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|LETTER TO EDITOR
|Year : 2020 | Volume
| Issue : 1 | Page : 209-218
The Association of Guillain–Barré Syndrome with Pulmonary Tuberculosis: Chance or Causal?
Abhijeet Singh, Viswesvaran Balasubramanian, Nitesh Gupta
Department of Pulmonary, Critical Care and Sleep Medicine, VMMC and Safdarjung Hospital, New Delhi, India
|Date of Web Publication||28-Feb-2020|
Dr. Abhijeet Singh
Department of Pulmonary, Critical Care and Sleep Medicine, VMMC and Safdarjung Hospital, New Delhi
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Singh A, Balasubramanian V, Gupta N. The Association of Guillain–Barré Syndrome with Pulmonary Tuberculosis: Chance or Causal?. Neurol India 2020;68:209-18
Guillain– Barré syndrome (GBS), an immune-mediated neuropathy, is the most common cause of acute flaccid paralysis worldwide with an estimated incidence of 0.8–1.9 cases per 100,000 persons. Although antecedent respiratory or gastrointestinal infection, vaccination or surgery are attributed to GBS, tuberculosis (TB) as a cause of GBS is rare with limited evidence suggesting an association. It is particularly important to diagnose and manage such cases early in an endemic country like India carrying a substantial global burden of TB. We are reporting a rare case of a hypertensive and diabetic 50-year-old male with concomitant pulmonary TB and GBS.
The patient presented with acute-onset weakness that developed in all four limbs ten days prior to his presentation. The weakness had begun abruptly and progressed symmetrically from the lower limbs to the upper limbs over a period of four days. Subsequently, he developed difficulty in speech and swallowing along with nasal regurgitation of food over a period of two days. The patient also complained of a low-grade intermittent fever and productive cough three weeks prior to presentation with an eventual weight loss of 10 kg. All these symptoms persisted at the onset of weakness. His background history revealed that he was hypertensive and diabetic, taking anti-hypertensive and oral anti-diabetic medicines regularly for the last 8 years. He sought symptomatic treatment from a local physician regarding these complaints until the occurrence of weakness. There was no sensory, bowel, or bladder involvement. He had no history of head injury, blurring of vision, diplopia, ptosis, vasculitis, antecedent diarrhoea, insect or animal bite, drug or heavy metal intoxication, upper respiratory tract symptoms, or a history of recent vaccination for influenza or meningococcus. On neurological examination, he had a Glasgow Coma Scale (GCS) score 15/15, quadriparesis with a grade of 1/5 according to the Medical Research Council (MRC) scale for muscle strength in the lower limbs (LLs') and 3/5 in the upper limbs (ULs'). Bulbar palsy was also evident on examination with nasal intonation, drooling of saliva, palatal palsy, and deviation of tongue. Gag reflex was absent. The deep tendon reflexes (DTRs) were diminished in bilateral (B/L) ULs' and absent in B/L LLs'. The patient also had a B/L flexor plantar response. There was no evidence of facial nerve involvement or autonomic dysfunction. On general examination, the patient had an arterial blood pressure of 100/70 mmHg, a heart rate of 120 beats/min, respiratory rate of 30 breaths/min and oxygen saturation of 88% on room air. The arterial blood gas on room air showed a PaO2 of 54 mmHg, PaCO2 of 27 mmHg, HCO3 of 20.2 mmol, pH of 7.49 and wide alveolar-arterial gradient (36 mm Hg) suggestive of acute hypoxemic respiratory failure. The rest of the general physical and systemic examination including laboratory tests was unremarkable. The erythrocyte sedimentation rate (ESR) was elevated (65 mm in the 1st h). Results of a nerve conduction velocity (NCV) study suggested axonal sensorimotor neuropathy in all four limbs. Analysis of cerebrospinal fluid (CSF) revealed elevated protein levels (140 mg/dl) with a normal glucose level and normal cell counts. Microbiological examination findings of CSF were unremarkable. Magnetic resonance imaging (MRI) of the brain and spine was normal with no evidence of meningeal enhancement or space occupying lesions. A chest radiograph revealed B/L infiltrates involving all zones of lungs with cavitation in B/L upper zones. Computed tomography (CT) of the chest revealed multiple mediastinal lymphadenopathy, fibrocavitation in B/L upper lobes and consolidation involving B/L lower lobes likely aspiration, as shown in [Figure 1]a-d. CT abdomen was normal. Overall, the diagnosis of GBS was established based on neurological findings. He