Focal Muscular Atrophies

Back

Background

Focal atrophy of an individual muscle or group of muscles, often encountered clinically, may create diagnostic and therapeutic challenges.

A wide variety of neurologic disorders may present with focal muscular atrophy (FMA). FMA also may be secondary to nonneurologic conditions, leading to disuse of part of a limb.

Pathophysiology

The organ ultimately affected is the muscle, although the pathology may be anywhere along the lower motor neuron (LMN) or, at times, secondary to nonneurologic disorders.

Etiologic factors include the following:

Epidemiology

Frequency

United States

FMA is a heterogenous disorder with diverse etiologies, so overall prevalence rates are not available.

An estimated 1.63 million polio survivors reside in the US; 28-50% of them will develop postpolio progressive muscular atrophy (PPMA).[1, 2]

International

For the same reasons outlined for the US, incidence and prevalence data are not available. Even for the individual diseases, considerable geographic variation exists. A population-based study revealed a PPMA prevalence of 92 per 100,000 population in a Swedish county.[3] The prevalence of post-polio syndrome in Kitakyushu, Japan was 18 per 100,000 population.[4] The frequencies of PPMA among survivors of polio in other countries (not community-based studies) are 60% in the Netherlands[5] , 58% in Norway[6] , 68% in Germany, and 22% in India[7] . An estimated 3000-5000 persons with PPMA reside in New Zealand.[8] These figures are likely to be overestimated.[9]

Many of the infectious causes of FMA (eg, polio, leprous neuropathy) are more frequent in developing countries.

Monomelic amyotrophy has been reported more often in India[10] , Korea[11] , and Japan than in other countries. In a hospital-based study from India, among 110 patients with anterior horn cell disease, 10.9% had progressive muscular atrophy; 1.8%, PPMA; and 22.7%, monomelic amyotrophy.[12]

Mortality/Morbidity

Most disorders that cause FMA are benign and do not lead to higher-than-normal mortality rates. Most patients do not suffer significant disability, except when the FMA involves an entire limb, becomes generalized, or has an acute onset.

Race-, age-, and sex-related demographics

Most conditions that cause FMA do not have any racial predilection. The geographic variations of some of these disorders probably reflect environmental conditions rather than genetic predisposition.

Bulbospinal muscular atrophy (an X-linked disorder) involves only males. Monomelic amyotrophy is more common in men. PPMA is more frequent in women.

Disorders such as polio and monomelic amyotrophy are more common in younger people.

History

Focal muscular atrophy (FMA) has various causes and, hence, various signs and symptoms.

Physical

Signs vary depending on the causative disorder.

Causes

FMA can arise from several anomalies that affect the LMN.

Laboratory Studies

The choice of investigations depends on the physical signs, symptoms, and clinical impression.

Blood counts, erythrocyte sedimentation rate (ESR), serum glucose, serum CPK.

When clinically indicated:

Cerebrospinal fluid analysis

Order lumbar puncture with cerebrospinal fluid (CSF) analysis when clinically or electrophysiologically indicated.

CSF proteins may be elevated in multifocal motor neuropathy.

Oligoclonal immunoglobulin G (IgG) bands and antibodies to the poliovirus may be detected in the CSF of patients with PPMA.

Imaging Studies

Radiographs

A chest radiograph may reveal cervical rib or apical lung lesions or hilar adenopathy

A spine radiograph may give evidence of vertebral lesions with secondary involvement of the cord or roots

MRI of the spine

This study may be useful when a disease of the spinal cord, spine, or roots is suspected.

In some patients with monomelic amyotrophy, MRI demonstrates focal and unilateral atrophy in the lower cervical cord, which is limited to the anterior horn region. MRI may also reveal forward displacement of the cervical dural sac and compressive flattening of the lower cervical cord during neck flexion.

MRI findings in white North American patients with Hirayama disease include loss of attachment (LOA) on neutral images and forward displacement of the dura with flexion. Findings are often present on neutral MRIs and are better delineated in the flexion MRI.[51]

MRI of the muscles

This study can provide information on the pattern of muscle involvement by showing the cross-sectional area of axial and limb muscles.[52]

It may demonstrate signal abnormalities in affected muscles secondary to inflammation and edema or replacement by fibrotic tissue.

Some authors have advocated MRI as a guide to decide which muscle to biopsy, although this recommendation is controversial.

Muscle ultrasound

Ultrasound can help visualize abnormalities such as muscle atrophy due to root, plexus, and nerve lesions.[53]

Spontaneous EMG activity correlates closely with abnormal ultrasonographic findings (especially with increased muscular echo intensity).

