Hereditary and Sporadic Inclusion Body Myositis

Disease/Disorder

Definition

Sporadic inclusion body myositis (s-IBM) is a subtype of idiopathic inflammatory myositis (IIM) first described in 1971 by Yunis and Samaha. s-IBM and h-IBM are distinguished from other inflammatory myopathies clinically by their pattern of weakness, selective muscle wasting and progressive course. It is pathologically distinct by a combination of inflammatory and myodegenerative features with multi-protein aggregates in muscle tissue.¹ s-IBM is an idiopathic slowly progressive inflammatory myopathy characterized by muscle weakness and atrophy most prominent in wrist and finger flexors in the forearm, as well as the quadriceps, resulting in severe disability. While h-IBM has a similar onset and clinical course, it is a non-inflammatory process and typically spares quadriceps musculature. It is associated with mutations in the DES, GNE, MYHC2A, and VCP genes.  

Etiology

The etiology of sporadic inclusion body myositis (s-IBM) is complex and likely multifactorial. It is believed s-IBM has an autoimmune component; however, it responds poorly to immune therapy leaving suggestion of a more complex etiology which may include muscle fiber degradation, inflammation, and the accumulation of abnormal proteins in muscle fibers leading to a secondary immune response.^1,2 The trigger for these events has not been definitively identified; however, it is likely related to gene expression and oxidative stress in the milieu of aging muscle.^2-4

Epidemiology including risk factors and primary prevention

• s-IBM is the most common acquired myopathy in patients aged over 50 years old.⁵
• s-IBM most commonly presents in the sixth decade of life.⁴
• It occurs more frequently in men than women by a ratio of approximately 3:1.⁶
• Prevalence range for s-IBM averages 5 to 9 cases per million.
• It is likely to be underdiagnosed, thus causing reported prevalences to vary. There are no identifiable risk factors for s-IBM, which can be modified to prevent onset or progression.