was intubated and placed on mechanical ventilation in view of airway protection and acute respiratory failure. Exhaustive tests were advised to determine the triggers of GBS and etiology of the accompanying symptoms like fever and weight loss. A routine stool examination was normal. Blood and urine cultures were sterile. Serology was negative for HIV, hepatitis B and C, scrub typhus, malaria, scrub typhus, leptospira, and viruses like chikungunya, cytomegalovirus (CMV), Zika virus, and Epstein–Barr virus (EBV). Serum as well as CSF was screened negative for complete XCyton panel. Throat swab was negative for any pathogen including swine flu. Complete vasculitis profile including serum angiotensin-converting enzyme (ACE) levels and the antinuclear antibody (ANA) test were unremarkable. Urine as well as serum was negative for toxins and porphyrin levels. Both creatine phosphokinase (CPK) and CPK-MB levels were not raised. Serum protein electrophoresis was normal. A 2D echocardiogram revealed normal heart chambers with preserved ejection fraction and no vegetations. Endotracheal aspirate (ETA) as well as bronchioalveolar lavage (BAL) specimen was positive for acid fast bacilli (AFB) (grade3+) on Ziehl Neelsen (ZN) staining. However, ETA for gram stain was negative and pyogenic culture was also sterile. GeneXpert and culture of the ETA samples revealed rifampicin sensitive Mycobacterium tuberculosis complex (MTBC). In light of the clinical features, mediastinal lymphadenopathy, fibrocavitation as well as consolidation on CT chest and bacteriological profile positive for AFB, the patient was diagnosed with pulmonary TB. The patient was treated with intravenous immunoglobulins (IV Ig) on the second day of admission at a dose of 0.4 g/kg/day for five days along with anti-tubercular (ATT) drugs, chest physiotherapy, steroids, and empirical antibiotics. However, the patient showed no response to treatment as there was no improvement in muscle strength. He also continued to be febrile and developed hemodynamic instability including vasopressor support and multi-organ dysfunction subsequently during the course of treatment. The patient finally succumbed to death on twelfth day of admission despite all aggressive measures taken to maintain vitals.
|Figures 1: (a-d) Computed tomography (CT) of the chest revealed fibrocavitation in bilateral upper lobes and consolidation involving bilateral lower lobes|
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GBS is an immune-mediated neuropathy characterized by areflexic ascending paralysis with or without sensory or cranial nerve involvement was first described in 1916. With the near elimination of polio worldwide, GBS has emerged as the most common cause of acute flaccid paralysis worldwide. It is potentially life threatening with a mortality rate of 5% and 20–30% develop respiratory failure requiring mechanical ventilation and further 20% develop potentially fatal autonomic dysfunction during course of illness. Two thirds of GBS cases are preceded by infection and is associated with bacterial infections like Campylobacter jejuni, Mycoplasma pneumonia, and viruses like dengue, chikungunya, CMV, Epstein–Barr virus, Zika, and human immunodeficiency virus (HIV). GBS may also be triggered by administration of vaccine or surgery. A history of symptoms suggestive of upper respiratory infection or diarrhea three days to 6 weeks prior to onset of GBS is observed but not universal as 30% cases have not reported such symptoms. The majority of patients present with numbness, paresthesia, weakness, pain in the limbs, or combination of these symptoms as the initial symptoms followed by progressive B/L and relatively symmetric weakness of the limbs characterized by generalized hyporeflexia or areflexia. The diagnosis of GBS involves exclusion of other possible etiologies (leptomeningeal malignancy, lymphoma, CMV radiculitis, transverse myelitis, HIV polyneuropathy, poliomyelitis, electrolyte disturbances, Vitamins B1 and B12 deficiency, diphtheria, porphyria, and myasthenia gravis) with demonstration of limb weakness and absent or decreased DTRS in the affected limbs as mandatory criteria and temporal association of symptoms, findings from lumbar puncture and neurophysiology testing as supporting criteria. Among variants of GBS, acute motor sensory axonal neuropathy (AMSAN) is associated with severe or longer lasting nerve injury of both sensory and motor axons and are associated with poor prognosis as compared to more frequent variants such as acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). In the present case, the