Ultrasonography is considered by some authors to be as sensitive as manual muscle testing and EMG in detecting muscle involvement. However, large studies comparing the sensitivity and specificity of muscle ultrasound and EMG in the diagnosis of neuromuscular diseases are not available.

Other Tests

Screening for systemic malignancy may be appropriate.

Test for hexosaminidase A in serum, leukocytes, or skin fibroblasts when deficiency is suspected.

Molecular diagnostic tests

Bulbospinal muscular atrophy (ie, Kennedy disease) is associated with an increase in the number of polymorphic tandem CAG repeats in exon 1 of the AR gene on the proximal long arm at Xq11 locus.

The gene candidates for spinal muscular atrophy include the genes for the survival motoneuron (SMN) and the neuronal apoptosis inhibitory protein (NAIP). Both genes are duplicated on chromosome 5. Genetic mutations have been identified in the major motor neuron diseases, including ALS (SOD1 gene), the hereditary spastic paraplegias, and rarer conditions such as GM2 gangliosidosis (hexosaminidase A deficiency).

Patients with hereditary neuropathy with tendency to pressure palsies may have a deletion on chromosome 17p11.2.

Xp21 deletion may suggest a diagnosis of Becker muscular dystrophy when the patient presents clinically with a quadriceps myopathy.

Electromyography

EMG is useful in differentiating a myopathic from a neurogenic disorder.

It can detect anterior horn cell involvement. Findings in a patient with FMA due to atypical anterior horn cell disease can be seen in the images below.



View Image

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 s....



View Image

EMG on voluntary effort from the right quadriceps muscle of a patient with atypical anterior horn disease and isolated atrophy of the right quadriceps....



View Image

EMG on maximal effort from the right quadriceps muscle of a patient with atypical anterior horn disease and isolated atrophy of the right quadriceps; ....

Paraspinal EMG may be valuable in spinal root lesions.

Spontaneous activity (eg, fibrillations, fasciculations) may be seen in ALS and to a lesser degree in SMA and PPMA.

Kennedy disease may be characterized by the presence of grouped repetitive motor unit discharges on needle EMG examination of the facial muscles, such as the mentalis muscle, which are present at rest but become prominent with mild activation of the facial muscles, such as with pursing the lips or whistling. Because these discharges occur with voluntary contraction rather than spontaneously, they are distinguished from myokymic or neuromyotonic discharges.[43]

Long-duration, high-amplitude motor unit potentials (which indicate a chronic denervation with reinnervation) are seen in PPMA and, to a lesser extent, in ALS and other anterior horn cell diseases such as SMA and monomelic amyotrophy.

Myopathic pattern with fibrillations suggests an inflammatory myopathy.

Nerve conduction studies

These studies may reveal evidence of peripheral nerve involvement: mononeuropathy, nerve entrapment, diabetic amyotrophy, and brachial or lumbosacral plexopathies.

The abnormalities may include prolonged distal latencies, slowed conduction velocities, reduced amplitude of CMAPs, and evidence of conduction block.

The F responses and H reflex studies may be useful in assessing proximal root lesions.

Disuse muscular atrophy from immobilization also is associated with a significant reduction in CMAP amplitude, which may vary according to muscle site and function.

Unlike other motor neuron diseases, including the spinal muscular atrophies, in Kennedy disease, diffusely low amplitude or absent SNAPs may occur, despite normal sensation on clinical examination.

Evoked potentials

Somatosensory evoked potentials are usually normal when the disorder involves only the motor system. They may be abnormal when the somatosensory pathway is affected.

Serial motor evoked potential (SMEP) recordings can be useful for the early detection of subclinical UMN dysfunction in motor neuron disease, which presents with pure LMN signs.

Procedures

Muscle biopsy, nerve biopsy, or lumbar puncture may be performed when clinically indicated.

Histologic Findings

Histologic findings are dependent on the underlying cause. Necropsy in one patient with monomelic amyotrophy[26] (who died of unrelated causes) revealed lesions only in the anterior horns of the spinal cord over a few segments. The anterior horn cells showed shrinkage and necrosis, various degrees of degeneration of large and small neurons, and mild gliosis. The posterior horn, white matter, and vascular system showed no abnormalities.

Autopsies of a few patients with PPMA[54] revealed the presence of persistent or new inflammation (lymphocytic infiltrates) in the meninges, spinal cord, and muscles of affected patients. In one of these patients, immunoperoxidase staining demonstrated that the inflammatory infiltrates were virtually pure populations of B lymphocytes. The other histologic features were the presence in spinal cord anterior horns of axonal spheroids and Wallerian degeneration in the lateral columns. No abnormalities were found in the brain. In patients with chronic disease, muscle histology in focal myositis may reveal variable fiber size, degenerating and regenerating fibers, inflammatory foci, vasculitis, and fibroblastic proliferation.