Patho-anatomy/physiology

• There are multiple pathophysiologic components of s-IBM, which result in the following clinical findings
  • Muscle fiber degradation.
  • Abnormal gene expression with subsequent protein mis-folding and accumulation.
• Protein unfolding, mis-folding, and accumulation is a prominent feature resulting from oxidative stress and abnormal genetic expression.
  • In general, known causes of misfolded proteins include oxidative stress, aging, molecular crowding, and toxins.
  • These abnormal proteins accumulate in the cytoplasm and nucleus of the muscle fiber.
• Inflammation is likely a response to misfolded proteins.
  • Major histocompatibility complex (MHC) class 1 and II are upregulated in the muscle fiber. Normally, this is not expressed.^4,7
  • Muscle fibers that express MHC class 1 then become antigen presenting, which stimulates an inflammatory response.⁸
  • Cytotoxic CD8 positive cytotoxic T cells accumulate and expand in the cytoplasm and nuclei of muscle fibers expressing MHC class I antigens.^9-11 The progression of the disease has been attributed with association with the RNA processing molecule, TDP-43, which is responsible for controlling interferon-gamma (IFN-y) responses to viral infection. Viral-induced triggering of IFN-y producing cytotoxic T cell expansion may contribute to s-IBM. Senescent CD8+ cells persistently being triggered by viruses or genetic predisposition contribute to the progressive nature of the disease.¹² The inflammatory cell invasion of the non-necrotic muscle fibers is seen in inflammatory myopathies and suggests a primary role of inflammation.
  • This lymphocytic inflammatory component has been clearly demonstrated; however, s-IBM does not respond to anti-inflammatory or immunosuppressive agents. This could argue against a primary role of inflammation in the disease and separates it from polymyositis and dermatomyositis. The pathophysiology of polymyositis is thought to be T-cell mediated in which CD8+ and CD4+ T-cells invade muscle fibers and lead to fiber necrosis, similarly to s-IBM. However, in inclusion-body myositis, rimmed vacuolar formation coexists with the immunological features. Further, the pathophysiology of dermatomyositis includes activation of the complement system leading to deposition of proteins in the walls of blood vessels, causing lysis of endomysial capillaries and muscle ischemia. Dermatomyositis and polymyositis are more commonly associated with the anti-Jo-1 autoantibody, when compared to s-IBM.¹³
• Abnormal protein formation leads to inclusion bodies identified histologically and muscle atrophy identified clinically.
  • As multiprotein aggregates form, lysosome-like vacuoles develop, possibly as an attempt to degrade these proteins.^4,5
  • Inclusion bodies are composed of amyloid beta, amyloid beta precursor protein, and phosphorylated tau protein, which have staining patterns consistent with beta-pleated sheet conformation.^4,5
  • Increased cholesterol deposition at sites of abnormal protein accumulation suggests impaired cholesterol transport and may promote further amyloid deposition.
• Mitochondrial deoxyribonucleic acid (MtDNA) abnormalities at the histologic level have been noted. Mitochondrial dysfunction has a role in s-IBM progression.^1,10,11
• Genetic susceptibility in s-IBM has shown increasing evidence.¹
  • Likely polygenic including both HLA and non-HLA forms.¹
  • There is a strong association with HLA-DRB1 * 03:01 which may portend a more severe phenotype and early age of onset.¹
  • The TOMM 40 gene on chromosome 19 plays a role in mitochondrial membrane function and may be associated with later age of onset.^1,14
• hIBM
  • Associated with mutations in the DES, GNE, MYHC2A, and VCP genes.
  • hIBM can be divided into three different groups based on the affected genes: IBM1, IBM2, and IBM3.
    • IBM1: Mutations in the DES (Desmin, 2q35) gene can lead to IBM1, so it is also therefore known as desmin related myopathy. Most DES gene mutations show autosomal dominant (AD) inheritance patterns.
    • IBM2: Mutations in the GNE gene are associated with IBM2 and is inherited in an autosomal recessive pattern.
    • IBM3: Mutations in the MYHC2A gene, which encodes the myosin heavy chain IIa is associated with IBM3 and inherited in an AD pattern.¹⁵
  • IBM with early-onset Paget disease and frontotemporal dementia (IBMPFD): Missense mutation in Valosin-containing protein (VCP) gene. It presents with early onset Paget’s disease of the bone and frontotemporal dementia in addition to proximal and distal myopathy presenting in the 4th or 5th decade of life. It is inherited in an autosomal dominant pattern.¹⁵
  • Shares pathologic features of s-IBM.

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

Inclusion body myositis (IBM) is a slowly progressive disease. Muscle deterioration by manual muscle testing (MMT) has been estimated at 3.5% per year with the greatest decline in the quadriceps muscle.

• Initial presentation will likely include difficulty rising from sit to stand and weak grasp.¹⁶
• Weakness in the quadriceps group and wrist/finger flexors progresses and may result in falls and impaired activities of daily living.
• Dysphagia is common and worse in the later stages of disease, however, 15% may present with dysphagia as initial symptom.¹
• Because of the late onset of the disorder and the slowly progressive nature of the process, patients may attribute early decline in functional status over years to the normative process of aging. This may contribute to a delay in diagnosis.
• Natural history studies have shown the life expectancy is not significantly decreased compared to the general population.
• In end stage severe disease, Weakness, dysphagia and respiratory involvement can be debilitating and result in failure to thrive and respiratory infections.¹

Specific secondary or associated conditions and complications

s-IBM is more frequent in patients with autoimmune disorders, such as rheumatoid arthritis, systemic lupus erythematosus, and Sjogren’s syndrome.^1,7

