eMedicine Specialties > Neurology > Neuromuscular Diseases
Focal Muscular Atrophies: Differential Diagnoses & Workup
Updated: Mar 13, 2007
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Differential Diagnoses
Other Problems to Be Considered
Anti-GM1 antibody multifocal motor neuropathy with conduction block
Becker dystrophy
Brainstem syndromes
Cervical disk syndromes
Congenital absence of muscles
Creutzfeldt-Jakob disease
Duchenne dystrophy
Focal myositis
Injection myopathy
Lipoatrophy
Monomelic amyotrophy
Peripheral nerve injuries
Plexopathy (from any cause)
Poliomyelitis
Postpolio progressive muscular atrophy
Postradiation toxicity and disease
Spinal cord tumors
Toxic neuropathies
Workup
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
- Thyroid functions
- Rheumatoid factor
- Serum ACE assay
- Serum anti-GM1 antibodies
- Viral studies
- Screening for toxins or systemic malignancy
- 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
- X-rays
- Chest - May reveal cervical rib or apical lung lesions or hilar adenopathy
- Spine - 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 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.
- 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
- 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 Images 3-5.
- 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.
- 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 (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 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.
More on Focal Muscular Atrophies |
| Overview: Focal Muscular Atrophies |
 Differential Diagnoses & Workup: Focal Muscular Atrophies |
| Treatment & Medication: Focal Muscular Atrophies |
| Follow-up: Focal Muscular Atrophies |
| Multimedia: Focal Muscular Atrophies |
| References |
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References
Abaza MM, Sataloff RT, Hawkshaw MJ, Mandel S. Laryngeal manifestations of postpoliomyelitis syndrome. J Voice. Jun 2001;15(2):291-4. [Medline].
Ahlstrom G, Gunnarsson LG, Leissner P. Epidemiology of neuromuscular diseases, including the postpolio sequelae, in a Swedish county. Neuroepidemiology. 1993;12(5):262-9. [Medline].
Amato AA, Barohn RJ. Evaluation and treatment of inflammatory myopathies. American Academy of Neurology annual meeting syllabi on CD-ROM. 1999.
Baba Y, Nakajima M, Utsunomiya H, et al. Magnetic resonance imaging of thoracic epidural venous dilation in Hirayama disease. Neurology. Apr 27 2004;62(8):1426-8. [Medline].
Belsh JM. Misdiagnosis, pitfalls, nonmotor neuron diseases. AAN annual meeting syllabi on CD-ROM. 1998.
Biondi A, Dormont D, Weitzner I Jr. MR Imaging of the cervical cord in juvenile amyotrophy of distal upper extremity. AJNR Am J Neuroradiol. Mar-Apr 1989;10(2):263-8. [Medline].
Brichta L, Holker I, Haug K. In vivo activation of SMN in spinal muscular atrophy carriers and patients treated with valproate. Ann Neurol. Jun 2006;59(6):970-5. [Medline].
Chen SS, Chien CH, Yu HS. Syndrome of deltoid and/or gluteal fibrotic contracture: an injection myopathy. Acta Neurol Scand. Sep 1988;78(3):167-76. [Medline].
Chetwynd J, Botting C, Hogan D. Postpolio syndrome in New Zealand: a survey of 700 polio survivors. N Z Med J. Sep 22 1993;106(964):406-8. [Medline].
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. Aug 13 2002;59(3):474; author reply 474-5. [Medline].
Dalakas MC, Sever JL, Madden DL. Late postpoliomyelitis muscular atrophy: clinical, virologic, and immunologic studies. Rev Infect Dis. May-Jun 1984;6 Suppl 2:S562-7. [Medline].
De Freitas MR, Nascimento OJ. Benign monomelic amyotrophy: a study of twenty-one cases. Arq Neuropsiquiatr. Sep 2000;58(3B):808-13. [Medline].
Dubowitz V, Platts M. Central core disease of muscle with focal wasting. J Neurol Neurosurg Psychiatry. Oct 1965;28(5):432-7. [Medline].
