Myopathic Muscle Research Articles

Acute Polymyositis Following Renal Transplantation

Myositis is a rare complication following renal transplantation and is most commonly the result of drug-mediated myotoxicity. Other causative disorders include viral infection, electrolyte imbalance and myositis of autoimmune origin. We describe a 60-year-old patient who developed acute polymyositis 4 weeks after a 000 human leukocyte antigen (HLA) mismatch cadaveric renal transplant. Following an uncomplicated transplant course with maintenance triple immunosuppression (prednisolone, mycophenolate mofetil and cyclosporine), the patient presented with severe symmetrical proximal muscle weakness associated with a rise in serum creatine kinase to 46 800 U/L. Electromyography confirmed myopathic changes and muscle biopsy demonstrated extensive muscle-fiber necrosis with an inflammatory infiltrate. There were no obviously culpable drugs and viral studies were negative. Prompt initiation of high-dose steroid therapy led to clinical and biochemical recovery. Acute polymyositis may occur following renal transplantation. Potential mechanisms include viral antigen transmission or a localized form of graft vs. host disease.

Ultrasound imaging distinguishes between normal and weak muscle

Chi-Fishman G, Hicks JE, Cintas HM, Sonies BC, Gerber LH. Ultrasound imagining distinguishes between normal and weak muscle. Arch Phys Med Rehabil 2004;85:980–6. Objective To determine whether real-time ultrasound imaging can provide quantitative data that distinguish pathologic from healthy muscle and that correlate with strength measures. Design Nonrandomized matched-pair, repeated-measures design. Setting Ultrasound imaging laboratory, rehabilitation medicine department, government research hospital. Participants Nine patients with stable active or inactive myositis, stratified into 3 groups based on their 10-point manual muscle test (MMT) scores, and 9 age- and gender-matched controls. Interventions Maximal isometric contraction of the rectus femoris muscle in 2 knee-flexion positions (60°, 90°) during simultaneous ultrasound imaging and muscle force dynamometry. Main outcomes measures Changes of the rectus femoris muscle in horizontal (X) and vertical (Y) diameters between relaxed and contracted states, and muscle force measurements. Results The X diameters decreased and the Y diameters increased during isometric contraction in all participants. For each group, average changes in cross-sectional diameters were consistently higher in controls than in patients. Patients with MMT less than 8 differed significantly from controls in both X and Y dimensions. A moderately strong correlation was found between muscle force and the Y diameter during contraction at 60° ( r=.78) and 90° ( r=.67) knee-flexion angles. Conclusions Ultrasonography provided a quantitative measure of change between relaxed and contracted state of muscle, which correlated with muscle force. Ultrasound identified significant differences in cross-sectional diameters between the myopathic and normal muscles sampled and may be useful for measuring muscle response to drug and exercise therapy.

119th ENMC international workshop: Trial design in adult idiopathic inflammatory myopathies, with the exception of inclusion body myositis, 10–12 October 2003, Naarden, The Netherlands

Department of Neurology, University Medical Center, Heidelberg laan 100, Utrecht, CX 3584, The Netherlands Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA The Walton Centre for Neurology and Neurosurgery, Liverpool, UK Department of Rheumatology, King’s College Hospital, London, UK Rheumatology Unit, Department of Medicine, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden King’s Neurosciences Centre, King’s College Hospital, London, UK Institute of Rheumatology, Prague, Czech Republic Department of Neurology, Academic Medical Centre, Amsterdam, The Netherlands Department of Clinical Neurosciences, Guy’s, King’s and Thomas’ School of Medicine, London, UK