In Kennedy disease, the muscle biopsy specimen reveals variability of fiber size with groups of angular atrophic fibers, fiber type grouping, and pyknotic nuclear clumps characteristic of chronic denervation with reinnervation. Nonspecific myopathic features, including increased central nuclei and necrotic fibers, are also seen. The histopathologic hallmark is the presence of nuclear inclusions containing mutant truncated ARs in the residual motor neurons in the brainstem and spinal cord as well as in some other visceral organs.

The histologic findings in inclusion body myositis are endomysial inflammation, small groups of atrophic fibers, eosinophilic cytoplasmic inclusions, and muscle fibers with one or more rimmed vacuoles that are lined with granular material. Amyloid deposition is evident on Congo red staining by using polarized light or fluorescence techniques. Electron microscopy demonstrates 15-21 nm cytoplasmic and intranuclear tubulofilaments.

Muscle histology in sarcoidosis is characterized by perivascular noncaseating granulomas consisting of clusters of epithelioid cells, lymphocytes, and giant cells.

Muscle histology in injection myopathy may reveal perimysial and endomysial fibrosis with nonspecific degeneration, regenerative changes and, in some cases, partial denervation signs. Electron microscopy reveals that endomysial and perimysial collagen fibrils have lost their normal unimodal diameter distribution. They instead show a broad spectral distribution of diameters, suggesting defective control of collagen formation.

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.

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.[55]

Some of the therapeutic strategies that have been tested in SBMA, fall into four main categories: (i) gene silencing; (ii) protein quality control and/or increased protein degradation; (iii) androgen deprivation therapies using leuprorelin and dutasteride; and (iv) 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.[56]

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.[57]  A randomized trial found no significant effect of dutasteride on the progression of muscle weakness in SBMA.[58]

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[56] , pyridostigmine[59] , modafanil[60] 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.[61, 62, 63, 64, 65]

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 FMA, except in rare instances in which FMA is secondary to a surgically treatable intraspinal or extraspinal lesion.

A randomized trial of 2 surgical techniques, namely anterior cervical discectomy decompression with autologous iliac crest bone grafting and internal plate fixation (DDF) or anterior cervical corpectomy, posterior longitudinal ligament resection, autologous iliac crest bone grafting, and internal plate fixation (CDF), for patients with monomelic amyotrophy followed up for 2 years revealed subjective and electrophysiological improvement in 60-65% of patients. Because of the benign nature of the illness, cervical collar treatment is the preferred treatment, while surgery could be an exceptional second-line alternative. If surgery is chosen, DDF carries lower procedural risk compared with CDF.[66]

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.

Medication Summary

The goal of pharmacotherapy is to reduce morbidity.

Intravenous immunoglobulin (IVIg)

Clinical Context:  Following features may be relevant to its efficacy: neutralization of circulating antibodies through anti-idiotypic antibodies; down-regulation of pro-inflammatory cytokines, including IFN-gamma; blockade of Fc receptors on macrophages; suppression of inducer T and B cells and augmentation of suppressor T cells; blockade of complement cascade.

Class Summary

These are useful in minimizing the effects of autoimmune reactions.

Prednisone (Sterapred)

Clinical Context:  Useful in treatment of inflammatory and immune reactions. By reversing increased capillary permeability and suppressing PMN activity, may decrease inflammation. Dosage and length of treatment vary depending on specific diagnosis.

Class Summary

These agents modify the body's immune response to diverse stimuli. Likely mechanisms of action are inhibition of synthesis/secretion of TNF-alpha, IL-6, IL-2, and IFN-gamma, and modulation of serum and leukocyte-bound levels of cell adhesion molecules.

Prognosis

The diseases that cause focal muscle wasting are mostly self-limiting and benign. They do not affect the lifespan of the individual.

