Introduction
Guillain-Barré syndrome (GBS) is an acute inflammatory demyelinating polyradiculoneuropathy usually associated with a preceding infection or, less frequently, vaccination, surgery, trauma, bone marrow transplantation, or neoplasm. GBS is an important cause of acute neuromuscular paralysis, potentially life threatening.1,2 Initial diagnosis is based on clinical findings and confirmed by cerebrospinal fluid (CSF) examination and clinical neurophysiology studies.2 A review of the literature recovers many case reports of GBS described in the context of malignancies, although the presence of a definite association is unproven.3Paraneoplastic neurological syndromes (PNS) occur in less than 1% of patients with malignancy and, in most cases, present months or years before the cancer diagnosis.3,4 Thus, as in this case, what leads patients to seek medical attention are the neurological symptoms.5
Hodgkin’s lymphoma is the most common malignancy associated with GBS.1,4We describe an unusual case of GBS as a possible initial manifestation of esophageal carcinoma.
Case Report
A 49-year-old man with hypertension, dyslipidemia, and smoking habits was admitted to the emergency department for presenting acroparesthesia and paraparesis with one week of evolution and progressive worsening.
On admission, he was slimmed and with fever. Neurologic examination disclosed a grade 4 paraparesis (Medical Research Council scale) with a predominance of deficit in knee flexion and finger extension, hypoesthesia in a stocking-glovepattern, kinesthesia, pallesthesia, proprioceptive errors, abolished deep-tendon reflexes in the lower limbs and ataxic gait. Muscle strength in the upper limbs was preserved and cutaneous plantar reflex was indifferent bilaterally. No meningeal signs, diarrhea, odynophagia, oropharyngeal lesions, or any other signs or symptoms of infection.
The results of CT of the brain were normal. The examination of the CSF revealed albuminocytological dissociation.
Treatment with intravenous immunoglobulin has been started in a regimen of 0.4 g/kg daily for five days, which resulted in improvement of the motor component but without improvement of sensory disturbances.
Electromyography performed on the fourteenth day after the onset of symptoms revealed sensorimotor polyneuropathy of sensory predominance, of primarily axonal character, with relatively symmetrical and distance-dependent attainment pattern, of moderate severity and subacute installation.
The clinical diagnosis of GBS in its acute motor and sensory axonal neuropathy (AMSAN) form was made. Physical therapy was initiated early during hospitalization with gradual improvement of the motor component of neuropathy.
A comprehensive etiological study was conducted. On blood testing, inflammatory markers were increased, with a total white cell count of 22.9x109/L and C reactive protein 251.7mg/L. Serologies for human immunodeficiency virus, hepatitis B and C viruses, cytomegalovirus, Epstein-Barr virus, syphilis, Mycoplasma pneumoniae, Borrelia and Campylobacter jejuni were negative. Blood and CSF cultures were negative. Onconeuronal antibodies were negative and IgM autoantibodies against ganglioside GM3 were borderline (with non-reactive IgG). The presence of spinal cord injuries was excluded by MRI of the dorsal and lumbar spine. An upper gastrointestinal endoscopy was performed: no white mucosal plaque-like lesions were noted but an exophytic and ulcerated neoplastic lesion was found in the upper esophagus. The histological examination was consistent with moderately differentiated invasive squamous cell carcinoma. The echoendoscopy performed for cancer staging showed an infiltrative lesion involving the entire esophageal wall. CT of the abdomen and pelvis revealed thickening and irregularity of the esophageal wall and locoregional lymph nodes with characteristics compatible with metastatic infiltration. The diagnosis of locally advanced esophageal cancer with suspicious paraesophageal adenopathies was made.
At the time of discharge, the patient did not present improvement of the sensory component of neuropathy but was capable of autonomous gait, although with a widened base of support and in need of supervision.
The treatment plan was established interdisciplinary, and the patient was proposed to neoadjuvant chemoradiotherapy (CRT) with cisplatin plus fluorouracil. Restaging after CRT revealed pulmonary metastases and, after chemotherapy with docetaxel, disease progression has been found. On neurologic examination, the patient kept lower limbs dysesthesia and areflexia. He was proposed for palliative treatment and died about 2 years after the initial diagnosis.
