Letter to the Editor: Is Dropped Head Syndrome in Sporadic Late-onset Nemaline Myopathy Always Untreatable?

| April 1, 2020

Dear Editor:

Dropped head syndrome (DHS) is a rare condition characterized by cervical paraspinal muscles weakness that causes a recognizable deformity with various degrees of “chin on chest” posture.1–3 Though the etiology of DHS is still unclear, some authors have suggested aging-related postural changes to be a mechanical cause of the disease.2,3 Moreover, DHS might be associated with neuromuscular diseases4, including amyotrophic lateral sclerosis,1 myasthenia gravis,1 polymyositis,5 isolated neck extensor myopathy,1 and Parkinson’s disease.1 However, other diseases, such as ankylosing spondylitis, hypokalemia, hypothyroidism, and postlaminectomy kyphosis, as well as the injection of botulinum toxin type A for neck pain6 or nemaline myopathy,7 might present with DHS. Most DHS-associated diseases typically occur in the elderly; therefore, it is more frequent in individuals older than 60 years of age.8 The impact of DHS on daily living is significant. DHS interferes with eating, walking, and the ability to maintain horizontal gaze, causing neck pain.1 Among the neuromuscular disorders, DHS might be associated with sporadic late-onset nemaline myopathy (SLONM), a rare, acquired myopathy that occurs in adult age and causes proximal or distal muscle weakness with subacute onset, with or without dysphagia and respiratory failure.9 Clinical examination and electrodiagnostic, laboratory, and molecular genetic testing might help achieve the right diagnosis, but muscle biopsy plays a critical role in the differential diagnosis, thus defining the possible disease etiology.10 However, muscle biopsy must not be considered the first-line approach to diagnosing neuromuscular disorders because of the potential risk of infection or bleeding. In DHS, the presence of a myopathic electromyography pattern, with spontaneous activity, is considered a common SLONM feature.9 Nonetheless, to confirm a SLONM diagnosis, muscle biopsy is fundamental,10 thanks to the presence of nemaline rods in myofibers.9 These nemaline rods can have either a genetic basis (as in the cases of inherited congenital nemaline myopathies11) or acquired causes, including monoclonal gammopathy of unknown significance and human immunodeficiency virus (HIV) associated nemaline myopathy.9 Although there isn’t a specific treatment for DHS,11 therapeutic strategy might improve the clinical symptoms in patients with SLONM (even though the disease has a poor prognosis, mainly when associated with monoclonal immunoglobulin G gammopathy12). In fact, growing evidence suggests that some patients might benefit from intravenous immunoglobulins,12 mycophenolate mofetil,12 rituximab,12 and melphalan followed by autologous stem cell transplantation, especially in patients with SLONM-monoclonal gammopathy of unknown significance.13 More recently, Nakamura et al14 reported on a 74-year-old previously healthy woman with DHS and proximal dominant limb weakness. The woman was diagnosed with SLONM without M-protein and was successfully treated with intravenous methylprednisolone.14 On the other hand, there are DHS cases attributed to SLONM plus multiple myeloma with muscle symptoms appearing after allogenic hematopoietic stem cell transplantation.7 Even in such cases, the association of lenalidomide with dexamethasone, in the presence of a myopathy with significant structural abnormalities, was successful.7

With this letter, we would like to support the importance of muscle biopsy to reach the proper diagnosis of SLONM and to include SLONM associated or not with multiple myeloma in the diagnosis of patients with DHS. In fact, in such cases, possible treatment strategy and muscle symptom resolution do exist.

References

  1. Drain JP, Virk SS, Jain N, Yu E. Dropped head syndrome: a systematic review. Clin Spine Surg. 2019;32(10):423–429.
  2. Katz JS, Wolfe GI, Burns DK, et al. Isolated neck extensor myopathy: a common cause of dropped head syndrome. Neurology. 1996;46(4):917–921.
  3. Mahjneh I, Marconi G, Paetau A, et al. Axial myopathy: an unrecognised entity. J Neurol. 2002;249(6):730–734.
  4. Suarez GA, Kelly JJ Jr. The dropped head syndrome. Neurology. 1992;42(8):1625–1627.
  5. Finsterer J, Frank M, Krexner E. Steroidresponsive dropped-head-syndrome due to polymyositis. Joint Bone Spine. 2010;77(5):485–486.
  6. Hogan KA, Manning EL, Glaser JA. Progressive cervical kyphosis associated with botulinum toxin injection. South Med J. 2006;99(8):888–891.
  7. Montagnese F, Portaro S, Musumeci O, et al. Sporadic late-onset nemaline myopathy in a woman with multiple myeloma successfully treated with lenalidomide/dexamethasone. Muscle Nerve. 2015;51(6):934–935.
  8. Liao JP, Waclawik AJ, Lotz BP, et al. Myopathic dropped head syndrome: an expanding clinicopathological spectrum. Am J Phys Med Rehabil. 2007;86(12):970–976.
  9. Schnitzler LJ, Schreckenbach T, Nadaj-Pakleza A, et al. Sporadic late-onset nemaline myopathy: clinico-pathological characteristics and review of 76 cases. Orphanet J Rare Dis. 2017;12(1):86.
  10. Joyce NC, Oskarsson B, Jin LW. Muscle biopsy evaluation in neuromuscular disorders. Phys Med Rehabil Clin N Am. 2012;23(3):609–631.
  11. Malfatti E, Romero NB. Nemaline myopathies: state of the art. Rev Neurol. 2016;172(10):614–619
  12. Monforte M, Primiano G, Silvestri G, et al. Sporadic late-onset nemaline myopathy: clinical, pathology and imaging findings in a single center cohort. J Neurol. 2018;265(3):542–551.
  13. Voermans NC, Benveniste O, Minnema MC et al. Sporadic late-onset nemaline myopathy with MGUS: long-term follow-up after melphalan and SCT. Neurology. 2014;83(23):2133–2139.
  14. Nakamura K, Shibuya K, Nishino I, Kuwabara S. Dropped head in sporadic late-onset nemaline myopathy. Intern Med. 2019;58(13):1967–1968.

With regards,

Simona Portaro, MD, PhD, and Rocco Salvatore Calabrò, MD, PhD

IRCCS Centro Neurolesi Bonino Pulejo Messina, Italy

Funding/financial disclosures. The authors have no conflict of interest relevant to the content of this letter. No funding was received for the preparation of this letter.

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Category: Current Issue, Letters to the Editor, Movement Disorders, Neurology

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