Rare cause of unilateral upper limb weakness in a young adolescent

Abstract

Slowly progressing unilateral upper limb weakness in a previously healthy child can occur due to number of causes which requires a thorough history, physical examination followed by radiological examination, electromyography and so on. Among the various aetiologies, a rare condition such as Hirayama disease is one of the differentials to be considered. There has been a wealth of literature reported on this disease and our case is a learning lesson for all paediatricians to be aware of Hirayama disease and its current concepts.

Background

Hirayama disease (HD), also termed juvenile unilateral muscular atrophy of the upper extremity, or monomelic atrophy, is an often-self-limiting cervical myelopathy which occurs due compression of spinal cord by forward displacement of the posterior dural sac during neck flexion. This is seen predominantly in young adults. HD may gradually slow down and become self-limited after 2–5 years of disease onset. However, there may be subset of patients who may experience repeated disease progression with an interval of stable stage. It is commonly misdiagnosed in patients presenting with isolated amyotrophy of upper limb due to other diagnoses. Our case highlights the clinical findings of an adolescent with HD and the differential diagnosis.

Case presentation

A 17-year-old right-handed young man previously healthy presented to neurology clinic with progressively worsening right upper extremity weakness since past 9 months. He had been having difficulty in writing, gripping and tying shoelaces and had been dropping things. There was no other weakness of rest of body. No sensory symptoms/bladder or bowel involvement/difficulty in speaking or swallowing. There was no h/o trauma or fever. The patient did not report any worsening of symptoms with cold exposure. Medical and family history was unremarkable, and there was no behaviour or cognitive impairment. There was no h/o drug abuse.

On examination, his growth and vital signs were within normal limits.

Examination showed weakness and muscular atrophy of the right upper limb (figures 1 and 2). Full abduction, adduction of the digits, opposition of the thumbs, and palmar grasps were impaired. Muscular weakness in the deltoid, infraspinatus, supraspinatus, and biceps brachii on right side was noted. Additionally, there was weakness and atrophy of intrinsic muscles of the hand and forearm but preserved brachioradialis muscle.

Figure 1.

Image of the child showing differential atrophy of right upper limb (arrow).

Figure 2.

Image of the child showing normal girth of left upper limb as compared with affected right upper limb. The atrophy is marked in the right forearm (arrow) as compared with left and very subtle in the upper arm muscles.

Right-hand tremors were noticed. The hand tremors were irregular and low amplitude tremors that worsened during neck flexion. There was no evidence of posterior column, cerebellum or cranial nerve involvement. Pyramidal signs including spasticity, slowing of rapid alternating movements and a Babinski sign were absent. No fasciculations were noticed. Deep tendon reflexes were 2+ bilaterally in the upper and lower limbs including the finger jerks.

Investigations

Initial blood investigations including complete blood count, sedimentation rate, renal, liver and thyroid function tests, creatine kinase, and vitamin B₁₂ were within normal range. GM1 antibodies were negative.

EMG was done at the time of initial diagnosis which was limited study due to patient needle phobia and anxiety.

Initial MRI C spine showed focal cord atrophy from C5 to C7 without cord compression or gliosis (figure 3).

Figure 3.

MRI spine showing focal cord atrophy from C5 to C7 without cord compression or gliosis (arrow).

MRI C spine was repeated with flexion view of the cervical spine demonstrate venous congestion of the posterior epidural space extending from C4 to C6. There was delamination of the posterior dura seen on T2 corresponding to the same region. There was flattening and atrophy of the cervical cord at the same area with no cord signal abnormality (figure 4).

Figure 4.

MRI showing flexion view of the cervical spine demonstrates venous congestion of the posterior epidural space extending from C4 to C6. There is a delamination of the posterior dura seen on T2 corresponding to the same region. There is flattening and atrophy of the cervical cord at the same area (in the area between the two arrows). There is no cord signal abnormality.

Differential diagnosis

1. The possible differentials include

1. Distal form of spinal muscular atrophy: this is an extremely rare disorder, which presents in the adults and has a slow progression with almost no effect on the patients' lifespan. It is characterised by progressive pure lower motor neuron involvement. Our index child did not have any generalised muscular atrophy but rather had specific symptoms of his right upper limb.

2. Amyotrophic lateral sclerosis (ALS): this disorder has upper and lower motor neuron signs of degeneration. However, in our case, distal muscles were involved, more compared with proximal muscles.