Discussion
The relationship between GBS and malignancy is uncertain and the existence of a paraneoplastic GBS remains unconfirmed.3,8 The pathophysiological mechanisms involved in this relationship remains to be elucidated, but it is conceivable that the tumor might predispose the development of GBS by disturbance of the immune system.5,8
Esophageal carcinoma has been rarely associated with PNS and, to the best of our knowledge, the association with GBS has been reported in only two cases.8,7 Our case documents a GBS that occurs as possible initial manifestation of esophageal carcinoma. The exclusion of etiological factors commonly triggering GBS and the diagnosis of both pathologies almost simultaneously suggests a possible pathogenic relationship between the two diseases, as well as a paraneoplastic nature of the GBS.7
Onconeural antibodies are found in patients with cancer and different types of PNS.5,9 However, not all patients with PNS have identifiable antibodies in their serum and CSF.5 In GBS-associated tumors, there is no specific serological profile7and that is why GBS has been considered as one of the non-classical PNS without onconeuronal antibodies.9,3
According to the recommended diagnostic criteria for PNS,9 the paraneoplastic etiology of the neurologic syndrome presented by our patient may be considered as possible. GBS diagnosis in a patient with known cancer is classified as definitely paraneoplastic if it resolves or significantly improves after cancer treatment without concomitant immunotherapy. Thus, in the light of current criteria, even if our patient had improved neuropathy after tumor treatment, it would not be possible to assume the paraneoplastic etiology as definitive, given that the patient was treated with immunotherapy.
Despite all the controversy, what we believe to be important to highlight is that in the presence of GBS of indeterminate etiology, an underlying neoplasm should always be considered in the differential diagnosis.7 In our case, it was this diagnostic suspicion that led to a search for cancer and, consequently, for its earlier diagnosis and treatment.
Conclusion
Recognition of GBS as possible PNS is important because, as in this case, it can lead to earlier detection of the tumor, and can help prevent unnecessary studies to determine the cause of the neurologic symptoms in patients with cancer.4
The investigation of an occult neoplasm should be part of the etiological investigation of neurological syndromes of undetermined etiology.
BIBLIOGRAFIA
1. Doorn PA, Ruts L, Jacobs BC. Clinical features, pathogenesis, and treatment of Guillain-Barré syndrome. Lancet Neurol. 2008;7(10):939-50.
2. Vatandoust S,Joshi R, Price TJ. Guillain-Barre syndrome in colorectal cancer. Asia-Pac J Clin Oncol. 2012; 8:205-08.
3. Hiew FL, Rajabally YA. Malignancy in Guillain-Barré syndrome: A twelve-year single-center study. J Neurol Sci. 2017; 375:275-8.
4. Rudnicki SA, Dalmau J. Paraneoplastic syndromes of the spinal cord, nerve, and muscle. Muscle Nerve. 2000;23(12):1800-18.
5. Darnell RB, Posner JB. Paraneoplastic syndromes involving the nervous system. N Engl J Med. 2003; 349:1543-54.
6. Avila-Funes JA, Mariona-Montero VA, Melano-Carranza E. Síndrome de Guillain-Barré: etiología y patogénesis [Guillain-Barre syndrome: etiology and pathogenesis]. Rev Invest Clin. 2002;54(4):357-63.
7. Zilli T, Allal AS. Guillain-Barré syndrome as an atypical manifestation of an esophageal carcinoma. Neurol Sci. 2011;32(1):151-3.
8. Vigliani MC, Magistrello M, Polo P, Mutani R, Chiò A; Piemonte and Valle dAosta Register for Guillain-Barré Syndrome. Risk of cancer in patients with Guillain-Barré syndrome (GBS). A population-based study. J Neurol. 2004; 251(3):321-6.
9. Graus F, Delattre JY, Antoine JC, Dalmau J, Giometto B, Grisold W, Honnorat J, Smitt PS, Vedeler Ch, Verschuuren JJ, Vincent A, Voltz R. Recommended diagnostic criteria for paraneoplastic neurological syndromes. J Neurol Neurosurg Psychiatry. 2004; 75(8):1135-40.
