Physical therapy improves motion in a patient with inclusion body myositis - a case report

Introduction. Inclusion body myositis (IBM) is a rare form of inflammatory myopathy with a slowly progressive course. It is manifested by early weakness and atrophy of skeletal muscles, especially forearm muscles and the quadriceps. At the very beginning of the disease, clinical symptoms are not pronounced, therefore it is difficult to diagnose. Case report. A forty-eight-year-old female patient visited her doctor due to the weakness of muscles in arms and legs. Five years prior to this, she was treated by a neurologist and a physiatrician on several occasions with different diagnoses for progressive muscle weakness. During the last hospitalization, IBM was diagnosed after the muscle biopsy findings. After the diagnosis, the patient underwent intensive physical therapy in order to preserve the ability to independently perform everyday activities and stability of walk. Conclusion. IBM is a rare clinical entity which often takes several years to be diagnosed. Progressive muscle weakness in elderly should point to possible IBM diagnosis, which is only confirmed by muscle biopsy. Physical therapy has a significant role in the treatment as it leads to improvement of functional abilities of the patients in their daily activities, thus reducing the disability degree.


Introduction
Inclusion body myositis (IBM) is a rare clinical entity which is classified in the group of idiopathic inflammatory myopathies 1, 2 . It is a complex disorder of an known etiological cause, but genetic, immunological and environmental factors are considered to have significant influence in the development of the disease. Numerous studies have hypothesized that IBM may be an autoimmune inflammatory muscle disorder. The lack of the adequate response to the administration of conventional therapeutic modalities which are used in the treatment of autoimmune diseases points to the role of other factors in the pathogenesis of this disorder 3,4 . It is thought that IBM is closely connected to both autoimmune and degenerative processes. Degenerative processes occur in muscle tissue by forming vacuoles, the so called "inclusion bodies", which are the clusters of various unfolded or misfolded proteins. For this reason, it was long believed that IBM was a degenerative disease of muscle tissue 5 . However, recent research has shown that viral infection could be a trigger which induces abnormal response of the immune system and contributes to the development of IBM 6 . Also, some people have genetic predisposition for this disease 7 .
IBM is characterised by chronic, progressive weakness and atrophy of skeletal muscles, especially distal parts of the upper and proximal parts of lower extremities, sometimes followed by the weakness of facial muscles and dysphagia 2,8 . Since muscle weakness is the main clinical symptom, the diagnosing of IBM often lasts for a long time due to rare occurrence of the disease. Pathological-histological confirmation of the existence of inclusion bodies in skeletal muscles is the fundamental diagnostic procedure. The lack of adequate pharmacological therapy for the IBM patients together with the progressive course of the disease reduces the performance of everyday activities and leads to disability and restricted movability 1, 2, 6, 9 .
The aim of this paper is to point to possibilities of occurrence of this disease in the patients with long-lasting muscle weakness, as well as emphasize the necessity of muscle biopsy as a fundamental diagnostic indicator. We also demonstrate the significance of physical therapy as the main treatment of the disease.

Case report
A forty-eight-year-old female patient visited a neurologist at the Clinical Centre in Kragujevac for the first time in 2011 for the weakness in arm and leg muscles, which first appeared eight months before. Electromiography (EMG) and nerve conduction studies (NCS) neurography were done and showed moderate to moderately strong demyelination polyneuropathy in the lower and upper extremities, which resembled the findings after acute inflammatory demyelination polyneuropathy (AIDP). The physical therapy, electrical therapy and kinesiotherapy were administered, which considerably improved general status; general motor strength (GMS) was also improved so that the patient was significantly more stable while moving.
In 2012 and 2013, the patient was hospitalized at the Clinics of Neurology and Physical Medicine, Clinical Centre Kragujevac twice each year due to the weakness in upper and lower extremities and impaired general condition with various diagnoses: sensorimotor polyneuropathy, status post AIDP and leukoencephalopathy. Each hospitalization at the Rehabilitation Centre lasted for twenty-one days. The treatment was conducted daily, six days per week. Kinesiotherapy programme included the exercises of diaphragm breathing, the exercises for thorax expanding, active exercises for maintaining general mobility, exercises for coordination of movement and when changing from lying to sitting position. Kinesiotherapy was conducted for the duration of 40-45 minutes. During each hospitalization, the functional abilities of the patient were evaluated by the Health Assessment Questionnaire (HAQ). At the first hospitalization, the value of HAQ score was 1, which pointed to slight decrease in functional abilities during everyday activities (moderate disability). Manual muscle test (MMT) was done at each hospitalization and had the values of -4/5 for the upper extremities (UE), and -3/5 for the lower extremities (LE). EMG and NCS showed significant worsening in relation to the ones, done in 2011. Magnetic resonance imaging (MRI) of the brain and cervical and lumbosacral spine showed old three lacunar infarctions in the right parietal lobe. Anosmia was diagnosed during the examination of an allergologist. In addition, ergometric tests were done, showing low probability for cardiovascular diseases; however, it should be noted that the test was not properly done due to the patient's incorrect walk ("leg shuffling"). The analysis of cardiolipin total antibodies (IgG, IgA, IgM) was negative. All laboratory parameters were within limits of reference values. After each hospitalization, rehabilitation treatment was indicated, combined with physical therapy in ambulatory and spa conditions, which led to better and more reliable motions of the patient.
In existence of Guillain-Barré syndrome, but the clinical picture gave rise to suspicion, and high creatine kinase values indicated the possibility of paraparesis flaccida or polyneuropathy specifica. Hypotrophy of the mimic muscles with light reduction of mimic movements was diagnosed together with a slightly dysarthric speech, reliance on help in changing position from sitting to standing, as well as the hypotrophy of all muscles of upper and lower extremities. The administration of 25 g i.v. of immune globulin IgG-7S did not lead to any improvement. The patient was treated with physical therapy (stable galvanization, electrical stimulation, magnetic therapy, diadynamic currents); kinesiotherapy treatment was conducted in order to reinforce global muscle strength (GMS) and improve walking coordination. HAQ questionnaire was 1, MMT for UE was 3/5, while for LE was 2-3/5. The finding of dual energy X-ray absorptiometry (DEX) of the neck and femur, T-score was -1.1, and regions L1-L4 showed osteopenia.
During the last hospitalization at the Clinic of Neurology (Clinical Centre Kragujevac) in September 2016, muscle biopsy showed IBM. A histological finding showed the presence of muscles of altered architecture with clearly visible necrosis and myofagocytes, due to the presence of inflammatory infiltrates. Inflammatory infiltrate was of the dominant T-lymphocyte type (CD4+, CD8+), with numerous histiocytes and CD8+ lymphocytes invading non-necrotic fibers. Both types of fibers were presented with elements of group atrophy, indicating moderate lesion. In many fibers, the presence of rimmed vacuoles was observed (Figure 1), fibers without cyclooxigenase (COX) activity were present, the expression of the major histocompatibility complexclass 1 (MHC-I class) of antigens in the inflammation zone, but also in fibers that were not necrotic, was amplified.

