Chiropractic-Responsive Vestibular Involvement in Mitochondrial Disorders

To the Editor

We read the article by Russel et al¹ about a 66-year-old man with chronic progressive external ophthalmoplegia (CPEO) and involvement of the vestibular system (CPEO plus). The case report suggests that the patient benefited from 18 sessions of chiropractic manipulation along with mobilization, stretching, and transverse massage.¹ We wish to provide the following comments.

The genetic cause of the condition was not provided in the case report. Chronic progressive external ophthalmoplegia is not diagnosed by the phenotype alone but requires genetic confirmation. In most cases, CPEO is due to single mitochondrial DNA (mtDNA) deletions² or point mutations (tRNA[Asp], tRNA[Ser], 12S rRNA, 16S rRNA, MT-TL1)^3,4. However, mutations in nuclear DNA genes, such as POLG1, Twinkle, DGUOK, SLC19A3, RNASEH1, and PRIMPOL,^5,6 also may go along with CPEO. Because the genetic cause is heterogeneous, the phenotype may vary considerably between different genotypes, particularly with progression of the disease.

We do not agree that the diagnosis of CPEO can be made with muscle biopsy findings.¹ According to the traditional approach, CPEO is diagnosed through patient history, blood tests, clinical exam, electromyography, muscle biopsy, and genetic tests.⁷ According to a more advanced approach, however, CPEO can be diagnosed directly by panel tests or whole exome sequencing. Because CPEO may be due to single mtDNA deletions, long-range polymerase chain reaction and Southern blotting of mtDNA should be carried out. If testing for single mtDNA deletions or point mutations is noninformative, sequencing of appropriate nuclear DNA genes needs to be carried out.

Headache is a frequent manifestation of a mitochondrial disorder (MID) and should be classified according to the International Headache Society. Particularly, in the case of tension headache, vertigo may be present.⁸ Because many of the MID patients also develop myopathy of the axial muscles,⁹ degeneration of the cervical spinal column with reactive increase of the muscle tone of cervical muscles, and thus tension headache, may ensue.

Although the authors state that no effective treatment for MIDs has been thus far established,¹ we point out that there are a number of regimens¹⁰ that significantly improve these conditions in some patients. For example, in thiamine-responsive Leigh disease, thiamine can be highly effective. In primary coenzyme-Q deficiency, application of coenzyme-Q orally may resolve most of the clinical manifestations. Most patients with Leber's hereditary optic neuropathy experience a beneficial effect from high-dose idebenone, and there is an effective method available to prevent the transmission of MIDs due to mtDNA defects, which currently is approved only in the United Kingdom.¹¹

To assess a patient for multisystem disease (CPEO plus), a systemic and prospective investigation should be performed.¹² Exclusion of neuropathy, myopathy, carotid stenosis, cardiac disease, and autonomic disturbance is crucial when assessing the therapeutic effect of chiropractic maneuvers because the therapeutic effect may be limited if not only the muscle and vestibular system but also the peripheral nerves, the central nervous system, the muscles, or the cardiovascular system are involved.