Muscle satellite cells

Skeletal muscle satellite cells are quiescent mononucleated myogenic cells, located between the sarcolemma and basement membrane of terminally-differentiated muscle fibres. These are normally quiescent in adult muscle, but act as a reserve population of cells, able to proliferate in response to injury and give rise to regenerated muscle and to more satellite cells. The recent discovery of a number of markers expressed by satellite cells has provided evidence that satellite cells, which had long been presumed to be a homogeneous population of muscle stem cells, may not be equivalent. It is possible that a sub-population of satellite cells may be derived from a more primitive stem cell. Satellite cell-derived muscle precursor cells may be used to repair and regenerate damaged or myopathic skeletal muscle, or to act as vectors for gene therapy. Cell facts: (1) Number of cells in body: 2×10 7 to 3×10 7 myonuclei/g, 20–25 kg muscle in average man; 2×10 5 to 10×10 5 satellite cells/g, i.e. ∼1×10 10 to 2×10 10 satellite cells per person. (2) Main functions: repair and maintenance of skeletal muscle. (3) Turnover rate: close to zero in non-traumatic conditions—high in disease or severe trauma.

Recombinant adeno-associated virus type 2 mediates highly efficient gene transfer in regenerating rat skeletal muscle.

The recent identification of genes responsible for several muscle diseases, particularly inherited myopathies, has made gene transfer to pathologic muscle tissue an attractive research field. As early pathologic changes in myopathic muscle involve repeated necrosis-regeneration cycles, leading to the coexistence of myofibers at different stages of maturity, a delivery system for efficient, durable gene therapy of inherited muscle diseases should allow gene transfer into myofibers at any stage of maturity. Experiments with rat skeletal muscles showed that recombinant adeno-associated virus (rAAV) type 2 can be highly efficient and even improve gene transfer in regenerating as compared with mature muscle, provided that vector injection is performed during the myotube growth period of the regenerative process. At this early period of muscle regeneration, young regenerating myotubes strongly express heparan sulfate proteoglycan AAV type 2 receptor. Improvement was associated with a greater number of transduced myofibers in muscle samples and an increase in viral genomic copies in transduced muscle. No significant deleterious effects on muscle phenotype or any evident alterations in the regenerative process were observed in transduced muscles. Unlike other available viral vectors, whose transduction efficiencies are highly maturation-dependent, rAAV type 2-based vectors provide efficient in vivo gene transfer in myofibers at various stages of maturity, making AAV a promising delivery system for pathological muscle tissue.

Differentiation of original and regenerated skeletal muscle fibres in mdx dystrophic muscles.

The differentiation of both original muscle fibres and the regenerated muscle fibres following necrosis in mdx muscles was investigated using immunoblotting and immunocytochemical procedures. Before the onset of necrosis, postnatal skeletal muscles in mdx mouse differentiated well with only a slight delay in differentiation indicated by the level of developmental isoforms of troponin T. Prior to the onset of apparent myopathic change, both fast and slow skeletal muscle fibre types in mdx leg muscles also differentiated well when investigated by analysis of specific myosin heavy chain expression pattern. While the original muscle fibres in mdx leg muscles developed well, the differentiation of regenerated myotubes into both slow and distinct fast muscle fibre types, however, was markedly delayed or inhibited as indicated by several clusters of homogeneously staining fibres even at 14 weeks of age. The number of slow myosin heavy chain-positive myotubes amongst the regenerated muscle clusters was quite small even in soleus. This study thus established that while muscle fibres initially develop normally with only a slight delay in the differentiation process, the differentiation of regenerated myotubes in mdx muscles is markedly compromised and consequently delayed.

Facioscapulohumeral (FSHD1) and other forms of muscular dystrophy in the same family: is there more in muscular dystrophy than meets the eye?

