONS: Slight brain atrophy is associated with CSE and there is a correlation between brain atrophy and the duration of exposure in years. However, all the MRI findings in CSE are non-specific and thus MRI is useful mainly in the differential diagnosis of CSE.

Spinal MRI in fighter pilots and controls: a 13-year longitudinal study.

INTRODUCTION: Although it is known that some degenerative changes occur in the spines of fighter pilots, it is not clear whether their frequent exposure to high acceleration is associated with premature development of such changes. This case-control study was designed help answer that question. METHODS: There were 12 Finnish Air Force pilot cadets and their controls who were examined using cervical and lumbar magnetic resonance imaging (MRI) before the pilots started fighter training (baseline) and 13 yr later (follow-up) when the pilots had accumulated a total of 1200 +/- 470 h in fighter aircraft. RESULTS: No statistical differences were found between groups with respect to the frequency of degenerative changes in either the cervical or lumbar spine. Cervical changes in pilots were for the most part observed in the lower part of the neck, while controls showed more variability as to location. In the lumbar region, pilots showed a non-significant tendency toward more changes in disks L4-S1, including changes in signal intensity, height, protrusions, and end plates. CONCLUSION: Occupational exposure to acceleration in fighter aircraft did not cause significant radiological changes in the spinal column during the first 13 yr of a fighter pilot's flying career. Assessments for the need of a fighter pilot's follow-up imaging should be based on clinical outcome, not on periodic imaging.

Severe ataxia with neuropathy in hereditary gelsolin amyloidosis: a case report.

Hereditary gelsolin amyloidosis (AGel amyloidosis) is a systemic disorder caused by a G654A or G654T gelsolin mutation, reported from Europe, North America, and Japan. Principal clinical signs are corneal lattice dystrophy, cutis laxa and cranial neuropathy, often deleterious at advanced age. Peripheral neuropathy, if present, is usually mild. We report a 78-year-old male Finnish patient who presented with ataxia and mainly sensory peripheral polyneuropathy (PNP) signs, causing severe disability and ambulation loss. Electrophysiological studies showed severe generalized chronic mainly axonal sensorimotor PNP with facial paralysis. In magnetic resonance imaging proximal lower limb and axial muscle atrophy with fatty degeneration as well as moderate spinal cord atrophy were seen. A G654A gelsolin mutation was demonstrated but no other possible causes of his disability were found. At age 79 years he became bedridden and died of pulmonary embolism. Neuropathological examination revealed marked gelsolin amyloid deposition at vascular and connective tissue sites along the entire length of the peripheral nerves extending to the spinal nerve roots, associated with severe degeneration of nerve fibers and posterior columns. Our report shows that advanced AGel amyloidosis due to degeneration of central and distal sensory nerve projections results in deleterious ataxia with fatal outcome. Severe posterior column atrophy may reflect radicular AGel deposition, although even altered gelsolin-actin interactions in neural cells possibly contribute to neurodegeneration with successive ataxia in carriers of a G654A gelsolin mutation.

Muscle changes in brachial plexus birth injury with elbow flexion contracture: an MRI study.

BACKGROUND: Muscle pathology of the arm and forearm in brachial plexus birth injury (BPBI) with elbow flexion contracture has not been evaluated with MRI. OBJECTIVE: To determine whether limited range of motion of the elbow in BPBI is correlated with specific patterns of muscular pathology. MATERIALS AND METHODS: For 15 BPBI patients, total active motion (TAM) of the elbow (extension-flexion) and the forearm (pronation-supination) were measured. MRI of the elbow joints and musculature allowed assessment of elbow congruency. Fatty infiltration and size reduction of the muscles were graded semiquantitatively. RESULTS: Mean TAM of the elbow was 113 degrees (50 degrees-140 degrees) and that of the forearm 91 degrees (10 degrees-165 degrees). The greater the size reduction of the brachioradialis muscle, the more diminished was elbow TAM. The more extensive the BPBI and muscle pathology of the pronator teres muscle, the more limited was the TAM of the forearm. Pathology of the supinator and brachialis muscles was evident in every patient. CONCLUSION: Extensive BPBI may result in marked limitation of TAM. Elbow flexion contracture seems to be caused mainly by brachialis muscle pathology. Prosupination of the forearm is better preserved when the pronator teres is not severely affected. MRI can reliably show the extent of muscle pathology in BPBI.

