The Chikungunya virus (CHIKV) is an arbovirus belonging to the genus Alphavirus family Togaviridae, which presents a single-stranded genome RNA positive sense (Hossain et al. 2018). It was first identified during a febrile polyarthralgia epidemic in Tanzania and since then has been kept in the wild by a transmission cycle involving vertebrate hosts and hematophagous mosquitoes of the genus Aedes (Ae.), especially Ae. aegypti and Ae. albopictus (Scott et al. 2017).

CHIKV causes a self-limiting disease known as Chikungunya fever, rash, myalgia, polyarthralgia, and headache. The clinical presentation disappears within a week, while joint pain may persist for months or years (Tanabe et al. 2018). However, neonates, the elderly, and patients with comorbidities are at increased risk for progression of severity, evolving with atypical and lethal manifestations, including neurological complications such as neuropathic pain, myelitis, encephalitis, polyradiculitis, or symptoms clinically associated with Guillain-Barré syndrome (Peper et al. 2016; Fred et al. 2018).

We describe herein the case of an elderly patient from a Brazilian Northeastern city who, in the course of a serious infection with the virus, presented clinical alterations due to axonal damage in the peripheral nervous system, characterized as one of the most common mechanisms in neuropathies with conduction disorders of the nervous system, congenitally acquired.

Case presentation

A 66-year-old woman was admitted to an emergency department with a complaint of fever for 4 days, severe arthralgia and myalgia, rash, ocular sensitization, nausea, abdominal pain with diarrhea, inappetence, weakness, and reduced range of motion. Patient did not refer diabetes, hypertension, rheumatoid arthritis, and autoimmune disease–associated.

CHIKV infection was diagnosed through the Reverse Transcription of the Polymerase Chain Reaction (RT-PCR), which amplifies the E1 and E2 gene regions of the virus. In addition, for the differential diagnosis, molecular tests were performed for the Dengue virus (DENV) and Mayaro virus (MAYV) and serological tests for DENV and hepatitis B and C, which presented negative results. Other complementary tests were requested according to Table 1. Along the first month after the onset of symptoms, there was exacerbation of polyarthralgia with the presence of distal edema, complaints of asthenia, and reduction of body weight. During this period, treatment with glucocorticoid was implemented. Methylprednisolone 20 mg/d was gradually reduced in the next 6 months.

Table 1 Predictive laboratory results in the diagnosis of CHIKV infection
Full size table

In the second month of follow-up, there was persistence of arthralgia and the appearance of signs of sensorial abnormalities, such as decreased strength and sensitivity in upper and lower limbs (Fig. 2). Nerve conduction studies (NCS), which showed sensory-motor axonal pattern of peripheral polyneuropathy with decreased nerve conduction velocity and amplitude of the sensory nerve action potential in the right and left ulnar and median nerves, respectively, were requested for the right superficial fibular (Fig. 1A, B, C, D, F).

Fig. 1
figure 1

Representative tracing of nerve conduction studies. Reduced amplitude of sensory nerve action potential recorded from right median (A), right ulnar (B), left median (C), left ulnar (D), right superficial peroneal (E) and left sural (F) nerves, (G) volitional electromyography recorded from right extensor digitorum brevis muscle. Incomplete interference pattern with increased duration and amplitude of motor unit action potentials

Full size image

After the myography (Fig. 1G), no abnormalities were observed in the muscular points of the right and left anterior deltoid, right and left brachial biceps, right and left common hand extensor, right and left medial vast, right and left anterior tibial, and right and left medial gastrocnemius. It was observed a reduction of some potentials of motor unit action in the muscular points examined of the short abductor, right and left thumb, and first dorsal interosseous of the right and left hand. There was a moderate reduction of the motor unit action potentials in the muscular points examined of the right extensor of the right and left toes and abductor right hallux, with motor unit action potentials of increased amplitude and duration and increase of the proportion of polyphasic potentials without signs of denervation at rest.

Ultrasound of hands, wrists, feet, ankles, femoral, and shoulders and synovitis with bilateral joint effusion showed the presence of bilateral tendinopathy and periarticular edema. By following the development of neuropathy, the antimetabolite Methotrexate with dosage of 15 mg per week was associated with the treatment of symptoms, with an improvement in arthralgia and recovery of sensitivity and motor activity, resolving entirely in a period of 6 months.

Discussion

The neurological manifestations associated with the Chikungunya virus are important and less common, but they have later progression and are most serious in the elderly and newborn infants. The reported cases and the description of the clinical process suggest an increase in the neurovirulence of CHIKV (Brizzi 2017).

Mehta et al. (2018) described 865 cases of neurological disease associated with Chikungunya; one of the main indications was encephalopathy, responsible for 40.5% of the cases, and 13.4% of the patients were affected in the peripheral nervous system and 9.3% presented changes in the CNS and peripheral nervous system.

In the Americas, Bank et al. (2015) described a patient who had traveled to the Dominican Republic suffering from myeloradiculopathy after CHIKV infection. The patient fully recovered after 6 months but had persistent neuropathic pain. The authors associated this condition with a secondary immunomediated phenomenon rather than direct viral activity, proposing the use of immunotherapy to treat chronic neuropathic pain.

In this study, neurological complications were noted. The patient reported progressive weakness associated with loss of sensitivity in the distal limbs, besides a process of joint inflammation (Fig. 2). Peripheral axonal polyneuropathy was confirmed by means of nerve conduction studies (Fig. 1).

Fig. 2
figure 2

Neuropathy characterized by motor alterations and muscular atrophy in symmetrical fists, hands, feet, and metacarpophalangeal joints

Full size image

The autoimmune nature of some diseases observed in CHIKV infection is increasingly recognized. The virus may travel through many pathways, including retrograde axonal transport along motor neurons, and because of the molecular mimicry between pathogenic organisms and nerve cells, autoantibodies are formed, causing demyelination and deceleration of nerve conduction or action against gangliosides and Ranvier nodules, in turn, causing intermittent blocks of conduction, and as the condition progresses, persistent axonal damage (Ludlow et al. 2015; Cerny et al. 2017).

The ideal treatment is still under investigation. Various therapeutic options are being studied, such as known antimicrobial compounds, synthesis of specific compounds, nucleic acid–based antivirals, antibody therapy, and targeting host cell pathways (Powers 2017). The association of corticosteroids has benefited patients with musculoskeletal disorders associated with CHIKV, aiming to oppose the process by blocking the immune process (Chen et al. 2014).

The patient’s satisfactory response to prednisolone corresponded to methotrexate, which acts by modulating the various aspects of immune and inflammatory responses, having as pathophysiological basis the situation in which it is linked to a T cell-mediated immune response and inflammatory cytokines.

We reinforce the need to investigate this emerging tendency of neuroinfections related to the CHIKV virus, through presentation of cases, randomized studies, and use of diagnostic methods that allow the early detection and prevention of neurological changes, supporting the implementation of treatment of the first chronic complications.