Xem mẫu

379 drugs, patients may require surgical drainage of the abscess, or removal of the parasite. HIV polymyositis is similar to disease in non-HIV patients and may improve with corticosteroids or immunosuppressive medications. Some pa-tients with the HIV wasting disorder, may respond to oxandrolone. The prognosis depends on the specific cause of the myositis. For a non-HIV related viral syndrome, the disease is usually self-limiting and prognosis is good. Where there is HIV infection or opportunistic infection the prognosis is poor. Removal of isolated parasites coupled with anti-protozoal medications may be all that is required to treat parasitic myositis. Banker BQ (1994) Parasitic myositis in myology. In: Engel AJ, Franzini-Armstrong C (eds), McGraw Hill, New York, pp 1453–1455 Chimelli L, Silva BE (2001) Viral myositis in structural and molecular basis of skeletal muscle diseases. In: Karpati G (ed), ISN Neuropathology Press, Basel, pp 231–235 Dalakas MC (1994) Retrovirus-related muscle diseases in myology. In: Engel AJ, Franzini-Armstrong C (eds), McGraw Hill, New York, pp 1419–1437 Prognosis References This is trial version www.adultpdf.com 380 Duchenne muscular dystrophy (DMD) Genetic testing +++ NCV/EMG ++ Laboratory – Imaging Biopsy + +++ Fig. 12. Muscle biopsy DMD. A Hematoxylin and eosin show-ing an increase in endomysial connective tissue (large arrows), inflammatory infiltrates (small arrows), and degenerating fibers (arrow head). B Normal dystro-phin staining. C Loss of dystro-phin staining in DMD Distribution Time course Onset/age Clinical syndrome Proximal muscles are more affected than distal muscles. Infants may have generalized hypotonia and be described as “floppy”. Progressive disorder resulting in significant disability in most children. DMD starts at age 3–5 years with symmetric proximal greater than distal weakness in the arms and legs. By 6–9 years they characteristically exhibit a positive Gower’s sign, and by 10–12 years patients often fail to walk. DMD results in a progressive muscular weakness affecting 1:3500 male infants. They often have calf muscle hypertrophy, muscle fibrosis, contractures in the lower extremities, and scoliosis of the spine. In general the average IQ of affected children is reduced compared to the general population to approxi-mately 85. Some patients (20%) may have more severe cognitive impairment. Other features include a retinal abnormality with night blindness, and a cardio- myopathy that develops by the mid-teens. In DMD, cardiac conduction de-fects, resting tachycardia, and cardiomyopathy are frequently encountered. Mitral valve prolapse and pulmonary hypertension may also be seen. Death normally occurs by the late teens to early twenties from respiratory or cardiac failure. This is trial version www.adultpdf.com 381 Most have a frameshift mutation (>95%), although 30% may have a new mutation. The molecular abnormality is unknown. However, in DMD there is an abnormality in dystrophoglycan development at the neuromuscular junc-tion. Dystrophoglycan may play a role in clustering of acetylcholine receptors and development of the neuromuscular junction, along with dystroglycan, a1-syntrophin, utrophin, and a-dystrobrevin. Laboratory: Serum CK is usually very high. Pathogenesis Diagnosis Electrophysiology: Nerve conduction studies are usually normal (except reduced CMAP in affected atrophic muscles). EMG shows increased insertional activity only in affected muscles. Short duration polyphasic motor unit action potentials, mixed with normal and long duration units are seen in the affected muscle/s. Imaging: Focal enlargement, edema, and fatty infiltration especially observed on T2 weighted and T1 images with gadolinium. Imaging may show hyperlor-dosis and scoliosis. Muscle biopsy: Characterized by endomysial fibrosis (Fig. 12), variation in muscle fiber size, muscle fiber degeneration and regeneration, small fibers are rounded, there are hypercontracted muscle fibers, and an increase in endomysial connective tissue. Muscle dystrophin staining is absent (Fig. 12C). Genetic testing: Exonic or multiexonic deletions (60–65%), duplication (5–10%), or missense mutations that generate stop codons may be found. Genetic testing is helpful in most affected cases. – Becker’s muscular dystrophy – Congenital myopathies – Inflammatory myopathies – Spinal muscular atrophies (SMA). – Prednisone therapy may prolong the ability to walk by a few years, and reduce falling. The doses are usually 0.75 mg/kg/day