BRIEF HISTORY AND PHYSICAL EXAM
A 16-yr-old right-hand dominant adolescent boy with no significant medical or family history presents for evaluation of bilateral hand weakness. The patient was playing in a hockey tournament out of town. He had played two full games the day before without incident when he suddenly experienced a “pinch” in his left forearm, followed by rapid onset of weakness in his left hand, which developed in his right hand for a few hours without numbness or tingling. He was unable to hold his hockey stick, which prompted presentation to a local emergency department. There was no recent trauma or unusual event before symptom onset. The patient denied any weakness in his lower limbs or proximal upper limbs. There was no neck pain, bowel or bladder incontinence, gait or balance disturbances, recent illness or sick contacts, fatigue, or bulbar symptoms. An initial magnetic resonance imaging (MRI) of his brain, cervical spine, and lumbar spine showed a possible syrinx at C6–C7, which neurosurgical evaluation did not feel corresponded to his degree of symptomatology. No fractures or instability was noted, and he was discharged from the emergency department with instructions to follow up at the university children’s hospital in his home town for further workup. His hand weakness persisted, and he presented to the University of Pittsburgh Medical Center Children’s Hospital of Pittsburgh 2 days later where he was admitted for expedited workup.
On physical examination, the patient was awake, alert, and oriented. Cranial nerves II-XII were intact. Cervical and upper limb range of motion was full, and no evidence of any focal atrophy of the upper limbs was present. Manual muscle testing demonstrated 5/5 strength in bilateral shoulder abduction, elbow extension, elbow flexion, wrist extension, and wrist flexion. Finger abduction strength and handgrip were 4/5 on the right and 3/5 on the left. Manual muscle testing demonstrated 5/5 strength in bilateral lower limbs. Muscle stretch reflexes were 1+ in biceps and triceps bilaterally. Lower limb reflexes were 2+. Sensation was intact and symmetric to light touch, pinprick, and vibration in bilateral upper and lower limbs. He did have decreased palmar sensation to temperature in the hands bilaterally. Hoffman sign was negative bilaterally, plantar responses were downgoing bilaterally, clonus was absent bilaterally, and there were no abnormalities in muscle tone. No fasciculations were noted. There were no abnormalities on finger-to-nose and heel-to-shin testing. Gait was normal.
What is the differential diagnosis and approach to management for asymmetric distal upper limb weakness without sensory changes in a juvenile?
DIFFERENTIAL DIAGNOSIS AND APPROACHES TO MANAGEMENT
The differential diagnosis for the presented patient is broad and can be organized by etiology including motor neuron diseases, demyelinating disorders, traumatic, infectious, rheumatologic, peripheral neuropathies, and vascular (Table 1). Notably, traumatic etiologies including cervical traumatic spinal cord injury, syringomyelia, or brachial plexopathy may present similarly. However, no trauma occurred before symptom onset. In addition, disorders of the peripheral nervous system including thoracic outlet syndrome, mononeuritis multiplex, toxic neuropathy, and multifocal motor neuropathy should be evaluated.
In this patient, multiple vascular etiologies must be considered. A spinal cord infarction could present with sudden onset of symptoms, although no subjective sensory changes, hyperreflexia, or other upper motor neuron signs were found on physical examination. In this case, a spinal cord infarction could result from an arterial dissection or a congenital partial diastematomyelia. Finally, monomelic amyotrophy, such as Hirayama disease or O’Sullivan–McLeod syndrome, must be taken into consideration.
What testing could be ordered to narrow and further clarify the differential diagnosis in this patient?
Extensive diagnostic testing was performed in the acute inpatient setting. A rheumatologic evaluation was unremarkable. From an infectious disease standpoint, all antibody titers were negative with the exception of mycoplasma IgG/IgM and HSV-1 IgG, which were positive but determined to be noncontributory per infectious disease consult. Laboratory erythrocyte sedimentation rate, C-reactive protein, and a comprehensive urine drug screen were all unremarkable. Cerebrospinal fluid analysis was without markers of infection or demyelination. Brain and thoracic spine MRI was unremarkable and cervical flexion and extension x-rays were not suggestive of cervical instability. Two days after his initial imaging at the outside hospital emergency department, repeat MRI of his cervical spine revealed a deep ventral cleft versus partial diastematomyelia at C6–C7 and new bilateral anterior horn gray matter T2 hyperintensities at C3–C4 and C6–C7 (Fig. 1). Magnetic resonance angiography of the brain and cervical spine revealed no vessel occlusion. Aspirin was started during his hospitalization given predisposition for vascular anomaly or arterial dissection at the level of deep ventral cleft versus partial diastematomyelia in his cervical spinal cord. However, after further review with neurosurgery and stroke neurology, consensus was that aspirin could pose a bleeding risk and was thus discontinued. Per neurosurgical consultation, he was given a lifetime ban on participation in contact sports given his spinal anatomic variant. The patient was discharged home with instructions to follow up with neurology, occupational therapy, and physical medicine and rehabilitation.
Two months after his discharge from inpatient, he presented to the physical medicine and rehabilitation clinic for electrodiagnostic evaluation. Manual muscle testing at that time demonstrated 5/5 strength in the left upper limb except for the left first dorsal interosseous that was 2−/5, left thumb opposition and abduction that was 1+/5, and left flexor digitorum profundus to digits 4 and 5 that was 4/5. Strength in the right upper limb was 5/5, except for the first dorsal interosseous that was 4/5. Tinel sign was negative at the wrist and elbow bilaterally. Nerve conduction study/electromyography (NCS/EMG) demonstrated pronounced evidence of bilateral active denervation in muscles innervated by the C8–T1 nerve roots with a reduced number of motor units noted on active contraction. The left arm was considerably more involved than the right. Sensory responses were unremarkable and similar bilaterally. There were no findings of any peripheral neuropathy, myopathy, or specific focal nerve entrapment. The left median F wave had no response. All remaining F wave latencies were within normal limits (Table 2).
