Inclusion Body Myositis Workup

Updated: Jun 08, 2018
  • Author: Michael P Collins, MD; Chief Editor: Nicholas Lorenzo, MD, MHA, CPE  more...
  • Print
Workup

Laboratory Studies

Standard studies pertinent to the evaluation of patients with progressive myopathic weakness include complete blood count, magnesium, calcium, phosphate, creatinine, creatine kinase (CK), erythrocyte sedimentation rate (ESR), antinuclear antibodies, rheumatoid factor, serum protein electrophoresis (+/- immunofixation), vitamin D levels, and thyroid function tests.

CK level should be assessed prior to the EMG study. In most cases of s-IBM, serum CK level is normal or elevated to a mild-to-moderate degree. Elevation greater than 12 times normal may occur but is rare.

If polyneuropathy is present based on clinical or electrodiagnostic criteria, then screening for diabetes mellitus and other potential etiologies for a polyneuropathy should be performed.

Myositis-specific antibodies occur more rarely in s-IBM than in DM or PM, but when present, they may identify a subgroup of immunosuppressive treatment-responsive patients. [86]

Next:

Imaging Studies

CT or MRI imaging of muscles may be useful in helping diagnose difficult cases. Findings involve selective atrophy of the quadriceps and forearm flexors. [87, 88]

Previous
Next:

Other Tests

Although not routinely indicated, quantitative sensory testing showed abnormal vibratory, thermal, and heat pain thresholds in more than one half of patients with s-IBM in one small series. [89]

Nerve conduction studies

Motor conductions should be performed in at least one lower and one upper extremity.

Sensory conductions should include at least one lower and one upper extremity nerve.

Needle electrode examination

A full discussion of electrodiagnostic approaches to myopathy is beyond the scope of this article. The reader is referred to a more extensive discussion. Pictures of some needle electrode examination findings are given at the end of the article.

The needle electrode examination aims at demonstrating the presence of a diffuse myopathic process. Conversely, the assumption should not be made that all muscles are affected equally (ie, side-to-side asymmetry, proximal versus distal muscle).

The presence of a polyneuropathy on nerve conduction studies should prompt caution in interpretation since 2 different processes may be occurring simultaneously (eg, denervation/reinnervation and myopathy).

Therefore, the study's focus should be primarily on weak proximal muscles in 3 extremities, where changes in the MUAPs would most likely reveal changes consistent with a myopathic process. The muscle to be biopsied should be avoided in the needle electrode examination.

Insertional activity is variable (ie, normal or mildly increased) but does not show the prominent, complex, repetitive, or myotonic discharges occasionally seen in polymyositis.

Spontaneous activity is present in the form of fibrillation potentials or positive sharp waves. In chronic cases, these may be low in amplitude and infrequent or absent.

In s-IBM, the MUAPs may be variable in shape and size within the same muscle. See the image below.

Composite of 20 motor unit action potentials (MUAP Composite of 20 motor unit action potentials (MUAPs) recorded with a concentric needle electrode from the biceps brachii of a patient with s-IBM. Note the wide range in size and complexity in the MUAPs. Copyright, Paul E Barkhaus, MD, 2000, with permission.

The MUAPs typically show normal to reduced amplitude—reduced duration for simple (nonpolyphasic) MUAPs and variable increase in complexity (phases and turns). When assessing duration, only simple MUAPs should be measured so as to increase diagnostic sensitivity.

Increase in complexity (eg, increases in phases, turns, or the presence of late components or satellites) is a nonspecific finding and may be seen as an early abnormal finding in neurogenic or myopathic processes.

Occasional MUAPs in s-IBM may appear "enlarged" or high amplitude. Careful assessment shows that these are narrow spikes with minimal area. See the image below.

Top - A large, complex motor unit action potential Top - A large, complex motor unit action potential (MUAP; 5 phases, approximately 2500 microV amplitude and 3 ms duration) firing at a progressively increasing rate (ie, shifting left) at about 13 Hz in apparent isolation. In normal muscle, other motor units typically would be recruited at this threshold (calibration 500 microV/division vertical; 10 ms/division horizontal). In the bottom trace the sensitivity is increased to 100 microV/division vertical (no change in horizontal time base), showing very small motor unit action potentials (MUAPs) in the baseline on either side of the large MUAP. This phenomenon may give rise to a mistaken "neurogenic" impression of the MUAP, as these small potentials are overlooked easily or mistaken for baseline noise or fibrillation potentials. Note also that despite the large amplitude of this MUAP, the spikes include essentially no area, giving them a needle-like appearance. Copyright, Paul E Barkhaus, MD, 2000, with permission.

