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Parkinsonism and Neck Extensor Myopathy
A New Syndrome or Coincidental Findings?
Håkan Askmark, MD, PhD;
Karin Edebol Eeg-Olofsson, MD, PhD;
Anders Johansson, MD;
Pelle Nilsson, MD, PhD;
Yngve Olsson, MD, PhD;
Sten-Magnus Aquilonius, MD, PhD
Arch Neurol. 2001;58:232-237.
ABSTRACT
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Background Dropped head in parkinsonism has been attributed to dystonia or unbalanced
muscle rigidity. To our knowledge, isolated neck extensor myopathy with parkinsonism
has been described in only one patient.
Objectives To assess the occurrence of neck extension weakness resulting in dropped
head in patients with parkinsonism and to explore whether the head drop might
be the consequence of neck extensor myopathy.
Patients and Methods All patients who were evaluated because of parkinsonism in the Department
of Neurology in our hospital between January 1, 1997, and December 31, 1999,
and were found to have both parkinsonism and neck extension weakness resulting
in head drop were studied. The patients underwent clinical examination, blood
tests including the levels of creatine kinase and myoglobin and neurophysiological
evaluation with needle electromyography and autonomic tests. Open biopsy on
a neck muscle was performed in the patients who could cooperate.
Results Of 459 patients evaluated because of parkinsonism, 7 were found to have
neck extensor weakness resulting in head drop. Needle electromyography revealed
myopathic changes in all 7 patients. Muscle biopsy, which was performed in
5 patients, disclosed myopathic changes in all 5 patients. Electron microscopy
revealed mitochondrial abnormalities in 2 of these 7 patients. Three of the
patients had concomitant neck rigidity that could contribute to the neck position.
All 7 patients had autonomic dysfunction and 6 responded poorly to levodopa
therapy, making a diagnosis of multiple system atrophy probable.
Conclusion Parkinsonism may be associated with isolated neck extensor myopathy
resulting in dropped head, and this condition should be suggestive of multiple
system atrophy.
INTRODUCTION
NECK EXTENSION weakness resulting in dropped head is often a part of
a generalized neuromuscular disorder such as myasthenia gravis, polymyositis,
or amyotrophic lateral sclerosis.1 The term
"dropped head syndrome" usually refers to a condition characterized by severe
weakness of the neck extensors due to a restricted noninflammatory myopathy.2, 3 There may be additional weakness affecting
periscapular, shoulder, and thoracic musculature or even more extensive distribution
of weakness, dropped head plus syndrome.4 A
similar condition in elderly patients with paraspinal myopathy resulting in
bent spine on standing has been designated "bent spine syndrome."5 It is unclear whether these 2 syndromes are 2 separate
entities or different manifestations of an axial myopathy.
Antecollis has been described in multiple system atrophy (MSA), diffuse
Lewy body disease, and Parkinson disease.6, 7, 8, 9
and it is has been suggested that this "dropped head sign" in parkinsonism
is caused by unbalanced muscle rigidity between the anterior and the posterior
neck muscles.9 Weakness of the neck extensors
have, however, not been described in these cases. To our knowledge, in the
literature there is only 1 report in Japanese about a case of isolated neck
extensor myopathy with parkinsonism.10 The
aim of this study was to estimate the occurrence of dropped head in patients
with parkinsonism and to explore if the head drop might be the consequence
of neck extensor myopathy.
PATIENTS AND METHODS
All patients who on examination in the Department of Neurology in our
hospital between January 1, 1997, and December 31, 1999, were found to have
both parkinsonism and neck extension weakness resulting in head drop were
studied. Parkinsonism was defined as the presence of at least 2 of the following
findings: hypokinesia, rigidity, and resting tremor. Probable MSA was defined,
according to the consensus statement on the diagnosis of MSA,11
as poorly levodopa-treated responsive parkinsonism plus autonomic failure.