Fig. 1 -Micrography with histological image of the muscle biopsy: A) Myophagocytosis shown on the modified Gomori trichrome staining (10×); B) The presence of a vacuole (arrow), Gomori trichrome staining (40×).
After IBM was diagnosed, the patient was hospitalized at the Centre for Physical Medicine and Rehabilitation, Clinical Centre Kragujevac, where she was administered physical therapy (stable galvanization, transcutaneus electro neural stimulation, diadynamic currents, kinesiotherapy program) and functional testing. MMT was conducted for UE and LE which showed the values of -3/5 and -2/5, respectively. The value of HAQ questionnaire was 2, which pointed to severe disability ( Figure 2). During the latter hospitalization, the weakness of body flexors and difficulties with motion in bed were noticed together with difficulties in standing up from the chair; however, the patient walked alone on flat surface with the help of a stick with four bottoming points; kinesiotherapy treatment was conducted in patient's room under the supervision of the therapist with daily exchange of tension and pulsation, since exertion had to be dosed during active exercises. At home, kinesiotherapy included active exercises for general motion and walking on flat surface 2 × 60 minutes, with occasional breaks.
Presentation of the patientʼs distal parts of upper extremities before and after several cycles of physical therapy is shown in Figure 3.

Discussion
IBM is a rare disease, which more often appears in male in comparison to female population aged over 50, with the ratio 3:1. The frequency of the disease is from 0.001% for those aged less than 50 years to about 0.005% for those aged over 50 2 . Because of such a low frequency and rare occurrence, several years usually pass before the disease is diagnosed, as was the case with our patient 3 .
IBM is characterized by progressive muscle weakness of distal upper extremities and proximal lower extremities for more than a year in the patients aged over 35, and a normal or moderately increased values of creatine phosphokinase (CPK) 2 . In our patient, muscle weakness was a predominant symptom which worsened overtime. In addition to these symptoms, the patient had diagnoses of anosmia and osteopenia, which have been described in other patients with idiopathic myositis 10,11 . The crucial parameter to confirm the diagnosis of this disease is a muscle biopsy, which was, in our case, performed 5 years after the onset of muscle weakness 1, 4, 7, 9 . Pharmacological therapy has a very small influence on a progressive course of IBM in comparison to other inflammatory myopathies, thus the patients lose the capacity to perform everyday activities and most often end up in a wheelchair 10-15 years after the onset of the disease 2,4,9,[12][13][14] . In our patient, administration of immunoglobulins did not lead to any improvement, while the muscle weakness progressed, so the patients could walk only with the help of aids. The aim of physical therapy was to maintain the function and mobility in all joints, thus providing independent mobility as long as possible. At first, the application of physical therapy in IBM was considered contraindicated due to possible increase of inflammatory process in muscles, but later studies pointed to its significance in muscle strength improvement, endurance and increase of functional abilities of the patients related to movement 1,15 . After the administration of physical therapy in several cycles, general condition of our patient improved. Mobility was made easier and extremity muscles were slightly strengthened. Her walk was more stable, which improved the quality of her life.

Conclusion
IBM is a rare disease which is often diagnosed after many years. Progressive muscle weakness should point to possible doubt about IBM, which is only confirmed by muscle biopsy. Physical therapy plays a significant role in the treatment of IBM, since it leads to improvement of the functional capacity of patients in daily activities, thus reducing their disability.