Age: 66.0
Sex: M
Vaccine: UNK
Symptoms: CSF red blood cell count positive, CSF white blood cell count increased, Computerised tomogram abdomen abnormal, Computerised tomogram pelvis abnormal, Cytology normal
Clinical narrative: Postvaccination Guillain-Barre syndrome; This is a literature case, initially received on 20-Aug-2019, concerning a 66-year-old, male patient.  The patient had a history of a right thigh melanoma resection 3 years before. The patient's current medical history included metastatic melanoma.   On an unknown date, the patient was administered Flu Vaccine [influenza vaccine, route of administration, anatomical location, batch number, expiry date and dose: not reported] for unknown indication.   On an unreported date, about 3 weeks after receiving a flu vaccination, the patient developed bilateral finger and toe paraesthesia followed by weakness of the lower and then upper limbs. Examination 12 days after the onset of initial symptoms and a day after he lost the ability to walk revealed strength of 3/5 in upper-limb muscles, hip flexors, quadriceps, hamstrings, and 2/5 in the ankle dorsiflexors and plantar flexors, as assessed according to the Medical Research Council scale. Pinprick sensation was diminished up to the ankles and fingertips, vibration was lost at the toes, and deep tendon reflexes were absent at the knees and ankles. Cerebrospinal fluid (CSF) analysis showed white blood cell, 7 (56% monocytes, 44% lymphocytes); red blood cell, 21; protein, 37 mg/dL; and a negative cytology. A nerve conduction study 34 days after the flu vaccination demonstrated absent bilateral sural and right median sensory responses, prolonged distal and F wave latencies of the right median nerve, as well as very low amplitudes and very slow conduction velocities of all the motor responses; needle electromyography (EMG) showed neurogenic recruitment in all the muscles tested in bilateral lower and right upper limbs and positive waves/fibrillation potentials in the cervical and lumbar paraspinal muscles.   The patient was diagnosed with postvaccination Guillain-Barre syndrome, and intravenous immunoglobulin (IVIg) 2 g/kg was then administered over a period of 5 days. Brain magnetic resonance imaging (MRI) showed a 4 x 5-mm enhancing lesion with associated T2 hyperintensity and restricted diffusion in the right superior medial precentral gyrus, consistent with a brain metastasis. Computed tomography scan of the abdomen and pelvis showed multiple hepatic hypodense nodules. His weakness initially improved after IVIg treatment to the point that he was able to ambulate 100 feet with an assistive device.   However, his weakness worsened about 3 weeks later when he lost his ability to ambulate. At that time, the treating physicians considered the possibility of acute onset chronic inflammatory demyelinating neuropathy or paraneoplastic neuropathy. He then received IVIg1 g/kg divided over a period of 2 days and was started on prednisone 60 mg/day and received nivolumab 240mg, which was repeated after 13 days. His motor strength further declined dramatically about 12 days after the first dose of nivolumab, so that he was unable to sit in the wheelchair, resulting in his transfer to Medical Center, Department of Neurology. Physical examination revealed motor strength of 3/5 in upper extremities, 1/5 hip flexion and hip extension, and 0/5 in remaining lower extremity muscle groups. His deep tendon reflexes were trace in the upper extremities and absent at the knees and ankles, and there was diminished pinprick sensation in stocking/glove distribution and absent vibratory sensation at the toes. CSF analysis showed white blood cell, 0; red blood cell, 0; and protein, 91 mg/dL.   A follow-up EMG study 91 days after the flu vaccination showed severely prolonged distal latencies, reduced amplitudes, very slow conduction velocities, and markedly prolonged F wave latencies. Temporal dispersion of the compound muscle action potential was present with distal stimulation of all the motor nerves, and there were conduction blocks in the right ulnar motor response with stimulation below and above the elbow. Needle EMG showed positive waves and fibrillation potentials and no motor unit activation in the right tibialis anterior and quadriceps, as well as severely reduced recruitment in right first dorsal interosseous, biceps, and deltoid.   Antibodies to ANNA-1, Amphiphysin, ANNA-2, CRMP-5, PCA-1, PCA-2, PCA-Tr, GM1, and GD1b were negative. On day 2 of hospitalization, he developed respiratory distress, tachycardia, and hypotension. He was intubated and placed on mechanical ventilation, and then started on plasma exchange (PLEX). During the hospitalization, there were wide fluctuations in heart rate and blood pressure, which were partly attributed to dysautonomia secondary to acute inflammatory demyelinating polyneuropathy (AIDP) because they were persistent between the sessions of PLEX and present after other potential causes such as possible sepsis and dehydration were appropriately treated.   The patient was started on midodrine on day 5 of hospitalization, but on day 9 became severely hypotensive and bradycardic, requiring pressure support, and subsequently died as the family withdrew life-sustaining therapies.   The reporter stated that dysautonomia, which contributed to fatal outcome in our patient, was the initial manifestation of GBS. Although it is likely that checkpoint inhibitors treatment with nivolumab given during a recovery stage of AIDP resulted in disease exacerbation, the possibility of primary disease progression in our patient cannot be completely excluded.  Company comment: Patient developed Guillain-Barre syndrome approximately three weeks after administration of unspecified Flu vaccine, therefore the temporal relationship is plausible. Several Flu vaccines have been linked to Guillain-Barre syndrome. Co-suspect drug nivolumab may have contributed to exacerbation of this adverse event. Based on the available information the event of Guillain-Barre syndrome is assessed as related to the suspect product.; Reporter's Comments: Patient developed Guillain-Barre syndrome approximately three weeks after administration of unspecified Flu vaccine, therefore the temporal relationship is plausible. Several Flu vaccines have been linked to Guillain-Barre syndrome. Co-suspect drug nivolumab may have contributed to exacerbation of this adverse event. Based on the available information the event of Guillain-Barre syndrome is assessed as related to the suspect product.; Reported Cause(s) of Death: Postvaccination Guillain-Barre syndrome