Isolated neck extensor myopathy

Suarez and Kelly ^[1] recently described a noninflammatory myopathy affecting predominantly neck extensors in four patients, aged 63 to 81 years. Named the ``dropped head syndrome,'' this new disorder was characterized by severe weakness of neck extensors, with milder weakness of shoulder girdle and proximal arm muscles. EMG demonstrated short-duration, low-amplitude motor unit potentials in cervical paraspinal muscles. Muscle biopsy results of cervical paraspinal muscles in two patients and proximal arm muscles in the other patients showed nonspecific myopathic features without inflammation. The weakness appeared nonprogressive over periods of 5 to 7 months and did not improve in the one patient treated with prednisone. Three patients described by Lange et al. ^[2] in an earlier report may have had the same syndrome. Laboratory testing, including muscle biopsy, did not establish a specific diagnosis in these three patients, and their neck extensor weakness did not progress over a follow-up period of 3 to 5 years, sharing the benign clinical course seen in dropped head syndrome.

Dropped head syndrome is a relatively benign condition that may be difficult to distinguish from more ominous neuromuscular disorders presenting with severe neck extensor weakness, including myasthenia gravis, motor neuron disease, and inflammatory myopathy Table 1. We reviewed four cases of dropped head syndrome from our neuromuscular clinic. Routine clinical and laboratory data supplemented by electrophysiologic, radiologic, and pathologic studies readily distinguish ``isolated neck extensor myopathy'' (INEM), a term we prefer to ``dropped head syndrome,'' from other neuromuscular disorders.

Methods

Of 790 new patients evaluated in our university-based neuromuscular clinic between July 1, 1993, and March 31, 1995, 12 presented with neck extensor weakness and the inability to hold the head upright. All patients underwent a neurologic examination, nerve conduction studies, and EMG. One semispinalis and two splenius capitis muscle biopsies were performed at the fifth cervical level in three patients thought to have INEM. Biopsy was also performed on a proximal arm muscle in these three patients. As a control, after postmortem intervals of approximately 8 hours, cervical paraspinal muscle was obtained from two human cadavers, ages 68 and 86, with no history of neck weakness or injury. The unfixed muscle tissue was snap frozen in liquid nitrogen. Cryostat sections were cut and stained with hematoxylin-eosin and modified Gomori's trichrome. Additional sections were stained with NADH-tetrazolium reductase (NADH-TR), ATPase, esterase, and acid phosphatase activities according to standard procedures.

Results

Illustrative case report.

An 85-year-old woman (Table 2 patient 1) developed severe neck extensor weakness over 6 weeks. She denied dysarthria, dysphagia, and dyspnea. Her medical history was unremarkable. Neck extension was grade 2 on a modified Medical Research Council scale Figure 1. ^[3] Neck flexion and shoulder abduction were grade 4 plus. Strength was otherwise normal. CK was 26 U/L. Serum electrolytes, including calcium, were normal. Acetylcholine receptor antibody was negative. MRI of the cervical spine showed mild spondylosis without frank disk herniation. Symmetric edematous changes were present in the splenius capitis and multifidus muscles at lower cervical levels Figure 2. Needle EMG revealed short-duration voluntary motor units with fibrillation potentials localized from lower cervical to mid-thoracic paraspinal muscles. EMG of the third cervical, ninth thoracic, and third lumbar paraspinals, deltoid, biceps, vastus lateralis, and anterior tibialis muscles was normal. Biopsy results of the splenius capitis revealed increased variation in fiber size, increased connective tissue, and central nuclei. Deltoid muscle biopsy results were normal. Her neck weakness has been stable for 6 months.

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Table 2. Clinical features of patients presenting with neck extensor weakness

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Figure 1. Photograph of patient 1 demonstrates severe neck extension weakness. She is unable to raise her head against gravity.

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Figure 2. MRI axial section through the lower cervical spine in patient 1 shows edematous changes in the splenius capitis and multifidus muscles (arrows).

Clinical findings in INEM patients.