What is focal muscular atrophy (FMA)?What is the pathophysiology of focal muscular atrophy (FMA)?What are the etiologic factors of focal muscular atrophy (FMA)?What is the prevalence of focal muscular atrophy (FMA) in the US?What is the global prevalence of focal muscular atrophy (FMA)?What is the mortality and morbidity associated with focal muscular atrophy (FMA)?Which patient groups have the highest prevalence of focal muscular atrophy (FMA)?What are the signs and symptoms of focal muscular atrophy (FMA)?Which physical findings are characteristic of focal muscular atrophy (FMA)?Which infectious anterior horn cell diseases cause focal muscular atrophy (FMA)?What is the role of injection myopathy in the etiology of focal muscular atrophy (FMA)?Which noninfectious anterior horn cell diseases cause focal muscular atrophy (FMA)?Which focal spinal lesions cause focal muscular atrophy (FMA)?What are miscellaneous causes of focal muscular atrophy (FMA)?Which spinal root lesions cause focal muscular atrophy (FMA)?Which brachial and lumbosacral plexus lesions cause focal muscular atrophy (FMA)?Which peripheral nerve diseases cause focal muscular atrophy (FMA)?Which muscle diseases cause focal muscular atrophy (FMA)?What causes focal muscular atrophy (FMA) confined to bulbar muscles?What are the most frequent causes of focal muscular atrophy (FMA)?What causes postpolio progressive muscular atrophy?What are the signs and symptoms of postpolio progressive muscular atrophy?What are the diagnostic criteria for progressive postpolio muscular atrophy (PPMA)?How is postpolio progressive muscular atrophy (PPMA) differentiated from amyotrophic lateral sclerosis (ALS)?What is monomelic amyotrophy?How is monomelic amyotrophy diagnosed?What are spinal muscular atrophies?What is bulbospinal muscular atrophy?What is distal spinal muscular atrophy?Which syndromes associated with amyotrophic lateral sclerosis (ALS) cause focal muscular atrophy (FMA)?What is the role of postradiation motor neuron disease and plexopathy in the etiology of focal muscular atrophy (FMA)?What is the role of multifocal motor neuropathy in the etiology of focal muscular atrophy (FMA)?What is the role of hexosaminidase deficiencies in the etiology of focal muscular atrophy (FMA)?What is the role of immune-mediated syndromes in the etiology of focal muscular atrophy (FMA)?What is the role of focal myositis in the etiology of focal muscular atrophy (FMA)?What is the role of infective myositis in the etiology of focal muscular atrophy (FMA)?What is the role of inclusion body myositis in the etiology of focal muscular atrophy (FMA)?What is the role of sarcoid myopathy in the etiology of focal muscular atrophy (FMA)?What is the role of congenital absence of muscle in the etiology of focal muscular atrophy (FMA)?What is the role of muscular dystrophies in the etiology of focal muscular atrophy (FMA)?What is the role of mononeuropathies in the etiology of focal muscular atrophy (FMA)?What is the role of neuralgic amyotrophy in the etiology of focal muscular atrophy (FMA)?What are the differential diagnoses for Focal Muscular Atrophies?What is the role of CSF analysis in the workup of focal muscular atrophy (FMA)?Which lab tests are performed in the workup of focal muscular atrophy (FMA)?What is the role of radiographs in the workup of focal muscular atrophy (FMA)?What is the role of spine MRI in the workup of focal muscular atrophy (FMA)?What is the role of MRI of the muscles in the workup of focal muscular atrophy (FMA)?What is the role of muscle ultrasound in the workup of focal muscular atrophy (FMA)?Which disorders should be screened for in the workup of focal muscular atrophy (FMA)?What is the role of genetic testing in the workup of focal muscular atrophy (FMA)?What is the role of EMG in the diagnosis of focal muscular atrophy (FMA)?What is the role of nerve conduction studies in the workup of focal muscular atrophy (FMA)?What is the role of evoked potentials in the workup of focal muscular atrophy (FMA)?What is the role of biopsy and lumbar puncture in the workup of focal muscular atrophy (FMA)?Which histologic findings are characteristic of focal muscular atrophy (FMA)?How is focal muscular atrophy (FMA) treated?How is postpolio progressive muscular atrophy (PPMA) treated?How is multifocal motor neuropathy treated?What is the role of surgery in the treatment of focal muscular atrophy (FMA)?Which specialist consultations are beneficial to patients with focal muscular atrophy (FMA)?What is the goal of drug treatment for focal muscular atrophy (FMA)?Which medications in the drug class Glucocorticoids are used in the treatment of Focal Muscular Atrophies?Which medications in the drug class Blood products are used in the treatment of Focal Muscular Atrophies?What is the prognosis of focal muscular atrophy (FMA)?

Author

Sridharan Ramaratnam, MD, MBBS, Director and Senior Consultant, The Nerve Centre, Chennai, India

Disclosure: Nothing to disclose.

