General
- Hirayama disease (HD) Aka monomelic amyotrophy (MMA),
Numbers
- It is most common in males in Asia.
- Most HD patients are from Asia
- >900 patients included in clinical studies in mainland China over the last two decades.
- Increasing in India, North America, Europe, and Australia.
- Inadequate understanding of the disease by pediatric neurologists in North America may lead to underdiagnosis.
- Male-to-female ratio varies significantly:
- In Japan, ratios of 8.3:1 (281 males to 34 females) and 20:1 have been reported.
- In China, ratios of 11:1 (67 males to 6 females) and 31.6:1 (348 males to 11 females) have been noted.
- In India, a ratio of 2.8:1 has been reported.
- Onset Age of HD
- Ranging from 12 to 31 years
- Mean of 18 ± 2.7 years.
Pathophysiology
- Cervical flexion-induced myelopathy
- Disproportionate length between the spinal cord (shorter) and the spinal canal (longer), particularly during the rapid growth spurt of puberty → The dura mater tethered to the spinal canal length is pull tought → Tightness of the spinal dura mater → During flexion the tight dura is pull anteriorly to the vertebral body → Cervical spinal cord pressed against cervical vertebrae body + Venous congestion → Chronic ischaemic damage and death of the anterior horn cells (primarily affecting the lower cervical spinal cord - C5-C7 cord level C7/T1 myotomes)
- Pathological features
- When the neck goes from flexion to neutral the dura is lax → dural sac dysplasia/ectasia ?
- The loss of attachment between the posterior dural sac and the subjacent lamina
- MRI finding during neck flexion.
- Venous Congestion and Compression:
- Seen as engorgement of the posterior epidural venous plexus, which is a consistent finding on dynamic (flexion) MRI scans in HD patients.
- The engorgement can occur due to:
- Negative pressure in the posterior epidural space caused by the anterior dural displacement.
- Impaired venous drainage in the jugular veins during cervical flexion, leading to a diversion of blood towards the posterior epidural plexus.
- Shifting of blood from the compressed anterior venous plexus to the posterior epidural compartment.
- Other Proposed Factors:
- Immunological factors:
- Possible contribution of immunological factors, with reports of coexistent atopic disorders, hyperIgEaemia, and IgA deficiency in HD patients.
- However, these are often retrospective studies with small sample sizes, and causality is not yet established.
- Musculoskeletal dynamic factors:
- Longer necks in HD patients compared to controls,
- An imbalance between flexor and extensor muscle strengths leading to dynamic instability
- Specific changes in cervical Cobb angles during flexion.
Natural history
- The disease has an insidious onset, usually in the teens or early twenties, with an initial progression lasting 3–5 years.
- This is often followed by a period where the disease stabilises or becomes relatively benign.
- However, the illness can assume a stationary phase after significant irreversible deficits have already occurred.
- Vengalil et al. 2023
- Age at onset ranging from 12 to 31 years, with a mean of 18 ± 2.7 years,
- Duration of illness from 1 to 96 months (mean, 32.7 ± 24.4).
Clinical presentation
- Typical Clinical Presentations:
- Distal upper limb weakness and Wasting:
- Predominantly on the ulnar side
- Can be uni or bilateral.
- Vengalil 2023:
- Symptoms started in the right upper limb (49.2%), left upper limb (36.5%), and both sides simultaneously (14.3%).
- At evaluation, 65.8% of patients had bilateral upper limb involvement. The time to involve the opposite limb ranged from 0 to 152 months (mean, 16 ± 28 months).
- Brachioradialis muscle sparing was noted in almost all patients, except for 4 (3%) who showed weakness and wasting.
- Reverse split hand syndrome
- More severe muscle atrophy on the ulnar side: a pattern of muscle weakness and wasting the hypothenar > Thenar muscles
- Differentiate HD from Amyotrophic Lateral Sclerosis (ALS) - Split hand syndrome: a pattern of muscle weakness and wasting the thenar > hypothenar muscles
- The anterior horn cells (AHCs) that innervate the hypothenar muscles are particularly susceptible to this damage.
- 100% in Vengalil 2023
- Irregular Coarse Tremors:
- In the fingers of the affected hand(s)
- Cold Paresis:
- A mild, transient worsening of symptoms upon exposure to cold conditions (known as cold paresis) is commonly observed.
- Possibly found in 97% of HD patients.
