A novel phenotype Of Zika virus-related neurological disease: Sensory neuronopathy.

Abstract

Zika virus (ZIKV) infection has become a major health problem in Latin America in the past few years.1 Peripheral nervous system involvement is one of the major complications related to this arbovirus.1, 2 This was particularly highlighted after the outbreaks of Guillain-Barre syndrome (GBS) in French Polynesia and Latin America soon after ZIKV epidemics.1, 3 Most reported patients had a rather typical GBS presentation with rapidly ascending paralysis, diffuse areflexia, and facial diplegia. Recently, atypical phenotypes have been also reported, including Miller-Fisher syndrome (MFS) and small-fiber neuropathy.4, 5 We now report a Brazilian patient with typical clinical and electrophysiological findings of a sensory neuronopathy (SN) that developed weeks after ZIKV infection. This description broadens the clinical profile of ZIKV-related neurological disease. In June 2015, a 42-year-old previously healthy woman from Northeastern Brazil had a febrile disease accompanied by a mild erythematous rash and joint pain that lasted 5 days and improved spontaneously. Three weeks later, she developed progressive numbness and gait abnormalities. When she was first seen in the emergency room 5 days after the onset of neurological symptoms, she required bilateral support to walk. On examination, she was fully alert, with intact cranial nerve functions and preserved muscle strength. Vibratory sense was absent in both legs, the right arm, and over her trunk. Proprioception was preserved only in her left upper limb. Romberg's sign was positive. Pseudoatethosis of the upper limbs was present, and muscle stretch reflexes were absent. Autonomic function was normal. Cerebrospinal fluid (CSF) analysis demonstrated protein 10 mg/dL, glucose 69 mg/dL, and <1 white blood cell/μL. MRI of the brain and spinal cord were unremarkable. Nerve conduction studies (NCSs; orthodromic technique for motor conduction studies and antidromic for sensory conduction studies)6 revealed exclusive sensory nerve involvement with asymmetric and non–length-dependent reduction of the sensory nerve action potential amplitudes (Table 1). H reflexes were absent bilaterally, and needle electromyography revealed no active or chronic denervation. Urine polymerase chain reaction exam result was positive for ZIKV RNA. She was treated with intravenous immunoglobulin (0.4 mg/kg/day for 5 days) without improvement in symptoms. Ten days after her admission, she was discharged. Physical rehabilitation was associated with some functional gains over the next several months. During this period, additional evaluation was performed, and no evidence of rheumatologic, infectious, or paraneoplastic etiologies was found. On examination 1 year later, she was able to walk but required a cane. Sensory ataxia was still severe and pseudoathetosis of the upper limbs remained prominent. There was no autonomic dysfunction, muscle weakness, or atrophy. This patient presented with asymmetrical and severe sensory deficits but with preserved muscle strength, the key features of SN. She fulfilled all the proposed criteria of Camdessanche et al.7 for SN. NCSs revealed widespread sensory abnormalities, but sural nerve amplitudes were not as affected as the sensory amplitudes of the median and ulnar nerves. Moreover, results from motor nerve studies and electromyography were normal. An important diagnostic consideration for our patient would be MFS. Both SN and MFS share ataxia as the core clinical feature. In addition, sensory NCS abnormalities are the predominant electrodiagnostic abnormalities in both disorders. Testing for antiganglioside Q1b antibodies would have been useful in this setting but, unfortunately, was not available. Despite that, we strongly believe that this was not MFS because she did not have cranial nerve involvement and also because of her prolonged clinical course with persistent deficits. There is a previous report of ZIKV-related sensory polyneuropathy, but, in that case, deficits followed a symmetric length-dependent distribution, small fibers were predominantly affected, and NCS showed exclusively sural abnormalities.5 We believe this patient had a postinfectious rather than a true direct complication of ZIKV infection because there was a 3-week delay between infection and the onset of SN and because the CSF profile at disease onset was not compatible with active viral infection. ZIKV might have triggered an aberrant immune response that inadvertently targeted the dorsal root ganglia. Several host and virus factors might have contributed to this. Specifically, the porous nerve–blood barrier8 makes sensory neurons accessible to toxins and antibodies. In addition, ZIKV is neurotropic9 and has surface peptides that share epitopes with peripheral nerve proteins, potentially leading to molecular mimicry9, 10 and immune-mediated SN. In conclusion, ZIKV should be included in the list of infectious etiologies that may trigger acute/subacute SN. The authors received funding from Fundação de Amparo à Pesquisa do Estado de São Paulo (Grant 13/01766-7 and 2014/19786-7) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior. Ethical Publication Statement: We confirm that all authors have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.