We report on two unrelated Brazilian families with members affected by two different forms of muscular dystrophy. In the first one, the 35-year-old male proband has limb-girdle muscular dystrophy with proximal weakness, elevated creatine kinase and a myopathic muscle biopsy. All the proteins known to be associated with limb-girdle muscular dystrophy were normal. Two of his sisters also complained of muscle weakness. The oldest sister showed clinical signs consistent with facioscapulohumeral muscular dystrophy, confirmed through molecular analysis. She presented a 30 kb EcoRI/ BlnI fragment which was found in another six relatives, but surprisingly not in the affected proband or the other sister. In the second family, a 57-year-old male with a typical facioscapulohumeral muscular dystrophy phenotype has a 17 kb EcoRI/ BlnI fragment, which was also present in other affected relatives. However in a 14-year-old severely affected male cousin, confined to a wheelchair since age 12, but without facial weakness, the small fragment was absent. These families illustrate the importance of testing all affected individuals in a family.

Magnesium abnormalities of skeletal muscle in dermatomyositis and juvenile dermatomyositis

To characterize abnormalities in magnesium levels in the muscles of patients with dermatomyositis (DM) and juvenile dermatomyositis (JDM) and to evaluate the beneficial effects of prednisone and immunosuppressive therapy in elevating free magnesium (Mg(2+)) and ATP-bound magnesium (Mg-ATP). The study groups consisted of 12 adult patients with DM and 10 juvenile patients with JDM. The 2 control groups were 11 normal adults and 6 healthy children. Levels of total ATP in the quadriceps muscles of the subjects were determined during rest, exercise, and recovery, using noninvasive P-31 magnetic resonance spectroscopy (MRS). Concentrations of the biologically active free Mg(2+) and the enzymatically active Mg-ATP complex were determined from the spectroscopy data by calculation of the chemical shifts of the beta-phosphate peak of ATP. Mg-ATP levels in DM and JDM myopathic muscles were at least 37% lower than those in normal muscles during rest, exercise, and recovery from exercise (P < 0.0005). Free Mg(2+) levels were normal in DM and JDM myopathic muscles at rest, but were significantly lower than control values during exercise and recovery (P < 0.029 and P < 0.005 for DM and JDM, respectively). Prednisone and immunosuppressive therapy partially reversed the magnesium abnormalities, as evidenced by elevation of the levels of Mg-ATP and free Mg(2+). Low levels of Mg-ATP and free Mg(2+) are concordant with weakness and fatigue observed in DM and JDM patients. Immunosuppressive therapy alleviates, in part, the magnesium deficits in the diseased muscles. Therefore, Mg-ATP and free Mg(2+) may play a significant role in the pathophysiology of these diseases.

Myopathy-dependent changes in activity of ATPase, SDH and GPDH and NOS expression in the different fibre types of hamster muscles

Proximal (vastus lateralis) and distal (gastrocnemius) muscles of 100-day-old normal and myopathic BIO TO-2 hamsters were analysed to study the effects of myopathy on the different muscle fibre types: SO (slow oxidative), FOG (fast oxidative glycolytic) and FG (fast glycolytic). Cytophotometric measurements of enzyme activities (myofibrillic adenosine triphosphatase, succinate dehydrogenase and glycerol-3-phosphate dehydrogenase), Western blot analysis of nitric oxide synthase (NOS) I, II, III isoforms and NOS II immunohistochemistry were performed. The following alterations were found in myopathic muscle fibres: all fibre types of both proximal and distal myopathic muscles showed decreased myofibrillic adenosine triphosphatase activity indicating depressed contractility. This was associated with depressed oxidative activity of the muscle fibres. A shift to more glycolytic metabolism was observed, mainly in FG fibres of proximal muscle. We found an increased NOS II expression in both myopathic muscle types investigated. It means that increased NO production inhibits force generation in myopathic muscle. NOS II immunoreactivity was found mainly in the cytoplasm of FG fibres. NOS I and NOS III expression was not significantly effected by this form of myopathy. Our findings demonstrate that muscle fibres of proximal and distal skeletal muscles of 100-day-old cardiomyopathic BIO TO-2 hamsters are altered with respect to contractility, metabolism and NOS II expression. FG fibres of the proximal muscle were effected most strongly.

