Progressive cervical kyphosis associated with botulinum toxin injection.

Abstract: Weakness of the neck extensors can lead to "dropped head syndrome," a condition of progressive cervical kyphosis in which a patient is unable to hold their head up against the force of gravity. This condition can be associated with structural abnormalities of the spine as found in ankylosing spondylitis and vertebral fractures. Neuromuscular disorders, such as myasthenia gravis, muscular dystrophies, inflammatory myopathies, and motor neuron disorders such as amyotrophic lateral sclerosis (ALS) have also been reported as etiologies of dropped head syndrome. In this article, we describe an elderly woman with rapidly progressive cervical kyphosis following an injection of botulinum toxin A into her neck extensor musculature.

Key Words: botulinum toxin, neck extensor musculature, cervical kyphosis

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Progressive cervical kyphosis may be the result of spinal degeneration or neuromuscular disease. Weakness of the neck extensors can lead to "dropped head syndrome," a condition in which a patient is unable to hold their head up against the force of gravity. This condition can be associated with structural abnormalities of the spine as found in ankylosing spondylitis and vertebral fractures. Neuromuscular disorders, such as myasthenia gravis, muscular dystrophies, inflammatory myopathies, and motor neuron disorders such as amyotrophic lateral sclerosis (ALS) have also been reported as etiologies of dropped head syndrome. (1) Rarer causes include licorice-induced hypokalemia, hypothyroidism, Parkinson disease, and cervical myelopathy. (1-3) In this article, we describe an elderly woman with rapidly progressive cervical kyphosis following an injection of botulinum toxin A (Botox) into her neck extensor musculature.

Case Report

An 86-year-old white female presented to our clinic complaining that she could no longer hold her head erect. She had previously undergone a C3-5 decompression and fusion without complications. Approximately a year before her presentation, she had a minor fall resulting in neck pain and spasm. She was initially treated by her primary care physician with a one time trigger point injection of botulinum toxin (Botox) into her neck extensor muscles. Records do not indicate the dose given. Within a few days of the injection, the patient experienced severe neck weakness and could no longer hold her head up. She rapidly developed significant worsening of her kyphosis and was unable to extend her neck enough to look straight ahead. This did not resolve with time. Physical therapy was ineffective. She tried numerous collars and braces but they resulted in skin breakdown and pressure sores. The patient reported significant interference with her daily activities. To see in front of her, she had to hold her head up with her hand. She had stopped exercising and socializing and was quite miserable.

Despite her age, she was otherwise healthy. She was retired, did not smoke or drink, and was quite active. She had no other complaints of muscle weakness.

On physical examination, she had a marked kyphotic deformity at the cervical thoracic junction. She had no active neck extension but could be passively extended 30 to 40[degrees]. When she stood upright, she extended her hips and increased the lordosis of her lumbar spine in an attempt to look straight ahead (Fig. 1). Neurologically, she was completely intact. She had no focal weakness or sensory loss. Reflexes were symmetric and she did not have a Hoffmann sign.

X-rays showed a severe kyphotic deformity of the cervical spine (Fig. 2). The prior instrumentation was intact. An MRI from 2003, before receiving the botulinum toxin, showed no evidence of prior kyphosis (Fig. 3A). Current CT scans showed no evidence of cord compression, disk herniation or additional fractures (Fig. 3B).

The patient desired surgical correction of the deformity. Two days before surgery, she was placed in a cervical halo. Five pounds of traction significantly improved her neck position. At surgery, she was placed prone and the posterior aspect of the halo vest removed. An in situ posterior cervical fusion was performed. Pedicle screws were placed in T1, T2, T3 and lateral mass screws in C4, C5, and C6 using anatomic landmarks and an image intensifier. Local bone graft was packed over the decorticated laminae and facet joints and the rods were inserted and secured. Somatosensory-evoked potential monitoring was utilized during the case. The halo was left in place until postoperative day 5 when she was placed in a rigid collar. She was discharged on postoperative day 8. She was maintained in a rigid collar for 2 months, after which its use was gradually weaned.

At 12 month follow up, her fusion was solid and there had been no loss of alignment (Fig. 4). The patient was extremely pleased that she could hold her head up without support and see in front of her when walking (Fig. 5). The patient gave consent for this case to be submitted for publication.

Discussion

Knowledge of the function of the neck extensor muscles is fairly limited in scope. Dissection of the cervical spine has shown that the semispinalis cervicus and capitis muscles appear to be primarily responsible for neck extension. (4) The semispinalis cervicus originates in the transverse processes of the thoracic vertebrae and inserts into the spinous processes of C2 through C7. The semispinalis capitis extends from T7 to the skull base. Using a biomechanical model, Nolan and Sherk (4) found that the minimum extensor force of these muscles required to balance the head against gravity in the prone position was 14.38 kg.