Essentials Of Assessment

History

• Initial presentation involves both proximal and distal muscle weakness. There is a predilection for weakness of the non-dominant hand and a distinctive pattern of asymmetric weakness affecting the flexors of the distal phalanges with sparing of the intrinsic hand muscles.
• Patients may also have mild facial weakness.¹
• Falls may be noted secondary to quadriceps weakness. This may result in difficulty ascending and descending stairs, and subjective report of knees giving out or buckling (less frequently noted in the h-IBM form). Recent studies have found a correlation between knee extensor strength and functional lower limb measures including the six-minute walk test.¹
• Patients often complain of progressive difficulty with functional tasks requiring strength and endurance of involved muscle groups, such as grooming hair, climbing stairs, grasping kitchen items, and rising from a seated position.
• Swallowing dysfunction occurs in 51-65% of cases,¹ more commonly found later in disease progression. Swallow studies can confirm dysphagia and demonstrate cricopharyngeal achalasia.¹⁷
• Sleep disordered breathing (SDB) due to weakness of the oropharyngeal muscles is now recognized as a common problem in IBM and a restrictive lung disease pattern noted by reduced vital capacity and nasal inspiratory pressures have been found in up to 75% of patients with IBM. Diaphragmatic weakness may also be involved.¹
• Cardiac involvement is not typical of IBM. However, there have been rare reported cases of cardiomyopathy and conduction abnormalities.¹

Physical examination

Prominent findings on physical examination include:

• Observable atrophy of quadriceps (except in h-IBM) and forearm musculature (scalloped forearms), in particular the wrist/finger flexor group is commonly effected.¹⁶
• Weak knee extension, hip flexion, and grasp are usually seen.
  • The pattern of quadriceps and long finger flexor weakness is common and diagnostic; this combination is rarely seen in other diseases.
  • Typically, if finger flexor strength is less than shoulder abduction, and quadriceps strength is less than hip flexors, s-IBM is suggestive rather than polymyositis or dermatomyositis.
• Normal sensation is common, though s-IBM is associated with a variable degree of peripheral neuropathy. About 30% of patients may have associated clinical peripheral neuropathy and/or electrophysiological evidence of a sensory neuropathy, though most do not have any apparent clinical manifestations.¹⁷
• Diminished patellar reflex is seen secondary to quadriceps wasting and reduced brachioradialis reflex may be seen with forearm wasting.

Functional assessment

• Mobility decreases slowly.
• Self-care abilities also diminish slowly.
• There is no evidence that s-IBM effects cognition, behavior, or affect. However, attention should be paid to effective coping skills, because the patient deals with loss of functional ability in the setting of a chronic progressive disease.¹⁸
• The inclusion body myositis functional rating scale (IBM-FRS), is a disease-specific, 10-point functional rating scale was found to be the most sensitive measure of change over the course of a multicenter pilot trial of clinical safety and tolerability of high-dose beta interferon-1a, as well as disease severity.¹⁹ The scale includes scoring (0 to 4, 4 being normal/independent) for Swallowing, Handwriting (with dominant hand prior to IBM onset), Cutting food and handling utensils, Fine motor tasks (e.g., using keys, opening doors), Dressing, Hygiene (bathing and toileting), Turning in bed and adjusting covers, Sit to stand, Walking, and Climbing stairs.²⁰

Laboratory studies

Creatine kinase (CK) levels are variable, ranging from normal to <15x the upper limit of normal.

Autoantibody testing has become an important tool for the diagnosis of s-IBM. Antibodies to cytosolic 5’-nucleotidase 1A (anti-cN1A) can be found in 33-55% of patients with s-IBM compared to <5% prevalence in other inflammatory IIM. Although, anti-cN1A reactivity may also be seen with a similar proportion in other autoimmune diseases such as Sjogren’s syndrome (SS) and systemic lupus erythematosus (SLE) and a high antibody titer is less reliable in patients who have associated autoimmune disease.^21-23

In a study that used addressable laser bead immunoassay (ALBIA) in patients with sporadic inclusion body myositis and disease control patients with other autoimmune, degenerative and neuromuscular disease and healthy controls, anti-NT5c1A was found to have moderate sensitivity and high specificity for sporadic inclusion body myositis.²⁴