Coauthor(s)

Nicholas Lorenzo, MD, MHA, CPE, Co-Founder and Former Chief Publishing Officer, eMedicine and eMedicine Health, Founding Editor-in-Chief, eMedicine Neurology; Founder and Former Chairman and CEO, Pearlsreview; Founder and CEO/CMO, PHLT Consultants; Chief Medical Officer, MeMD Inc; Chief Strategy Officer, Discourse LLC

Disclosure: Nothing to disclose.

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Helmi L Lutsep, MD, Professor and Vice Chair, Department of Neurology, Oregon Health and Science University School of Medicine; Associate Director, OHSU Stroke Center

Disclosure: Medscape Neurology Editorial Advisory Board for: Stroke Adjudication Committee, CREST2; Physician Advisory Board for Coherex Medical; National Leader and Steering Committee Clinical Trial, Bristol Myers Squibb; Consultant, Abbott Vascular, Inc. .

Acknowledgements

Lakshmi Narasimhan Ranganathan, MD Tutor, Institute Of Mental Health, Chennai, India; Senior Civil Assistant Surgeon, Tamil Nadu Medical Services

Disclosure: Nothing to disclose.

References

  1. Jubelt B, Drucker J. Post-polio syndrome: an update. Semin Neurol. 1993 Sep. 13(3):283-90. [View Abstract]
  2. Ramlow J, Alexander M, LaPorte R, Kaufmann C, Kuller L. Epidemiology of the post-polio syndrome. Am J Epidemiol. 1992 Oct 1. 136(7):769-86. [View Abstract]
  3. Ahlstrom G, Gunnarsson LG, Leissner P, Sjoden PO. Epidemiology of neuromuscular diseases, including the postpolio sequelae, in a Swedish county. Neuroepidemiology. 1993. 12(5):262-9. [View Abstract]
  4. Takemura J, Saeki S, Hachisuka K, Aritome K. Prevalence of post-polio syndrome based on a cross-sectional survey in Kitakyushu, Japan. J Rehabil Med. 2004 Jan. 36(1):1-3. [View Abstract]
  5. Ivanyi B, Nollet F, Redekop WK, et al. Late onset polio sequelae: disabilities and handicaps in a population-based cohort of the 1956 poliomyelitis outbreak in The Netherlands. Arch Phys Med Rehabil. 1999 Jun. 80(6):687-90. [View Abstract]
  6. Wekre LL, Stanghelle JK, Lobben B, Oyhaugen S. The Norwegian Polio Study 1994: a nation-wide survey of problems in long-standing poliomyelitis. Spinal Cord. 1998 Apr. 36(4):280-4. [View Abstract]
  7. Sehgal H. New dimensions to poliomyelitis. Indian Pediatr. 1990 May. 27(5):433-6. [View Abstract]
  8. Chetwynd J, Botting C, Hogan D. Postpolio syndrome in New Zealand: a survey of 700 polio survivors. N Z Med J. 1993 Sep 22. 106(964):406-8. [View Abstract]
  9. Nagashima T. [Post-poliomyelitis late progressive muscular atrophy (PPMA)--clinical analyses of Japanese cases]. Rinsho Shinkeigaku. 1991 Dec. 31(12):1319-21. [View Abstract]
  10. Gourie-Devi M, Suresh TG, Shankar SK. Monomelic amyotrophy. Arch Neurol. 1984 Apr. 41(4):388-94. [View Abstract]
  11. Kim JY, Lee KW, Roh JK, Chi JG, Lee SB. A clinical study of benign focal amyotrophy. J Korean Med Sci. 1994 Apr. 9(2):145-54. [View Abstract]
  12. Saha SP, Das SK, Gangopadhyay PK, Roy TN, Maiti B. Pattern of motor neurone disease in eastern India. Acta Neurol Scand. 1997 Jul. 96(1):14-21. [View Abstract]
  13. Cone LA, Nazemi R, Cone MO. Reversible ALS-like disorder in HIV infection. An ALS-like syndrome with new HIV infection and complete response to antiretroviral therapy. Neurology. 2002 Aug 13. 59(3):474; author reply 474-5. [View Abstract]
  14. Ueyama H, Kumamoto T, Johno M, Mita S, Tsuda T. Localized muscle wasting as an initial symptom of skeletal muscle lymphoma. J Neurol Sci. 1998 Jan 21. 154(1):113-5. [View Abstract]
  15. Dubowitz V, Platts M. Central core disease of muscle with focal wasting. J Neurol Neurosurg Psychiatry. 1965 Oct. 28(5):432-7. [View Abstract]
  16. Dalakas MC, Sever JL, Madden DL, et al. Late postpoliomyelitis muscular atrophy: clinical, virologic, and immunologic studies. Rev Infect Dis. 1984 May-Jun. 6 Suppl 2:S562-7. [View Abstract]