patient had definite evidence of GBS with a temporal association of low grade intermittent fever 3 weeks prior accompanied by characteristic ascending quadriparesis with areflexia, lumbar puncture suggestive of albumino-cytological dissociation, and NCV revealing axonal sensorimotor neuropathy. Though TB can present with myriad of neurological manifestations like meningitis, arachinoditis, radiculomyelitis, tuberculoma, and hydrocephalus, the association of GBS with tuberculosis is rare and to the best of our knowledge only few cases are reported in the literature. Two studies reported 8/1,100 (7.3%) and 2/104 (1.9%) GBS cases with TB as preceding infection., A brief review of prior case reports including clinical profile, management, and outcome characteristics are mentioned in [Table 1], [Table 2], [Table 3], [Table 4].,,,,,,,,,,,,,,, The impact of infectious agents endemic to Indian subcontinent in causation of GBS remains uncertain as majority of the data are from western population and only few have been reported from India.,,,, There is significant heterogeneity among all cases reported regarding these characteristics. The factors responsible for heterogeneity were co-morbid illnesses or associated diseases and variation in demographic profile, clinical presentations, type of GBS variant recognized, mode of establishment of diagnosis as well as treatment modality used. The earlier studies reporting association of TB with GBS were lacking bacteriological as well as electrophysiological evidence and also use of treatment modalities such as IV Ig and/or plasmapheresis. Recent reports have used bacteriological examination and/or GeneXpert of BAL or tracheobronchial aspirate by performing bronchoscopy in those patients who had difficulty in producing sputum due to poor cough reflex, associated bulbar involvement or intubated in view of impending respiratory distress. The occurrence of GBS has been reported not only with pulmonary TB but also with extra-pulmonary TB based on bacteriological and histopathology examination of samples from involved sites such as lymph node, intestine, pleura, and pericardium. Neuropathies coexisting with TB infections is less common. The factors responsible for such association are malnutrition, alcoholism, comorbid illness such as diabetes and the neuropathic effects of ATT especially isoniazid as reported in previous studies. The patient had microbiological and radiological evidences of active pulmonary TB. As no other possible etiology could be identified and temporal causation was evident, TB as a causation of GBS was confirmed in this case. Various postulated hypotheses of M. tuberculosis causing GBS include delayed cell mediated immunity, molecular mimicry leading to nerve damage or a direct invasion of nerve root by tubercular bacilli.,, However, extensive research is required to explore complex immunopathogenetic mechanisms for the basis of this association and need to establish any genetic marker or antibodies for framing diagnosis. Both IV Ig and plasmapheresis have proved to be effective in management of GBS.,, However for a patient with concomitant active TB and GBS, there are no randomized controlled studies to guide effective treatment strategies. With limited knowledge from prior case reports,,,,,,,,,,,,,,,, the decision to treat the patient with combined first line ATT and IV Ig was made. Though favorable recovery has been reported in prior case reports, our patient could not survive probably due to extensive involvement of lung parenchyma by active TB associated with evidence of acute respiratory failure on ABG analysis, presence of comorbid illnesses, rare AMSAN variant of GBS with bulbar involvement leading to aspiration pneumonia (bilateral basal consolidation on CT thorax) carrying poor prognosis, bedridden requiring invasive mechanical ventilation, and delay in presentation of ten days with possibility of progressive deterioration prior to initiation of IV Ig. IV Ig was used in this case as it was readily available and also easy to administer. Plasmapheresis could have been other option but it requires special equipment and not easily available at all centers. It is also to be used cautiously in GBS patients with autonomic dysfunction with cardiovascular instability as large volume shifts are required. It is also difficult to ascertain whether the occurrence of multi-organ dysfunction is due to progression of primary disease or adverse events as well as paradoxical response to ATT or IV Ig. Although plasmapheresis and IV Ig both proven to have pleiotropic immunomodulatory effects, it is yet to ascertain