Imaging

Magnetic resonance imaging (MRI) with T1 and T2 weighted (STIR images) will reflect atrophy of affected skeletal muscles and compliments the physical examination and can assist with sights of target for muscle biopsy.4 The pattern of weakness and edema seen on MRI has been shown to be highly specific and distinguishable from other myopathies. Features on MRI in the upper limbs include forearm flexor involvement with preference for the flexor digitorum profundus (FDP) and sparing of the flexor digitorum superficialis (FDS) and forearm extensors are seen. In the lower limbs, quadriceps are involved early with sparing of adductors and hamstrings even in the later stage of disease.^25,26

Muscular ultrasound (US) will reveal muscle atrophy. Flexor digitorum profundus and flexor carpi ulnaris echo intensity in muscle US is a sensitive diagnostic indicator of s-IBM when compared to s-IBM mimicking diseases.^25,26

Muscle biopsy is the definitive diagnostic procedure for s-IBM.

• The biopsy should be taken from a moderately affected muscle (ideally MRC grade 4) not previously studied by needle electromyography.
• Histopathological features of s-IBM
  • Predominantly endomysial inflammatory infiltration of non-necrotic muscle cells on hematoxylin & eosin stain
  • Vacuoles rimmed by a membranous cytoplasmic material (“rimmed vacuoles”)
  • Congophilic inclusions that may be intra or extravacuolar
  • Mitochondrial changes including increased number of cytochrome c oxidase negative fibers
  • Eosinophilic inclusions can be seen in up to 50% of IBM patients
  • Additionally, p62 immunostaining can assist with differentiating diagnosis of sIBM from polymyositis and dermatomyositis, as its accumulation in muscle tissue is unique to sIBM²⁷

Supplemental assessment tools

Electromyography plays a crucial role in clinical practice and may be used to clarify the nature of this disease and differentiate a myopathy from a neuropathy. However, EMG findings in s-IBM are non-specific and have been excluded from the most recent diagnostic research criteria for IBM.^1,21

• Abnormal spontaneous activity can be seen commonly (56-100%) and includes fibrillations, positive sharp waves and less frequently reported are myotonic and myokymic discharges.
• Myopathic motor units are not specific to s-IBM. They are identifiable on needle electromyography with decreased amplitude, short duration, and polyphasic. With later stages of disease the motor unit action potential duration may become larger and longer secondary to muscle fiber necrosis followed by regeneration. These findings can be misconstrued as neuropathic, however, careful attention to the recruitment pattern will distinguish myopathic motor units which will have early recruitment from neurogenic which will have reduced.
• There also may be a sensory axonal neuropathy found on electrodiagnostic studies in up to 30% of cases.¹⁶
• Single Fiber EMG studies may show mildly increased fiber density, abnormal jitter and blocking; however, these findings are non-specific.
• EMG examination of the flexor muscles including the FDP should be included.

Early predictions of outcomes

• There is no clear evidence that IBM affects life expectancy
• About 1/3 of patients require wheelchair 14 years after disease onset, nearly all patients require wheelchair 20 years after disease onset²⁸
• There is preliminary evidence that patients with positive cN-1A antibodies may have mildly higher adjusted mortality risk²⁹

Environmental

There are no environmental risk factors associated with h-IBM or s-IBM.

Social role and social support system

As with any myopathy, communication with the patient and family regarding functional deficits needs to occur.

Professional issues

Open and honest discussion with the patient and family regarding the course of this disease is necessary. Because life expectancy is not shortened and there are no treatments at this time that improve strength, ongoing communication regarding adaptive equipment and environmental modifications to improve quality of life is appropriate.

In individuals identified as having h-IBM, appropriate genetics counseling of family members is recommended for potential issues in family planning.