In s-IBM, MUAPs are generally stable. In other words, jitter typically is not increased. See the image below.

On the left are 3 motor unit action potentials (MU On the left are 3 motor unit action potentials (MUAPs) that have been "captured" from the same site and analyzed using a computer-assisted method. Note that the middle one has a satellite or "early" potential linked to it, characterized by the blackened/blurred area created by their superimposition to the left of the main portion of the MUAP. The reason for this is the increased variability in the interpotential interval on successive sweeps (ie, increased jitter). On the right, this middle MUAP is displayed in faster mode (9 sweeps). Note that on the fifth trace, the early component is absent, indicating a block. This shows the infrequent phenomenon in s-IBM of increased jitter and blocking, Copyright, Paul E Barkhaus, MD, 2000, with permission.

Table 2. MUAP Features in Myopathy (Open Table in a new window)

Condition

Changes in MUAP Features

Nonspecific abnormality

Increased complexity (ie, phases, turns, late components)

Only amplitude reduced

Specific for myopathy

Shortened duration (simple or nonpolyphasic MUAPs)

Area reduced

Recruitment of MUAPs is "early" in myopathic processes. This is interpreted as a more rapid recruitment of motor units for level of effort. Thus, discharging motor units appear to be firing faster and interference pattern (ie, pattern at full effort) appears full but reduced in amplitude. See the image below.

Interference pattern in biceps brachii. Top trace Interference pattern in biceps brachii. Top trace - Normal interference pattern at full effort (calibration - 500 microV/division vertical; 1 s/division horizontal). The middle trace is an interference pattern from a patient with severe s-IBM (calibration - 100 microV/division vertical; 1 s/division horizontal). This epoch of signal actually shows the patient going from minimal activation at the left (beginning of the sweep) to full effort on the far right. The "notch" just to the right of the second division mark shows a baseline shift from needle electrode movement. Overall, no amplitude change of "fullness" is seen going from minimal to full effort, and the amplitude of the signal epoch is less than half of what might be expected in normal muscle. The bottom trace is an expanded segment showing interference pattern from biceps brachii; this trace is from a patient with advanced s-IBM (calibration - 100 microV/division vertical; 10 ms/division horizontal), from the early or far left portion of the middle sweep (see "H" bar position between the middle and lower sweeps). This shows a relatively full baseline of small-amplitude, complex motor unit action potentials (MUAPs). Copyright, Paul E Barkhaus, MD, 2000, with permission.

Respiratory testing

Investigators in one study suggested that respiratory function testing, including sleep study, be performed routinely in patients with s-IBM because they found that in 16 patients with biopsy proven IBM, asymptomatic impairment of respiratory function was common and sleep-disordered breathing was present in all patients tested. Four patients reported excessive daytime sleepiness; 8 had at least mild dysphagia; forced vital capacity was < 80% predicted normal in 7; sniff nasal inspiratory pressure was reduced in 3; daytime hypoxemia was present in 9; and hypercapnia was present in 1. Sleep study was performed in 15 and revealed sleep disordered breathing in all. [90]

Previous
Next:

Procedures

Muscle biopsy is the criterion standard for ascertaining the diagnosis of s-IBM.

  • Selection of muscle to be biopsied

    • Findings may be patchy. Therefore, care must be taken in the preparation and examination of sufficient tissue to avoid sampling error.

    • The biopsy sample should be taken from a muscle that is affected moderately (ie, Medical Research Council grade 4 to 4 minus), yet one that is conventionally examined (eg, quadriceps, deltoid, biceps brachii). A severely atrophied, "end-stage" muscle should be avoided.

