See discussions, stats, and author profiles for this publication at: https://www.researchgate.

net/publication/23572759

A cervical myelopathy with a Hirayama disease-like phenotype

Article  in  Neurological Sciences · January 2009

DOI: 10.1007/s10072-008-1058-3 · Source: PubMed

CITATIONS READS

8 3,047

4 authors, including:

Chiara Cerami Francesca Valentino

University School for Advanced Studies IUSS Pavia Università degli Studi di Palermo
100 PUBLICATIONS   2,472 CITATIONS    26 PUBLICATIONS   613 CITATIONS   

SEE PROFILE SEE PROFILE

Vincenzo La Bella
Università degli Studi di Palermo
155 PUBLICATIONS   4,018 CITATIONS   

SEE PROFILE

Some of the authors of this publication are also working on these related projects:

In vivo assessment of FDG-PET metabolic dysfunctions in neurodegenerative dementias View project

Social cognition in neurodegenerative disorders View project

All content following this page was uploaded by Chiara Cerami on 11 April 2014.

The user has requested enhancement of the downloaded file.

Neurol Sci (2008) 29:000–000
DOI 10.1007/s10072-008-1034-y
C A S E R E P O RT
A cervical myelopathy with a Hirayama disease-like phenotype
Chiara Cerami · Francesca Valentino · Federico Piccoli · Vincenzo La Bella
Received: 24 May 2008 / Accepted: 7 November 2008
© Springer-Verlag 2008
Abstract A 21-year-old man with a muscular atrophy of
the left distal upper extremity is presented. The disorder
had been progressive over a few years, showing an exac-
erbation of the hand’s weakness when the patient worked
in a chilled environment (i.e., in a cold room). The
patient’s diagnostic work-up was extensive and the MRI
documented the presence of a cervical myelopathy, asso-
ciated to an inversion of the physiological lordosis at the
C5-C6 level, with a phenotype highly resembling
Hirayama disease. This case indirectly supports the
debated hypothesis that juvenile amyotrophy of the upper
limb (Hirayama disease) is actually a type of cervical
myelopathy, with a likely ischaemic pathogenesis of the
ventral horns.
Keywords Cervical myelopathy • Hirayama disease •
Muscular atrophy • MRI
C. Cerami · F. Valentino · F. Piccoli · V. La Bella (쾷)
ALS Clinical Research Center
Department of Clinical Neurosciences
University of Palermo
Via G La Loggia 1
90129 Palermo, Italy
e-mail: labella@unipa.it
Introduction
Juvenile muscular atrophy of the distal upper extremity has
been reported in young men, mainly in Asian countries [1].
Only sporadic cases have been described in Europe [2, 3].
The onset is insidious and characterised by muscular
weakness and atrophy in the hand and forearm, whose
progressive course ceases within several years after
onset. The amyotrophy is unilateral in most patients and
asymmetrically bilateral in a few. It often shows cold
paresis (i.e., weakness exaggerated by cold) and a mild
contraction tremor upon finger extension [1]. Sensory
function is normal and there is no cranial nerve involve-
ment, no pyramidal signs and no urinary disturbances.
Pathophysiology is still controversial. While some inves-
tigators favour the view that the underlying pathology is
due to compression of the lower cervical spinal cord
(from C5 to T1) on neck flexion leading to microcircula-
tory ischaemic changes in the territory of the anterior
spinal artery [4, 5], others suggest that Hirayama disease
is an anterior horn cell degenerative disorder [2, 6].
In this report, we present a young patient in whom an
inversion of the physiological cervical lordosis caused a
compressive myelopathy with an unusual phenotype
resembling Hirayama disease.
Case report
A 21-year-old right-handed Caucasian man was referred
to our Neurology Ward because of a four-year history of
a slowly progressive distal weakness and atrophy of both
hands and forearms. For the first few years signs were
unilaterally confined to the left hand but more recently
spread to the right side.
2 Neurol Sci
