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Case Report

Clinical Pain 2023; 22(2): 127-130

Published online December 31, 2023 https://doi.org/10.35827/cp.2023.22.2.127

Copyright © Korean Association of Pain Medicine.

Kennedy’s Disease with Chronic Low Back Pain and Muscle Weakness

만성요통과 경미한 근위약을 주소로 내원한 케네디병 환자

Jae Yeon Kim, Young Sook Park, Hyun Jung Chang, Jin Gee Park, Eun Sol Cho, Da Hye Kim, Jeong Hwan Lee, Se Jin Kim

김재연ㆍ박영숙ㆍ장현정ㆍ박진기ㆍ조은솔ㆍ김다혜ㆍ이정환ㆍ김세진

Department of Physical Medicine and Rehabilitation, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea

성균관대학교 의과대학 삼성창원병원 재활의학과

Correspondence to:박영숙, 창원시 마산회원구 팔용로158 ㉾ 51353, 성균관대학교 의과대학 삼성창원병원 재활의학과
Tel: 055-233-5450, Fax: 055-233-5454
E-mail: jijibaeheiwon@hanmail.net

Received: May 30, 2023; Revised: July 5, 2023; Accepted: July 12, 2023

Kennedy’s disease (KD) or bulbospinal muscular atrophy is an uncommon x-linked recessive genetic disorder. Its diagnosis is challenging due to its wide array of clinical manifestations and difficulty distinguishing it from other motor neuron diseases. Thus, diagnosis is confirmed through DNA testing. 52-year-old male patient presented to the hospital with chronic low back pain (LBP) and muscle weakness. The patient had mild weakness in some proximal muscles, increased deep tendon reflex. Lumbar spine magnetic resonance imaging (MRI) showed degenerative changes. Motor nerve conduction test results showed close to the normal. Sensory nerve conduction test results showed decreased latency and amplitude in most nerves. Needle electromyography revealed fasciculation potentials, diffuse fibrillation potentials, and positive sharp waves were detected. Thus, molecular genetic testing was performed. Consequently, KD was diagnosed. These results suggest the importance of detailed history taking and neurological examination even for patients with chronic LBP to rule out severe diseases.

KeywordsKennedy’s disease, Low back pain, Muscle weakness

Kennedy’s disease (KD) is an x-linked recessive spinal muscular atrophy that is characterized by slowly progressing bulbar and proximal atrophy, as opposed to distal, and limb weakness.1 It presents with symptoms similar to most neuromuscular disorders, but early clinical diagnosis is challenging due to its slow progression and rarity of cases involving sensory loss or neuropathic pain.2 Moreover, it is characterized by clinical features, such as gynecomastia, testicular atrophy, erectile dysfunction, and diabetes mellitus. Furthermore, since the first case reported by Kennedy in 1968,3 cases have been rarely reported both worldwide and in Korea.4,5 This disease has an x-linked recessive inheri-tance pattern and is thought to be caused by a mutation in the androgen receptor gene that causes an abnormal increase in trinucleotide Cytosine-Adenine-Guanine (CAG) repeats, which results in the abnormal aggregation of the androgen receptor and dysfunction of the cytoskeletal system within nerve cells due to impaired tubulin regulation.4,6 Although the disease can be confirmed through molecular genetic analysis, the turnaround time is more than a month.4

The most common symptom of KD is muscle spasms, followed by lower limb muscle weakness, gynecomastia, and upper limb muscle weakness.7 We report the case of a patient who presented with chronic LBP and mild muscle weakness as chief complaints and suspected with KD based on thorough physical examination and electrophysiological testing. KD was subsequently confirmed through molecular genetic testing.

A 52-year-old male patient presented to a secondary hospital in 2018 due to chronic LBP and persistent muscle weakness that began since 2013. The patient did not have notable history or family history. Blood test and radiologic examination were performed under the suspicion of myopathy and degenerative spinal disorder. And result, only creatinine phosphokinase (CPK) was increased and lumbar spine MRI showed degenerative changes. The patient used to run a secondhand shop, which involved frequent lifting and moving of heavy objects. Considering this occupational history, suspected a renal lesion caused by rhabdomyolysis or chronic LBP caused by degenerative spinal disorder and provided conservative treatment; however, the patient did not respond. In the past few years, chronic LBP was exacerbated, and the patient’s exercise endurance declined.

