Extraocular muscle (EOM) enlargement may be due to a variety of causes. These causes can be classified in three ways: according to pathogenesis and histopathological features, according to the site, and according to the clinical features. Diagnosis of the cause is dependent upon history, clinical examination, and investigations. Imaging with computed tomography or magnetic resonance imaging and muscle biopsy is typically necessary to make the correct diagnosis. Treatment of the patient must be directed toward the specific cause. This review emphasizes important clinical and pathological guidelines for appropriate diagnosis and treatment of patients with EOM enlargement.

Chronic progressive external ophthalmoplegia (CPEO) is a mitochondrial encephalomyopathy that is characterized by progressive ptosis and impaired ocular motility. Owing to its nonspecific clinical manifestations, CPEO is often misdiagnosed as other conditions. Herein, we present the case of a 34-year-old woman who primarily presented with incomplete left eyelid closure and limited bilateral eye movements. During the 6-year disease course, she was diagnosed with myasthenia gravis and cranial polyneuritis. Finally, skeletal muscle tissue biopsy confirmed the diagnosis. Biopsy revealed pathological changes in mitochondrial myopathy. Furthermore, mitochondrial gene testing of the skeletal muscle revealed a single chrmM:8469-13447 deletion. In addition, we summarized the findings of 26 patients with CPEO/Kearns-Sayre syndrome who were misdiagnosed with other diseases owing to ocular symptoms. In conclusion, we reported a rare clinical case and emphasized the symptomatic diversity of CPEO. Furthermore, we provided a brief review of the diagnosis and differential diagnosis of the disease.

Diabetic myonecrosis, also known as diabetic muscle infarct, is a rare complication of diabetes mellitus, generally associated with poor glycemic control. It is often difficult to diagnose due to its nonspecific presentation and lack of awareness of the complication. Routine laboratory investigations often do not aid in diagnosis. Magnetic resonance imaging (MRI) may assist in diagnosis but is not routinely ordered due to cost-effectiveness and nonspecific radiologic appearance. Muscle biopsy can provide a definite diagnosis; however, it is often avoided due to its invasiveness. Treatment consists of glycemic control, rest, and analgesics for pain control. Our case describes a 42-year-old male with uncontrolled diabetes who presented with four weeks of progressively worsening right-sided lower extremity pain. The patient was taken to the operating room for concern for necrotizing fasciitis; however, it was ultimately ruled out. A diagnosis of diabetic myonecrosis was made. Recommendations were given for strict blood sugar control and to start aspirin 81 mg daily. The patient was later seen in the outpatient clinic with improvement in the lower extremity pain.

OBJECTIVE: Muscle biopsy techniques range from needle muscle biopsy (NMB) and conchotome biopsy to open surgical biopsy. It is unknown whether specific biopsy techniques offer superior diagnostic yield or differ in procedural complication rates. Therefore, we aimed to compare the diagnostic utility of NMB, conchotome and open muscle biopsies in the assessment of neuromuscular disorders.
METHODS: A systematic literature review of the EMBASE and Medline (Ovid) databases was performed to identify original, full-length research articles that described the muscle biopsy technique used to diagnose neuromuscular disease in both adult and paediatric patient populations. Studies of any design, excluding case reports, were eligible for inclusion. Data pertaining to biopsy technique, biopsy yield and procedural complications were extracted.
RESULTS: Sixty-four studies reporting the yield of a specific muscle biopsy technique and, or procedural complications were identified. Open surgical biopsies provided a larger tissue sample than any type of percutaneous muscle biopsy. Where anaesthetic details were reported, general anaesthesia was required in 60% of studies that reported open surgical biopsies. Percutaneous biopsies were most commonly performed under local anaesthesia and despite the smaller tissue yield, moderate- to large-gauge needle and conchotome muscle biopsies had an equivalent diagnostic utility to that of open surgical muscle biopsy. All types of muscle biopsy procedures were well tolerated with few adverse events and no scarring complications were reported with percutaneous sampling.
CONCLUSIONS: When a histological diagnosis of myopathy is required, moderate- to large-gauge NMB and the conchotome technique appear to have an equivalent diagnostic yield to that of an open surgical biopsy.

We report the case of a young woman with CMV infection, high level of creatine kinase and myopathy. Electromyography showed a myopathic pattern. Muscle biopsy showed a marked increase of NADH enzymatic activity in the central area of almost all type I fibres, few degenerative and necrotic fibres and scattered mononuclear cell infiltrates. Ultrastructural analysis showed a marked disarrangement of sarcomeric structure and large inclusions of thin filaments in some fibres, while immunohistochemistry evidenced alteration in desmin, actin and αB-crystallin protein signals. PCR for CMV detection on muscle sections was negative. Histological, immunological and ultrastructural evaluations were compatible with a necrotic inflammatory myopathy. The correlations between CMV liver infection and the myopathic pattern are discussed. This case underscores the need to consider CMV infection in the differential diagnosis of myopathy with undetermined aetiology, quickly providing directions for a targeted muscle pharmacological intervention.

