Sex: M
Vaccine: FLUX, UNK
Symptoms: Hypotension, Immunoglobulin therapy, Mechanical ventilation, Muscular weakness, Nerve conduction studies abnormal
Clinical narrative: weakness of the lower and then upper; lost the ability to walk; Tendon reflex absent; respiratory distress; tachycardia; severely hypotension; possible sepsis; dehydration; Guillain-Barre syndrome/relapse of postvaccination GBS; dysautonomia; acute inflammatory demyelinating polyneuropathy; severely bradycardic; bilateral finger and toe paresthesia; This case was reported in a literature article and described the occurrence of guillain barre syndrome in a 66-year-old male patient who received Flu unspecified (Flu vaccine) for prophylaxis.   Co-suspect products included nivolumab for metastatic melanoma.   Concurrent medical conditions included melanoma limited to extremity (right thigh melanoma resection 3 years before), metastatic melanoma (BRAF-V600 wildtype) and brain metastases.   On an unknown date, the patient received Flu vaccine at an unknown dose and nivolumab 240 mg at an unknown frequency. On an unknown date, 21 days after receiving Flu vaccine, the patient experienced guillain barre syndrome (serious criteria death, hospitalization and GSK medically significant), dysautonomia (serious criteria death and hospitalization), demyelinating polyneuropathy (serious criteria hospitalization and GSK medically significant), weakness of limbs (serious criteria hospitalization), unable to walk (serious criteria hospitalization), tendon reflex absent (serious criteria hospitalization), respiratory distress (serious criteria hospitalization and GSK medically significant), tachycardia (serious criteria hospitalization), hypotension (serious criteria hospitalization), bradycardia (serious criteria hospitalization and GSK medically significant), sepsis (serious criteria hospitalization and GSK medically significant), dehydration (serious criteria hospitalization) and paresthesia. The patient was treated with immunoglobulins nos (Immunoglobulin), prednisone, operations and procedures (Plasma Exchange) and mesalazine (Midodrine (Mesalazine)). The action taken with nivolumab was unknown (Dechallenge was unknown). On an unknown date, the outcome of the guillain barre syndrome and dysautonomia were fatal and the outcome of the demyelinating polyneuropathy, weakness of limbs, unable to walk, tendon reflex absent, respiratory distress, tachycardia, hypotension, bradycardia, sepsis, dehydration and paresthesia were unknown. The reported cause of death was guillain barre syndrome and dysautonomia.   The reporter considered the guillain barre syndrome, dysautonomia, demyelinating polyneuropathy, weakness of limbs, unable to walk, tendon reflex absent, respiratory distress, tachycardia, hypotension, bradycardia, sepsis, dehydration and paresthesia to be related to Flu vaccine.  Additional information was provided.  This case was reported in a literature article and described the occurrence of Guillain-Barre Syndrome in a 66-year-old male who was vaccinated with unspecified flu vaccine (manufacturer unknown) for prophylaxis.  He had a history of right thigh melanoma resection 3 years before. No information on patient's family history or concomitant medication was provided.  On an unspecified date, the patient received unspecified flu vaccine (administration route and site unspecified, dosage unknown; batch number not provided). The age of vaccination was not provided. The patient could be 65 or 66 years of age. The co-suspect product included Nivolumab.  On an unspecified date, about 3 weeks after receiving a flu vaccination, the patient developed bilateral finger and toe paresthesia 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. The results of nerve conduction study for the right median motor nerve were motor distal latency (MDL) was 8.2 milliseconds (ms) (normal value 4.1 ms), Distal amplitude was 1.0 millivolts (mV) (normal value 5.0), Proximal amplitude was 1.0 mV, conduction velocity in meter per second (CV (m/s)) was 44.5 (48.0), F Wave latency was found to be 40.5 mV (30.0). The results of nerve conduction study for the reft tibial motor nerve were MDL was found to be 5.8 ms (6.0), distal amplitude was 0.5 mV (5.0), Proximal amplitude was 0.07 mV, CV was 25.4 m/s (38.0). The results of nerve conduction study for the right tibial motor nerve were MDL was found 6.5 ms (6.0), distal amplitude was 0.15 mV (5.0), Proximal amplitude was 0.1 mV, CV was 23.5 m/s (38.0). The results of nerve conduction study for the right radial sensory nerve were distal amplitude was found to be 18.2 mV (15.0), CV was 57.5 m/s (50). The distal amplitude for the bilateral median sensory nerve was found to be 0 mV (15). The distal amplitude for the bilateral sural sensory nerve was found to be 0 mV (5). 