- Absence of objective sensory disturbance
- Absence of lower limb involvement
- Atypical Clinical Manifestations:
- Pyramidal Signs:
- Particularly the Hoffmann sign, can be present in some patients.
- 2.4% of patients in Japan and 10.6% in China
- Could be a sign of severe spinal cord injury.
- Atrophy of the Muscles of the Proximal Upper Extremity:
- Proximal forms may indicate a worse functional outcome.
- Long Progression:
- Although typically self-limiting within 3–5 years, some cases exhibit disease progression lasting more than 10 years, where the patient's condition continues to deteriorate even after a stable period.
- Sensory Deficits:
- A number of patients have reported sensory deficits, occurring due to compression injuries to sensory tracts.
- These are more likely to become severe with increased stress.
- A Japanese survey reported sensory deficits in 19.2% of HD patients.
- Mild transient worsening of symptoms due to cold conditions (cold paresis).
Huashan diagnostic criteria for HD
Investigation
- MRI
- MRI + C cervical spine in full flexion.
- Imaging of choice
- A cervical flexion angle of 35° is recommended for optimal results and accurate diagnosis.
- Features
- Anterior displacement of the posterior wall of the cervical dura during neck flexion,
- Also described as a "loss of attachment (LOA)" between the posterior dural sac and the subjacent lamina, or the presence of a crescent-shaped high-intensity mass at the posterior epidural space on T2-weighted imaging (T2WI) during flexion.
- Cord flattening and atrophy of the lower cervical cord
- Often seen in the middle and lower cervical spinal cord on both neutral and flexion MRI. This atrophy can be unilateral or bilateral.
- The morphology of the cord may appear pyriform (hemicord atrophy) or triangular (bilateral atrophy).
- Maximal cord atrophy was most common at the C5-6 level (56.9%), followed by C6-7 (40.6%).
- Cord atrophy was observed in 97.1% of cases.
- Engorgement of the posterior epidural venous plexus
- Post-gadolinium T1 fat-suppressed images show an enhanced posterior epidural venous plexus with flow voids.
- 100% in Vengalil 2023
- Narrowing or absence of the anterior spinal space on neck flexion MRI.
- Vengalil 2023
- The extent of dural displacement ranged from C3-D8, extending beyond D1 in 78.8% of patients.
- MRI T2
- High-intensity signs located in the anterior horn areas on T2WI in parts of patients.
- A symmetrical bilateral high-signal-intensity lesion on axial T2WI, termed "snake-eye appearance," indicates an irreversible lesion and a poor prognosis.
- Electrophysiological Examinations:
- Aim to confirming neurogenic lesions and excluding other conditions.
- Electromyography (EMG):
- Shows segmental neurogenic damage of the anterior horn cells (AHCs) or anterior roots of the spinal nerves, typically located in the lower cervical spinal cord (C7-T1 myotomes).
- In the progressive phase, it may show fibrillations and positive sharp waves (indicating ongoing denervation).
- In longer-standing disease, decreased motor unit number estimation (MUNE) and large potentials (due to denervation and re-innervation) are observed.
- Motor Nerve Conduction Studies (NCS):
- Typically show decreased amplitudes and delayed latencies in the affected upper limb muscles.
- Normal or only mild abnormal conduction velocity in peripheral nerves of the upper limbs is expected.
- A decreased ulnar/median compound muscle action potential ratio is often seen, consistent with the more severe ulnar-side involvement.
- Sensory Nerve Conduction Studies (NCS):
- Normal
- F-waves:
- May show decreased frequency and conduction velocity
- But normal latency,
- An increase in the percentage of median repeater F waves, and higher average peak-to-peak amplitude during neck flexion, suggest inhibition of remnant AHCs.
- Somatosensory Evoked Potentials (SEP) and Motor Evoked Potentials (MEP):
- Results are variable
Management
Conservative
- Option:
- Cervical collar.
- Mechanism:
- Collar to restrict neck flexion → preventing compression injury to the spinal cord during movement.
- Studies have also shown that the venous plexus, which can become engorged, may decrease in size after cervical collar treatment.
- Outcome:
- Reported effective in 57.2% of cases.
- For patients within 2.5 years of onset, with studies showing relief of muscle weakness and cold paralysis.
- Subjective muscle strength has been noted to increase after brace use.
- Shown to reduce the duration of the disease.
- Cons:
- Compliance
- Other non-surgical methods:
- Exercise therapy aimed at strengthening cervical spine muscles can be beneficial for improving cervical spine function.