Clinical Delineation and Localization to Chromosome 9p13.3–p12 of a Unique Dominant Disorder in Four Families: Hereditary Inclusion Body Myopathy, Paget Disease of Bone, and Frontotemporal Dementia

Autosomal dominant myopathy, Paget disease of bone, and dementia constitute a unique disorder (MIM 605382). Here we describe the clinical, biochemical, radiological, and pathological characteristics of 49 affected (23 male, 26 female) individuals from four unrelated United States families. Among these affected individuals 90% have myopathy, 43% have Paget disease of bone, and 37% have premature frontotemporal dementia. EMG shows myopathic changes and muscle biopsy reveals nonspecific myopathic changes or blue-rimmed vacuoles. After candidate loci were excluded, a genome-wide screen in the large Illinois family showed linkage to chromosome 9 (maximum LOD score 3.64 with marker D9S301). Linkage analysis with a high density of chromosome 9 markers generated a maximum two-point LOD score of 9.29 for D9S1791, with a maximum multipoint LOD score of 12.24 between D9S304 and D9S1788. Subsequent evaluation of three additional families demonstrating similar clinical characteristics confirmed this locus, refined the critical region, and further delineated clinical features of this unique disorder. Hence, autosomal dominant inclusion body myopathy (HIBM), Paget disease of bone (PDB), and frontotemporal dementia (FTD) localizes to a 1.08–6.46 cM critical interval on 9p13.3–12 in the region of autosomal recessive IBM2.

Dermal fibroblasts participate in the formation of new muscle fibres when implanted into regenerating normal mouse muscle.

Both in vitro and in vivo studies have described the conversion of fibroblasts to myogenesis when in the presence of dysfunctional myogenic cells. Myogenic conversion of fibroblasts subjected to a normal, as opposed to a diseased muscle environment has only been reported in vitro. The primary aim of this work was to determine if fibroblasts can convert to a myogenic lineage and contribute to new fibre formation when implanted into the regenerating muscle of a normal mouse. Dermal fibroblasts were prepared from neonatal mouse skin and labelled prior to implantation with the fluorescent nuclear marker 4',6-diamidino-2-phenylindole (DAPI). Cells were implanted into muscles of host mice that had been subjected to either cold/crush or minced muscle injury. Some host muscles were x-irradiated to deplete the muscle of endogenous muscle precursor cells. Muscles were removed at 3 wk postimplantation and analysed both histologically and for the presence of DAPI labelled nuclei. Fibres containing DAPI labelled central nuclei indicated that the implanted cells had participated in the regenerative process. Mouse dermal fibroblasts therefore do contribute to muscle fibre formation in regenerating normal mouse muscle but the extent of their contribution is dependent on the nature of the trauma induced in the host muscle. The study also showed that regeneration was more successful in muscles which had not been irradiated, which is contrary to the previous studies where dermal fibroblasts were introduced into myopathic mouse muscle.

Expression of Messenger RNA of the Cardiac Isoforms of Troponin T and I in Myopathic Skeletal Muscle

In the absence of clinical signs, elevated values of the cardiac isoforms of troponin T (cTnT) and I (cTnI) can be found in the serum samples of some patients with skeletal muscle myopathies; the cause is unclear. We studied the messenger RNA (mRNA) expression of cTnT and cTnI in the skeletal muscles of 24 patients with histologically proven myopathies and in 18 patients in whom a myopathy could be excluded. For cTnT- and cTnI-mRNA determination, we designed specific primer pairs for nested polymerase chain reaction. After amplification, the products were digested with 2 restriction enzymes and visualized. We found cTnT mRNA in 7 skeletal muscle biopsy specimens (6 patients with Duchenne muscular dystrophy, 1 patient with a primary sarcoglycanopathy) and cTnI mRNA in 6 (5 with Duchenne muscular dystrophy, 1 patient with a histologically negative biopsy). The mRNA of the cardiac isoforms, cTnT and cTnI, is expressed in the skeletal muscles of patients with Duchenne muscular dystrophy, but also in some other myopathies. Further studies are needed to show whether the mRNA is translated into the protein, but serum levels of cTnT and cTnI in patients with Duchenne muscular dystrophy would seem to indicate this.

