Hirayama Disease (Non-progressive Juvenile Spinal Muscular Atrophy)

Article Author:
Sara Lay
Article Editor:
Sandeep Sharma
Updated:
5/3/2018 2:13:14 PM
PubMed Link:
Hirayama Disease (Non-progressive Juvenile Spinal Muscular Atrophy)

Introduction

Hirayama is a rare, nonfamiliar, monomelic amyotrophy originally described by Dr. Hirayama in the 1950s. Classical findings are muscle atrophy and weakness of the forearms and hands, either bilateral or unilateral, that is without sensory change and usually progresses for a one or two years before plateauing. The condition is caused by chronic ischemic changes to the anterior horn cells of the cervical spine, caused by limited dural sac laxity. Although commonly considered a non-progressive and self-limiting disease, this has been noted to be a source of significant disability for some affected individuals. Early intervention has been identified to limit the progression and decrease the degree of disability. Other names used to describe this process are benign juvenile brachial spinal muscular atrophy, juvenile asymmetric segmental spinal muscular atrophy, juvenile muscular atrophy of the distal upper extremity, monomelic amyotrophy, and oblique amyotrophy. However, Hirayama disease is the most common name. 

Etiology

Although idiopathic, two theories are generally accepted based on cadaveric and imaging findings.

The more commonly accepted etiology has been described as an increased laxity of the dura mater from its superior anchors on the dorsal surfaces of C2 and C3 providing increased cord movement with cervical flexion. This increased laxity permits anterior displacement of the spinal cord, causing multiple episodes of subclinical cervical trauma and resulting in micro ischemia during cervical flexion to the anterior horn of the spinal cord. This eventually leads to myelopathy and degeneration evident by asymmetric lower cervical cord thinning correlating within the C7 and C8.

It has been further suggested that this laxity may be caused by a growth imbalance in the vertebral column and dural canal. This imbalance is particularly noted during growth spurts and may lead to increased laxity, allowing for anterior displacement of the posterior dura. As growth slows down or stops, dural displacement decreases, causing a plateau of the disease process.

A second theory is based on the posterior longitudinal ligament structure. Two cellular matrixes have been described, one with fine elastic ligament and the other of larger elastic ligaments. It has been proposed that these ligaments designed to secure the posterior dura mater are unequally dispersed, allowing only part of the cord to have anterior displacement and accounting for the unilateral presentation based on decreased elasticity found on some surgical and cadaveric specimens.

Epidemiology

This process has been noted to affect males more than females at a 3:1 ratio. The highest prevalence is found among the Asian population, with the most prevalence in Japan but also noted in China, Taiwan, Malaysia, India, and Sri Lanka, with few cases from Europe and North America.

The insidious unilateral weakness onset usually has been reported to occur at the start of puberty, in the early to mid-teens. Peak onset age is approximately two years later than the longitudinal peak on the growth curve of juvenile males in Japan. The plateau occurs on average 1 to 4 years after onset but occasionally lasting until the early twenties.

Most reported cases have involved the right upper limb at a 2.8:1 ratio, regardless of hand dominance. However, the few described cases of bilateral upper limb involvement seen in this same age group are considered to be more severe presentations. 

Pathophysiology

Findings on autopsy demonstrated a reduction in the anterior-posterior diameter of the cervical cord by greater than 50% with central necrosis and decreased large and small nerve cells without macrophage infiltration at the C7-C8 levels, correlating with reported symptoms and indicative of a chronic ischemic process. However, there was no indication of vascular vessel change to explain the cause of ischemic changes.

History and Physical

Patients usually complain of progressive decline in functional ability in the right hand caused by decreased hand strength and dexterity. Such limitations may be manifested as decreased ability to complete daily self-care activities requiring a fine motor function such as eating, dressing, and grooming. Patients report that symptoms are worsened by cold temperatures. Rarely, symptoms will be reported with a triggering event. Depending on the time of presentation, patients already may have noted a decline in symptom progression.

Based on the rate of progression, initial presentation may be a complaint of deformity related to muscle atrophy. Sensory changes are rarely reported, and patients do not complain of pain until the atrophy has reached the upper arm and shoulder girdle, as seen in more severe cases.

The patient also may report increased fatigue and may have increased atopy or allergies. 

This constellation of symptoms causes patients to quit or decrease participation in sports and other activities. Such decreased activity or deformity may result in a change in socialization. 

Appearance

Common presentation is noted with gross deformity described as unilateral atrophy in the distal upper limb. Most atrophy occurs in the thenar, intrinsic hand muscles, hypothenar, and forearms. Depending on its severity, patients may also have limb length discrepancies.

Strength

Weakness noted in flexor and extensors of the wrist and digits based on the neural involvement of the C7-T1 nerve roots. Fine motor motions and grasp are limited by weakness, and patients may be unable to perform pinch or key grasp. Contralateral hand and digits remain at full strength and dexterity. Typically, elbow flexion, extension, pronation, and supination are unaffected. Generally, other proximal muscle groups are also spared.