Head drop was defined as the patient's inability to hold the head up against
gravity while sitting or standing. The strength of the neck muscles was tested
manually with the patient in the sitting position and graded according to
the Medical Research Council scale,12 where
grade 0 indicates no contraction and grade 5 indicates normal power. With
the patient in the sitting position, rigidity in the neck was also tested
and graded as mild, moderate, or pronounced. In addition to clinical examination,
the patients underwent blood tests including the levels of creatine kinase
and myoglobin, neurophysiological evaluation with needle electro + myography
(EMG), and autonomic tests (R-R–interval variation testing parasympathetic
function, galvanic skin response, and digital vasoconstriction for sympathetic
function). Open biopsy on a neck muscle was performed in the patients who
could cooperate. The biopsy specimens were cut in cryostat and transverse
sections were stained with hematoxylin-eosin, van Gieson, and Gomori 1-step
trichrome. Histochemical stainings were also performed for demonstration of
adenosine triphosphatase at pH 9.4 and 4.6, nicotinamide adenine dinucleotide,
and cytochrome oxidase. Other samples from the biopsy were fixed in glutaraldehyde,
postfixed in osmium tetroxide, and embedded in epoxy resin (Epon) for electron
microscopy.
REPORT OF CASES
CASE 1
A 62-year-old woman was seen with a 2-year history of slowly progressive
walking difficulties, poor balance, orthostatic hypotension, and urinary incontinence
and a 1-year history of weakness and pain in the neck. Levodopa therapy, 500
mg/d, had very limited effect on improving walking difficulties. Neurological
examination disclosed pronounced weakness of the neck extensors (grade 1)
resulting in maximal head drop. The neck extensors were tense on palpation.
The sternocleidomastoid muscles were atrophic. There was mild rigidity in
the neck and in the limbs. The patient walked slowly, taking short steps,
and had no arm swing. Retropulsion was noted when the pull test was performed.
Diadochokinesis was impaired on both sides. There was no tremor. Blood pressure
was 170/95 mm Hg when the patient was lying down and 110/80 mm Hg when the
patient was standing. Except for these findings, the physical examination
revealed no other abnormalities. Serum myoglobin was 71 µg/L (reference
range, <50 µg/L); all other laboratory findings including the creatine
kinase level were normal. Magnetic resonance imaging of the brain disclosed
unspecific high-signal changes in the pons, but no atrophy. Magnetic resonance
imaging of the neck did not show any abnormality of the medulla or of the
cervical nerve roots. Needle EMG revealed myopathic changes in paraspinal
muscles at the cervical and upper thoracic levels (C6, T2) and in the left
sternocleidomastoid muscle. Autonomic test results disclosed dysfunction of
both the sympathetic and parasympathetic nervous system. A biopsy specimen
from the semispinalis capitis muscle (Figure
1A) revealed marked fiber-size variability, degeneration and regeneration
of muscle fibers, and an increased amount of extracellular matrix. There were
no signs of inflammation. A few ragged-red fibers were observed in the Gomori
staining. Electron microscopy revealed mitochondrial abnormalities (Figure 2A-B). A biopsy specimen from the
left deltoideus muscle did not show any pathological changes.
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Figure 1. A, Patient 1. Cryostat section
from the muscle biopsy specimen showing myogenic features with 1 necrotic
fiber in the center (asterisk). There is also variation in fiber diameters
and an increased extracellular matrix between the fibers (hematoxylin-eosin,
original magnification x150). B, Patient 2. Muscle biopsy specimen showing
loss of muscle fibers, a marked increase of extracellular matrix between the
fibers, and large variations in fiber diameters (hematoxylin-eosin, original
magnification x75).
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Figure 2. A, Patient 1. Electron microscopy
of the muscle biopsy specimen showing a collection of abnormal mitochondria
with variation of their size and internal changes with abnormal positions
of circular profiles (original magnification x3000). B, Another region
of the biopsy specimen showing abnormal mitochondria and crystalline inclusions
(original magnification x30 000).