Reducing body myopathy (RBM) is a rare disease marked by progressive muscle weakness caused by a mutation in FHL1 gene. We describe a new pathogenic variant and contrasted it with 44 other cases identified in the literature. A male child presented at age 3 suffering frequent falls and progressive muscular weakness. At age 8, he was wheelchair-bound and required ventilatory support. His mother and sister died due to the same problem. Creatine kinase was 428 IU/L (<190). Muscle biopsy showed typical reducing bodies, and genetic analysis identified a novel pathogenic hemizygous variant, c.370_375del. We identified 44 previous reported cases separated in two groups: 28 cases with mean age onset 7.6 ± 5 years and 16 with 26.7 ± 4.2 years. The time for the diagnosis was shorter to younger group. The initial symptoms, rigid spine, contractures, scoliosis and axial and neck weaknesses, dysphagia, cardiac involvement, were predominant in younger group. The variant c.369C > G predominated in younger group and c.448T > C in older one. Pathogenic variants positions seemed related to severe phenotype. Most wheelchair patients belonged to younger group. The data from this compilation and our case provided a general characterization spectrum and prognosis between two groups of age onset with RBM.

BACKGROUND: Rhabdomyolysis is a potentially fatal condition which occurs due to skeletal muscle injury and classically presents with myalgia and red-brown coloured urine. Presence of excess myoglobin in the glomerular filtrate forms myoglobin casts which causes severe obstruction and necrosis of the tubules leading to acute renal failure.
METHODS: We report two fatal cases of rhabdomyolysis associated acute renal failure. The first victim died in police custody and the second victim died due to severe physical exertion.
RESULTS: In both the cases, creatine kinase levels were elevated and myoglobin was detected in urine in the second case. Myoglobin immunohistochemistry detected the presence of myoglobin cast in the glomerular tubules of kidney in both the cases.
CONCLUSIONS: Myoglobin immunohistochemistry of renal tissues, serum creatine kinase, urine myoglobin analysis and muscle histopathology are the laboratory tests that should be considered at autopsy where rhabdomyolysis is suspected.

Objective: To investigate the clinical features, skeletal muscle imaging, and muscle pathological characteristics of normokalemic periodic paralysis (NormoKPP) caused by mutation of SCN4A gene p.R675Q. Methods: The clinical data, skeletal muscle imaging, pathological data, and gene test results of a family with NormoKPP were collected in detail in October 2018. The previous literature was reviewed and used for comparative analysis. Results: The proband was a 28-year-old male with paroxysmal weakness of both lower limbs for 14 years. Limb weakness was mainly manifested in the proximal extremities of both lower limbs, which occurred two to three times a year. The muscle weakness of each attack lasted for 1-2 weeks and gradually recovered. The blood potassium levels were normal. The abnormal signals of the posterior thigh muscle group and the medial calf muscle group could be seen on the magnetic resonance imaging (MRI) of the skeletal muscle, and the target-fiber could be seen in some muscle fibers in muscle pathology. The father of the proband and his brother had the same symptoms. In the same family, 10 people received genetic testing. The results showed that five had a mutation of SCN4A gene p.R675Q. The mutation gene came from the father of the proband. Conclusion: NormoKPP is a clinically rare form of sodium ion channel disease. The clinical manifestations, skeletal muscle imaging, and pathological changes are different from the common hypokalemic periodic paralysis. SCN4A gene detection is an important means for the diagnosis of NormoKPP.

Muscle biopsy has been practiced as a well-established part of paraclinical workup in patients with neuromuscular diseases since late 1960s. In this narrative review paper, the role of some pre and post muscle biopsy factors and their importance in achieving the best diagnostic results will be explained. Considering the new advances in diagnostic molecular techniques and the availability of local standard myopathology laboratory as well as the presence of a dedicated myopathologist, the indications of muscle biopsy in four major types of neuromuscular diseases will be shortly reviewed. Moreover, indications of muscle biopsy in four major types of neuromuscular diseases will be shortly discussed based on literature review of recent published diagnostic algorithms and our 11 years\' experience of performing about 4000 muscle biopsies cases in the only standard referral diagnostic center for muscle biopsy in Iran. Although diagnostic algorithms of some muscle diseases have been changed based on recent advances in biochemical and molecular diagnostic techniques, still muscle biopsy continues to play a major role in the diagnosis and management of variety of neuromuscular disorders and has proved to be a preferable diagnostic procedure by some neuromuscular specialists for the cases who can benefit from rapid therapeutic management. The application of diagnostic algorithms should be practiced in accordance with geographic distribution of the diseases, the availability of diagnostic techniques and the presence of specialists in each center considering the local insurance coverage and the cost to be paid by the patient in every center.

BACKGROUND: Myalgia is a common but unspecific set of symptoms that may be caused by orthopedic, neurological and internal medical conditions, often resulting in a diagnostic challenge. Muscular polyarteritis nodosa (PAN) is a rare differential diagnosis of myalgia with elevated serological inflammatory markers.
OBJECTIVE: Based on three clinical cases and the literature this review describes the essential clinical and diagnostic features of muscular PAN.
RESULTS: Muscular PAN typically presents with immobilizing myalgia confined to the lower limbs and elevated serological inflammatory markers but often normal creatine kinase (CK) levels. Contrast-enhanced magnetic resonance imaging of the affected muscles, which can often mimic myositis, and muscle biopsy provide the relevant histological findings that lead to the diagnosis of a vasculitis.
CONCLUSIONS: With respect to own experiences and the reviewed literature, muscular PAN should be considered as a possible diagnosis in cases of myalgia with elevated inflammatory markers but normal CK levels and a lack of further symptoms typical for vasculitis.