Medical Care
Treatment of focal muscular atrophy (FMA) varies according to the cause. The common causes (eg, monomelic amyotrophy, PPMA, SMA) have no specific treatment.
When patients with these conditions have disability, the treatment consists of physical and occupational therapy and rehabilitation.
Early immunomodulating treatment, steroids/IVIG, and identifying phrenic neuropathy is important for optimal recovery of patients with neuralgic amyotrophy. [57]
A report of increase in the SMN2 messenger RNA levels in vivo among 7 of 13 patients with spinal muscular atrophy treated with valproic acid raises possibilities of in vivo activation of causative genes in inherited diseases. [58]
Some of the therapeutic strategies that have been tested in SBMA, fall into four main categories: (1) gene silencing; (2) protein quality control and/or increased protein degradation; (3) androgen deprivation therapies using leuprorelin and dutasteride; and (4) modulation of androgen receptor function. Various therapeutic strategies have been effective in transgenic animal models, and research is ongoing to translate these strategies into safe and effective treatment in humans. [59]
An open trial of clenbuterol among patients with spinal and bulbar muscular atrophy (SBMA) found significant and sustained increase in walking distance covered in 6 minutes and forced vital capacity between the baseline and the 12-month assessments (P< .001), suggesting class IV evidence that clenbuterol may be effective in improving motor function. [60] A randomized trial found no significant effect of dutasteride on the progression of muscle weakness in SBMA. [61] A randomized placebo-controlled trial assessed the effect of BVS857, an insulin-like growth factor-1 mimetic, among patients with spinal and bulbar muscular atrophy and found no improvement in muscle strength or function. [62]
Gene therapy approaches involving the delivery of antisense oligonucleotides into the central nervous system (CNS) are being tested in clinical trials for ALS patients with mutations in SOD1, C9orf72, and FUS genes. Viral vectors can be used to deliver therapeutic sequences to stably transduce motor neurons in the CNS. Vectors derived from adeno-associated virus (AAV) can efficiently target genes and have been tested in several pre-clinical settings with promising outcomes. [63]
Counsel patients concerning the benign nature of the illness once the diagnosis is confirmed.
Treatment of PPMA
Trials with amantadine, high-dose steroids, human growth hormone, co-enzyme Q [64] , pyridostigmine [65] , modafanil [66] , citrulline [67] and bromocriptine all have been disappointing.
In a study of subcutaneous insulinlike growth factor-1 in 22 patients with PPMA, patients had enhanced recovery after fatiguing exercise. However, the treatment had no impact upon strength or exercise-induced fatigue.
Intravenous immunoglobulin probably has no beneficial effect on activity limitations but may have modest beneficial effect on muscle strength and pain. [68, 69, 70, 71, 72]
One trial with weak methods found that lamotrigine might be effective in reducing pain and fatigue, resulting in fewer activity limitations. Data from 2 single trials suggest that muscle strengthening of thumb muscles (very low-quality evidence) and static magnetic fields (moderate-quality evidence) are beneficial for improving muscle strength and pain, respectively, with unknown effects on activity limitations. These interventions, however, need further investigation.
Screening and treating patients for osteopenia or osteoporosis may be appropriate.
Treatment of multifocal motor neuropathy
IV immunoglobulins are effective and commonly used for treating patients with multifocal motor neuropathy.
Either high-dose cyclophosphamide or monthly plasma exchange followed by pulse IV cyclophosphamide has been found effective in patients who do not respond to IV immunoglobulins. These patients do not respond to prednisone or plasmapheresis alone.
Whether the presence of anti-GM1 antibody or its titer has any bearing on the response to therapy is controversial.
Inclusion body myositis does not respond well to immunosuppressive medication.
Immunosuppressive treatment with corticosteroids may benefit focal myositis and sarcoid myopathy.
Surgical Care
Surgery has no role in focal muscular atrophy (FMA), except in rare instances in which FMA is secondary to a surgically treatable intraspinal or extraspinal lesion.
A review of surgical procedures for Hirayama disease found that clinical improvement following surgery was seen in 80% (95% confidence interval (CI) 76 to 84%). The most commonly used surgical technique was anterior cervical discectomy and fusion (ACDF) with cervical plating. The improvement following ACDF with plating was seen in 96% (95% CI 62 to 100%) compared to ACDF without plating (57% (95% CI 20 to 88%)).Because of the benign nature of the illness, cervical collar treatment is the preferred treatment, while surgery could be an exceptional second-line alternative. The indications of surgical treatment in patients with Hirayama disease include poor patient compliance for neck collar or rapidly progressing weakness with severe disability. [73]
Consultations
When the diagnosis is uncertain, referral to a tertiary care center with expertise in neuromuscular disorders may be appropriate.
Consultation with a physical and occupational therapist may prove useful. Vocational rehabilitation training can be used when appropriate.
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A man with neuralgic amyotrophy presenting with wasting of deltoids involving the right side more than the left.
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A middle-aged man with (atypical) anterior horn cell disease presenting with wasting of the right quadriceps.
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EMG at rest from the right quadriceps muscle of a patient with atypical anterior horn cell disease and isolated atrophy of the right quadriceps; EMG shows spontaneous activity.
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EMG on voluntary effort from the right quadriceps muscle of a patient with atypical anterior horn disease and isolated atrophy of the right quadriceps; EMG shows motor unit potentials that exhibit prolonged duration and polyphasia.
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EMG on maximal effort from the right quadriceps muscle of a patient with atypical anterior horn disease and isolated atrophy of the right quadriceps; EMG shows an impaired interference pattern.
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Clinical photograph of a subject with monomelic amyotrophy showing wasting of left forearm. Note the characteristic feature of oblique atrophy, where a normal brachioradialis dominates the atrophied forearm.
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Wasting of right forearm and both hand muscles in a patient with Hirayama Disease. Note the oblique atrophy of right forearm.
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Wasting of small muscles of the hands in a patient with Hirayama Disease.
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T2-weighted cervical spine MRI of a patient with Hirayama disease showing focal cord hyperintensity at C5-C6 level.
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T2-weighted cervical spine MRI of the same patient during neck flexion showing anterior displacement of the posterior dural wall with flattening and compression of the cord against the bodies of the vertebrae with prominent dorsal epidural flow voids.