Neurologic Exam

The sensory exam is intact for vibration, temperature, sharp, dull, and light touch on all extremities. Muscle stretch reflexes are generally normal and symmetric. Hoffman and Holman are noncontributory.

Cardiovascular

Pulses are present. Limbs are warm and have a good capillary refill.

Standards on physical examination were defined to help identify and diagnose this condition. These standards were described by Tashiro et al. as follows: 

  • Predominant distal muscle weakness with hand and forearm atrophy. 
  • Unilateral upper limbs almost always involved.
  • Onset between the ages of 10 to early 20s. 
  • Has sudden onset and gradual progression for several years, then stabilizes.
  • No lower extremity involvement.
  • No irregular sensory disturbances or tendon reflexes. 
  • Other disease exclusion.

Evaluation

Laboratory, imaging studies, and electromyogram (EMG)/nerve conduction study (NCS) studies are very helpful in distinguishing this process from other similar physical presentations. Routine blood work is noncontributory. Other blood tests, specifically serum IgE has shown a noted increase. However, the clinical significance of this finding is not known. Traditional x-rays also present with nonspecific findings. Occasionally, a degeneration of C2 may be noted.

MRI 

MRI tends to show some minor changes in structure that have been noted as a crescent-shaped lesion in the posterior epidural space of the lower cervical cord or an atrophic spinal cord, mild asymmetric cord flattening and increased signal intensity. It is only with specialized flexion MRIs that the etiology can be explained. Flexion MRIs have shown a distinct change in the alignment of the soft tissue structures, specifically an anterior shift of the cervical dural sac from the lamina at the C4 -C7 region allowing for chronic microtrauma, with a corresponding post contrast enhancement indicative of ischemia.

Electromyogram/Nerve Conduction Study

EMG and NCS significant findings are noted in the C7, C8 and T1 innervated muscles. NCS have intermittently demonstrated decreased compound muscle action potential (CMAP) amplitude most noticeable in the median nerve.

EMG findings are indicative of chronic denervation seen as a high amplitude of action potential with a prolonged duration, without active denervation (absence of positive sharp waves or fibrillation potentials) and no resting fasciculations in the C7, C8 and T1  innervated muscles. Findings are increased when the temperature is decreased.

Treatment / Management

Although considered to be a self-limited condition, the long-term effects warrant treatment. Conservative treatments are focused on decreasing the number or frequency of injuries. A cervical collar with the idea that decreased cervical movement and prevention of neck flexion is the first line of treatment. The protocol is to wear the collar for 3 to 4 years until growth spurts are completed, or expected plateau of the condition is seen. This treatment is focused on limiting the progression of symptoms.

For more advanced or severe presentations, surgical options may be recommended. Such patients will present with atypical muscular involvement and severe spinal cord atrophy seen on MRI. Surgical intervention (duroplasty with tenting) has been associated with an improved success rate and prognosis. Immediate effects of the procedure can be noted with an intraoperative ultrasound, demonstrating decreased spinal cord pulsation and increased amplitude of conductive spinal cord potentials noted after dural incision. Later, functional improvements are noted as increased hand strength following typical rehabilitation.

Differential Diagnosis

Myotonic dystrophy: An autosomal dominant genetic disorder, commonly seen in middle-aged men and traditionally identified with a tonic contraction of muscles in the upper limbs. It is associated with systemic changes including cataracts, pulmonary dysfunction, endocrine pathology, infertility, and cardiac conduction changes. It is distinguished from Hirayama by systemic involvement and EMG Findings, absent MRI findings and muscle biopsy findings.

Tephromalacie Anterieure: Anterior horn infarction demonstrated with muscle wasting of the distal upper limbs, caused by an occlusion of spinal arteries, commonly seen in middle-aged adults, and associated with arteriosclerosis. It presents bilaterally.

Syringomyelia: Chronic central degeneration associated with motor and sensory changes seen in bilateral upper limbs, commonly seen after injury in geriatric populations without preference to gender. Structural changes can be seen on imaging. 

Pronator syndrome: Commonly presents unilaterally and is associated with a chronic injury. Symptoms increase with specific activities. Increased reports of pain help to identify this condition with physical findings and also indicate more than one peripheral nerve involvement.

Prognosis

Hirayama disease has a good prognosis, in part due to its slow progression and expected plateau.

Consultations

While considered to be a self-limited condition, with a plateau after a few years, some involved presentations may warrant a referral to Occupational Therapy for adaptive techniques to maintain independence and function which symptoms hinder or limit age appropriate self-care and social interactions. Severe or rapidly progressing presentations also require a Neurosurgical consult to evaluate the stability of structures, monitor progression while providing conservative treatment to assess the need of definitive Surgical treatment.