MRI of rotator cuff muscle atrophy in relation to glenohumeral joint incongruence in brachial plexus birth injury.

PURPOSE: To evaluate rotator cuff muscles and the glenohumeral (GH) joint in brachial plexus birth injury (BPBI) using MRI and to determine whether any correlation exists between muscular abnormality and the development of glenoid dysplasia and GH joint incongruity. MATERIALS AND METHODS: Thirty-nine consecutive BPBI patients with internal rotation contracture or absent active external rotation of the shoulder joint were examined clinically and imaged with MRI. In the physical examination, passive external rotation was measured to evaluate internal rotation contracture. Both shoulders were imaged and the glenoscapular angle, percentage of humeral head anterior to the middle of the glenoid fossa (PHHA) and the greatest thickness of the subscapular, infraspinous and supraspinous muscles were measured. The muscle ratio between the affected side and the normal side was calculated to exclude age variation in the assessment of muscle atrophy. RESULTS: All muscles of the rotator cuff were atrophic, with the subscapular and infraspinous muscles being most severely affected. A correlation was found between the percentage of humeral head anterior to the middle of the glenoid fossa (PHHA) and the extent of subscapular muscle atrophy (r(s)=0.45, P=0.01), as well as between its ratio (r(s)=0.5, P P=0.01). Severity of rotator cuff muscle atrophy correlated with increased glenoid retroversion and the degree of internal rotation contracture. CONCLUSIONS: Glenoid retroversion and subluxation of the humeral head are common in patients with BPBI. All rotator cuff muscles are atrophic, especially the subscapular muscle. Muscle atrophy due to neurogenic damage apparently results in an imbalance of the shoulder muscles and progressive retroversion and subluxation of the GH joint, which in turn lead to internal rotation contracture and deformation of the joint.

The diagnostic value of contrast-enhanced magnetic resonance imaging in the detection of experimentally induced anular tears in sheep.

STUDY DESIGN: An investigation of the visualization of experimental anular tears using contrast-enhanced magnetic resonance imaging. OBJECTIVES: To investigate how different kinds of experimentally induced anular tears can be visualized on contrast-enhanced magnetic resonance imaging. SUMMARY OF BACKGROUND DATA: Because the outer part of the anulus is innervated, tears of this part of disc are considered one cause for lumbar back pain. Moreover, clinical and experimental studies suggest that anular injuries may lead to a progressive degeneration of the entire disc. In the human disc, vascularized anular tears associated with disc degeneration can be visualized with contrast-enhanced magnetic resonance imaging, but acute peripheral anular injuries, probably caused by sudden trauma, have not been studied with this method. METHODS: Two adjacent lumbar discs in adult sheep (n = 11) were injured with a scalpel blade. The L2-L3 discs were injured superficially, whereas in the L3-L4 discs, the incision reached the nucleus pulposus (full-thickness injury). In seven animals, only a stab incision was made to the disc, and in four animals, a small fragment (5 x 2 x 3 mm) of anulus was cut and removed. The animals were killed 3 weeks (acute injury, n = 5) and 3 months (subacute injury, n = 6) after surgery. Five minutes before death, gadolinium-diethylenetriaminepentaacetic acid was injected intravenously. After death, the whole lumbar spines were excised and 1.5-T high-field magnetic resonance imaging was immediately performed. Thereafter, the disc samples were examined histologically to determine the existence of blood capillaries. RESULTS: In all injured discs, the injured area was macroscopically visible. Histologically, blood capillaries, lamellar destruction, and granulation tissue were clearly seen in every injured anulus. Contrast-enhanced magnetic resonance imaging showed that the superficial injuries were only occasionally visible in magnetic resonance imaging (3 of 11), whereas the full-thickness injuries were visible in a majority of the discs (8 of 11). In magnetic resonance imaging, the size of the injury did not relate to the enhancement intensity. The subacute injuries, particularly the full-thickness injuries, were more often visualized than the acute ones. CONCLUSION: Even though macroscopically visible and histologically evident, it was not always possible to demonstrate experimental anulus injuries by contrast-enhanced magnetic resonance imaging. This experimental study shows that further research work is needed to develop more sensitive methods to detect peripheral, relatively small, but probably clinically important disc injuries.