Rehabilitation Management And Treatments

Available or current treatment guidelines

• Presently, there are no effective pharmacologic treatments that alter the course of the disease. Appropriate adaptive equipment including orthotics, wheelchairs, and assistive lift devices will improve the quality of life.
• Patients typically respond poorly to treatment with steroids or other immunotherapeutic agents.^1,7 Some patients may show a temporary improvement or period of stabilization, however, the disease will progress despite this treatment.^26,30 Muscle biopsy subsequent to this treatment notes progression of amyloid deposition and vacuolization.¹ These are still used as empiric agents and may have a positive effect in those with comorbid autoimmune disorders. As it is difficult to predict which subsets of patients may respond to treatment, current practice is to offer only supportive treatment.¹ If a trial of immunosuppressive therapy is used, tolerability and efficacy are carefully monitored.¹

At different disease stages

Rehabilitation

• Rehabilitation efforts may improve function and quality of life. Goals include maximizing functional independence through environmental adaptation, task modification, and provision of mobility aids.
• Exercise-based therapy is safe for strength and endurance with no subsequent increase in CK.^31,32
• Orthotics may help prolong independent mobility and prevent falls.
  • Ground reaction force ankle foot orthosis (AFO), limited dorsiflexion range of motion AFO, or standard knee-ankle-foot orthosis with locking mechanism in knee extension during gait may be helpful in patients with dorsiflexion weakness and varying degrees of quadriceps weakness.
  • Knee orthoses, such as a Swedish knee cage, may prevent genu recurvatum to stabilize knee during gait.
• Tendon transfers (extensor carpi radialis longus / brachioradialis to finger flexors) can improve function and reduce disability.¹
• Assistive devices may include straight cane, quad cane, and walker; however, diminished finger/wrist flexor strength may make this difficult. Lofstrand crutches with elbow support or a platform walker may be an option also.
• Environmental modifications to optimize accessibility is appropriate as disease progresses and functional impairments emerge.

Dysphagia Management

• Various treatment and management strategies including cricopharyngeal myotomy, botulinum toxin injections or insertion of a PEG tube to maintain nutrition exist, however, there are no currently established guidelines.¹

Coordination of care

All members of the rehabilitation team should be actively involved in the ongoing management of patients with IBM, including the physical therapist, occupational therapist, speech therapist, orthotist, nutritionist, social worker, psychologist, neurologist, physiatrist and otolaryngologist.

Emerging/unique interventions

New therapeutic trials are focused on targeting inflammatory and degenerative pathways of muscle degradation. There have been no studies to date showing that treatment modifies course of the disease.

Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

Rehabilitation medicine impacts patients with IBM through ongoing functional evaluation and provision of adaptive equipment to optimize function and quality of life.

Weakness and atrophy in the quadriceps or wrist/finger flexor groups suggest s-IBM.

Coinciding sensory neuropathy may disguise underlying myopathy and result in a delay in diagnosis.

Diagnosis is made by characteristic findings on muscle biopsy.

Distinguishing s-IBM from polymyositis and dermatomyositis is important to direct treatment and management.

Cutting Edge/Emerging And Unique Concepts And Practice

• IVIG in an open-label uncontrolled and 2 placebo-controlled studies showed marginal to no improvement. IVIG is not recommended for use in clinical practice. There was some reported improvement in swallowing in patients with severe dysphagia.³³
• Beta-interferon at standard and high dosing showed no improvement in muscle strength in 2 randomized controlled studies.³⁴
• Bimagrumab, an activin receptor II inhibitory monoclonal antibody, did not show any statistical improvement in muscle function.³⁵
• Follistatin, a myostatin antagonist, needs further study to determine efficacy.³⁶

Gaps In The Evidence-Based Knowledge

There is debate regarding whether inflammation leads to muscle fiber degeneration or whether fiber degeneration leads to an inflammatory response.

