Diagnostic Considerations

Other problems to be considered include the following:

Autosomal dominant cerebellar ataxia type I
Bulbar hereditary motor neuropathy affecting the lowest 6 cranial nerves (Fazio-Londe disease)
Cervical spondylosis
Cytoplasmic-body myopathy^[63]
Facial onset sensory and motor neuropathy (FOSNM syndrome)^{[60, 61]}
Hereditary proximal motor neuropathy
Hereditary distal motor neuropathy
Hereditary motor neuronopathy with oculopharyngeal involvement
Hexosaminidase A deficiency
Lead neuropathy^[64]
Motor neuron disease with macroglobulinemia^[59]
Myasthenia gravis - Adult acquired form
Oculopharyngeal muscular dystrophy
Polymyositis
Sandhoff disease^[65]
Scapuloperoneal hereditary motor neuropathy
Syphilis (neurovascular form)

Differential Diagnoses

Workup

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Media Gallery

Note wasting in the thighs and shoulders. The arms hang down and are rotated internally so that the thumbs point toward the patient (ie, simian posture) rather than forward, as in a healthy individual. This observation strongly suggests weakness in shoulder girdle muscles.
Prominence of breast tissue consistent with gynecomastia in Kennedy disease.
The forehead of this patient with Kennedy disease is smooth, in fact, too smooth for a man this age. The smoothness is particularly noticeable when the patient tries to perform upgaze, when wrinkling of the forehead due to contraction of the frontalis is expected.
Photographs show asymmetry at rest due to facial weakness, which is enhanced when the muscles are activated by pursing the lips.
Note the scalloping of the borders of the tongue, which strongly suggests wasting. In addition, the marked wasting of the large group of glossal muscles on each side has caused them to separate and form a midline furrow.
Motor-unit action potentials recorded from the biceps brachii in a patient with Kennedy disease. Upper tracing shows 2 action potentials discharging during low-to-moderate effort. In a healthy person, additional discharges are expected. (Calibration is 1 mV per division on the vertical axis and 10 ms per division on the horizontal axis.) Potential on the left is approximately 1.2 mV and 26 ms. It is moderately increased in amplitude, almost twice the upper limit in duration, and shows marked irregularity or serrations (ie, turns) in the main component. Potential to the right is markedly increased in amplitude (approximately 3.3 mV), and its duration is at least 30 ms but cannot be measured on this tracing because it extends off to the right and qualifies as a giant motor-unit action potential. Bottom tracing shows the same 2 potentials at standard setting used to view motor-unit action potentials (0.1 mV per vertical division), which emphasizes their large size and complexity (ie, increased number of changes in polarity of the waveform).
Recording of motor-unit action potentials from the pectoralis muscle in a patient with Kennedy disease. Calibration is 1 mV per division on the vertical axis and 10 ms per division on the horizontal axis. The patient's level of effort in activation is high. Therefore, the number of motor unit action potentials clearly is reduced, and the individual potentials observed are enlarged, consistent with a chronic neurogenic process.

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Table 1. Primary Differential Diagnoses of Kennedy Disease

Disease	Differentiating Characteristics or Tests
ALS	Upper motor neuron involvement with tendency for distal-greater-than-proximal weakness^[58]
Spinal muscular atrophy	See Table 2 below
Fascioscapulohumeral muscular dystrophy	Autosomal dominant pattern with myopathic findings on muscle biopsy and EMG, positive genetic marker
Myasthenia gravis - Adult acquired form	Extraocular muscle frequently involved, EMG consistent with neuromuscular transmission disorder, acetylcholine receptor antibodies frequently positive
Oculopharyngeal muscular dystrophy	Autosomal dominant pattern, late onset, predominant involvement of bulbar muscle with ptosis and mild ophthalmoparesis, EMG and muscle biopsy results consistent with myopathic process, positive genetic marker
Hexosaminidase A deficiency	Rectal biopsy, enzyme assay
Sandhoff disease	Rectal biopsy, enzyme assay
Syphilis (neurovascular form)	Positive serology
Lead neuropathy	Index of suspicion based on potential exposure; anemia; elevated serum, blood, and urine lead levels
Motor neuron disease with macroglobulinemia	Monoclonal gammopathy^[59]
Autosomal dominant cerebellar ataxia type I	Amyotrophy occasionally prominent finding in SCAs, particularly types II and III; other clinical and laboratory findings suggest condition other than a pure motor-neuron process; appropriate tests of genetic markers for SCA
Polymyositis	Elevated serum creatine kinase, EMG and muscle-biopsy results consistent with inflammatory myopathy
Cervical spondylosis	Rostral cervical segmental myotomes (eg, C5, C6) commonly affected, but pattern on EMG testing is highly localizing; possible pyramidal-tract signs if spondylosis compresses spinal cord at same segmental level; no evidence of lower motor-neuro involvement in legs; imaging (eg, cervical MRI, myelography with low-dose CT) findings correlated with suspected lesion
Facial onset sensory and motor neuropathy (FOSMN syndrome)^{[60, 61]}	Slow progressing, trigeminal-onset sensory loss that may spread to upper limbs and torso, associated with lower motor syndrome with prominent bulbar involvement