  17. Halstead LS, Silver JK. Nonparalytic polio and postpolio syndrome. Am J Phys Med Rehabil. 2000 Jan-Feb. 79(1):13-8. [View Abstract]
  18. Trojan DA, Collet J, Pollak MN, et al. Serum insulin-like growth factor-I (IGF-I) does not correlate positively with isometric strength, fatigue, and quality of life in post-polio syndrome. J Neurol Sci. 2001 Jan 1. 182(2):107-15. [View Abstract]
  19. Gonzalez H, Olsson T, Borg K. Management of postpolio syndrome. Lancet Neurol. 2010 Jun. 9(6):634-42. [View Abstract]
  20. Farbu E, Rekand T, Tysnes OB, Aarli JA, Gilhus NE, Vedeler CA. GM1 antibodies in post-polio syndrome and previous paralytic polio. J Neuroimmunol. 2003 Jun. 139(1-2):141-4. [View Abstract]
  21. Gonzalez H, Ottervald J, Nilsson KC, et al. Identification of novel candidate protein biomarkers for the post-polio syndrome - implications for diagnosis, neurodegeneration and neuroinflammation. J Proteomics. 2009 Jan 30. 71(6):670-81. [View Abstract]
  22. Fordyce CB, Gagne D, Jalili F, Alatab S, Arnold DL, Da Costa D. Elevated serum inflammatory markers in post-poliomyelitis syndrome. J Neurol Sci. 2008 Aug 15. 271(1-2):80-6. [View Abstract]
  23. Östlund G, Wahlin Å, Sunnerhagen KS, Borg K. Post polio syndrome: fatigued patients a specific subgroup?. J Rehabil Med. 2011 Jan. 43(1):39-45. [View Abstract]
  24. Gourie-Devi M, Nalini A. Long-term follow-up of 44 patients with brachial monomelic amyotrophy. Acta Neurol Scand. 2003 Mar. 107(3):215-20. [View Abstract]
  25. De Freitas MR, Nascimento OJ. Benign monomelic amyotrophy: a study of twenty-one cases. Arq Neuropsiquiatr. 2000 Sep. 58(3B):808-13. [View Abstract]
  26. Hirayama K, Tomonaga M, Kitano K, Yamada T, Kojima S, Arai K. Focal cervical poliopathy causing juvenile muscular atrophy of distal upper extremity: a pathological study. J Neurol Neurosurg Psychiatry. 1987 Mar. 50(3):285-90. [View Abstract]
  27. Moreno Martinez JM, Garcia de la Rocha ML, Martin Araguz A. [Monomelic segmental amyotrophy: a Spanish case involving the leg]. Rev Neurol (Paris). 1990. 146(6-7):443-5. [View Abstract]
  28. Oryema J, Ashby P, Spiegel S. Monomelic atrophy. Can J Neurol Sci. 1990 May. 17(2):124-30. [View Abstract]
  29. Serratrice G, Pellissier JF, Pouget J. [Nosological study of 25 cases of chronic monomelic amyotrophy]. Rev Neurol (Paris). 1987. 143(3):201-10. [View Abstract]
  30. Hirayama K, Tokumaru Y. Cervical dural sac and spinal cord in juvenile muscular atrophy of distal upper extremity. Neurology. 2000 May 23. 54(10):1922-6. [View Abstract]
  31. Biondi A, Dormont D, Weitzner I Jr, Bouche P, Chaine P, Bories J. MR Imaging of the cervical cord in juvenile amyotrophy of distal upper extremity. AJNR Am J Neuroradiol. 1989 Mar-Apr. 10(2):263-8. [View Abstract]
  32. Huang YL, Chen CJ. Hirayama disease. Neuroimaging Clin N Am. 2011 Nov. 21(4):939-50, ix-x. [View Abstract]
  33. Baba Y, Nakajima M, Utsunomiya H, et al. Magnetic resonance imaging of thoracic epidural venous dilation in Hirayama disease. Neurology. 2004 Apr 27. 62(8):1426-8. [View Abstract]
  34. Guglielmo GD, Brahe C, Di Muzio A. Benign monomelic amyotrophies of upper and lower limb are not associated to deletions of survival motor neuron gene. J Neurol Sci. 1996 Sep 15. 141(1-2):111-3. [View Abstract]
  35. Fetoni V, Briem E, Carrara F, Mora M, Zeviani M. Monomelic amyotrophy associated with the 7472insC mutation in the mtDNA tRNASer(UCN) gene. Neuromuscul Disord. 2004 Nov. 14(11):723-6. [View Abstract]
  36. Ito S, Kuwabara S, Fukutake T, Tokumaru Y, Hattori T. HyperIgEaemia in patients with juvenile muscular atrophy of the distal upper extremity (Hirayama disease). J Neurol Neurosurg Psychiatry. 2005 Jan. 76(1):132-4. [View Abstract]