Based on the diagnostic results, what would be considered as a diagnosis and how should this patient be optimally managed?
This patient’s NCS/EMG findings were most consistent with either a bilateral anterior horn cell process (left more than right), which is relatively acute at the C8–T1 level or at the level of the C8–T1 ventral roots. Sensory responses were unremarkable and similar bilaterally, which goes against any significant peripheral nerve or plexus problem. The lack of lower limb symptoms leads away from mononeuritis multiplex. In addition, the absence of conduction block makes multifocal motor neuropathy less likely.1 Based on the clinical, laboratory, MRI, and NCS/EMG findings in the absence of trauma, the working diagnosis was felt to be Hirayama disease (HD).
Hirayama disease, a type of monomelic amyotrophy, is a rare focal ischemic cervical poliomyelopathy with less than 1000 reported cases.2 Young males in their teens or twenties are primarily affected.3 Although most cases have been reported in Asia and India, reports from Europe and North America have been increasing.2,4 Whether ethnicity plays a significant role in this disorder is still unclear. Hirayama disease is nonfamilial in most patients; although familial cases have been published, there is currently no information known about the genetics involved.3 Although the onset of symptoms is not well described, typical clinical signs of HD include progressive asymmetric muscular weakness and atrophy of the hands and forearms with relative sparing of biceps brachii and brachioradialis muscles, usually over months to years, followed by a spontaneous arrest of symptom progression within several years.2,3 Unusual features of our case include the onset of symptoms within 1 day, rather than over months.5 Sensory disturbances, autonomic, and upper motor neuron signs are rare.3
Although the pathogenesis of HD is unclear, it is speculated to be caused by an imbalance between the growth of the vertebral column and the spinal canal contents, resulting in anterior shifting of posterior dura of the lower cervical dural canal during neck flexion and causing spinal cord compression.3,6 This tension is believed to lead to focal ischemia of the anterior horn cells of the lower cervical spinal cord.3 Another type of monomelic amyotrophy, O’Sullivan McLeod syndrome, has slower progression,7 later onset (mean age at onset of 34.3 yrs), and typically unremarkable neuroimaging studies8; thus, this diagnosis was considered less likely.
Diagnosis of HD is based on clinical suspicion correlated with cervical flexion MRI findings of anterior displacement of the dural sac with the posterior dura shifting anteriorly away from the lamina.4 Noncompressed intramedullary high-signal intensity on T2-weighted images is common at the level of C4–C7, corresponding with the site of cord atrophy and asymmetric flattening.3,4 On axial T2-weighted MRI, high-intensity signal lesions are seen in bilateral anterior horns, indicating either ischemia or gliosis3; this effect is referred to as the “snake-eyes appearance,” which indicates poor prognosis in patients with HD and potentially a progression to cervical spondylotic myelopathy.4 If these findings are observed on traditional MRI, additional cervical flexion MRI studies should be obtained to confirm the diagnosis of HD.
Electrophysiology in HD reveals denervation of affected muscles, with more than 90% of patients also showing contralateral denervation of the same muscles.9 Motor nerve conduction velocities are normal with the exception of occasional minimal slowing in the ulnar nerve.9 Compound muscle action potential demonstrate asymmetric reduced amplitudes without conduction block in the atrophied musculature, and F waves are consistent with denervation and reinnervation, showing a mild increased latency, low persistence, and singular high-amplitude waveforms.9 Motor-evoked potentials demonstrate increased latency and reduced amplitudes, which are worsened by cervical flexion.2 Muscle biopsy and cerebrospinal fluid analysis are not required to make the diagnosis but may be helpful in excluding motor neuron diseases with similar presentations.
Given that neck flexion is believed to underlie the pathogenesis of HD, prevention of this motion is the cornerstone of treatment. A cervical collar for 3 to 4 yrs is recommended and has been shown to slow progression of symptoms in patients.10 Surgical intervention can be considered in patients with severe spinal cord atrophy, clinical signs of severe myelopathy, or neurologic deterioration despite conservative management. Anterior cervical decompression and fusion have shown promising results.6 Laminectomy with cervical duroplasty and tenting sutures has also been studied in HD without major complications.6 At this time, there is no consensus on which surgical method is superior. The role of rehabilitation in the treatment of HD has not been reported in the literature.
The patient’s congenital deep ventral cleft versus partial diastematomyelia in combination with years of subacute repetitive trauma from hockey likely predisposed him to local ischemia in his anterior horn cells, resulting in the clinical development of HD. At time of presentation to the physical medicine and rehabilitation clinic, the patient reported improvement in hand function but remains significantly below his baseline strength. In most cases, HD stabilizes within approximately 5 yrs of symptom onset.2 Therefore, he will continue occupational therapy to enhance functional recovery. Because HD is uncommon and symptoms are similar to other motor neuron diseases, this clinical entity has a tendency to be misdiagnosed.6 Careful physical examination, thorough electrodiagnostic studies, and dynamic cervical flexion MRI assist in narrowing of the differential diagnosis. An early detection and correct diagnosis have the potential to slow progression and improve the hand function in young patients. This study conforms to all CARE guidelines and reports the required information accordingly (see Supplemental Checklist, Supplemental Digital Content 1, http://links.lww.com/PHM/A905).
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