Diagnostic effectiveness of muscle biopsy in neuromuscular diseases; Four years retrospective critical review

Abstract

Most of the neuromuscular diseases are genetic and progressive. It is important to make a timely and correct diagnosis for treatment guide, follow-up of the progression and genetic counseling to be given to the family. The aim of this study is to analyze the histopathological evaluation process and results of muscle biopsies and to evaluate the contribution to the diagnosis and management decisions of the disease. Method. Muscle biopsy evaluation has been started on January 2013 in Anatomic Pathology Laboratories at Eskisehir Community Hospital. Support had been taken from Izmir 9 Eylul University Pathology Department for two years in order to get technical standards and academic experience. A retrospective study was carried out in 160 muscle biopsies evaluated between 2013 and 2017 in the laboratory. Electronic hospital records and pathology reports were reviewed all together for preanalytic and analytic process data; gender, age, symptoms, signs, age of beginning of the symptoms, duration between the symptoms and muscle biopsy, family history, creatinine kinase level (CK), electromyography (EMG), prediagnosis, specimen adequacy, histopathologic diagnosis. Results. 53,8% (n = 86) of the muscle biopsy specimen belong to children (C) and 46,3% (n = 74) belong to adults (A); 40% female (F), 60% male (M) predominates this ratio is (F: 29,1%, M: 70,9%) in the children and (F: 52,7%, M: 47,3%) in the adults. Muscle weakness was most common associated symptom in 42,6% (n = 66), hypothonic infant in 15,5% (n = 24), fatigue in 12,9% (n = 20) and coincident high CK levels in 11,6% (n = 18). Duration between beginning of the symptoms and muscle biopsy was between one month and 360 months, with the mean 57 months (Children (C) 23 months, Adults (A) 98 months). EMG before biopsy was reported in 50,6% (n = 81) (C 22,1%, A: 83,8%). Myopathic changes were found in 52 (32,5%) of these cases. 71,2% (n = 114) of cases had CK levels of them 27,5% (n = 44) were normal levels, 15,6% (n = 25) were slightly elevated, 28,1% (n = 45) were high. Consanguinity or suspected family history of muscle disease incidence was 33,1% (n = 53). Of the patients 33,1% (n = 53) had negative family history. Muscle weakness was reported most common with a rate of 42,6% (n = 66), hypotonic infant 15,5% (n = 24), fatigue was 12,9% (n = 20). Clinical preliminary diagnosis before muscle biopsy was myopathy/dystrophy in 60,1% (n = 96) [myopathy in 41,9% (n = 67), myopathy/dystrophy in 14,4% (n = 23), dystrophy in 3,8% (n = 6)], patients searched for high CK levels in 11,3% (n = 18), metabolic/mitochondrial disease in 10% (n = 16), hypothonic infant (myopathy?) in 6,9% (n = 11), inflammatory myopathy in 7,5% (n = 12). Routine histochemical evaluation revealed myopathic/dystrophic diagnosis in 71,2% (n = 114). 57% (n = 65) of these (40,6% of all patiens) were specified more with enzyme histochemical and immune histochemical methods. Neuropathic change has been observed in 9,4% of the cases. Nonspecific muscle biopsy results were 8,8% (n = 14), normal histology results were 10,6% (n = 17). Secondary diagnosis with additional tests revealed dystrophinopathy in 11,3% (n = 18), metabolic/mitochondrial diseases in 9,4% (n = 15), dysferlinopathy in 6,2% (n = 10), inflammatory myopathy in 5% (n = 8) (DM: 1, PM: 4, IBM: 3), lipid storage disease in 1,9% (n = 3), glycogen storage disease in 2,5% (n = 4), sarcoglycanopathy in 1,3% (n = 2), alpha distroglycanopathy in 1,3% (n = 2), myotonic dystrophy in 0,6% (n = 1), central core disease in 0,6% (n = 1). Discussion. The first step in the clinical approach is to obtain adequate and accurate information on disease symptoms. Signs and symptoms were provided in 96,9% (n:155) of patients. Muscle weakness was the most common sign with 42,6% (n = 66) in our study. If weakness distribution is at proximal part of legs and arms myopathy is the most probable diagnosis; If the neurology examination is normal general weakness and fatigue does not correlate myopathy but the duration of the exercise that elaborates fatigue and weakness is important. Hypotonic infant is a feature of some muscular disease like spinal muscular atrophy (SMA), congenital muscular dystrophy (CMD), congenital myopathy. Muscle biopsy evaluation is essential for neuromuscular hypotonia. In our study hypotonia was most common symptom at pediatric population in 27,9% (n = 24), it was 15,5% in all cases. Age onset of the symptoms, duration, course are important to determine. Myopathy may cause constant weakness (inflammatory myopathy, muscle dystrophy) or episodic weakness (glycolytic pathway disturbances, periodic paralysis). Episodic disorders are characterized with acute weakness resolving within hours or days. Most of the myopathy are transmitted genetically the family history takes importance. Family tree must be described for autosomal dominant, recessive, X-linked inheritance. Electromyography (EMG) is use full for differential diagnosis between denervation myopathy, myotonia, muscle-nerve junction disease. Electromyography is also hard to perform for myopathic process at pediatric population, sufficient contraction may not be obtained, at young age groups it may not give precise results. Muscular dystrophy (Dystrophinopaty, sarcoglycanopathy, merosinopathy), congenital myopathy, myositis (Dermatomyosistis, polymyositis, inclusion body myositis), vasculitis, especially meatbolic myopathies (type 2 glycogenosis, phosphorylase defficiency, phosphofructokinase defficiency, lysosomal storage disease, lipid myopathies, mitochondrial myopathies) are the primary disease that require muscle biopsy In our study it is remarkable that there were 6 patients also genetically diagnosed as glycogen storage disease and lipid storage disease. Five of them had admitted with refractory polymyositis, one was exploring for CK height. Pathologic diagnosis is indispensable when progression of treatment is considered. Duration between muscle biopsy and onset of the symptoms is one of the most important indicator in the study. This interval was 23 months in pediatric patients, 98 months in adult patients. This long interval reflects difficulty of the diagnosis. Conclusion The disadvantage of our study is that due to the limitation of immunohistochemistry panel, necessary additional tests could not be done in some patients and results could not be supported with Western Bloot, Electron microscopy. less number of confirmatory molecular genetic support is a major drawback. Muscle biopsy is indispensable to establish an etiologic diagnosis and is a component of the identification of prognostic prediction and therapeutic planning as well as diagnostic data. Only 21 patient had both pathological and genetic diagnosis confirmed. Genetic diagnosis did not confirm the pathologic daignosis at one patient who had mitochondrial myopathy at the muscle biopsy. We believe that improving the technical infrastructure, eliminating immunohistochemical panel deficiencies, adding Western Bloot studies, and providing EM and molecular genetic research support, produce more productive results.