    • Beyond establishing electrodiagnostic evidence for a myopathic process, the needle electrode examination may be used to determine which muscle would be optimal for biopsy based on electrodiagnostic findings. However, the biopsy sample should not be taken directly from the site of the needle electrode insertion to avoid artifact directly related to changes in the muscle due to insertion of the needle electrode.

    • Polyneuropathy may be present in a number of cases; thus, the sampling of distal muscles should be avoided. Nerve biopsy generally is not indicated in the evaluation of s-IBM.

Previous
Next:

Histologic Findings

Muscle biopsy sample shows myopathic changes with varying degrees of inflammation, predominantly within the endomysium.

The inflammatory infiltrates consist mainly of T cells and macrophages, which focally surround and invade nonnecrotic MFs.

Modified Gomori trichrome stained section showing Modified Gomori trichrome stained section showing (1) 2 muscle fibers (MFs) containing intracytoplasmic vacuoles (open arrows) and (2) mononuclear inflammatory infiltrates invading a nonnecrotic MF (solid arrow). Copyright, Isabel P Collins, MD, 2000, with permission.

Fiber size variability is increased with atrophic fibers consisting of both small rounded and angular MFs. Hypertrophied fibers are seen as well.

Scattered fiber necrosis and regeneration are typically seen.

The presence of rimmed vacuoles is a characteristic feature of s-IBM. The vacuoles occur singly or in multiples and are either subsarcolemmal or centrally located. These also may be seen in other conditions, such as inherited distal myopathies and oculopharyngeal muscular dystrophy. (see Table 1 in Other Problems to be Considered).

In a retrospective study, the morphology and distribution of p62 aggregates in s-IBM were characteristic, and in a myopathy with rimmed vacuoles, the combination of characteristic p62 aggregates and increased sarcolemmal and internal major histocompatibility complex class I expression or endomysial T cells were diagnostic for s-IBM, with a sensitivity of 93% and a specificity of 100%. In an inflammatory myopathy lacking rimmed vacuoles, the presence of mitochondrial changes was 100% sensitive and 73% specific for s-IBM; characteristic p62 aggregates were specific (91%), but they lacked sensitivity (44%). [91]

Ragged red fibers and cytochrome C-oxidase (COX) negative fibers are frequently observed to a greater degree than is expected with age.

Sections stained with Congo red and examined under polarized light demonstrate amyloid as apple green birefringent deposits within MFs.

Congo red-stained section showing apple green bire Congo red-stained section showing apple green birefringent amyloid deposits within muscle fibers (MFs) (arrow). The MF on the right side of the section is focally surrounded and invaded by inflammatory cells. Courtesy of Jerry R Mendell, MD.

If amyloid deposits are not seen with this method, fluorescent technique should be used as an alternative means to detect amyloid. The amyloid deposits tend to occur adjacent to vacuoles and are wispy or plaquelike in appearance. Examination under high power (X40 objective) is often required. [92]

MHC-1 upregulation is reported in as much as 100% of biopsy specimens and, though nonspecific, it may be helpful in distinguishing s-IBM from noninflammatory conditions.

Immunohistochemical staining for phosphorylated neurofilament (SMI-31) has been recommended as an alternative to electron microscopy.

Electron microscopy shows intranuclear and intracytoplasmic 15- to 21-nm tubulofilaments. In contrast, oculopharyngeal dystrophy has 8- to 11-nm intranuclear tubulofilaments as a specific marker.

Electron micrograph showing characteristic 15-to18 Electron micrograph showing characteristic 15-to18-nm tubulofilaments (arrow). Copyright, Isabel P Collins, MD, 2000, with permission.

Proposed morphologic criteria for diagnosis of s-IBM (adapted from Griggs et al) [93] :

  • Inflammatory myopathy with endomysial mononuclear cell infiltration and invasion of non-necrotic MFs

  • Vacuolated MFs

  • Intracellular amyloid deposits, 15- to 21-nm nuclear and cytoplasmic tubulofilaments on electron microscopy, or positive SMI-31 staining.

Recent studies have shown that TDP-43, a nucleic acid binding protein normally located predominantly in myofiber nuclei, is found in IBM muscle sarcoplasm. TDP-43 immunoreactivity was noted to be more frequent than other biomarkers of IBM, with high sensitivity and specificity for the disease. [94]

Previous