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CASE 2
A 66-year-old woman was seen because of a 1-year history of walking
difficulties and stiffness in the body. On physical examination she walked
slowly, taking short steps, and had decreased arm swing. There was rigidity
in the right arm, but no tremor. A diagnosis of Parkinson disease was made
and the patient was treated with levodopa, up to 500 mg/d. Her gait initially
was moderately improved. On reexamination 1 year later she reported an inability
to raise her head over the previous 3 months. She had pronounced weakness
(grade 1) in neck extension resulting in maximal head drop (Figure 3). Her voice was monotonous and weak. She walked slowly,
taking short steps, and had decreased arm swing, There was moderate rigidity
in the neck and mild rigidity in the arms, but no tremor. Blood pressure was
120/65 mm Hg when the patient was lying down and the systolic blood pressure
was 80 to 90 mm Hg when the patient was standing. Except for these findings,
physical examination disclosed no other abnormalities. Myoglobin level was
82 µg/L (reference range, <50 µg/L), but all other blood test
results were normal. Autonomic test results disclosed dysfunction of both
the sympathetic and the parasympathetic nervous system. Needle EMG disclosed
marked myopathic changes in a paraspinal muscle at the C7 level (Figure 4) and in the splenius muscle. A muscle
biopsy specimen from the splenius muscle (Figure 1B) revealed a pronounced increase in interstitial connective
tissue, uniform fiber atrophy, and areas with internal nuclei and "ring fibers."
Electron microscopy disclosed areas with mitochondrial aggregates. One year
after undergoing biopsy, the rigidity of the neck had increased to such an
extent that her head was completely fixated in a maximal flexed position.
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Figure 3. Patient 2. Severe neck extensor
weakness is present.
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Figure 4. Patient 2. Electromyogram showing
21 motor unit potentials (MUPs) from right paraspinal muscle (C7 level). Most
MUPs have reduced amplitudes (Amp) and durations (Dur) as well as a small
size index (SI), ie, features consistent with a marked myopathy. Phases and
turns are normal as well as frequency (Freq) of firing at a slight voluntary
activation. Absence of denervation activity in the muscle at rest indicates
that the myopathic changes are not of short-term occurrence or progressive.
Ellipsis indicates not applicable.
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RESULTS
Of 459 patients with parkinsonism evaluated in the Department of Neurology,
University Hospital, Uppsala, between January 1, 1997, and December 31, 1999,
7 patients were unable to hold their head upright. These 7 patients were all
found to have neck extensor myopathy. In 3 of the subjects there was also
rigidity of the neck to such an extent that it could contribute to the head
drop. All 7 patients had autonomic dysfunction and 6 responded poorly to levodopa
therapy, making a diagnosis of MSA probable. Patients 1 and 2 were described
earlier and the characteristics of all 7 patients are summarized in Table 1 and Table 2. Muscle biopsy specimens could not be obtained on patients
6 and 7 as these patients developed confusion and could not cooperate.
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Table 1. Clinical Characteristics of 7 Patients
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Table 2. Neurophysiological and Muscle Biopsy Findings
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COMMENT
The dropped head syndrome resulting from neck extensor myopathy seems
to be a heterogeneic condition with different causes. In most reported cases
an unspecific, restricted, noninflammatory myopathy has been found,2, 3 but there are also reports about inclusion
body myositis,13 focal myositis,14
congenital myopathy,15 nemaline myopathy,16 and hyperparathyroidism17
presenting with severe neck weakness. The origin of the myopathy in our patients
is unknown. It has been suggested that mechanical stretching produces the
injury in isolated neck extensor myopathy.3
Kyphotic postural changes and loss of tissue elastic associated with aging18 may place increasing workloads on cervical spinal
muscles that leave some individuals susceptible to injury. Patients with parkinsonism,
especially those with MSA, may be more vulnerable because of their posture.
