Herpes zoster ophthalmicus (HZO) presents as a painful vesicular rash in the trigeminal nerve dermatome. Unilateral ophthalmoplegia appears in approximately 7-31% of patients with HZO and possibly occurs weeks after the onset of HZO symptoms. However, bilateral external ophthalmoplegia after suffering from unilateral HZO is rare.

Shima et al. recently described the case of an 80-year-old female who suffered from right-sided HZO with meningoencephalitis and developed bilateral third, fourth, and sixth cranial nerve palsies and Syndrome of inappropriate antidiuretic hormone secretion (SIADH) almost simultaneously (1). All bilateral cranial palsies spontaneously resolved within a few months. In their discussion, they described three possible mechanisms: Varicella-zoster virus (VZV)-induced vasculopathy, a reactive immunological response to VZV, and a direct cytotoxic effect of VZV. They concluded that a reactive immunological response, such as Miller-Fisher syndrome (MFS), was the most likely mechanism of ophthalmoplegia in their case (1).

MFS is characterized by the acute onset of ophthalmoplegia, ataxia, and areflexia, and it is considered to be a variant of GBS. The most common agents are Campylobacter jejuni, Haemophilus influenzae, and Mycoplasma pneumoniae (2). Infection with VZV may also be a significant antecedent factor that triggers both Guillain-Barré syndrome (GBS) and MFS, but a significant statistical association has not yet been confirmed (2). Rizoo et al. reported the case of a 78-year-old man with MFS who developed right third cranial nerve palsy with hypoflexia and was seropositive for serum GQ1b autoantibodies (3). These two reports, including the report by Shima T et al., suggest that infection with VZV may trigger the development of MFS.

SIADH is a rare complication of VZV. A possible mechanism underlying the association between SIADH and HZO is that VZV infection may involve the regulatory pathway of ADH secretion (4). On the other hand, Shima T et al. noted that SIADH may occur as a complication in patients with MFS. An association between SIADH and GBS has been reported, but SIADH associated with MFS is extremely rare. To our knowledge, there have been 3 case reports that describe MFS complicated by SIADH (5-7). Anti-anglioside GD2 antibodies, which recognize disialosyl residue and react with the myelin sheaths in the peripheral nerves as well as with the pituicyte cytoplasm in the posterior lobe of the pituitary gland, may explain the association between SIADH and MFS, because some patients developed sensorimotor demyelinating polyneuropathy with SIADH after treatment of melanomas with anti-GD2 monoclonal antibodies (5,8).

This case report firstly describes the development of both MFS and SIADH after unilateral HZO. The further accumulation of case reports and research is required to clarify the association between HZO and MFS.

The author states that he has no Conflict of Interest (COI).