References

1. Needham M, Mastaglia FL. Sporadic inclusion body myositis: a review of recent clinical advances and current approaches to diagnosis and treatment. Clinical Neurophysiology. 2016;127(3):1764-1773.
2. Needham M, Mastaglia FL. Inclusion body myositis: current pathogenetic concepts and diagnostic and therapeutic approaches. The lancet neurology. 2007;6(7):620-631.
3. Askanas V, Engel WK. Inclusion-body myositis and myopathies: different etiologies, possibly similar pathogenic mechanisms. Current opinion in neurology. 2002;15(5):525-531.
4. Askanas V, Engel WK. Inclusion-body myositis, a multifactorial muscle disease associated with aging: current concepts of pathogenesis. Current opinion in rheumatology. 2007;19(6):550-559.
5. Callan A, Capkun G, Vasanthaprasad V, Freitas R, Needham M. A systematic review and meta-analysis of prevalence studies of sporadic inclusion body myositis. Journal of neuromuscular diseases. 2017;4(2):127-137.
6. Panginikkod S, Musa R. Inclusion body myositis. 2019;
7. Dalakas M, Karpati, G. The inflammatory myopathies. In: G. Karpati DH-J, K. Bushby, R.C. Griggs, ed. Disorders of Voluntary Muscle. 8th ed. Cambridge: Cambridge University Press; 2010.
8. Griggs RC, Askanas V, DiMauro S, et al. Inclusion body myositis and myopathies. Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society. 1995;38(5):705-713.
9. Atluri RB. Inflammatory myopathies. Missouri medicine. 2016;113(2):127.
10. Catalán-García M, Garrabou G, Morén C, et al. Mitochondrial DNA disturbances and deregulated expression of oxidative phosphorylation and mitochondrial fusion proteins in sporadic inclusion body myositis. Clinical Science. 2016;130(19):1741-1751.
11. Rygiel KA, Miller J, Grady JP, Rocha MC, Taylor RW, Turnbull DM. Mitochondrial and inflammatory changes in sporadic inclusion body myositis. Neuropathology and applied neurobiology. 2015;41(3):288-303.
12. Văcăraş V, Vulturar R, Chiş A, Damian L. Inclusion body myositis, viral infections, and TDP-43: a narrative review. Clinical and Experimental Medicine. 2024;24(1):1-13.
13. Dalakas MC, Hohlfeld R. Polymyositis and dermatomyositis. The Lancet. 2003;362(9388):971-982.
14. Mastaglia F, Rojana-Udomsart A, James I, et al. Polymorphism in the TOMM40 gene modifies the risk of developing sporadic inclusion body myositis and the age of onset of symptoms. Neuromuscular Disorders. 2013;23(12):969-974.
15. Murnyák B, Bodoki L, Vincze M, et al. Inclusion body myositis–pathomechanism and lessons from genetics. Open Medicine. 2015;10(1)
16. Herbert MK, Stammen-Vogelzangs J, Verbeek MM, et al. Disease specificity of autoantibodies to cytosolic 5′-nucleotidase 1A in sporadic inclusion body myositis versus known autoimmune diseases. Annals of the rheumatic diseases. 2016;75(4):696-701.
17. Mohannak N, Pattison G, Hird K, Needham M. Dysphagia in patients with sporadic inclusion body myositis: management challenges. International Journal of General Medicine. 2019:465-474.
18. McDonald C, Han, JJ, Carter, GT. Myopathic disorders. In: Braddom R, ed. Physical Medicine and Rehabilitation. 4th ed. Elsevier Saunders; 2011.
19. Jackson C, Barohn R, Gronseth G, Pandya S, Herbelin L, Group MS. Inclusion body myositis functional rating scale: a reliable and valid measure of disease severity. Muscle & nerve. 2008;37(4):473-476.
20. Amato A, Barohn R. Inclusion body myositis: old and new concepts. Journal of Neurology, Neurosurgery & Psychiatry. 2009;80(11):1186-1193.