Table 2. Patterns of Hereditary Spinal Muscular Atrophies that May Resemble Kennedy Disease

Pattern	Characteristics*
Bulbar hereditary motor neuropathy affecting lowest 6 cranial nerves (Fazio-Londe disease)	Autosomal recessive, onset in childhood, limbs not affected; when associated with deafness, pattern called Vialleto-van Laere disease, which may be X-linked or autosomal dominant
Scapuloperoneal hereditary motor neuropathy	Variable transmission: dominant, recessive, X-linked; pattern of weakness as described; bulbar muscles spared
Fascioscapulohumeral hereditary motor neuropathy	Autosomal dominant, pattern of weakness as described
Hereditary motor neuronopathy with oculopharyngeal involvement	Described in Japanese individuals; autosomal recessive or dominant; ophthalmoplegia, dysarthria, and dysphagia
Hereditary proximal motor neuropathy	Variable dominant or recessive inheritance; onset usually in first 2 decades; bulbar muscles spared
Hereditary distal motor neuropathy	Usually recessive inheritance; onset usually in first 2 decades; bulbar muscles spared; autosomal-dominant distal spinal muscular atrophy linked to chromosome 7 (same locus as that of hereditary sensorimotor neuropathy type 2D)^[62]
*In none of these diseases are results of test for the KD marker positive, and associated endocrinopathy or sensory nerve conduction abnormality should be absent.

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Author

David A Shirilla, DO Neuromuscular Medicine Fellow, University of Kansas Medical Center

David A Shirilla, DO is a member of the following medical societies: American Academy of Neurology, American Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

Paul E Barkhaus, MD, FAAN, FAANEM Professor of Neurology and Physical Medicine and Rehabilitation, Chief, Neuromuscular and Autonomic Disorders Program, Director, ALS Program, Department of Neurology, Medical College of Wisconsin

Paul E Barkhaus, MD, FAAN, FAANEM is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Clinical Neurophysiology Society, American Neurological Association

Disclosure: Nothing to disclose.

Specialty Editor Board

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.

Neil A Busis, MD Chief of Neurology and Director of Neurodiagnostic Laboratory, UPMC Shadyside; Clinical Professor of Neurology and Director of Community Neurology, Department of Neurology, University of Pittsburgh Physicians

Neil A Busis, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: American Academy of Neurology<br/>Serve(d) as a speaker or a member of a speakers bureau for: American Academy of Neurology<br/>Received income in an amount equal to or greater than $250 from: American Academy of Neurology.

Chief Editor

Nicholas Lorenzo, MD, CPE, MHCM, FAAPL 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; Former Chief Medical Officer, MeMD Inc

Nicholas Lorenzo, MD, CPE, MHCM, FAAPL is a member of the following medical societies: Alpha Omega Alpha, American Academy of Neurology, American Association for Physician Leadership

Disclosure: Nothing to disclose.

Additional Contributors

Rodrigo O Kuljis, MD Esther Lichtenstein Professor of Psychiatry and Neurology, Director, Division of Cognitive and Behavioral Neurology, Department of Neurology, University of Miami School of Medicine

Rodrigo O Kuljis, MD is a member of the following medical societies: American Academy of Neurology, Society for Neuroscience

Disclosure: Nothing to disclose.

Sumit Verma, MD Assistant Professor of Pediatrics, Assistant Professor of Neurology, Emory University School of Medicine; Pediatric Neurologist, Medical Director, Neuromuscular Program, Director, EMG Laboratory, Director, MDA Clinic Care Center, Children’s Healthcare of Atlanta

Sumit Verma, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, Child Neurology Society, Indian Academy of Pediatrics

Disclosure: Nothing to disclose.

Acknowledgements

The author acknowledges support in part from the Department of Veterans Affairs.

Disclaimer: This article does not necessarily reflect the views of the Department of Veterans Affairs or the United States Government.