Guillain-Barre Syndrome and Miller Fisher Variant in Zika Virus Disease

1.1 History

In 1916, two French Neurologists Georges Charles Guillain and Jean Alexandre Barre and French Physiologist Andre Strohl reported an original paper encountered new syndrome in two soldiers with muscle weakness, absence of deep tendon reflexes and sensory impairment and described the key diagnosis of albumin-cytologic disassociation in the cerebrospinal fluid along with changes in electromyography and nerve conduction studies. Both patients were managed with massage therapy and Strychnine injection and showed clinical recovery after few months [1].

GBS is rare but the commonest cause for acute ascending paralytic polynephropathy. GBS is considered to be an acute immune-mediated disorder that causes peripheral polyneuropathy. Most cases of GBS are preceded by either viral or bacterial infection, which triggers the immune system affecting the peripheral nervous system causing a rapid progressive demyelinating polyneuropathy [2, 3].

The incidence of GBS has been increased since the outbreak of certain infections such as Zika virus epidemic in Latin America in 2015. GBS is the most leading cause of acute ascending muscle paralysis with an annual incidence of 1–2 per 100,000 persons per year worldwide. GBS is more common in males than females [2, 3].

GBS is a rapid demyelinating peripheral neuropathy that typically manifest as ascending muscle weakness that is symmetric in nature associated with reduced or absent deep tendon reflexes. GBS has been also associated with pain along with sensory impairment [4].

GBS is an acute immune-mediated demyelinating polyneuropathy and it is the commonest cause of acute muscle paralysis in pediatric age group patients [5, 6].

MFS is a rare neurological disorder which was initially recognized in 1932 by James Collier as a classical triad of ophthalmoplegia, ataxia and absent deep tendon reflexes. Later in 1956 Charles Miller Fisher a Canadian Neurologist described and reported details isolated clinical entity of three patients who presented with ophthalmoplegia, ataxia and areflexia [7].

MFS has an annual incidence of 0.9 per 1000,000 populations and affect males more than females at ratio of 2:1 and commonly affect Asian population especially at their fourth decade of life [7].

MFS most commonly preceded by Campylobacter jejuni infection and has strong association with positive anti-GQ1b antibodies [7].

Zika virus infection has been associated with different neurological disorders such as microcephaly and since the initial outbreak of Zika virus infection the number of GBS cases has been increased in endemic countries [8].

3.1 Clinical subtypes of Guillain-Barre syndrome (GBS)

A number of clinical subtypes of Guillain-Barre Syndrome (GBS) are identified.

Acute inflammatory demyelinating polyradiculoneuropathy (AIDP) is considered to be the most common subtype and account for approximately of 90 percent of GBS patients in the Unites States. Patients with this subtype typically present with progressive ascending symmetric muscle weakness and areflexia associated with severe pain and autonomic dysfunction such as fluctuation in blood pressure, urinary incontinence or syncope. This clinical subtype typically shows a slow nerve conduction velocity with no clear anti-ganglioside antibodies association [14].

Other subtype of GBS is the acute motor axonal neuropathy (AMAN) that accounts for 5% of Guillain-Barre syndrome (GBS) patients in United States. This subtype purely presents with motor weakness without sensory symptoms. Nerve conduction study shows axonal polyneuropathy with normal sensory nerve action potential. Patients with acute motor axonal motor neuropathy have strong association with Campylobacter jejuni (C. jejuni) infection with positive antibodies against gangliosides GM1, GD1a, GaINac-GD1a and GD1b [14].

The acute motor-sensory axonal neuropathy (AMSAN) is a rare and severe variant of GBS [15], which has similar clinical features to acute motor axonal neuropathy but with predominantly sensory loss and positive antibodies against GM1 and GD1a. Nerve conduction study showed axonal polyneuropathy with reduced or absent sensory nerve action potential [14].

The pharyngeal-cervical brachial syndrome (PCB) is another rare subtype of GBS [16]. Patient with PCB syndrome typically present with rapid and progressive oropharyngeal and shoulder muscle weakness associated with absent deep tendon reflexes in the upper limbs. The nerve conduction study in patients with PCB syndrome is generally normal but sometimes showed axonal neuropathy in the arms. PCB syndrome associated with positive IgG anti-GT1a antibodies [17].

Miller Fisher syndrome is one of the GBS variant. It is an uncommon neurological disorder which account of about 5% of GBS cases. Patients with Miller Fisher syndrome typically present with clinical trial of ophthalmoplegia which is bilateral symmetric in most patients, ataxia and absent deep tendon reflexes. The commonest initial presenting symptoms in patients with Miller Fisher syndrome is diplopia (double vision) which is due to acute onset-ophthalmoplegia. Other less frequent signs and symptoms of MFS include headache, difficulty swallowing and photophobia (Table 1). MFS is an immune-mediated neurological disorder and more than 80% of patients with MFS showed positive IgG anti-GQ1b antibodies. Electrophysiological findings in patients with MFS commonly showed reduced sensory nerve action potentials and absent H reflexes (Figure 2 and Table 2) [7, 12, 18].

Bickerstaff brainstem encephalitis currently considered to be another variant of Fisher syndrome associated with central nervous system involvement. Patients with Bickerstaff brainstem encephalitis typically present with ophthalmoplegia, ataxia, hyperreflexia and altered sensorium [19].

Bickerstaff brainstem encephalitis is an immune-mediated neurological disorder usually preceded by infection and associated with positive anti-GQ1b antibodies [19].

Zika virus belongs to the virus family Flaviviridae. This virus was first isolated in 1947 from a monkey in the Zika forest of Uganda. Zika virus spread mainly by Aedes mosquitos as well as by intrauterine transmission, blood and sexual intercourse [20]. Most cases of Zika virus infection are associated with mild symptoms such as fever, headache, maculopapular skin rash, red eyes (conjunctivitis) and joint or muscle pain [21, 22, 23].

The outbreak of Zika virus infection in Brazil in 2015 has been associated with a more serious neurological complication such as Guillain-Barre syndrome [24]. This outbreak has been also resulted in increase in the incidence of babies with microcephaly [25, 26].

During Zika outbreak in Brazil, patients who developed Guillain-Barre syndrome secondary to Zika virus infection were found to have a higher level of anti-ganglioside antibodies of both IgM and IgG isotypes as compared to other patients with Zika infection in the absence of GBS [27].

Since Zika virus associated with serious devastating neurological complications such as Guillain-Barre syndrome and congenital anomalies in the newborn babies, several methods have been developed in order to detect the virus in early course of infection. Nonstructural protein 1 (NS1) is considered to be an essential biomarker for early detection and diagnosis of Zika virus. The development of double-antibody sandwich ELISA (DAS-ELISA) has been also used for early and rapid detection of ZIKA-NS1 protein in patients who newly infected with Zika virus [28].

At the present time, there is no antiviral treatment or specific vaccines approved for patients infected with Zika virus. Supportive care remains the main modality of managing these patients, yet the challenge remains to prevent congenital Zika syndrome in pregnant women [29].