Changes of enzyme activities in the myocardium and skeletal muscle fibres of cardiomyopathic hamsters.A cytophotometrical study

Cytophotometrical measurements of enzyme activities were performed in the myocardium and skeletal muscle fibres from normal and cardiomyopathic hamsters (BIO 8262) during ageing from 12-14 to 120-190 days. Myocardium as well as vastus lateralis muscles of cardiomyopathic hamsters showed changes in enzyme activities. The skeletal muscle fibres were typed into slow-oxidative, fast-oxidative glycolytic and fast-glycolytic to investigate fibre type-related changes in muscles of cardiomyopathic hamsters. The following myopathic changes were mainly found: Myofibrillic ATPase was depressed in the myocardium of both ventricles in all investigated age stages. The ATPase activity of the right ventricle was more decreased than that of the left one. Additionally, a metabolic shift was observed in myocardium and slow-oxidative muscle fibres at the onset of clinical symptoms, which appeared from day 150 to day 190. During the period from 42 up to 190 days of life an increase of oxidative (succinate dehydrogenase) activity was measured in the myocardium of both ventricles and in slow oxidative fibres of vastus lateralis muscle as a proximal muscle. At earlier ages, the fast fibres of myopathic vastus lateralis muscle showed higher glycolytic (glycerol-3-phosphate dehydrogenase) activity than those of normal muscles. However, at the age of 120-190 days the metabolic profile of fast fibres was normalized. In gastrocnemius muscle as a distal muscle no changes of enzyme activities were measured, suggesting the investigated hereditary myopathy effected proximal, but not distal muscles.

Einfluß der Amplitudenschwelle auf die Parameter der Turns/Amplituden-Analyse

In this study we examined the relationship between the amplitude threshold used for the determination of the turns of the electromyographic interference pattern and the classical parameters of the turns/amplitude analysis: mean amplitude and number of turns per second. We investigated whether the choice of an appropriate amplitude threshold could help to discriminate better between myopathic and neuropathic muscles on the one hand and normal muscles on the other. In 16 patients with myopathies, 33 patients with neuropathies and 59 controls the interference patterns of the tibialis anterior muscle were recorded using concentric needle electrodes. Analysis was performed via a computer programme, systematically varying the amplitude threshold between 10 μV and 200 μV. Amplitudes as well as the number of turns per second showed a non-linear relation with the amplitude threshold. By reducing the amplitude threshold to 20 μV we obtained a clearly better separation of the distributions of the number of turns of myopathic, neuropathic and normal EMG, compared to the traditional threshold value of 100 μV. The reduction of the amplitude threshold had no effect on the distributions of amplitude values. The Kolmogoroff-Smirnov distance between the turns parameter distributions of myopathic patients and controls as well as between the distributions of neuropathic patients and controls increased with decreasing amplitude threshold values until a maximum at a threshold value of 20 μV. Hence, for the turns/amplitude analysis of the tibialis anterior muscle it is better to reduce the amplitude threshold to 20 μV.

The diagnostic power of motor unit potential analysis: an objective bayesian approach.

The notion of a "myopathic" or "neuropathic" electromyogram (EMG) is usually based on qualitative visual and acoustical impressions. Conventional quantification defines abnormality but not diagnosis, which requires interpretation of patterns of change. Discriminant analysis is a model for this multivariate decision. It tells how probable it is that a motor unit potential (MUP) comes from a normal, myopathic, or neuropathic muscle. Accumulation of single MUP information by a sequential Bayesian algorithm produced diagnostic probabilities above 0.95 in 91% of all muscles (223 biceps brachii muscles from 80 patients with motoneuron disorders, 56 patients with neuropathies, 71 patients with myopathies, and 34 controls). Two muscles from patients with neurogenic disorders were misclassified as "myopathic." Misclassification was more frequent only in myositis (4 of 28 muscles) and in oculopharyngeal muscular dystrophy (2 of 4 muscles). MUP discriminant classification was as sensitive as, and more specific than, conventional quantitative EMG, which discriminated between myopathic and neuropathic in only 22% of the muscles. This rate was 59% for discriminant analysis. As a knowledge-based expert system, MUP discriminant analysis successfully distinguishes between myopathic, neuropathic, and unclassifiable MUP samples. It discloses more information than conventional quantitative MUP analysis.

