Miller Fisher Variant of Guillain-Barre Syndrome Secondary to Pulmonary Tuberculosis: A Case Report with Review of Literature

Abstract Guillain-Barre syndrome (GBS) is one of the common causes for acute flaccid paralysis in adults and mostly preceded by infection. Miller Fisher syndrome (MFS) is a rare variant of GBS with incidence of 1 to 2 in 1,000,000. This syndrome has a triad of ataxia, areflexia, and ophthalmoplegia and diagnosed when two out above three features are present. It usually preceded by viral infection, most commonly Campylobacter jejuni , cytomegalovirus, and Epstein–Barr virus. However, it is very rarely reported in pulmonary tuberculosis. The pathogenesis involves an aberrant immune response due to molecular mimicry against myelin gangliosides. Hereby we are presenting an unusual case of MFS variant of GBS associated with pulmonary tuberculosis.


Introduction
Guillain-Barre syndrome (GBS) is an immune-mediated polyradiculoneuropathy affecting peripheral nerves and nerve roots with an incidence of one to two cases/per 100,000 persons. 1 The diagnostic criteria include clinical evidence of bilateral symmetric ascending areflexic weakness, with albumin-cytologic dissociation in cerebrospinal fluid (CSF) supported by neurophysiological studies.Miller Fisher syndrome (MFS) is one of the rare variants of GBS. 2 MFS manifests as ophthalmoplegia, ataxia, and areflexia.Two-thirds of cases of GBS are associated with antecedent gastrointestinal or respiratory tract infections.
Tuberculosis (TB) is rampant in the Indian subcontinent.The literature is replete with reports describing an association between GBS and TB.However, an association between the MFS variant of GBS with TB is rarely reported.We show a rare MFS form of GBS with pulmonary TB (PTB).

Case Report
A 58-year-old male presented to the emergency room with complaints of dysphagia, cough with shortness of breath, and slurring of speech for 4 days.He had a history of chronic cough and weight loss of more than 10% in the last 3 months.There was no history of gastrointestinal symptoms or flu-like symptoms in the recent past.He was hemodynamically stable, having a temperature of 38.40C and right-sided bronchial breath sounds with course crepitation in the infraclavicular area.Neurological examination revealed diminished deep tendon reflexes in both lower limbs and ascending motor weakness with Medical Research Council grade 3) in all four limbs.He also had dysarthria and bilateral lower limb ataxia.][5][6][7] Exhaustive tests were advised to determine the triggers/etiology of GBS.A routine stool examination was negative for Campylobacter jejuni.Blood and urine cultures were sterile.Serology was negative for human immunodeficiency virus (HIV), hepatitis B and C, scrub typhus, malaria, Leptospira, cytomegalovirus, and Epstein-Barr virus.Hematological and biochemical profiles were average.Antinuclear antibody titer and antineutrophil cytoplasmic antibodies were negative.Brain magnetic resonance imaging with angiography revealed the regular study.Sputum was positive for acid-fast bacilli, and a cartridge-based nucleic acid amplification test detected Mycobacterium tuberculous.Chest radiograph revealed a nonhomogenous opacity of the right upper lobe, and highresolution computerized tomography showed consolidation and fibrosis of the correct upper zone (►Fig. 1),confirming the diagnosis of PTB.He was intubated for airway protection, given poor cough reflex.On the 8th day of illness, CSF analysis revealed glucose of 83 mg/dL (blood glucose of 110 mg/dL), protein 86 mg/dL, and cell count of 2 cell/mL suggestive of albumin-cytological dissociation.Nerve conduction studies (NCS) revealed slow motor conduction velocities with reduced amplitude of sensory nerve action potential in bilateral ulnar and peroneal nerves and absent F-wave responses in ulnar, peroneal, and tibial nerves consistent with MFS.
He was started on antitubercular therapy (ATT) (isoniazid, rifampicin, pyrazinamide, and ethambutol) and underwent five sessions of plasmapheresis.There was an improvement in cough reflex and motor power after the third plasmapheresis session.He got extubated on day 10 of the intensive care unit stay, but after 3 days, he developed hospital-acquired pneumonia (multidrug-resistant Klebsiella pneumoniae) and was reintubated again.Antibiotics were upgraded according to the culture sensitivity report.The next day he developed abdominal distension, oozing of blood from the central venous catheter site and hypotension.On further workup, he was found to have a drop in hemoglobin to 5 g/dL; total platelet count was 89000 cells/μL, international normalized ratio was 3.2, and fibrinogen was 77 mg/dL suggestive of disseminated intravascular coagulation (DIC).To exclude the possibility of ATT-induced hepatitis, liver function test was sent, which was expected.Contrastenhanced computer tomography abdomen showed a large retroperitoneal hematoma over the left iliac fossa.He was transfused with multiple packed blood cells and blood products, including cryoprecipitate, but finally, he succumbed to septic shock and DIC.

Discussion
GBS is a disease of peripheral nerves known for its association with various infections.The mean age of onset is 40 years, and the incidence increases after age 50.Besides acute inflammatory demyelinating polyneuropathy, other clinical variants of GBS are axonal motor and sensorimotor neuropathy (AMAN, AMSAN), MFS, and Bickerstaff brainstem encephalitis.Our patient had ataxia and areflexia with typical MFS NCS and CSF findings.The most frequently identified infection for precipitation of GBS is Campylobacter jejuni, and less often by cytomegalovirus, dengue, chikungunya, Zika, and HIV. 2 The causes mentioned above trigger the host immune system and produce antibodies against gangliosides of myelin of peripheral nerves, which in turn lead to neuropathy and muscle weakness. 2B has both pulmonary and extrapulmonary manifestations.Neurological manifestations of TB include tuberculomas, meningitis and brain abscesses.The pathogenesis of GBS in TB is best explained by molecular mimicry involving both cell-mediated and humoral immune responses. 3he review of reported cases is mentioned in ►Table 1. [3][4][5][6][8][9][10] The most common clinical features of the presentation of GBS are ascending quadriparesis with areflexia or hyporeflexia, and few case reports showed sensory involvement.4,8 According to the American Academy of Neurology, intravenous immunoglobulins (IVIG) are as effective as plasmapheresis for treating GBS. 10 Mohta et al described the AMSAN variant of GBS, where the patient underwent five sessions of plasmapheresis and showed improvement during the hospitalization and discharged.5 Another 40-year-old male patient presented with the AMSAN variant, where IVIG was given for 5 days, but as there was no improvement at day 21, he underwent plasmapheresis, but there was no neurological improvement.He progressed to chronic inflammatory demyelinating polyradiculoneuropathy. 8 Our patient also underwent plasmapheresis and showed neurological improvement.To our knowledge, only one case of MFS due to PTB has been reported in a 70-year-old male who recovered after treatment with IVIG and ATT. 6 Our patient also showed clinical improvement in motor power and cough reflex after treatment and to the best of our knowledge, this is probably the first reported case report of MFS secondary to PTB from the Indian subcontinent.
From the pattern of disease progression and clinical response after starting ATT, TB was considered the cause of MFS in this case.However, the possibility of both occurring by chance could not be ruled out.

Fig. 1
Fig. 1 Consolidation and fibrosis of the right upper zone (black arrowhead).