as a starting dose and then changing to a weekly dose of 5 to 10 mg/kg, or Oxandrolone 0.1 mg/ kg/day. – Non-surgical treatment of contractures consists of night splints and daytime passive stretch. – Surgical treatment of contractures consists of early contracture release, Achilles tenotomy, posterior tibial tendon transfer followed by early ambu-lation. – Scoliosis – back bracing. Spinal fusion may be required where there is respiratory compromise: according to Hart and McDonald, fusion should be used before the curvature is greater than 30° and vital capacity is less than 35% of predicted. Differential diagnosis Therapy This is trial version www.adultpdf.com 382 – Patients with cardiomyopathy and pulmonary hypertension may be helped by angiotensin converting enzyme inhibitors and supplemental oxygen. Digoxin may be used in selected patients. Carriers should also be checked for cardiac defects. – Respiratory compromise may require portable positive pressure ventilation. – Prophylactic antibiotics should be used for dental and surgical procedures in patients with mitral valve prolapse. – In the future, adeno-associated viruses show the greatest promise of transfer of normal DNA to affected muscles. Myoblast, DNA, and stem cell transfer are potential therapies. Prognosis References Patients usually survive to their mid-twenties. Cohn RD, Campell KP (2000) Molecular basis of muscular dystrophies. Muscle Nerve 23: 1456–1471 Fenichel GM, Griggs RC, Kissel J, et al (2001) A randomized efficacy and safety trial of oxandrolone in the treatment of Duchenne dystrophy. Neurology 56: 1075–1079 Grady RM, Zhou H, Cunningham JM, et al (2000) Maturation and maintenance of the neuromuscular synapse: genetic evidence of for the roles of the dystrophin-glycoprotein complex. Neuron 25: 279–293 Hart DA, McDonald CM (1998) Spinal deformity in progressive neuromuscular disease. Phys Med Rehab Clin N America 9: 213–232 Jacobsen C, Cote PD, Rossi SG, et al (2001) The dystrophoglycan complex is necessary for stabilization of acetylcholine receptor clusters at neuromuscular junctions and formation of the synaptic basement membrane. J Cell Biol 152: 435–450 Mirabella M, Servidei S, Manfredi G, et al (1993) Cardiomyopathy may be the only clinical manifestation in female carriers of Duchenne muscular dystrophy. Neurology 43: 2342– 2345 This is trial version www.adultpdf.com 383 Becker muscular dystrophy (BMD) Genetic testing +++ NCV/EMG ++ Laboratory – Imaging Biopsy + +++ BMD affects proximal greater than distal muscles. Worse in the quadriceps and hamstrings. BMD is a progressive disorder with a slower rate of progression than DMD. BMD is much milder than DMD with later clinical onset. Patients may have difficulty walking by their late teens. BMD often causes calf pain, cramps, and myalgias. Weakness is present in approximately 20% of affected patients. Patients may have no symptoms. In general the severity and onset age correlate with muscle dystrophin levels. As with DMD, affected subjects may have calf muscle hypertrophy and contrac-tures in the lower extremities. Patients with BMD often have a severe cardio-myopathy as part of the muscle weakness syndrome, or may have an isolated dilated cardiomyopathy. In general the average IQ of affected children is re-duced compared to the general population and may be a major presenting symptom in BMD. Some patients may present with an atypical neuromuscular disorder mimicking SMA, a focal myopathy, or a limb girdle muscular dystrophy. Most are exonic or multiexonic (70–80%), although duplications can occur in 10%, and missense mutations in <10%. Although dystrophoglycan is reduced in BMD, the molecular abnormality is unknown although it is likely similar to DMD. In some affected subjects there is a deficiency of mitochondrial enzymes and downregulation of several mitochondrial genes. Laboratory: Serum CK is high in 30% of subjects. Electrophysiology: Nerve conduction studies are usually normal. If the EMG is abnormal it shows increased insertional activity only in affected muscles. Short duration polypha-sic motor unit action potentials, mixed with normal and long duration units are seen in the affected muscles. Imaging: Focal enlargement, edema and fatty tissue replacement is observed on T2 and T1 weighted images with gadolinium in more severely affected patients. Distribution Time course Onset/age Clinical syndrome Pathogenesis Diagnosis This is trial version www.adultpdf.com ... - tailieumienphi.vn
nguon tai.lieu . vn