that effects explain their therapeutic efficacy in GBS, and whether the same effects are involved in all patients and all subtypes of GBS. Most clinical trials for IV Ig were conducted in Western Europe or North America and reported favorable response in AIDP that was the most common subtype in that population. The results of these trials might not be generalized to other parts of the world, especially where AMAN and AMSAN are prevalent. It remains questionable whether patients with AMAN or AMSAN subtype should receive the same treatment as those with AIDP as controlled trials are still lacking. A study reported that patients with AMAN might have better outcomes after treatment with plasma exchange than after IV Ig therapy. Few other issues raise concern for physicians. All previous cases including current one have reported association of GBS with active TB that might represent tip of an iceberg. India carries one-fifth global burden of active TB with prevalence of approximately 40% (range 5–80%) latent or asymptomatic TB cases that pose a great hurdle for disease control. Active screening should be undertaken to reveal more and more cases with such association and also managed effectively in order to interrupt further TB transmission. The course of the illness in the current case seems to be unusual for acute or fulminant TB infection as he was symptomatic 3 weeks prior to onset of weakness. The association of GBS could not only be limited to acute, fulminant, or disseminated form of TB but also to chronic form. The clinician can misdiagnose such cases as pyogenic bacterial or viral pneumonia and possibility of further delay in definitive treatment could be expected leading to disease progression, complications, and mortality. The treatment modalities seems to be effective if the patient is reporting early during the course of illness and type of GBS variant identified. One should also keep the paradoxical response to ATT in mind that has been observed in previous case reports. More cases have been reported in literature citing association of TB with GBS but whether this is a chance or causal association require further evaluation by conducting prospective studies and randomized controlled trials in near future. However, health workers from high burden countries of TB including India should keep such an association in mind in order to manage these cases effectively.
|Table 1: Characteristics of cases reporting coexistence of tuberculosis and Guillain–Barré syndrome|
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|Table 2: Clinical and diagnostic characteristics of Guillain–Barré syndrome component among cases reporting coexistence of tuberculosis and Guillain–Barré syndrome|
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|Table 3: Clinical and diagnostic characteristics of tuberculosis component among cases reporting coexistence of tuberculosis and Guillain–Barré syndrome|
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|Table 4: Treatment and outcome of cases reporting coexistence of tuberculosis and Guillain–Barré syndrome|
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Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
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| » References|| |
Guillain G, Barré, JA, Strohl, A. Sur un syndrome de radiculonévrite avec hyper-albuminose du liquide céphalo-tachidien sans réaction cellulaire. Remarques sur les caractères cliniques et graphiques des réflexes tendineux. Bul Mém Soc Med Hôp Paris 1916;40:1462-70.
Willison HJ, Jacobs BC, van Doorn PA. Guillain-Barré syndrome. Lancet 2016;388:717-27.
Yuki N, Hartung HP. Guillain-Barré syndrome. N
Engl J Med 2012;366:2294-304.
Mateen FJ, Cornblath DR, Jafari H, Shinohara RT, Khandit D, Ahuja B, et al
. Guillain-Barré Syndrome in India: Population based validation of the Brighton Criteria. Vaccine 2011;29:9697-701.
Dimachkie MM, Barohn RJ. Guillain-Barré syndrome and variants. Neurol Clin 2013;31:491-510.
Sharma SK, Mohan A. Extra-pulmonary tuberculosis. Indian J Med Res 2004;120:316-53.
Leneman F. The Guillain-Barré syndrome. Definition, etiology, and review of 1,100 cases. Arch Intern Med 1966;118:139-44.
Soysal A, Aysal F, Caliskan B, DoganAk P, Mutluay B, Sakalli N, et al
. Clinico-electrophysiological findings and prognosis of Guillain-Barré syndrome-10 years' experience. Acta Neurol Scand 2011;123:181-6.
Vyravanathan S, Senanayake N. Guillain-Barré syndrome associated with tuberculosis. Postgrad Med J 1983;59:516-7.
Ramarao T, Bhaskar Y, Vijaya Bhaskar M. Guillain–Barré syndrome in pulmonary tuberculosis. Ind J Tub 1983;30:118-20.