Oxidants, antioxidants and alcohol: implications for skeletal and cardiac muscle.

The chronic form of alcoholic skeletal myopathy is characterized by selective atrophy of Type II fibers and affects up to two thirds of all alcohol misusers. Plasma selenium and alpha-tocopherol are reduced in myopathic alcoholics compared to alcoholic patients without myopathy. Plasma carnosinase is also reduced in myopathic alcoholics, implicating a mechanism related to reduced intramuscular carnosine, an imidazole dipeptide with putative antioxidant properties. Together with the observation that alcoholic patients have increased indices of lipid peroxidation, there is evidence suggestive of free radical (i.e., unpaired electrons or reactive oxygen species) mediated damage in the pathogenesis of alcohol-induced muscle disease. Protein synthesis is a multi-step process that encompasses amino acid transport, signal transduction, translation and transcription. Any defect in one or more of the innumerable components of each process will have an impact on protein synthesis, as determined by radiolabelling of constituent proteins. Both acute and chronic alcohol exposure are associated with a reduction in skeletal muscle protein synthesis. Paradoxically, alcohol-feeding studies in rats have shown that the imidazole dipeptide concentrations are increased in myopathic muscles though alpha-tocopherol contents are not significantly altered. In acutely dosed rats, where protein synthesis is reduced, protein carbonyl concentrations (an index of oxidative damage to muscle) also decline slightly or are unaltered, contrary to the expected increase. Alcoholic cardiomyopathy can ensue from heavy consumption of alcohol over a long period of time. The clinical features include poor myocardial contractility with reduced left ventricular ejection volume, raised tissue enzymes, dilation of the left ventricle, raised auto- antibodies and defects in mitochondrial function. Whilst oxidant damage occurs in experimental models, however this issues remains to be confirmed in the clinical setting. In the rat, circulating troponin-T release increases in the presence of ethanol, a mechanism ascribed to free radical mediated damage, as it is prevented with the xanthine oxidase inhibitor and beta-blocker, propranolol. However, whilst propranolol prevents the release of troponin-T, it does not prevent the fall in whole cardiac protein synthesis, suggestive of localized ischemic damage due to ethanol.

Oxidants, antioxidants and alcohol: implications for skeletal and cardiac muscle

The chronic form of alcoholic skeletal myopathy is characterized by selective atrophy of Type II fibers and affects up to two thirds of all alcohol misusers. Plasma selenium and alpha-tocopherol are reduced in myopathic alcoholics compared to alcoholic patients without myopathy. Plasma carnosinase is also reduced in myopathic alcoholics, implicating a mechanism related to reduced intramuscular carnosine, an imidazole dipeptide with putative antioxidant properties. Together with the observation that alcoholic patients have increased indices of lipid peroxidation, there is evidence suggestive of free radical (i.e., unpaired electrons or reactive oxygen species) mediated damage in the pathogenesis of alcohol-induced muscle disease. Protein synthesis is a multi-step process that encompasses amino acid transport, signal transduction, translation and transcription. Any defect in one or more of the innumerable components of each process will have an impact on protein synthesis, as determined by radiolabelling of constituent proteins. Both acute and chronic alcohol exposure are associated with a reduction in skeletal muscle protein synthesis. Paradoxically, alcohol-feeding studies in rats have shown that the imidazole dipeptide concentrations are increased in myopathic muscles though alpha-tocopherol contents are not significantly altered. In acutely dosed rats, where protein synthesis is reduced, protein carbonyl concentrations (an index of oxidative damage to muscle) also decline slightly or are unaltered, contrary to the expected increase. Alcoholic cardiomyopathy can ensue from heavy consumption of alcohol over a long period of time. The clinical features include poor myocardial contractility with reduced left ventricular ejection volume, raised tissue enzymes, dilation of the left ventricle, raised auto- antibodies and defects in mitochondrial function. Whilst oxidant damage occurs in experimental models, however this issues remains to be confirmed in the clinical setting. In the rat, circulating troponin-T release increases in the presence of ethanol, a mechanism ascribed to free radical mediated damage, as it is prevented with the xanthine oxidase inhibitor and beta-blocker, propranolol. However, whilst propranolol prevents the release of troponin-T, it does not prevent the fall in whole cardiac protein synthesis, suggestive of localized ischemic damage due to ethanol.