3. Cervical spondylotic amyotrophy: this entity is characterised with weakness and wasting of upper limb muscles without sensory or lower limb involvement. It is typically a unilateral condition which predominantly affects males, with age of onset ranging from the third to sixth decade. The underlying pathophysiology is considered to be mechanical impingement or ischaemic injury to the ventral root or anterior horn cells. Our index child was young child with weakness of forearm of hand predominantly whereas patients with cervical spondylotic amyotrophy have weakness mainly in arm and to lesser degree in forearm and hand. MRI is helpful in differentiating the two disease entities.

4. Post polio syndrome: this clinical condition usually occurs at least 10 years after a person has been affected by polio and characterised by gradual deterioration of muscle function and increased weakness which usually happens in the limbs that were most severely affected by polio. This clinical history was missing in our patient.

5. Multifocal motor neuropathy (MMN) with conduction block: this is thought to be autoimmune condition with progressive symptoms. This is treatable unlike ALS. In contrast to ALS which affects both upper and lower motor neuron pathways, MMN involves only the lower motor neuron pathway. It specifically involves the peripheral nerves emanating from the lower motor neurons. Antibodies may be directed against ‘GM-1’, which is a ganglioside located at the Node of Ranvier. The primary treatment is IVIg, with about 80% of patients responding. Regular infusions at intervals of 1 week to several months are usually required. Our child tested negative for GM1 antibodies.

6. Toxic neuropathy: medications leading to muscle weakness include: metronidazole, fluoroquinolones, lithium, phenytoin, amiodarone, statins, cisplatin, stavudine, didanosine, alcohol, infliximab, chloroquine and so on.

   The above drug or toxin history was absent in our child.

7. g. Structural lesions of the cervical cord (syringomyelia): in this condition, fluid filled cyst (syrinx) within the spinal cordcan expand or elongate over time, destroying surrounding spinal cord tissue leading to pain, paresthesia and cape like distribution of paralysis. These findings were absent in our child.

Treatment

Collar therapy or surgical intervention has been proposed as treatment for HD.

Surgical treatment (anterior cervical fusion procedure or posterior cervical duraplasty) may be considered if collar treatment fails or there is worsening of symptoms.

Long-time cervical collar treatment was started on our index child.

Outcome and follow-up

The child has been on follow-up with Paediatric Neurology Clinic and stable so far with no worsening or improvement and has a static clinical course so far.

Discussion

HD is rare motor neuron disease, which results due to asymmetric microcirculatory changes in the anterior horn cells of the distal cervical spinal cord resulting from neck flexion. The relatively shorter length ratio of the dura mater to vertebral column creates an ‘overstretching’ of the posterior Dural canal wall and causes anterior displacement of the dura on repetitive flexion. Over the period of time, the displaced dura causes compression of the cord and leads to microcirculatory disturbances resulting in necrosis of the anterior horn cells with repeated flexion of the neck. As the disease progresses, the circulatory changes lead to cord atrophy, which manifests as upper extremity weakness.¹

The proposed criteria for the diagnosis were established by a clinician-led guideline for the diagnosis and treatment of HD using a modified Delphi technique published in 2020² and include the following:

1. Onset between the ages of 10 to early 20s.

2. Insidious onset with gradual progression for the first several years, followed by stabilisation.

3. Distal predominant muscle weakness and atrophy in forearm and hand.

4. Involvement of the unilateral upper extremity almost always all the time.

5. No sensory disturbance and tendon reflex abnormalities.

6. No lower extremity involvement.

7. Exclusion of other diseases such as motor neuron disease, MMN, cervical vertebral abnormalities, brachial plexopathy, syringomyelia, spinal cord tumours, anterior interosseous or deep ulnar neuropathy.

HD is a self-limiting disorder and there is no consensus on the definitive treatment.

The following treatment guidelines are recommended by the expert group.²

Long-time cervical collar treatment is an optional conservative treatment. It is suggested that surgical treatment may be reasonable in at least one of the following circumstances: (1) the disease continues to progress even after long-time wearing cervical collar; (2) if the patient cannot tolerate the long time wearing cervical collar; (3) the disease progresses again after a period of spontaneous arrest.

Anterior cervical fusion or posterior cervical duraplasty procedure could be an appropriate operation mode.

Learning points.

• Hirayama disease is rare condition where the hallmark of diagnosis is the involvement of a single limb with lower motor neuron features which are more common in distal muscles rather than proximal muscles.

• This is a type of cervical myelopathy related to flexional movements of the neck.

• The primary principle of treatment is a restriction of neck flexion by using cervical collars and so on.

• The prognosis is good in Hirayama’s disease compared with other forms of motor neuron diseases with less morbidity.