The four patients with INEM ranged in age from 64 to 85 years Table 2. Neck weakness developed over a period of 1 week to 3 months. Patient 1 also had mild neck flexion and proximal arm weakness. Neurologic examination was otherwise normal. CK was normal and acetylcholine receptor antibodies were negative in all INEM patients. MRI of the cervical spine demonstrated mild spondylosis without neural impingement in all four patients, neck extensor atrophy in patient 4, and edema-like alterations in neck extensor muscles in patients 1 and 2 Figure 2. CSF was normal in patients 2, 3, and 4. Patient 1 did not undergo lumbar puncture. Nerve conduction studies were normal in all INEM patients except for incidental carpal tunnel syndrome in patient 1. Repetitive stimulation at 3 Hz of the ulnar, spinal accessory, and facial nerves showed no evidence of decrement at rest or after exercise. EMG in all patients demonstrated fibrillations and positive sharp waves isolated to the lower cervical, and upper to mid-thoracic paraspinal muscles. In all patients, short-duration (less than 2.0 msec) voluntary motor units with early recruitment were observed in these muscles. EMG of proximal and distal limb muscles was normal. Results of cervical paraspinal muscle biopsies showed increased internal nuclei and connective tissue, marked fiber-size variability, fiber splitting, and prominent myofibrillar disarray in hypertrophic fibers without evidence of inflammation or vacuoles Figure 3. In patient 4, a decrease in central staining with patchy increases in subsarcolemmal staining was observed on NADH-TR reaction Figure 4. Cervical paraspinal specimens from two cadavers showed mild variation in myofiber diameter without other abnormalities on routine sections. Oxidative enzyme activity was mildly diminished on control NADH-TR sections, reflecting post-mortem change, but was normally distributed. Results of deltoid biopsy in patient 4 and biceps biopsies in patients 2 and 3 were normal. Treatment with pyridostigmine bromide and prednisone was attempted in patients 2, 3, and 4 without clinical improvement. Neck extension weakness progressed initially by history, but by the time we saw the patients the weakness had stabilized and remained unchanged in follow-up.

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Figure 3. Photomicrograph of paraspinous muscle from patient 2. (A) Striking variation in myofiber diameter is apparent, reflecting the presence of both atrophic and hypertrophic fibers. Diameters of some of the larger fibers exceed 160 micro meter. Well-developed fiber splitting is present among hypertrophied fibers (hematoxylin-eosin, times 200, before 48% reduction). (B) NADH-TR staining demonstrates substantial myofibrillar disarray within hypertrophic fibers (times 200, before 48% reduction).

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Figure 4. Section of skeletal muscle from patient 4, stained for NADH-TR activity, demonstrating reduced central enzyme activity in a number of fibers (times 200, before 48% reduction).

Discussion

Our series describes four patients with INEM. We prefer the term ``isolated neck extensor myopathy'' to ``dropped head syndrome'' because it is more specific with regard to clinical presentation and pathology. As in the earlier published cases, EMG showed fibrillations with short-duration motor unit potentials in cervical paraspinal muscles. Results of cervical paraspinal muscle biopsies demonstrated nonspecific myopathic features not seen in cadaveric controls. Occasional fibers from one biopsy specimen showed reduced central staining to NADH-TR with small increases in subsarcolemmal activity, a pattern also observed in a specimen from a previous biopsy. ^[1] Our patients differed slightly from those reported earlier in that only one of our patients had involvement of neck flexors and proximal arm muscles. Of the eight patients now reported with this syndrome, all were more than 60 years of age.

Neck or truncal weakness may be the presenting feature of several neuromuscular disorders. These include myasthenia gravis, motor neuron disease, and inflammatory myopathy. In a series of 1,036 patients with myasthenia gravis, neck weakness was the initial manifestation in three percent. ^[4] Neck and trunk weakness may be severe in motor neuron disease and was the first symptom in two percent of patients with amyotrophic lateral sclerosis. ^[5,6] Neck flexion weakness is typical of these disorders. However, neck extensor weakness has been the prominent feature in several clinical reports. In the group of 12 patients reported by Lange et al. ^[2] with the floppy head syndrome, four had isolated weakness of neck extension, and eight had evidence of a generalized neuromuscular disorder. A diagnosis was established in nine of these patients: myasthenia gravis in four, motor neuron disease in three, and myopathies in two. Neck extensor and flexor weakness may be a prominent feature of carnitine deficiency but is accompanied by generalized features of myopathy, including ptosis, proximal limb weakness, scapular winging, and waddling gait. ^[7,8] A young woman developed severe and relatively restricted neck extension weakness during a relapse of chronic inflammatory demyelinating polyneuropathy. ^[9] She could balance her head in the upright position, but her head fell with any movement, and she was unable to raise her chin off her chest. Plasmapheresis, prednisone, and azathioprine produced modest improvement in limb strength and ambulation, but neck extensors did not respond. Recent reports have described severe neck and trunk extensor weakness in congenital myopathy, ^[10] hyperparathyroidism, ^[11] and inclusion body myositis. ^[12,13]