Subsequently, the patient was referred to the rehabilita-tion medicine department at our hospital in 2023. Physical examination showed mild muscle weakness in some proximal muscles (i.e., grade 4 for quadriceps femoris and biceps on manual muscle test), increased deep tendon reflex, and tongue muscle atrophy, but the patient did not show fasciculation and pathological reflex. Overall, a motor neuron disorder was suspected. Lumbar spine MRI was performed to rule out central nervous lesion and radiculopathy, and there was no significant difference from the previous examination in 2018, such as showing only some degenerative changes (Fig. 1).

Figure 1.T2 weighted images of the lumbar spine show degenerative changes.

In terms of the electrophysiological examination, the motor nerve conduction test showed decreased latency and amplitude in some nerves but was close to normal compared to that in the sensory nerve conduction test. Sensory nerve conduction tests showed decreased latency and amplitude in most nerves (Table 1). F-wave and H-reflex test results were unremarkable.

Table 1 Findings of Nerve Conduction Study

NerveStimulationRightLeft
Latency (ms)Amplitude (mV)CV (m/s)Latency (ms)Amplitude (mV)CV (m/s)
Motor
Median at APBWrist4.4310.24.489.8
Elbow8.339.256.88.399.653.2
Ulnar at ADMWrist3.3311.83.0211.0
Below elbow6.5111.666.76.5110.355.6
Peroneal at EDBAnkle4.012.24.901.8
Fibular head10.421.544.010.941.946.5
Tibial at AHAnkle3.9119.83.7018.0
Fibular head11.6715.845.411.3015.246.2
Sensory
Median at Digit IIWrist3.446.1413.498.840
Ulnar at Digit VWrist2.767.1512.606.354
SuralCalf3.285.1433.234.843
Superficial peronealLateral leg3.332.5423.393.941

CV: conduction velocity, APB: abductor pollicis brevis, EDB: extensor digitorum brevis, AH: abductor hallucis.


Needle electromyography (EMG) revealed widespread reduction in motor unit action potential recruitment with large amplitude and long duration. Fasciculation potentials, diffuse fibrillation potentials and positive sharp waves were detected.1

Thus, molecular genetic testing was performed under the suspicion of KD. CAG repeats were increased to 46, based on which KD was confirmed (Fig. 2).

Figure 2.The number of CAG repeats increased to 46, confirming the diagnosis of Kennedy’s disease.

A study on 57 patients with KD in the United States reported that the most common symptom was muscle spasms, followed by lower limb muscle weakness, gynecomastia, and upper limb muscle weakness. In a study on 46 British patients with KD, the most common symptom was lower limb weakness, followed by upper limb weakness, tremor, bulbar weakness, and gynecomastia.7 In a Korean case report, the chief complaint was lower limb weakness and dysarthria.4,5 Muscle biopsy, a painful procedure, is commonly performed for the diagnosis of KD since molecular genetic testing, which is the definitive diagnostic test for this diseases, is costly and time-consuming.4 Thus, patient consent is difficult to obtain without a strong suspicion of diagnosis. However, unlike other motor neuron diseases (MNDs), sensory nerve action potentials on EMG have reduced amplitude or are unobtainable in KD, while compound muscle action potentials are characteristically normal. Needle EMG reveal muscle fiber fasciculations and prominent abnormal spontaneous activity, similar to other MNDs.1

The patient in our case had chief complaints of chronic LBP and mild muscle weakness only, without the other common symptoms, such as gynecomastia, testicular atrophy, erectile dysfunction, and diabetes mellitus.3 Furthermore, the patient also had no notable family history. This seems to be similar to previous reports that 74% of patients with KD have no family history.8 However, physical examination revealed more significant muscle weakness affecting the proximal than the distal muscles, along with prominent increase in deep tendon reflex, tongue atrophy, and elevated CPK on blood test. Thus, we performed EMG to differentiate myopathy and MND. As characteristic EMG findings of KD were observed, we were able to confirm KD through molecular genetic testing.

A non-negligible percentage (12.8%) of chronic LBP cases is caused by other diseases, including congenital abnormalities and deformities,9 and 1% of the cases may be caused by a severe disease, including spondylitis, spinal tumor, and genetic disorders, as opposed to a simple structural issue. This highlights the importance of detailed history taking and neurological testing.10

The reported patient had only received symptomatic treatment for chronic LBP and mild muscle weakness before presenting to our hospital; however, his symptoms progressed without marked improvement. This case is significant since KD, an uncommon genetic disorder, was diagnosed subsequently based on detailed history taking and neurological testing.

