Kennedy Disease Workup

Updated: Jun 08, 2016
  • Author: Paul E Barkhaus, MD; Chief Editor: Nicholas Lorenzo, MD, MHA, CPE  more...
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Workup

Laboratory Studies

Depending on level of suspicion, immediate genetic testing for Kennedy disease (KD) may be performed to confirm the diagnosis, obviating other tests, such as EMG and enzyme studies for hexosaminidase deficiency. The availability of genetic testing markedly expedites the evaluation for KD. [66]

Problems may arise in resolving apparent positive results obtained before genetic testing is done. For instance, serum creatine kinase (CK) testing is not indicated, yet the CK level may be elevated substantially. One of the author's patients had been treated for inflammatory myopathy for years before the correct diagnosis was made. In another case, the patient was aggressively treated for myasthenia gravis (including thymectomy) before KD was diagnosed. [67] Sorenson and Klein have also reported elevation in CK and transaminases levels in asymptomatic patients with KD. [68]

Appropriate initial testing and monitoring is indicated because of associated conditions such as diabetes mellitus, lipid disorders, and other endocrine disorders.

If genetic findings are negative in an individual who has clinical findings suggestive of KD, other laboratory investigations may be indicated (see Table 1, Table 2).

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Imaging Studies

Patients with KD tend to be middle aged or elderly, and they may have common neurologic conditions, such as spondylosis.

If cervical spondylosis is a consideration, or if marked asymmetry in muscle weakness is noted on follow-up of a patient with KD, imaging of the cervical spine is indicated.

MRI of the brain is indicated if clinical symptoms or endocrinologic testing suggest microadenoma.

Hamano et al reported MRI studies of the leg muscle in patients with KD and amyotrophic lateral sclerosis. [69] In contrast to patients with amyotrophic lateral sclerosis who showed atrophy, patients with KD showed associated high-signal intensity with atrophy consistent with fatty degeneration. This was seen in both proximal as well as distal muscles.

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Other Tests

Other tests may not be needed if the results of genetic testing are positive.

Other tests may include electrodiagnostic studies. [70, 55]

  • Somatosensory evoked potentials: The potentials may be abnormal, reflecting dysfunction in the pathways of the posterior column.
  • Nerve conductions: Compound muscle action potentials have normal or reduced amplitude. Sensory conductions show normal, reduced, or absent sensory-nerve action potentials.

Needle-electrode examination may be needed. A full discussion of electrodiagnostic approaches to motor neuropathy is beyond the scope of this article. In a slowly progressive disease such as KD, fibrillation potentials may be relatively infrequent and small in amplitude. Other insertional and spontaneous activities, such as complex repetitive discharges, myokymia, and fasciculation potentials, also vary in prominence. When clinical myokymia is present, spontaneous discharges of grouped motor-unit action potentials (MUAPs) may be recorded. When present in the mentalis muscle they may correspond to the clinical observation of the quivering chin when the patient is at rest.

Needle-electrode examination should reveal a diffuse, chronic neurogenic process based on changes in the MUAPs, such as complexity, increased amplitude and duration, and reduced recruitment rate. Muscles are affected unequally (side-to-side asymmetry, proximal vs distal muscle).

The study should be planned to demonstrate multisegmental involvement of muscles (myotomes) in at least 3 of 4 regions (ie, bulbar, cervical, thoracic, or lumbar), similar to the El Escorial criteria [58] used to support the diagnosis of ALS. In the limbs, 2 muscles supplied by 2 different roots and peripheral nerves should be studied to ascertain the presence of a diffuse chronic neurogenic process. In KD examination of the bulbar region should be emphasized.

Increase in MUAP complexity (eg, increase 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.

If the process is established and weakness is present, a reduced number of moderately to markedly enlarged MUAPs may be observed. This finding is expected in a slowly progressive, chronic neurogenic process in which one third to half the motor neurons in a given muscle may be lost before clinical weakness manifests (see images below).

Motor-unit action potentials recorded from the bic 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 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.

Meriggioli and Rowin reported a case of KD with increased jitter on single-fiber EMG in a patient with KD who had fatigue with normal muscle strength on clinical evaluation. [71] Routine needle-electrode examination showed evidence of chronic motor axonopathy or neuronopathy. The authors postulated that abnormal neuromuscular transmission was the underlying mechanism of the patient's fatigue.

Fiber-optic endoscopic evaluation or swallow study is recommended for dysphagia as 80% of KD patients have swallowing dysfunction [72]

Tongue pressure is decreased in KD. It has shown to be an early and reliable biomarker of swallowing dysfunction in KD, much before subjective dysphagia symptoms. [73]

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Procedures

Given the availability of genetic testing, muscle and nerve biopsy are not indicated for diagnostic work-up in KD.

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Histologic Findings

In some instances, nerve and muscle biopsy may have been performed in cases of KD when the diagnosis was not suspect.

  • Sural-nerve biopsy may show loss of large-diameter myelinated axons. [11]
  • In the author's series, muscle biopsy showing marked predominance of type I muscle fibers with variable and diffuse atrophy was present in 2 patients in whom biopsy material was available. [67]
  • Predominance of type II muscle fibers has been described in other cases.
  • In another series, both neurogenic and myopathic changes were reported in muscle biopsies from patients with KD, as well as in female carriers of KD. [74]
  • When such muscle fiber type predominance is present, fiber-type grouping is not easily appreciated.
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