Soehard YZ, Yuhanissa A, Thein SS, Rohana AG, Fauzi AR, Norlinah MI. AMSAN variant of Guillain-Barré syndrome progressing to Chronic Inflammatory Demyelinating Polyneuropathy in a patient with Marfan's syndrome and pulmonary tuberculosis. Med J Malaysia 2005;60:655-6.
Chong VH, Joseph TP, Telisinghe PU, Jalihal A. Chronic Inflammatory demyelinating polyneuropathy associated with intestinal tuberculosis. J Microbiol Immunol Infect 2007;40:377-80.
Fernández-Fúnez A, Gómez Garrido J, Alamillo A, Sáez L. Demyelinating polyneuropathy as the honest form of lymph node tuberculosis. Paradox response in an immunocompetent patient. Med Clin 2007;129:78-9.
de la Torre RG, Moris G, Martinez DP, Montes IC. Guillain-Barré syndrome, tuberculosis and inflammatory bowel disease: A multiple association. Int Arch Med 2010;3:15.
Kotti A, Daghfous H, Bouhawel W, Kahloul O, Slim L, Tritar F. Pulmonary tuberculosis with polyneuro-radiculopathy: Not forget Guillain Barré syndrome! Eur Respir J 2011;38:2586.
Taha AAM, Tee KHA. Guillain-Barré syndrome associated with pulmonary tuberculosis. BMJ Case Rep 2012; doi: 10.1136/bcr-01-2012-5484.
Suleiman N, Eledrisi M. Guillain-Barré Syndrome associated with pulmonary tuberculosis. J Med Cases 2013;4:696-8.
Canham EM, Iseman MD. Guillain-Barré syndrome related to pulmonary tuberculosis. Ann Am Thorac Soc 2014;11:855-7.
Chandra S, Momi H. Guillain-Barré syndrome with pulmonary tuberculosis in a child. J Pediatr Neurol 2014;12:91-3.
Rekha MC, Prakash GM. Guillain-Barré syndrome due to pulmonary tuberculosis. Indian. J Fundamental Appl Life Sci 2014;4:408-10.
Vergnon-Miszczycha D, Suy F, Robert F, Carricajo A, Fresard A, Cazorla C, et al
. Guillain-Barré syndrome associated with Mycobacterium bovis lymphadenitis. Infection 2015;43:603-8.
Kebede D, Ahmed M, Haile T, Bekele A, Mengistu G. Guillain-Barré syndrome associated with pulmonary tuberculosis: A case report. Ethiop Med J 2016;55:139-41.
Lakhotia AN, Chouksey D, Jain R, Sodani AK. Guillain–Barré Syndrome following Tuberculosis: A Rare Association. J Neurosci Rural Pract 2017;8:296-9.
] [Full text]
Mohta S, Soneja M, Vyas S, Khot W. Tuberculosis and Guillain-Barré syndrome: A chance association? Intractable Rare Dis Res 2017;6:55-7.
Peiris JB, Wickremasinghe HR, Chandrasekara MA. Letter: Tuberculous polyradiculitis. Br Med J 1974;4:107.
Hughes RA, Swan AV, Raphaël JC, Annane D, van Koningsveld R, van Doorn PA. Immunotherapy for Guillain– Barré syndrome: A systematic review. Brain 2007;130:2245-57.
Hughes RA, Swan AV, van Doorn PA. Intravenous immunoglobulin for Guillain–Barré syndrome. Cochrane Database Syst Rev 2014;9:CD002063.
Raphaël JC, Chevret S, Hughes RA, Annane D. Plasma exchange for Guillain–Barré syndrome. Cochrane Database Syst Rev 2012;7:CD001798.
van den Berg B, Walgaard C, Drenthen J, Fokke C, Jacobs BC, van Doorn PA. Guillain-Barré syndrome: Pathogenesis, diagnosis, treatment and prognosis. Nat Rev Neurol 2014;10:469-82.
Dada MA, Kaplan AA. Plasmapheresis treatment in Guillain–Barré syndrome: potential benefit over IV Ig in patients with axonal involvement. Ther Apher Dial 2004;8:409-12.
Gupta KB. Challenges in diagnosis and treatment of latent tuberculosis infection. Indian J Tuberc 2012;59:1-5.
[Table 1], [Table 2], [Table 3], [Table 4]