The patient, a grocer in a supermarket since he was 16,
often spent part of his working day lifting large heavy
salamis and cheeses in a cold room. He noticed the first
symptom in the fifth left finger, which felt weak when he
was slicing salami. The weakness slowly spread to the other
fingers of the left hand, with a worsening of symptoms when
he was working in the cold room. This “cold paresis” had
remained confined to the left hand for a long time.
More recently, the weakness and atrophy spread to
the right hand, giving a mild motor dysfunction. The
young man is still working as a grocer albeit with
reduced efficiency.
There were no sensory or sphincter symptoms, but he
described recurrent muscle tenderness in the neck and
shoulders, and cramps in the left hand after lifting heavy
weights. When referred to our ward, there had been no
significant progression of symptoms during the previous
couple of years. There was no history of trauma or expo-
sure to toxins. Family history was negative for neuromus-
cular disorders.
General examination did not disclose any abnormali-
ties, other than a skinny body. There was a prominent,
asymmetrical atrophy and weakness of intrinsic hand and
forearm muscles in both hands (MRC scale: (i)
interosseous muscles, left 3/5 and right 4/5; (ii) flexion of
the fourth and fifth fingers, left 3–4/5 and right 4–5/5
(Fig. 1)). Muscle strength in biceps, triceps and del-
toideus was 4–5/5 on both sides. Tone was slightly
reduced in the upper limbs and normal in the lower
limbs.
We observed a mild contraction tremor in the left
hand. Deep tendon reflexes were preserved in the upper
and lower limbs. The plantar reflexes showed normal
flexion and the abdominal reflexes were present. Cranial
nerves were normal and there were no sensory (i.e.,
touch, temperature, joint position or vibration sensations)
abnormalities or ataxia. Gait was normal.
Fig. 1 Photographs of the patient showing atrophy mainly in the left
forearm and hand muscles (arrows)
An extensive biochemical work-up, including serum
creatine phosphokinase level and CSF examination, gave
negative results.
Concentric needle EMG showed increased and
polyphasic motor unit potentials (MUPs) in abductor pol-
licis brevis (APB), abductor digiti minimi (ADM),
interossei dorsalis 1, biceps and deltoideus of both sides,
and in the left brachioradiali. Fibrillation potentials were
infrequently detected in the left deltoideus, ABP and
interossei dorsalis 1. Sensory and motor nerve conduc-
tion studies were normal. The amplitudes of compound
muscle action potentials (CMAP) obtained from left APB
(medianus nerve) and ADM (ulnaris nerve) were slightly
decreased. No conduction blocks were documented.
Somatosensory evoked potentials (SEP) of the left
median and ulnar nerves showed a significant amplitude
reduction of N13 potential, expression of the cord com-
pression and vascular changes through the spinal cord
[7], whereas the motor evoked potentials after transcra-
nial magnetic stimulation were normal.
Brain and cervical spinal cord MRI was performed on
a 1.5-T scanner; axial and sagittal T1-weighted and T2-
weighted images were obtained. The brain MRI did not
show any abnormality; a lateral T2-weighted cervical
spine MRI with the neck in a neutral position demon-
strated a kyphosis of the spine with fulcrum at C5–C6
levels. At those levels the spinal cord appeared mildly
atrophic with a large hyperintensity between C4 and C7.
Several disc herniations between C4 and C7 were detect-
ed (Fig. 2).
On the basis of the clinical and neurophysiological
examination and MRI images a diagnosis of cervical
myelopathy with a Hirayama-like phenotype was made.
The patient was referred to a neurosurgery department
and he is on a waiting list for corrective surgery of the
spine abnormality.
Discussion
We have shown in our young patient that a compressive
cervical myelopathy has caused a focal and slowly pro-
gressive amyotrophy resembling Hirayama disease. This