  37. Nalini A, Lokesh L, Ratnavalli E. Familial monomelic amyotrophy: a case report from India. J Neurol Sci. 2004 May 15. 220(1-2):95-8. [View Abstract]
  38. Serratrice G. Focal forms of denervating disorders. Progress in Clinical Neurosciences Ed. By Sinha KK, Chandra P, Neurological Soci. 1990. 6(2):49-54.
  39. Tandan R, Sharma KR, Bradley WG, Bevan H, Jacobsen P. Chronic segmental spinal muscular atrophy of upper extremities in identical twins. Neurology. 1990 Feb. 40(2):236-9. [View Abstract]
  40. Serratrice G, Pou-Serradel A, Pellissier JF, Roux H, Lamarco-Civro J, Pouget J. Chronic neurogenic quadriceps amyotrophies. J Neurol. 1985. 232(3):150-3. [View Abstract]
  41. Merry DE. Molecular pathogenesis of spinal and bulbar muscular atrophy. Brain Res Bull. 2001 Oct-Nov 1. 56(3-4):203-7. [View Abstract]
  42. Katsuno M, Adachi H, Tanaka F, Sobue G. Spinal and bulbar muscular atrophy: ligand-dependent pathogenesis and therapeutic perspectives. J Mol Med (Berl). 2004 May. 82(5):298-307. [View Abstract]
  43. Ferrante MA, Wilbourn AJ. The characteristic electrodiagnostic features of Kennedy's disease. Muscle Nerve. 1997 Mar. 20(3):323-9. [View Abstract]
  44. Lederman RJ, Salanga VD, Wilbourn AJ, Hanson MR, Dudley AW Jr. Focal inflammatory myopathy. Muscle Nerve. 1984 Feb. 7(2):142-6. [View Abstract]
  45. Lawrentschuk N, Falkenberg MP, Pirpiris M. Primary bacterial pyomyositis associated with septic arthritis caused by Streptococcus pyogenes: a case report. Am J Orthop. 2003 Mar. 32(3):148-50. [View Abstract]
  46. Wang JY, Lee LN, Hsueh PR, et al. Tuberculous myositis: a rare but existing clinical entity. Rheumatology (Oxford). 2003 Jul. 42(7):836-40. [View Abstract]
  47. Chen SS, Chien CH, Yu HS. Syndrome of deltoid and/or gluteal fibrotic contracture: an injection myopathy. Acta Neurol Scand. 1988 Sep. 78(3):167-76. [View Abstract]
  48. Seror P. Neuralgic amyotrophy. An update. Joint Bone Spine. 2017 Mar. 84 (2):153-158. [View Abstract]
  49. van Alfen N. Clinical and pathophysiological concepts of neuralgic amyotrophy. Nat Rev Neurol. 2011 May 10. 7(6):315-22. [View Abstract]
  50. van Alfen N, van Engelen BG, Hughes RA. Treatment for idiopathic and hereditary neuralgic amyotrophy (brachial neuritis). Cochrane Database Syst Rev. 2009 Jul 8. (3):
  51. Lehman VT, Luetmer PH, Sorenson EJ, Carter RE, Gupta V, Fletcher GP. Cervical spine MR imaging findings of patients with Hirayama disease in North America: a multisite study. AJNR Am J Neuroradiol. 2013 Feb. 34(2):451-6. [View Abstract]
  52. Fleckenstein JL, Peshock RM, Lewis SF, Haller RG. Magnetic resonance imaging of muscle injury and atrophy in glycolytic myopathies. Muscle Nerve. 1989 Oct. 12(10):849-55. [View Abstract]
  53. Schwennicke A, Bargfrede M, Reimers CD. Clinical, electromyographic, and ultrasonographic assessment of focal neuropathies. J Neuroimaging. 1998 Jul. 8(3):136-43. [View Abstract]
  54. Miller DC. Post-polio syndrome spinal cord pathology. Case report with immunopathology. Ann N Y Acad Sci. 1995 May 25. 753:186-93. [View Abstract]
  55. Brichta L, Holker I, Haug K, Klockgether T, Wirth B. In vivo activation of SMN in spinal muscular atrophy carriers and patients treated with valproate. Ann Neurol. 2006 Jun. 59(6):970-5. [View Abstract]
  56. Peel MM, Cooke M, Lewis-Peel HJ, Lea RA, Moyle W. A randomized controlled trial of coenzyme Q10 for fatigue in the late-onset sequelae of poliomyelitis. Complement Ther Med. 2015 Dec. 23 (6):789-93. [View Abstract]
  57. Querin G, D'Ascenzo C, Peterle E, Ermani M, Bello L, Melacini P. Pilot trial of clenbuterol in spinal and bulbar muscular atrophy. Neurology. 2013 Jun 4. 80(23):2095-8. [View Abstract]
  58. Fernández-Rhodes LE, Kokkinis AD, White MJ, et al. Efficacy and safety of dutasteride in patients with spinal and bulbar muscular atrophy: a randomised placebo-controlled trial. Lancet Neurol. 2011 Feb. 10(2):140-7. [View Abstract]
