Hirayama Disease: A Report of Two Cases and Review of Imaging Findings

Valentina Munera Orozco1; Angela Maria Restrepo Gil2; Jose Luis Ascencio Lancheros2; Alejandro Londoño Mesa3; Yensa Rodríguez Alvarez4* 1Department of Radiology, Universidad Pontificia Bolivariana Medellín, Antioquia, Colombia 2Department of Radiology, Instituto Neurológico de Colombia, Medellín, Antioquia, Colombia 3Department of Physical Medicine and Rehabilitation, Hospital San Vicente Fundación, Medellín, Antioquia, Colombia 4Department of Radiology, Hospital Universitari Mútua Terrassa, Barcelona, Spain


Introduction
Hirayama Disease (HD) is a non-progressive cervical myelopathy that differs from motor neuron disease. It was first described by Keizo Hirayama in 1959 [1]. The disease is prevalent in male individuals ranging from 15 to 25 years of age. Males are more affected than females [2]. Common clinical characteristics of HD include insidious onset of unilateral or asymmetric wasting and weakness of muscles in C7 to T1 myotomes, with a relative sparing of the brachioradialis muscle, followed by spontaneous arrest within 3 to 5 years [3].
It has been considered a benign and self-limited disease. However, the disease may have atypical characteristics, such as, progressive and irreversible course with poor prognosis, impairing the patient's quality of life [2,4].
Dynamic MRI of the cervical spine (neutral and flexion position) is the imaging modality of choice for the diagnosis of HD [2,3,5]. Several cases of HD remain undetected, probably as a result of a lack of diagnostic criteria. In this report we describe the most remarkable findings observed during MRI in patients with HD, all these findings, are illustrated in two cases diagnosed in Colombia, South America.

Case 1
A 13 year-old man presented with one-year progression of sudden loss of strength and atrophy of upper limb, compromising the right forearm and hand.
The physical examination revealed asymmetry of the upper limbs and atrophy of forearms and hands, predominantly in the right side ( Figure 1a). No alterations were observed on the cranial nerves, nor on reflexes and sensitivity. Deep reflexes were normal (++), except for a decreasing in styloradial reflexes (+). A brain MRI was conducted, and no pathological findings were observed.
A small decreasing of the anteroposterior diameter of the spinal cord at C5 and C6 was found through MRI of the cervical spine in neutral position. Bilateral hyperintensities of the anterior horns with a multilevel and asymmetrical compromise from C5 to C7 was also found. Greater compromise in C5-C6 was observed due to focal myelomalacia as shown by the 'Snake Eye' sign ( Figure 1b). T1 and T2 sequence of the cervical spine in neutral and flexion position were conducted. On T1 with neck flexion duramater was shown to be only slightly deatached from the posterior lamina, with an increasing of the laminodural space (LDS) at C5-C6 of about 4.2mm ( Figure 1c).

Case 2
A 13 year-old man presented with a background of moderate cervical trauma, which occurred twice before evaluation. Patient came due to a cervicalgia associated to dysesthesia on the lateral sides of the fingers in both hands and sensitivity alteration in the back of the limbs when flexion of the neck was forced. The physical exam revealed hyperreflexia of the four limbs, predominantly in left side, and symptoms of cervical instability with positive Lhermitte's sign.
A decrease in volume of the cervical spinal cord with subtle hyperintensity at C5-C6 was observed through an MRI of the cervical spine during neutral and flexed position (Figure 2a). Likewise, an increase of the LDS of about 6mm with a decrease of the amplitude of the canal was observed in the T2 sagittal image during flexion. Figure 2b shows that dura mater has migrated and disinserted from the posterior dural sac (up to 6mm). In addition,  -Transverse T2 weighted MR image at pedicular level of C5 and C6 shows the typical snake eyes sign that is characterized as a small high-signal-intensity of the bilateral anterior horns, in this case asymmetric predominantly in the right side.

Discussion
The literature describes several clinical criteria for HD, including onset of symptoms in late adolescence or young adulthood, restricted motor function in the upper limbs, asymmetrical muscular changes, a period of clinical progression following a relative stable condition, and the non-existence of alternative assessments for symptoms identified during evaluation [ 6].   region of the dural sac and the subjacent lamina, displayed an accuracy level of over 80% in the identification of the disease [7]. The identification of a separation over 33% of the dural sac with its corresponding subjacent lamina is related to HD with a sensitivity and specificity rate of 93.5% and 98%, respectively [7]. T2 sequences in axial plane visualized from C4 to C6 allows for better detection of this sign, as described in the study by Chen et al [7].
The increasing of the LDS and the widening of the posterior epidural space are adequately displayed in the MRI when obtained between 30 to 50° of cervical angle. This is an essential condition for the diagnosis of HD. These findings seem to be a secondary outcome of the unbalanced bone development of the vertebral column and its content [2,3,[7][8][9][10][11].
Different measurement values of LDS have been described between 3 to 9,8mm and a mean of 6mm [2,6,10,11]. While other studies have reported a maximum displacement distance of 1.0 to 4.2mm in healthy subjects compared to the distance between 6.1 to 7.8mm in individuals diagnosed with HD [10]. The first patient in our case shows an LDS distance of 4.2mm ( Figure 1c) and the second patient has a LDS of 6mm ( Figure  2b).
The dynamic compression in flexion position over the arterial microvasculature of the anterior spinal cord horns produces hypoperfusion that resulted in ischemia. This is seen in the hyperintensity of the anterior horns displayed in the MRI -a.k.a, Snake Eyes Sign- [2,4,[8][9][10][11][12][13] (Figure 1b) 'Snake Eyes Sign' is a radiological finding of focal myelomalacia of the anterior horns signaling late and irreversible damage of the medullary cord in HD. It is correlated with a bad prognosis of pyramidal signs and spinal cord atrophy, which indicates that it is not a benign, reversible disease, as described in the first studies published about the disease [2,4].
Based on these hypotheses, to limit neck flexion is crucial in order to avoid the progression of the disease. The use of a cervical collar for the span of 3 to 4 years has been proven to be the least invasive treatment. An appropriate evolution and slow progression of the disease has been reported with this treatment [2,11].

Conclusion
Although Hirayama Disease was initially described in Asian patients, recently it has been described in Western countries, where the compromise of the disease is found at a higher level (C5 and C6), as attested in our cases described on this paper [2]. Patient 1 presented atypical characteristics, including age and sudden onset of motor loss. The average age of the onset of the disease ranges between 15 to 25 years of age. This is due to the rapid growth that characterizes this stage of life [2,4,11] In conclusion, despite its low frequency, HD must be considered as a differential diagnosis in young males with atrophy and strength loss predominantly in distal upper limbs. An active search of the signs by means of conventional and contrasted MRI in neutral and flexion position with an angle of at least 30º-45º is required for its early diagnosis and treatment. This will improve the prognosis of the disease.