case supports the disputed hypothesis that Hirayama dis-
ease is indeed an ischaemic focal cervical myelopathy,
mostly involving the ventral horns.
Juvenile muscular atrophy of the distal upper extrem-
ity, named Hirayama disease after the author who first
described this type of motor neuron disorder some 45
years ago [1], occurs predominantly in young men in
their teens and early twenties and is rarely familial. The
onset is insidious and unilateral with muscular weakness
and wasting in the hand and forearm, usually sparing the
Neurol Sci
a b
c ground the diagnosis of Hirayama disease was highly
Fig. 2 Spinal MRI, sagittal T1- and T2-weighted (A, B) and trans-
verse T2-weighted (C) sequences of the patient showing the kyphosis
of the cervical spine and a mildly atrophic spinal cord with hyperin-
tense signal extending from C4 and C7 levels. Note that the hyperin-
tense signal on the T2-weighted transverse sequences appears more
pronounced in the left side of the ventral spinal cord (C)
brachioradialis muscle. Most patients report a worsening
of the weakness of fingers on exposure to cold environ-
ment. Fasciculations are rarely reported, whereas some
patients show slight hypoaesthesia in localised parts of
the hand [1, 8].
The disease is slowly progressive followed by a sponta-
neous arrest within five years in the majority of patients [8].
The pathophysiology of the illness is unknown; since
the description of the disease, Hirayama has always
favoured the hypothesis that it is a type of cervical
ischaemic myelopathy caused by dynamic changes
induced by neck flexion in adolescence [5, 8]. The author
has provided neuroradiologic data, based on MRI and CT
myelography, that the neck flexion induces a forward dis-
placement of the cervical dural sac and a compressive
flattening of the cervical spinal cord [5]. Further, he
demonstrated, in an autopsy case, ischaemic changes in
the ventral horn with shrinkage of the grey matter,
decreased number of motor neurons and thin anterior
roots from C5 through C8/T1 [9]. Other authors suggest
that Hirayama disease is indeed an intrinsic motor neuron
disorder: Schröder et al. [2] showed a forward movement
on neck flexion and a mild reduction in the anteroposte-
rior diameter of the cervical cord in both controls and
patients, while Misra et al. [10, 11] observed a normal
central motor conduction time, suggesting lack of pyram-
idal tract dysfunction, and an insignificant change in N13
3
and F wave parameters in the affected patients. These
observations argue against the cervical myelopathy
hypothesis.
Our patient is affected by a compressive myelopathy
but he shows a Hirayama disease-like phenotype: weak-
ness and wasting of left hand were slowly progressive
and spread to the contralateral hand, which is much less
involved; weakness of the left hand often worsened in a
cold environment. Further, the patient had noticed a
rather clinical stability for a couple of years.
We could not detect signs or symptoms of pyramidal,
sensory or bladder dysfunction. On the sole clinical
plausible, but the imaging and neurophysiological stud-
ies led to the correct diagnosis. The MRI demonstrated a
cord hyperintensity consistent with ischaemic damage
and the SEP on median and ulnar nerves documented the
changes of N13 parameters.
It is intriguing that the cervical myelopathy in our
patient presented with a clinical picture of a nearly pure
motor neuron disease. Although only indirect, this sup-
ports Hirayama’s hypothesis that the disorder that bears
his name can actually be a type of cervical myelopathy
[5, 8]. In our case we detected SEP abnormalities and the
MRI documented a spinal cord hyperintensity with a
higher expression at C5–C6 myelomers, which corre-
sponded to the maximum kyphotic bending of the spine.
This malformation actually reproduced in the neutral
position what Hirayama observed in his case series, that