Isometric strength testing has shown that neck extensor strength is greater than flexor strength in healthy males without neck pain. (5) In healthy male and female volunteers, cervical isometric strength has been shown to decrease significantly with age. These age-related changes appear to affect all muscle groups equally; however, the ratio of flexor-extensor strength remains consistent. Women were 30 to 40% weaker than men in all age groups in this study. (6)

In this case, the development of progressive cervical kyphosis resulting in a dropped head is believed to be the result of a botulinum injection into the neck extensor musculature. Botulinum toxins are naturally occurring substances which affect the release of acetylcholine at the neuromuscular junction of striated muscles. The toxin, upon ingestion or injection, binds to presynaptic neurons. It is then internalized into the neuron, acting on a zinc-dependent endoprotease to disrupt some of the peptides required for acetylcholine release. This process, which may take up to two weeks to complete, effectively destroys the neuromuscular junction. The therapeutic effects of botulinum toxin depend on this blockade of peripheral neuromuscular activity, which ultimately results in muscular weakness. Regeneration of the neuromuscular junctions occurs rapidly and complete muscle function returns in 3 to 6 months.

Botulinum toxin type A (Botox), has been FDA approved in the United States for use for treatment of cervical dystonia and blepharospasm. It has also been used to treat many chronic pain syndromes in the head and neck region, including cervicogenic headache, cervical dystonia, chronic neck pain, and temporomandibular disorders. (7) Although a consensus has yet to be reached, the mechanism of relief in these pain syndromes may be the result of a decrease in sympathetic transmission and reduction of dorsal root ganglion hypersensitivity. (8)

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No evidence has linked the use of botulinum toxin to permanent degeneration or atrophy of muscles, even in patients injected with high levels of botulinum repeatedly over an extended period of time. (8) The most common result of repeated injections is the development of antibodies which limits the effectiveness of subsequent injections. (9) Generalized paresis is rare, but has been reported as a complication. Bhattia and colleagues (10) reported three cases of generalized muscle weakness following botulinum toxin injection for cervical dystonia. However, to our knowledge, there are no prior reports of dropped head syndrome following botulinum toxin injection.

The effects of botulinum toxin injections typically "wear off" in approximately (3) months as regeneration of nerve endings occur. The weakness experienced by this patient did not resolve, however. Katz and colleagues (11) observed the same effect in patients with myasthenia gravis and polymyositis with kyphosis who were treated for their condition without concurrent improvement in neck extensor strength. They hypothesized that as the head falls forward, the neck extensors progressively stretch and are thus unable to generate adequate tension during contraction. A cycle of continued injury and weakness develops, and as a result, muscle strength cannot be regained even when the inciting cause is rectified. (11)

The use of botulinum toxin as a potential therapy for both cervical muscle spasm and cervical pain has generally proved to be effective, with very few adverse side effects. However, this case illustrates that care must be taken in using botulinum toxin in the neck extensor muscles. Older women, especially those with pre-existing cervical kyphosis or prior surgery, would be expected to have weaker neck extensors than older men and may be particularly susceptible to this complication. Posterior spinal fusion was successful in improving functional posture in our patient with significant improvement in her ability to perform daily activities.

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References

1. Mahjneh I, Marconi G, Paetau A, et al. Axial myopathy: an unrecognised entity. J Neurol 2002;249:730-734.

2. Yoshida S, Takayama Y. Licorice-induced hypokalemia as a treatable cause of dropped head syndrome. Clin Neurol Neurosurg 2003;105: 286-287.

3. Kawaguchi A, Miyamoto K, Sakaguchi Y, et al. Dropped head syndrome associated with cervical spondylotic myelopathy. J Spinal Disord Tech 2004;17:531-534.

4. Nolan JP Jr, Sherck HH. Biomechanical evaluation of the extensor musculature ofo the cervical spine. Spine 1988;13:9-11.

5. Seng KY, Lee Peter VS, Lam PM. Neck muscle strength across the sagittal and coronal planes: an isometric study. Clin Biomech 2002;17:545-547.

6. Garces GL, Medina D, Milutinovic L, et al. Normative database of isometric cervial strength in a healthy population. Med Sci Sports Exerc 2002;34:464-470.

7. Sycha T, Kranz G, Auff E, et al. Botulinum toxin in the treatment of rare head and neck pain syndromes: a systematic review of the literature. J Neurol 2004;251 (Suppl I):119-130.

8. Smith HS, Audette J, Royal MA. Botulinum toxin in pain management of soft tissue syndromes. Clin J Pain 2002;18:S147-S154.

9. Klein AW. Complications and adverse reactions with the use of botulinum toxin. Dis Month 2002;48:336-356.

10. Bhattia KP, Munchau A, Thompson PD. Generalized muscle weakness after botulinum toxin injections for dystonia: a report of three cases. J Neurol Neurosurg Psychiatry 1999;67:90-93.

11. Katz J, Wolfe GI, Burns DK, et al. Isolated neck extensor myopathy: a common cause of dropped head syndrome. Neurology 1996;46:917-921.

I've never known any trouble that an hour's reading didn't assuage.
--Charles De Secondat

Kathleen A. Hogan, MD, Erika L. Manning, PHD, and John A. Glaser, MD

From the Department of Orthopaedic Surgery, Medical University of South Carolina, Charleston, SC.

Reprint requests to Kathleen A. Hogan, MD, Medical University of South Carolina, Department of Orthopaedic Surgery, 96 Jonathan Lucas Street, Suite 708, Charleston, SC 29425. Email: [e-mail]

RELATED ARTICLE: Key Points

* There may be unknown complications associated with botulinum toxin injections.

* Injections of botulinum toxin should be used with caution, especially in elderly patients.