If this hypothesis would be correct, it is, however, difficult to explain
why the neck weakness may precede the parkinsonism by years, as in our patients
4 and 5. All 7 patients described herein had autonomic dysfunction and 6 responded
poorly to levodopa therapy, making a diagnosis of MSA probable.11
It cannot be excluded that higher levodopa doses might have induced a better
response, but because of orthostatic hypotension and psychiatric side effects,
it was impossible to increase the doses further. "Disproportionate antecollis"
has been reported to be much more frequent in MSA than in Parkinson disease.6 It is possible that a neck extensor myopathy may be
overlooked in a patient with pronounced rigidity in the neck. Yoshiyama et
al9 reported that the muscle strength in the
neck was almost normal in all of their patients who had parkinsonism and the
dropped head sign, but conventional needle EMG was only performed in 2 of
their 7 patients. Our patients 2, 5, 6, and 7 illustrate that pronounced rigidity
and myopathy in the neck can occur in the same patient. In patient 2, the
neck rigidity increased over time to such an extent that at the latest physicial
examination it was impossible to assess the patient's muscle strength. It
is essential to differentiate neck muscle weakness from hyperactive neck flexors.
In our patient there were, however, no signs of hyperactivity of the neck
flexors whether on palpation or on the needle EMG. As the biopsy findings
confirmed myopathy in all 5 cases in which biopsies were performed, we do
not think that we have overdiagnosed myopathy on needle EMG. For most limb
muscles, as well as facial muscles, reference values for motor unit potential
size have been collected. However, for paraspinal and neck muscles, reference
studies are difficult for practical and ethical reasons. Therefore, needle
EMG findings from these muscles are not evaluated as myopathic unless they
are convincing enough. Around 20 motor unit potentials have been collected
from each examined muscle to participate in analysis of amplitude, duration,
and the number of phases. At maximal voluntary activation of a muscle a dense
interference pattern was obtained in congruence with myopathy. No denervation
activity was seen in any of our patients, indicating that the myopathies found
had had a longer course.
A mitochondrial disease may be a possibility, when 2 organ systems are
involved as in our patients. Mitochondrial changes were also observed in the
neck muscles from patients 1 and 2. However, it is doubtful if the findings
of ragged-red fibers and mitochondrial abnormalities in the semispinalis capitis
muscle of patient 1 is due to a true mitochondrial myopathy, as no such findings
were observed in the deltoid muscle biopsy specimen from the same patient.
It has also been reported that paraspinal cervical muscles develop pathologic
abnormalities with increasing age and that both ragged-red fibers and accumulation
of mitochondria are frequent findings in these cases.19
All of our patients were older than 60 years and it seems that age is a contributing
factor to the development of neck extensor myopathy in patients with parkinsonism.
In predisposed persons, age is, on the whole, a risk factor for neurodegenerative
diseases.
During this 3-year period we found in total 10 patients with isolated
neck extensor myopathy among 4782 patients investigated by quantitative needle
EMG. Seven of these patients, whom we have described herein, also had parkinsonism.
We do not think that the combination of these conditions is coincidental,
but that it represents a clinical entity. It is impossible from this study
to determine the true prevalence of this disorder and we can only make a crude
estimation. We can establish that 1.5 % (7 of 459 patients) of the patients
with parkinsonism examined in the Department of Neurology, University Hospital,
Uppsala, during this study period had neck extensor myopathy. Five of the
patients came from our primary reception area, which has a population of 300 000
and 2 of the patients were referred from other parts of the country. As the
symptoms are so striking and unusual, it is probable that every patient with
this disorder in our primary reception area has been referred to our department.
If this is true, the prevalence should be 1 to 2 per 100 000 in the population.
We conclude that parkinsonism may be associated with isolated neck extensor
myopathy resulting in dropped head and that this condition should be suggestive
of MSA.
AUTHOR INFORMATION
Accepted for publication May 27, 2000.
From the Departments of Neurology (Drs Askmark, Johansson, and Aquilonius),
Clinical Neurophysiology (Dr Edebol Eeg-Olofsson), Neurosurgery (Dr Nilsson),
and Pathology (Dr Olsson), University Hospital, Uppsala, Sweden.
Corresponding author: Håkan Askmark, MD, PhD, Department of
Neurology, University Hospital, S-75185 Uppsala, Sweden (e-mail: hakan.askmark{at}neurologi.uu.se).
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