Farbu E, Rekand T, Tysnes OB, et al. GM1 antibodies in post-polio syndrome and previous paralytic polio. J Neuroimmunol. Jun 2003;139(1-2):141-4. [Medline].
Ferrante MA, Wilbourn AJ. The characteristic electrodiagnostic features of Kennedy''s disease. Muscle Nerve. Mar 1997;20(3):323-9. [Medline].
Fetoni V, Briem E, Carrara F, et al. Monomelic amyotrophy associated with the 7472insC mutation in the mtDNA tRNASer(UCN) gene. Neuromuscul Disord. Nov 2004;14(11):723-6. [Medline].
Fleckenstein JL, Peshock RM, Lewis SF. Magnetic resonance imaging of muscle injury and atrophy in glycolytic myopathies. Muscle Nerve. Oct 1989;12(10):849-55. [Medline].
Gonzalez H, Sunnerhagen KS, Sjöberg I. Intravenous immunoglobulin for post-polio syndrome: a randomised controlled trial. Lancet Neurol. Jun 2006;5(6):493-500.
Gourie-Devi M, Suresh TG, Shankar SK. Monomelic amyotrophy. Arch Neurol. Apr 1984;41(4):388-94. [Medline].
Gourie-Devi M, Nalini A. Long-term follow-up of 44 patients with brachial monomelic amyotrophy. Acta Neurol Scand. Mar 2003;107(3):215-20. [Medline].
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. Sep 15 1996;141(1-2):111-3. [Medline].
Halstead LS, Silver JK. Nonparalytic polio and postpolio syndrome. Am J Phys Med Rehabil. Jan-Feb 2000;79(1):13-8. [Medline].
Hirayama K, Tomonaga M, Kitano K. Focal cervical poliopathy causing juvenile muscular atrophy of distal upper extremity: a pathological study. J Neurol Neurosurg Psychiatry. Mar 1987;50(3):285-90. [Medline].
Hirayama K, Tokumaru Y. Cervical dural sac and spinal cord in juvenile muscular atrophy of distal upper extremity. Neurology. May 23 2000;54(10):1922-6. [Medline].
Horemans HL, Nollet F, Beelen A, et al. Pyridostigmine in postpolio syndrome: no decline in fatigue and limited functional improvement. J Neurol Neurosurg Psychiatry. Dec 2003;74(12):1655-61. [Medline].
Ito S, Kuwabara S, Fukutake T, et al. HyperIgEaemia in patients with juvenile muscular atrophy of the distal upper extremity (Hirayama disease). J Neurol Neurosurg Psychiatry. Jan 2005;76(1):132-4. [Medline].
Ivanyi B, Nollet F, Redekop WK. Late-onset polio sequelae: disabilities and handicaps in a population-based cohort of the 1956 poliomyelitis outbreak in The Netherlands. Arch Phys Med Rehabil. Jun 1999;80(6):687-90. [Medline].
Jubelt B, Drucker J. Post-polio syndrome: an update. Semin Neurol. Sep 1993;13(3):283-90. [Medline].
Jubelt B, Berger JR. Does viral disease underlie ALS? Lessons from the AIDS pandemic. Neurology. Sep 25 2001;57(6):945-6. [Medline].
Katsuno M, Adachi H, Tanaka F, Sobue G. Spinal and bulbar muscular atrophy: ligand-dependent pathogenesis and therapeutic perspectives. J Mol Med. May 2004;82(5):298-307. [Medline].
Kidd D, Williams AJ, Howard RS. Poliomyelitis. Postgrad Med J. Nov 1996;72(853):641-7. [Medline].
Kim JY, Lee KW, Roh JK. A clinical study of benign focal amyotrophy. J Korean Med Sci. Apr 1994;9(2):145-54. [Medline].
Lawrentschuk N, Falkenberg MP, Pirpiris M. Primary bacterial pyomyositis associated with septic arthritis caused by Streptococcus pyogenes: a case report. Am J Orthop. Mar 2003;32(3):148-50. [Medline].