  1. Dumitru D, Amato AA, Zwarts MJ. Electrodiagnostic medicine. Philadelphia: Hanley & Belfus; 2002. p. 593-4.
  2. Pradat PF, Bruneteau G. Differential diagnosis and atypical subsets of amyotrophic lateral sclerosis. Rev Neurol (Paris) 2006;162:S81-90.
    Pubmed
  3. Kennedy WR, Alter M. Progressive proximal spinal and bulbar muscular atrophy of late onset: a sex-linked recessive trait. J Clin Neuromuscul Dis 2000;2:3-5.
    Pubmed CrossRef
  4. Choi DH KD, Lee SU. A Case Showing Specific Electrophysiological Findings of Bulbospinal Muscular Atrophy (Kennedy’s Disease). J Korean Assoc EMG Electrodiagn Med 2006;8:56-61.
  5. Hyun YY, Bom PS, Wook YH, Ok PY. X-linked Recessive Bulbospinal Muscular Atrophy (Kennedy’s Syndrome): A case report. Ann Rehabil Med 2002;26:626-30.
  6. Gallo JM. Kennedy’s disease: a triplet repeat disorder or a motor neuron disease?. Brain Res Bull 2001;56:209-14.
  7. Finsterer JS, G. Onset Manifestations of Spinal and Bulbar Muscular Atrophy (Kennedy’s Disease). J Mol Neurosci 2016;58:321-9.
  8. Ferrante MA, Wilbourn AJ. The characteristic electrodiagnostic features of Kennedy’s disease. Muscle Nerve 1997;20:323-9.
  9. Hart LG, Deyo RA, Cherkin DC. Physician office visits for low back pain. Frequency, clinical evaluation, and treatment patterns from a U.S. national survey. Spine (Phila Pa 1976) 1995;20:11-9.
    Pubmed CrossRef
  10. Park JY. Diagnosis and management of chronic low back pain. Korean J Fam Med 2001;22:1349-58.

Article

Case Report

Clinical Pain 2023; 22(2): 127-130

Published online December 31, 2023 https://doi.org/10.35827/cp.2023.22.2.127

Copyright © Korean Association of Pain Medicine.

Kennedy’s Disease with Chronic Low Back Pain and Muscle Weakness

Jae Yeon Kim, Young Sook Park, Hyun Jung Chang, Jin Gee Park, Eun Sol Cho, Da Hye Kim, Jeong Hwan Lee, Se Jin Kim

Department of Physical Medicine and Rehabilitation, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea

Correspondence to:박영숙, 창원시 마산회원구 팔용로158 ㉾ 51353, 성균관대학교 의과대학 삼성창원병원 재활의학과
Tel: 055-233-5450, Fax: 055-233-5454
E-mail: jijibaeheiwon@hanmail.net

Received: May 30, 2023; Revised: July 5, 2023; Accepted: July 12, 2023

Abstract

Kennedy’s disease (KD) or bulbospinal muscular atrophy is an uncommon x-linked recessive genetic disorder. Its diagnosis is challenging due to its wide array of clinical manifestations and difficulty distinguishing it from other motor neuron diseases. Thus, diagnosis is confirmed through DNA testing. 52-year-old male patient presented to the hospital with chronic low back pain (LBP) and muscle weakness. The patient had mild weakness in some proximal muscles, increased deep tendon reflex. Lumbar spine magnetic resonance imaging (MRI) showed degenerative changes. Motor nerve conduction test results showed close to the normal. Sensory nerve conduction test results showed decreased latency and amplitude in most nerves. Needle electromyography revealed fasciculation potentials, diffuse fibrillation potentials, and positive sharp waves were detected. Thus, molecular genetic testing was performed. Consequently, KD was diagnosed. These results suggest the importance of detailed history taking and neurological examination even for patients with chronic LBP to rule out severe diseases.

Keywords: Kennedy&rsquo,s disease, Low back pain, Muscle weakness

INTRODUCTION

Kennedy’s disease (KD) is an x-linked recessive spinal muscular atrophy that is characterized by slowly progressing bulbar and proximal atrophy, as opposed to distal, and limb weakness.1 It presents with symptoms similar to most neuromuscular disorders, but early clinical diagnosis is challenging due to its slow progression and rarity of cases involving sensory loss or neuropathic pain.2 Moreover, it is characterized by clinical features, such as gynecomastia, testicular atrophy, erectile dysfunction, and diabetes mellitus. Furthermore, since the first case reported by Kennedy in 1968,3 cases have been rarely reported both worldwide and in Korea.4,5 This disease has an x-linked recessive inheri-tance pattern and is thought to be caused by a mutation in the androgen receptor gene that causes an abnormal increase in trinucleotide Cytosine-Adenine-Guanine (CAG) repeats, which results in the abnormal aggregation of the androgen receptor and dysfunction of the cytoskeletal system within nerve cells due to impaired tubulin regulation.4,6 Although the disease can be confirmed through molecular genetic analysis, the turnaround time is more than a month.4

The most common symptom of KD is muscle spasms, followed by lower limb muscle weakness, gynecomastia, and upper limb muscle weakness.7 We report the case of a patient who presented with chronic LBP and mild muscle weakness as chief complaints and suspected with KD based on thorough physical examination and electrophysiological testing. KD was subsequently confirmed through molecular genetic testing.