21. Benveniste O, Stenzel W, Allenbach Y. Advances in serological diagnostics of inflammatory myopathies. Current opinion in neurology. 2016;29(5):662-673.
22. Limaye VS, Lester S, Blumbergs P, Greenberg SA. Anti-C N1A antibodies in South Australian patients with inclusion body myositis. Muscle & nerve. 2016;53(4):654-655.
23. Lundberg IE, Miller FW, Tjärnlund A, Bottai M. Diagnosis and classification of idiopathic inflammatory myopathies. Journal of internal medicine. 2016;280(1):39-51.
24. Amlani A, Choi MY, Tarnopolsky M, et al. Anti-NT5c1A autoantibodies as biomarkers in inclusion body myositis. Frontiers in Immunology. 2019;10:745.
25. Noto YI, Shiga K, Tsuji Y, et al. Contrasting echogenicity in flexor digitorum profundus–flexor carpi ulnaris: a diagnostic ultrasound pattern in sporadic inclusion body myositis. Muscle & nerve. 2014;49(5):745-748.
26. Dalakas MC, Sonies B, Dambrosia J, Sekul E, Cupler E, Sivakumar K. Treatment of inclusion-body myositis with IVIg: a double-blind, placebo-controlled study. Neurology. 1997;48(3):712-716.
27. Nogalska A, Terracciano C, D’Agostino C, King Engel W, Askanas V. p62/SQSTM1 is overexpressed and prominently accumulated in inclusions of sporadic inclusion-body myositis muscle fibers, and can help differentiating it from polymyositis and dermatomyositis. Acta neuropathologica. 2009;118:407-413.
28. Benveniste O, Guiguet M, Freebody J, et al. Long-term observational study of sporadic inclusion body myositis. Brain. 2011;134(11):3176-3184.
29. Lilleker J, Rietveld A, Pye S, et al. Cytosolic 5′-nucleotidase 1A autoantibody profile and clinical characteristics in inclusion body myositis. Annals of the rheumatic diseases. 2017;76(5):862-868.
30. Rose M, Group eiW. 188th ENMC international workshop: inclusion body myositis, 2–4 December 2011, Naarden, The Netherlands. Neuromuscular Disorders. 2013;23(12):1044-1055.
31. Arnardottir S, Alexanderson H, Lundberg IE, Borg K. Sporadic inclusion body myositis: pilot study on the effects of a home exercise program on muscle function, histopathology and inflammatory reaction. Journal of rehabilitation medicine. 2003;35(1):31-35.
32. Rutkove S, Parker R, Nardin R, Connolly C, Felice K, Raynor E. A pilot randomized trial of oxandrolone in inclusion body myositis. Neurology. 2002;58(7):1081-1087.
33. Dobloug C, Walle-Hansen R, Gran JT, Molberg O. Long-term follow-up of sporadic inclusion body myositis treated with intravenous immunoglobulin: a retrospective study of 16 patients. Clin Exp Rheumatol. 2012;30(6):838-42.
34. Group MS. Randomized pilot trial of high-dose βINF-1a in patients with inclusion body myositis. Neurology. 2004;63(4):718-720.
35. Amato AA, Sivakumar K, Goyal N, et al. Treatment of sporadic inclusion body myositis with bimagrumab. Neurology. 2014;83(24):2239-2246.
36. Greenberg SA. Unfounded claims of improved functional outcomes attributed to follistatin gene therapy in inclusion body myositis. Molecular Therapy. 2017;25(10):2235-2237.

Original Version of the Topic

Lisa Williams, MD. Hereditary and sporadic inclusion body myositis. 11/27/2012

Previous Revision(s) of the Topic

Lisa Williams, MD. Hereditary and sporadic inclusion body myositis. 3/24/2017

Shailesh Reddy, MD. Hereditary and Sporadic Inclusion Body Myositis. 12/9/2021

Author Disclosure

Christopher D. Meserve, MD
Nothing to Disclose

Michael V. Nguyen, MD, MPH
Nothing to Disclose

Dianna H. Nguyen, DO, PhD
Nothing to Disclose

Agam B. Jagota, DO
Nothing to Disclose

Derrick Williams, MD
Nothing to Disclose