is the flattening and compression of the spinal cord in the
neck flexion [8]. It is conceivable that, in our teenager
patient with this very unusual spine malformation, the
repeated flexions and extensions of the neck throughout
each day predisposed him to repeated mechanical injury
on the spinal cord that eventually led to an ischaemic
myelopathy. A question arises of why our patient did not
show signs and symptoms of pyramidal tract dysfunc-
tion. Although the anterior horn cells are highly suscep-
tible to ischaemia following microcirculatory disturbance
in the anterior spinal cord, the cortico-spinal tracts (CST)
should be affected as well, because of their strategic loca-
tion in the border zone. CST still undergoes a maturation
process during adolescence and it is electrophysiologi-
cally fully functional only after the age of 13 in most
teenagers [12, 13]. The relative immaturity of CST in
adolescence [14] might explain why young patients with
Hirayama disease (or, as in our case, with a compressive
myelopathy) do not show appreciable CST deficits. An
indirect support to this speculative hypothesis comes
from the common observation that adult or elderly
patients with spondylotic cervical myelopathy, with a
fully matured CST, often present with a spastic parapare-
sis, the clinical sign of a CST dysfunction.
4 Neurol Sci
In conclusion, our case report, in which a compres-
sive cervical myelopathy presented with a clinical pheno-
type resembling Hirayama disease, strongly, although
indirectly, supports the hypothesis that this type of motor
neuron disease is a cervical myelopathy with an
ischaemic pathogenesis.
References
1. Hirayama K, Tsubaki T, Toyokura Y, Okinaka S (1963) Juvenile
muscular atrophy of unilateral upper extremity. Neurology
13:373–380
2. Schröder R, Keller E, Flacke S et al (1999) MRI findings in
Hirayama’s disease: flexion-induced cervical myelopathy or
intrinsic motor neuron disease? J Neurol 246:1069–1074
3. Tataroglu C, Bagdatoglu C, Apaydin FD et al (2003) Hirayama’s
disease: a case report. Amyotroph Lateral Scler Other Motor
Neuron Disord 4:264–265
4. Chen CJ, Chen CM, Wu CH et al (1998) Hirayama disease: MR
diagnosis. AJNR Am J Neuroradiol 19:365–368
5. Hirayama K, Tokumaru Y (2000) Cervical dural sac and spinal
cord in juvenile muscular atrophy of distal upper extremity.
Neurology 54:1922–1926
6. Robberecht W, Aguirre T, Van den Bosch et al (1996) Familial
AUTHOR QUERIES
- Please provide a conflict of interest declaration.
View publication stats
juvenile focal amyotrophy of the upper extremity (Hirayama dis-
ease). Superoxide dismutase 1 genotype and activity. Arch Neurol
54:46–50
7. Suyama C, Suzuki T, Sugimoto Y et al (1994) Efficacy of short-
latency somatosensory evoked potential (S-SEP) in cases of
Hirayama disease. Igaku Kensa 43:1717–1723 (abstract in
English)
8. Hirayama K (2000) Juvenile muscular atrophy of distal upper
extremity (Hirayama disease). Intern Med 39:283–290
9. Hirayama K (2000) Juvenile muscular atrophy of distal upper
extremity (Hirayama disease): focal cervical ischaemic polyom-
yelopathy. Neuropathology 20:S91–S94
10. Misra UK, Kalita J (1995) Central motor conduction in Hirayama
disease. Electroenceph Clin Neurophysiol 97:73–76
11. Misra UK, Kalita J, Mishra VN et al (2006) Effect of neck flexion
on F wave, somatosensory evoked potentials, and magnetic reso-
nance imaging in Hirayama disease. J Neurol Neurosurg
Psychiatry 77:695–698
12. Nezu A, Kimura S, Uehara S et al (1997) Magnetic stimulation of
motor cortex in children: maturity of corticospinal pathway and
problem of clinical application. Brain Dev 19:176–180
13. Paus T, Zijdenbos A, Worsley K et al (1999) Structural matura-
tion of neural pathways in children and adolescents: in vivo study.
Science 283:1908–1911
14. Yoshimura K, Kurashige T (2000) Age-related changes in the
posterior limb of the internal capsule revealed by magnetic reso-
nance imaging. Brain Dev 22:118–122