Double discharges of motor units in neuromuscular disorders

Repetitive discharges (RDs) are observed in electromyograms recorded from healthy as well as diseased muscles. We have evaluated the prevalence of RDs in some neuromuscular diseases and analysed the time parameters of recordings displaying RDs as well as shapes of the potentials. In our clinical material, RDs have been observed exclusively in lower motor neuron lesions, never in healthy or in myopathic muscles. The prevalence index of RDs in amyotrophic lateral sclerosis (0.06) was found to be different from that in chronic spinal muscle atrophy (0.004). The types of double potential shape have been categorised. The relationships between the amplitude of the second component and the interspike duration and that between the interspike duration and the jitter were calculated. The amplitude of the second component diminished and jitter of the components increased with the shortening of the interval between components. The authors suggest that in lower motor neuron lesions, the RDs of the motorunit (MU) may be one of the first signs of the MU's dysfunction.

Autonomic dysfunction in chronic intestinal pseudo-obstruction

Fifteen tests were used to assess adrenergic, non-vagal cholinergic, and cardiovagal functions in 11 patients with chronic intestinal pseudo-obstruction (CIP). The three aims of this study were: 1) to ascertain the presence of and spectrum of autonomic involvement; 2) to assess the level of autonomic dysfunction; and 3) to compare the results of autonomic function tests with gastrointestinal motility patterns. Gastrointestinal motility displayed a neuropathic pattern in 10 patients. Adrenergic functions were abnormal in nine patients and non-vagal cholinergic functions in 10 patients. Cardiovagal functions were abnormal in only seven patients. The autonomic dysfunction was localized mostly to the postganglionic pathways. One patient, who had a myopathic pattern and muscle degeneration on small bowel biopsy, demonstrated normal responses to autonomic function tests. The patients with neuropathic CIP demonstrated widespread, mostly postganglionic autonomic dysfunction. Neuropathic CIP can occur with or without cardiovagal involvement.

Ｆｒｅｅｍａｎ−Ｓｈｅｌｄｏｎ症候群患児の小口症に対する手術経験の１例

This case report describes the surgical plastic reconstruction of the lips and an enlarged aperture of the mouth in an 8-year-old Japanese girl who was given a diagnosis of Freeman-Sheldon syndrome.In this patient, it was difficult to decide where to make the incision in the myopathic orbicularis oris muscle and there by positively affect the future morphology and function of the lips. The operation was performed to obtain sufficient intercommissural distance of the lips, and care was taken to prevent ptosis of both commissures of the lips.At present, 6 years after the operation, the outcome is generally satisfactory with respect to the function of mouth opening. However, the patient still lacks a complete or sufficient lip shield, and the upper incisors have gradually become exposed.Lateral cephalogram analysis conducted 6 years postoperatively indicated that the upper incisiors had inclined labially and the lips had moved forward. These changes due to plastic correction apparently led to reduced lip pressure against the upper incisors.