CASE

A 52-year-old male patient presented to a secondary hospital in 2018 due to chronic LBP and persistent muscle weakness that began since 2013. The patient did not have notable history or family history. Blood test and radiologic examination were performed under the suspicion of myopathy and degenerative spinal disorder. And result, only creatinine phosphokinase (CPK) was increased and lumbar spine MRI showed degenerative changes. The patient used to run a secondhand shop, which involved frequent lifting and moving of heavy objects. Considering this occupational history, suspected a renal lesion caused by rhabdomyolysis or chronic LBP caused by degenerative spinal disorder and provided conservative treatment; however, the patient did not respond. In the past few years, chronic LBP was exacerbated, and the patient’s exercise endurance declined.

Subsequently, the patient was referred to the rehabilita-tion medicine department at our hospital in 2023. Physical examination showed mild muscle weakness in some proximal muscles (i.e., grade 4 for quadriceps femoris and biceps on manual muscle test), increased deep tendon reflex, and tongue muscle atrophy, but the patient did not show fasciculation and pathological reflex. Overall, a motor neuron disorder was suspected. Lumbar spine MRI was performed to rule out central nervous lesion and radiculopathy, and there was no significant difference from the previous examination in 2018, such as showing only some degenerative changes (Fig. 1).

Figure 1. T2 weighted images of the lumbar spine show degenerative changes.

In terms of the electrophysiological examination, the motor nerve conduction test showed decreased latency and amplitude in some nerves but was close to normal compared to that in the sensory nerve conduction test. Sensory nerve conduction tests showed decreased latency and amplitude in most nerves (Table 1). F-wave and H-reflex test results were unremarkable.

Table 1 . Findings of Nerve Conduction Study.

NerveStimulationRightLeft
Latency (ms)Amplitude (mV)CV (m/s)Latency (ms)Amplitude (mV)CV (m/s)
Motor
Median at APBWrist4.4310.24.489.8
Elbow8.339.256.88.399.653.2
Ulnar at ADMWrist3.3311.83.0211.0
Below elbow6.5111.666.76.5110.355.6
Peroneal at EDBAnkle4.012.24.901.8
Fibular head10.421.544.010.941.946.5
Tibial at AHAnkle3.9119.83.7018.0
Fibular head11.6715.845.411.3015.246.2
Sensory
Median at Digit IIWrist3.446.1413.498.840
Ulnar at Digit VWrist2.767.1512.606.354
SuralCalf3.285.1433.234.843
Superficial peronealLateral leg3.332.5423.393.941

CV: conduction velocity, APB: abductor pollicis brevis, EDB: extensor digitorum brevis, AH: abductor hallucis..



Needle electromyography (EMG) revealed widespread reduction in motor unit action potential recruitment with large amplitude and long duration. Fasciculation potentials, diffuse fibrillation potentials and positive sharp waves were detected.1

Thus, molecular genetic testing was performed under the suspicion of KD. CAG repeats were increased to 46, based on which KD was confirmed (Fig. 2).

Figure 2. The number of CAG repeats increased to 46, confirming the diagnosis of Kennedy’s disease.

DISCUSSION

A study on 57 patients with KD in the United States reported that the most common symptom was muscle spasms, followed by lower limb muscle weakness, gynecomastia, and upper limb muscle weakness. In a study on 46 British patients with KD, the most common symptom was lower limb weakness, followed by upper limb weakness, tremor, bulbar weakness, and gynecomastia.7 In a Korean case report, the chief complaint was lower limb weakness and dysarthria.4,5 Muscle biopsy, a painful procedure, is commonly performed for the diagnosis of KD since molecular genetic testing, which is the definitive diagnostic test for this diseases, is costly and time-consuming.4 Thus, patient consent is difficult to obtain without a strong suspicion of diagnosis. However, unlike other motor neuron diseases (MNDs), sensory nerve action potentials on EMG have reduced amplitude or are unobtainable in KD, while compound muscle action potentials are characteristically normal. Needle EMG reveal muscle fiber fasciculations and prominent abnormal spontaneous activity, similar to other MNDs.1

The patient in our case had chief complaints of chronic LBP and mild muscle weakness only, without the other common symptoms, such as gynecomastia, testicular atrophy, erectile dysfunction, and diabetes mellitus.3 Furthermore, the patient also had no notable family history. This seems to be similar to previous reports that 74% of patients with KD have no family history.8 However, physical examination revealed more significant muscle weakness affecting the proximal than the distal muscles, along with prominent increase in deep tendon reflex, tongue atrophy, and elevated CPK on blood test. Thus, we performed EMG to differentiate myopathy and MND. As characteristic EMG findings of KD were observed, we were able to confirm KD through molecular genetic testing.