  59. Horemans HL, Nollet F, Beelen A, et al. Pyridostigmine in postpolio syndrome: no decline in fatigue and limited functional improvement. J Neurol Neurosurg Psychiatry. 2003 Dec. 74(12):1655-61. [View Abstract]
  60. Vasconcelos OM, Prokhorenko OA, Salajegheh MK, Kelley KF, Livornese K, Olsen CH. Modafinil for treatment of fatigue in post-polio syndrome: a randomized controlled trial. Neurology. 2007 May 15. 68(20):1680-6. [View Abstract]
  61. Koopman FS, Uegaki K, Gilhus NE, Beelen A, de Visser M, Nollet F. Treatment for postpolio syndrome. Cochrane Database Syst Rev. 2011 Feb 16. CD007818. [View Abstract]
  62. Bertolasi L, Frasson E, Turri M, Gajofatto A, Bordignon M, Zanolin E. A randomized controlled trial of IV immunoglobulin in patients with postpolio syndrome. J Neurol Sci. 2013 Jul 15. 330(1-2):94-9. [View Abstract]
  63. Gonzalez H, Khademi M, Borg K, Olsson T. Intravenous immunoglobulin treatment of the post-polio syndrome: sustained effects on quality of life variables and cytokine expression after one year follow up. J Neuroinflammation. 2012. 9:167. [View Abstract]
  64. Ostlund G, Broman L, Werhagen L, Borg K. IVIG treatment in post-polio patients: evaluation of responders. J Neurol. 2012 Dec. 259(12):2571-8. [View Abstract]
  65. Werhagen L, Borg K. Effect of intravenous immunoglobulin on pain in patients with post-polio syndrome. J Rehabil Med. 2011 Nov. 43(11):1038-40. [View Abstract]
  66. Lu F, Wang H, Jiang J, Chen W, Ma X, Ma X. Efficacy of anterior cervical decompression and fusion procedures for monomelic amyotrophy treatment: a prospective randomized controlled trial: clinical article. J Neurosurg Spine. 2013 Oct. 19(4):412-9. [View Abstract]
  67. Moulignier A, Moulonguet A, Pialoux G, Rozenbaum W. Reversible ALS-like disorder in HIV infection. Neurology. 2001 Sep 25. 57(6):995-1001. [View Abstract]
  68. Jubelt B, Berger JR. Does viral disease underlie ALS? Lessons from the AIDS pandemic. Neurology. 2001 Sep 25. 57(6):945-6. [View Abstract]
  69. Kidd D, Williams AJ, Howard RS. Poliomyelitis. Postgrad Med J. 1996 Nov. 72(853):641-7. [View Abstract]

A man with neuralgic amyotrophy presenting with wasting of deltoids involving the right side more than the left.

A middle-aged man with (atypical) anterior horn cell disease presenting with wasting of the right quadriceps.

Wasting of right forearm and both hand muscles in a patient with Hirayama Disease. Note the oblique atrophy of right forearm.

Wasting of small muscles of the hands in a patient with Hirayama Disease.

T2-weighted cervical spine MRI of a patient with Hirayama disease showing focal cord hyperintensity at C5-C6 level.

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.

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.

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.

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.

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.

A man with neuralgic amyotrophy presenting with wasting of deltoids involving the right side more than the left.

A middle-aged man with (atypical) anterior horn cell disease presenting with wasting of the right quadriceps.

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.

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.

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.

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.

Wasting of right forearm and both hand muscles in a patient with Hirayama Disease. Note the oblique atrophy of right forearm.

Wasting of small muscles of the hands in a patient with Hirayama Disease.

T2-weighted cervical spine MRI of a patient with Hirayama disease showing focal cord hyperintensity at C5-C6 level.

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.