Three of the four patients with INEM were referred to our clinic with the diagnosis of amyotrophic lateral sclerosis. Using clinical and laboratory data, we could confidently distinguish INEM from more serious neuromuscular diseases. Only one of eight patients diagnosed with other neuromuscular disorders had weakness restricted initially to cervical paraspinal muscles; within 2 months, the patient developed more generalized weakness and ptosis, consistent with myasthenia gravis. Right arm weakness, tongue fasciculations, elevated CK levels, and diffuse denervation on EMG helped to identify the patient with amyotrophic lateral sclerosis. The patient with myotonic dystrophy had facial weakness, increased CK levels, and myotonic potentials on EMG. Characteristic quadriceps atrophy and weakness of finger flexors were present in the patient with inclusion body myositis. ^[14] The patient with polymyositis had moderate proximal limb weakness, an elevated CK, and myopathic changes on deltoid biopsy.

All of our INEM patients had brief motor unit potentials on EMG of cervical paraspinal muscles. Travlos et al. ^[15] recently analyzed cervical paraspinal muscles of healthy elderly patients using monopolar electrodes. Calculated motor unit durations were 4.7 plus minus 1.9 msec. Each of our INEM patients had numerous cervical paraspinal motor units of less than 2.0-msec duration with early recruitment. Since these EMG abnormalities are also seen in other muscle diseases, biopsy of a mildly to moderately affected muscle is the best way to distinguish a treatable inflammatory myopathy from INEM.

Cervical MRI in three of our INEM patients showed edema-like changes and atrophy in paraspinal muscles. These MRI changes are not specific for INEM and are also seen in denervating disorders and a variety of myopathies. ^[16] The radiologic appearance of muscle is normal in myasthenia gravis ^[17] and, therefore, MRI may be useful in distinguishing INEM from antibody-negative myasthenia.

The etiology of this myopathy is unknown. Weakness in our patients and those reported by Suarez and Kelly ^[1] developed over 1 week to 3 months. Further progression did not occur. This presentation may suggest a monophasic inflammatory process restricted to neck extensor muscles that later resolves. Polymyositis occasionally presents as a focal disorder but tends to generalize over a period of 3 to 6 months. ^[18] An alternative explanation that we favor is that mechanical stretching produces the injury. Kyphotic postural changes and loss of tissue elasticity associated with aging ^[19] may place increasing work-loads on cervical paraspinal musculature that leave some individuals susceptible to injury. As the head falls forward, greater and greater stress is placed on neck extensors attempting to maintain the head erect. The overly stretched muscle may be unable to generate adequate tension during contraction. ^[20,21] These factors may combine to produce further injury and weakness, initiating a vicious cycle. Elderly individuals who develop kyphosis but no neck extensor weakness presumably maintain adequate elastic and tensile properties of muscle. Mechanical injury may explain why neck extensor strength did not improve in patients we otherwise successfully treated for myasthenia gravis and polymyositis, or in the young woman with chronic inflammatory demyelinating polyneuropathy. ^[9]

We conclude that INEM is an important consideration in patients presenting with neck weakness. INEM appears to be the most likely diagnosis in those patients with isolated neck extensor involvement. Four of our five patients with this presentation were diagnosed with INEM. Routine electrophysiologic, radiologic, and histologic studies should be performed to confirm an isolated myopathy and exclude other disorders. Clinicians who recognize the distinct features of INEM can reassure patients of its relatively benign course and avoid misdiagnosis of more ominous neuromuscular conditions.