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Acute-onset chronic inflammatory demyelinating polyneuropathy after Zika virus infection
  1. Sonja E Leonhard1,
  2. Alexander G Munts2,
  3. Annemiek A van der Eijk3,
  4. Bart C Jacobs4
  1. 1 Department of Neurology, Erasmus University Medical Center, Rotterdam, The Netherlands
  2. 2 Department of Neurology, Spaarne Gasthuis Hospital, Haarlem, The Netherlands
  3. 3 Department of Viroscience, Erasmus University Medical Center, Rotterdam, The Netherlands
  4. 4 Department of Neurology and Immunology, Erasmus University Medical Center, Rotterdam, The Netherlands
  1. Correspondence to Drs Sonja E Leonhard, Department of Neurology, Erasmus University Medical Center, Rotterdam 3000CB, The Netherlands; s.leonhard{at}

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Case description

In December 2016, a 69-year-old man with a history of hypertension, hypercholesterolaemia and knee operations developed an erythematous pruritic rash on his trunk, cold shivers and swollen hands and feet with paraesthesias and numbness while on holiday in Curaçao. Eight days later he developed pain in his right leg and back, provoked by walking and stretching. This pain slowly increased over the next 5 weeks to the point that it became difficult to walk. He was admitted to the neurology ward of a regional hospital in The Netherlands, and neurological examination showed an antalgic gait, hypaesthesia of fingertips and feet and normal muscle strength and tendon reflexes. MRI of the cervical, thoracic and lumbar spine without gadolinium was normal. Eight days after admission he developed a progressive weakness of the legs starting in the right leg. Neurological examination showed a proximal and distal flaccid paraparesis with absent reflexes of the legs and normal reflexes of the arms. Cerebrospinal fluid (CSF) examination 3 days after admission showed a leucocyte count of 1/10 E6/L and a protein level of 620 mg/L. Electrolytes, liver and kidney function and inflammatory parameters were normal. Nerve conduction studies (NCS) 5 days after admission showed slightly prolonged distal motor latencies of the peroneal and tibial nerves, mildly prolonged F-wave latencies of the ulnar and tibial nerves and a low amplitude of the sural nerve, compatible with a poly(radiculo)neuropathy.

He was diagnosed with Guillain–Barré syndrome (GBS) and a preceding Zika virus (ZIKV) infection was suspected. Blood, urine and CSF samples collected 50 days after onset of infectious symptoms were negative for ZIKV qRT-PCR. Serology was positive for ZIKV IgM and IgG at days 50 and 83 detected by an NS1-based ELISA (Euroimmun, Lübeck, Germany). This was confirmed by neutralising antibodies against ZIKV in paired testing. Dengue virus serology was negative for IgM and NS1, and weakly positive (1.163/P) for IgG, most likely due to cross-reactivity. Serology for other recent infections associated with GBS, including Campylobacter jejuni, Mycoplasma pneumoniae, cytomegalovirus, Epstein–Barr virus and hepatitis E virus, was negative. The patient improved shortly after treatment with a standard course intravenous immunoglobulin (IVIg) (0.4 mg/kg/day for 5 days). During admission he did not develop upper limb weakness, cranial nerve or respiratory dysfunction. A second opinion at Erasmus Medical Center confirmed the diagnosis GBS.

Unexpectedly, he deteriorated 6 weeks after start of weakness (figure 1) with increased weakness of all limbs causing inability to walk without aid. He was diagnosed with a treatment-related fluctuation and treated with another course of IVIg, after which he improved. Eleven weeks after start of weakness, he had a second deterioration with increased weakness of the legs. Repeated NCS were compatible with a demyelinating polyneuropathy, showing decreased motor amplitudes, absent sensory amplitudes, severely prolonged distal motor latencies of the median, ulnar and peroneal nerves, conduction slowing of the median and peroneal nerves and prolonged minimal F-waves latencies of the median and ulnar nerve. The clinical symptoms and NCS fulfilled the diagnostic criteria for definite chronic inflammatory demyelinating polyneuropathy (CIDP).1 Maintenance therapy was started with biweekly IVIg infusions, and he had a good clinical response. At the last follow-up, 41 weeks after onset of weakness, he had a distal sensibility loss with normal strength in all limbs and he was able to walk without aid.

Figure 1

Clinical course and treatment in patient with acute-onset chronic inflammatory demyelinating polyneuropathy after Zika virus infection. IVIg, intravenous immunoglobulin (30 g/day during 5 days); IVIg maintenance, intravenous immunoglobulin (30 g biweekly); Medical Research Council (MRC) sum score: sum of score on MRC scale for muscle weakness of bilateral shoulder abduction, elbow flexion, wrist extension, hip flexion, knee extension, ankle dorsiflexion; ZIKV, Zika virus infection.


The ZIKV epidemic in 2015–2016 was followed by a drastic rise in reported GBS cases in 23 countries, including Curaçao.2 Evidence of an association between ZIKV and GBS has been substantiated by numerous case series and case–control studies. A specific clinical phenotype of ZIKV-related GBS has not emerged from these reports, but based on the NCS most patients have been classified as the demyelinating variant (acute inflammatory demyelinating polyneuropathy (AIDP)).3 Many other complications of the central and peripheral nervous system have been reported as well, including myelitis, encephalitis and acute transient polyneuritis.4 The pathogenesis of these ZIKV associated disorders is unknown, but direct infection and immune-mediated injury of nerves may both play a role.

Approximately 5% of patients initially diagnosed as GBS will develop CIDP. Patients with this acute-onset CIDP (A-CIDP) often do not have cranial nerve involvement or respiratory failure, but these clinical characteristics lack the specificity to discriminate between GBS and A-CIDP in the acute phase of disease. Moreover, NCS cannot be used to discriminate between AIDP and CIDP in individual patients. A-CIDP is usually diagnosed during follow-up and should be considered when clinical deteriorations occur more than two times or beyond 8 weeks from onset, as in the patient described here.5 Our patient initially fulfilled the current diagnostic criteria for GBS as the progression of weakness was <4 weeks, but the pain and sensory symptoms before the start of weakness may have been a first indication of a more chronic form of neuropathy.

This case indicates that ZIKV infection may trigger a chronic peripheral nervous system disorder, most likely caused by prolonged inflammation, that can present as GBS. The lack of ZIKV genome in blood, urine and CSF further argues against a direct infection and implicates an immune-mediated cause of nerve damage in this case. The clinical implication is that all patients initially diagnosed with GBS after ZIKV infection need careful follow-up as they may develop CIDP that can respond well to maintenance treatment with IVIg.


The authors thank Judith Drenthen (Erasmus MC, University Medical Center Rotterdam) for helping with the analysis of the nerve conduction study data.



  • Contributors SEL: study concept and design, acquisition, interpretation of the data and draft of the first manuscript. AGM and AAvdE: acquisition and interpretation of the data, and revision of the manuscript for intellectual content. BCJ: study concept and design, analysis and interpretation of data and revision of the manuscript for intellectual content.

  • Funding The study was funded by a grant from the European Union (Horizon 2020, ZikaPLAN Grant Agreement No. 734584).

  • Competing interests SEL is supported by a grant from the European Union (Horizon 2020, ZikaPLAN project ID: 734584). AAvdE receives funding by Fujirebio NV, TKI, LSH aka Match, Health HollandBart C. BCJ is supported by a grant from the European Union (Horizon 2020, ZikaPLAN project ID: 734584).

  • Patient consent Obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.