- Drugs have been found to be ineffective.
Surgery
- Indications:
- Progressive symptoms
- Intolerance to the cervical collar or poor compliance.
- Ineffectiveness of conservative treatment.
- Surgical options:
- Anterior
- ACDF:
- Aim: relieve the compression on the spinal cord caused by the abnormal tightness of the dural sac during neck flexion.
- The level of surgery is often determined by the fulcrum of movement of the subaxial cervical spine and the level of maximum compression seen on T2W sagittal images during maximal flexion.
- Corpectomy
- Posterior
- Duraplasty (with tenting sutures)
- This procedure involves repairing or augmenting the dura mater, sometimes with tenting sutures, to create more space for the spinal cord and address the "tight dural canal in flexion" without spinal fusion.
- Decompression and Fusion:
- Multilevel posterior cervical facetal fixation.
- Fusion only without decompression
- Cervical laminectomy and micro-resection of the posterior venous plexus.
- Posterior lateral mass screw fixation (without decompression or fusion but with removal of internal fixation after four years).
- Surgical Outcomes:
- Significant percentage of patients achieve excellent/good outcomes (e.g., 54% in one study) or satisfactory outcomes after ACDF.
- Surgery may not only prevent the progressive loss of motor units but also restore functionally inhibited or incompletely necrotic motor units.
- Vangalli 2023:
- 97.2% were stable or improved in finger movements and fine hand functions immediately post-operatively, with 84% reporting excellent or good outcomes at 1 year follow-up.
- Long-term follow-up showed sustained improvement, with 53.6% reporting excellent/good outcomes and 39.3% satisfactory outcomes at a mean of 44.9 months post-operatively.
- Factors Influencing Outcome: (good outcome)
- A younger age at onset
- Shorter duration of illness,
- Higher preoperative Fugl-Meyer scores (indicating lesser disability at baseline)
DDx
Points | HD | Cervical spondylosis amyotrophy | ALS |
Age of onset | Puberty, 12–20 years old predominantly | Middle-aged and elderly people, 40–60 years old predominantly | Middle-aged and elderly people, 40–60 years old predominantly |
Course of illness | Insidious onset, with a plateau after 3–5-year progression | Long course, with slow progression | Insidious onset, continuous progression, and death after 3–5 years |
Pathology | Damages of the anterior horns or (and) the anterior nerve roots of cervical spinal cord caused by cervical flexion | Compressions of the anterior horns or nerve roots of cervical spinal cord caused by cervical degeneration | A group of chronic progressive neurodegeneration that mainly damages the anterior horns of the spinal cord, cranial nerve motor nuclei and pyramidal tracts |
Atrophic muscle | Mainly the hand inner muscles, the forearm muscles affected usually | Mainly deltoid and biceps in the proximal type; dominantly hand inner muscles in the distal type | Only the localized muscles of any limb maybe affected in the early stage; and muscles of the limbs, even the neck, tongue, and throat muscles maybe affected gradually in the late stage |
Sensory deficits | There is no hypoesthesia generally, and a small number of patients with a long course may complained mild sensory deficits in the upper limbs | Most cases have no or only slight sensory deficits, and those with a long course of illness may have sensory deficits in limbs with different degrees | There is no sensory deficits generally |
Muscle weakness | The distal muscles of the upper limbs mainly | Muscles of proximal or distal upper extremity depending on different types | Localized muscles of a single limb in the early stage; and a wide range, involving muscles of the limbs, oropharynx, and respiratory muscles in the late stage |
Deep tendon reflex | Generally normal or mildly decreased reflexes in the upper limbs; and active or hyperactive reflexes of lower limbs parts of patients | Generally normal or mildly decreased reflexes in affected upper limb; and active or hyperactive reflexes of lower limb in patients with a long course | Active or hyperactive reflexes in all extremities |
Pyramidal signs | Generally negative, but positive in parts of patients | Positive in patients with long course of illness | Generally positive |
Electrophysiological examination | Damages to the anterior horns and/or anterior roots of the middle and lower cervical spinal cord, and asymmetrically generally | Damages to the anterior horns and/or anterior roots of the middle and lower cervical spinal cord, and asymmetrically generally | Atypical in the early stage of the illness, and damages to the nerves in multiple regions (cranial, cervical, thoracic, lumbar, and sacral) in the late stage |
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