Lederman RJ, Salanga VD, Wilbourn AJ. Focal inflammatory myopathy. Muscle Nerve. Feb 1984;7(2):142-6. [Medline].
Merry DE. Molecular pathogenesis of spinal and bulbar muscular atrophy. Brain Res Bull. Oct-Nov 1 2001;56(3-4):203-7. [Medline].
Miller DC. Post-polio syndrome spinal cord pathology. Case report with immunopathology. Ann N Y Acad Sci. May 25 1995;753:186-93. [Medline].
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. [Medline].
Moulignier A, Moulonguet A, Pialoux G, Rozenbaum W. Reversible ALS-like disorder in HIV infection. Neurology. Sep 25 2001;57(6):995-1001. [Medline].
Nagashima T. [Post-poliomyelitis late progressive muscular atrophy (PPMA)--clinical analyses of Japanese cases]. Rinsho Shinkeigaku. Dec 1991;31(12):1319-21. [Medline].
Nalini A, Lokesh L, Ratnavalli E. Familial monomelic amyotrophy: a case report from India. J Neurol Sci. May 15 2004;220(1-2):95-8. [Medline].
Oryema J, Ashby P, Spiegel S. Monomelic atrophy. Can J Neurol Sci. May 1990;17(2):124-30. [Medline].
Ramlow J, Alexander M, LaPorte R. Epidemiology of the post-polio syndrome. Am J Epidemiol. Oct 1 1992;136(7):769-86. [Medline].
Saha SP, Das SK, Gangopadhyay PK. Pattern of motor neurone disease in eastern India. Acta Neurol Scand. Jul 1997;96(1):14-21. [Medline].
Schwennicke A, Bargfrede M, Reimers CD. Clinical, electromyographic, and ultrasonographic assessment of focal neuropathies. J Neuroimaging. Jul 1998;8(3):136-43. [Medline].
Sehgal H. New dimensions to poliomyelitis. Indian Pediatr. May 1990;27(5):433-6. [Medline].
Serratrice G, Pou-Serradel A, Pellissier JF. Chronic neurogenic quadriceps amyotrophies. J Neurol. 1985;232(3):150-3. [Medline].
Serratrice G, Pellissier JF, Pouget J. [Nosological study of 25 cases of chronic monomelic amyotrophy]. Rev Neurol (Paris). 1987;143(3):201-10. [Medline].
Serratrice G. Focal forms of denervating disorders. Progress in Clinical Neurosciences Ed. By Sinha KK, Chandra P, Neurological Soci. 1990;6(2):49-54.
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. Jan 2004;36(1):1-3. [Medline].
Tandan R, Sharma KR, Bradley WG. Chronic segmental spinal muscular atrophy of upper extremities in identical twins. Neurology. Feb 1990;40(2):236-9. [Medline].
Tandan R. ALS-like syndromes, ALS variants, and adult-onset spinal muscular atrophies. AAN annual meeting syllabi on CD-ROM. 1998.
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. Jan 1 2001;182(2):107-15. [Medline].
Ueyama H, Kumamoto T, Johno M. Localized muscle wasting as an initial symptom of skeletal muscle lymphoma. J Neurol Sci. Jan 21 1998;154(1):113-5. [Medline].
Wang JY, Lee LN, Hsueh PR, et al. Tuberculous myositis: a rare but existing clinical entity. Rheumatology (Oxford). Jul 2003;42(7):836-40. [Medline].
Wekre LL, Stanghelle JK, Lobben B. The Norwegian Polio Study 1994: a nationwide survey of problems in long-standing poliomyelitis. Spinal Cord. Apr 1998;36(4):280-4. [Medline].
Further Reading
Keywords
anti-GM1 antibody, multifocal motor neuropathy with conduction block, benign focal amyotrophy, congenital absence of muscles, focal myositis, Hirayama disease, injection myopathy, monomelic amyotrophy, peripheral nerve injuries, plexopathy, poliomyelitis, postpolio progressive muscular atrophy, postradiation toxicity and disease, spinal cord tumors, toxic neuropathies, wasted leg syndrome