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. He was diagnosed with postvaccination GBS, and intravenous immunoglobulin (IVIg) 2 g/ kg was then administered over a period of 5 days. Brain 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, biopsy of which demonstrated metastatic melanoma, BRAF-V600 wildtype. 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 IVIg 1 g/kg divided over a period of 2 days and was started on prednisone 60 mg/day and received nivolumab 240 mg, 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 hospital. 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 was conduction blocks in the right ulnar motor response with stimulation below and above the elbow. On day 91 after vaccination nerve conduction study was performed, The results of nerve conduction study for the right median motor nerve were MDL was 20.52 ms (4.1), distal amplitude was 1.0 mV (5.0), Proximal amplitude was 0.9 mV, CV was 26.5 m/s (48.0), F Wave Lat. was 66.0 mV (30.0). The results of nerve conduction study for the right ulnar motor nerve were MDL was 6.51 ms (3.8), distal amplitude was 1.0 mV (5.0), proximal amplitude was 0.6 mV (B.elbow) and 0.3 mV (A.elbow), CV was 27.2 m/s (48.0) and 21.6 m/s (48.0), F Wave Lat. (mV) was not reported (31.0). The results of nerve conduction study for the left tibial motor nerve were MDL was 18.28 ms (6.0), Distal amplitude was 0.3 mV (5.0), proximal amplitude was 0.1 mV, CV was found to be 16.1 m/s (38.0). The results of nerve conduction study for the right peroneal motor nerve were MDL was 22.5 ms (6.0), distal amplitude was 0.1 mV (3.0), proximal amplitude was 0.0 mV. The distal amplitude for the right radial sensory nerve, Bilateral median sensory nerve and Bilateral sural sensory nerve was respectively found to be 0 mV (15), 0 mV (15) and 0 mV (5). 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. He was started on midodrine on day 5 of hospitalization, but on day 9 became severely hypotensive and bradycardic, requiring pressure support, and subsequently expired as the family withdrew life-sustaining therapies. His GBS disability score during the course of his disease starting with administration of influenza vaccine was 2 (between day 20 and 30); 2-4 (between day 30 and 40), 3-4 (between day 40 and 60), 3-4 (between day 60 and 90), 5-6 (between day 90 and 100). Dysautonomia contributed to fatal outcome in the patient. It was unknown if autopsy was performed.  The case is considered serious due to death and hospitalization. The author considered the event of Guillain-Barre Syndrome related to unspecified flu vaccine. The author stated The subacute course of the neuropathy in our patient and the timing of vaccination were consistent with a postinfluenza virus vaccination GBS'.  The authors concluded, Our patient is the first report of severe GBS relapse after treatment with nivolumab, which was administered during a treatment-related fluctuation. We conclude that administration of checkpoint inhibitor. treatment during the acute stage of GBS may result in a severe, potentially fatal exacerbation and recommend exercising caution in starting administration of such treatments in patients who are in the acute stage or early in the recovery phase of GBS. Further studies for targeted therapies to treat life threatening AEs are warranted".      Lab Comments: Lab tests were performed on unspecified dates 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 response; 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. 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 our center. 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. 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 was 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.; Reported Cause(s) of Death: Guillain Barre syndrome; dysautonomia