A non-negligible percentage (12.8%) of chronic LBP cases is caused by other diseases, including congenital abnormalities and deformities,9 and 1% of the cases may be caused by a severe disease, including spondylitis, spinal tumor, and genetic disorders, as opposed to a simple structural issue. This highlights the importance of detailed history taking and neurological testing.10

The reported patient had only received symptomatic treatment for chronic LBP and mild muscle weakness before presenting to our hospital; however, his symptoms progressed without marked improvement. This case is significant since KD, an uncommon genetic disorder, was diagnosed subsequently based on detailed history taking and neurological testing.

Fig 1.

Figure 1.T2 weighted images of the lumbar spine show degenerative changes.
Clinical Pain 2023; 22: 127-130https://doi.org/10.35827/cp.2023.22.2.127

Fig 2.

Figure 2.The number of CAG repeats increased to 46, confirming the diagnosis of Kennedy’s disease.
Clinical Pain 2023; 22: 127-130https://doi.org/10.35827/cp.2023.22.2.127

Table 1 Findings of Nerve Conduction Study

NerveStimulationRightLeft
Latency (ms)Amplitude (mV)CV (m/s)Latency (ms)Amplitude (mV)CV (m/s)
Motor
Median at APBWrist4.4310.24.489.8
Elbow8.339.256.88.399.653.2
Ulnar at ADMWrist3.3311.83.0211.0
Below elbow6.5111.666.76.5110.355.6
Peroneal at EDBAnkle4.012.24.901.8
Fibular head10.421.544.010.941.946.5
Tibial at AHAnkle3.9119.83.7018.0
Fibular head11.6715.845.411.3015.246.2
Sensory
Median at Digit IIWrist3.446.1413.498.840
Ulnar at Digit VWrist2.767.1512.606.354
SuralCalf3.285.1433.234.843
Superficial peronealLateral leg3.332.5423.393.941

CV: conduction velocity, APB: abductor pollicis brevis, EDB: extensor digitorum brevis, AH: abductor hallucis.


References

  1. Dumitru D, Amato AA, Zwarts MJ. Electrodiagnostic medicine. Philadelphia: Hanley & Belfus; 2002. p. 593-4.
  2. Pradat PF, Bruneteau G. Differential diagnosis and atypical subsets of amyotrophic lateral sclerosis. Rev Neurol (Paris) 2006;162:S81-90.
    Pubmed
  3. Kennedy WR, Alter M. Progressive proximal spinal and bulbar muscular atrophy of late onset: a sex-linked recessive trait. J Clin Neuromuscul Dis 2000;2:3-5.
    Pubmed CrossRef
  4. Choi DH KD, Lee SU. A Case Showing Specific Electrophysiological Findings of Bulbospinal Muscular Atrophy (Kennedy’s Disease). J Korean Assoc EMG Electrodiagn Med 2006;8:56-61.
  5. Hyun YY, Bom PS, Wook YH, Ok PY. X-linked Recessive Bulbospinal Muscular Atrophy (Kennedy’s Syndrome): A case report. Ann Rehabil Med 2002;26:626-30.
  6. Gallo JM. Kennedy’s disease: a triplet repeat disorder or a motor neuron disease?. Brain Res Bull 2001;56:209-14.
  7. Finsterer JS, G. Onset Manifestations of Spinal and Bulbar Muscular Atrophy (Kennedy’s Disease). J Mol Neurosci 2016;58:321-9.
  8. Ferrante MA, Wilbourn AJ. The characteristic electrodiagnostic features of Kennedy’s disease. Muscle Nerve 1997;20:323-9.
  9. Hart LG, Deyo RA, Cherkin DC. Physician office visits for low back pain. Frequency, clinical evaluation, and treatment patterns from a U.S. national survey. Spine (Phila Pa 1976) 1995;20:11-9.
    Pubmed CrossRef
  10. Park JY. Diagnosis and management of chronic low back pain. Korean J Fam Med 2001;22:1349-58.
Korean Association of Pain Medicine

Vol.22 No.2
December 2023

eISSN: 2765-5156

Frequency: Semi Annual

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