Sex: M
Vaccine: FLUX
Symptoms: Bradycardia, Computerised tomogram abdomen abnormal, Computerised tomogram pelvis abnormal, Cytology normal, Death
Clinical narrative: Guillain-Barre syndrome, acute inflammatory demyelinating polyneuropathy (AIDP); weakness of the lower and upper limbs; bilateral finger and toe paresthesia; dysautonomia; paraneoplastic neuropathy; respiratory distress; expired as the family withdrew life-sustaining therapies; dehydration; metastatic melanoma; tachycardia; hypotension; bradycardic; Sepsis; lost the ability to walk; Initial unsolicited valid serious case report received from a literature article on 16-Aug-2019.   The following is verbatim from the article: Cancer immunotherapy with checkpoint inhibitors may result in neuromuscular immune-related adverse reactions, including Guillain-Barre syndrome (GBS)-like disease. On the other hand, checkpoint inhibitor therapy may result in exacerbation of underlying autoimmune diseases such as myasthenia gravis and multiple sclerosis. We present a patient who developed a severe and fatal relapse of postvaccination GBS after he was treated with nivolumab, a monoclonal antibody directed to programmed death-1 (PD-1), during a GBS treatment-related fluctuation. We recommend that caution be exercised in starting treatment with PD-1 inhibitors in the acute stage or early in the recovery period of GBS. Key Words: Guillain-Barre syndrome, checkpoint inhibitor, dysautonomia, nivolumab, PD-1.  This case involves a 66 years old male patient who experienced weakness of the lower and upper limbs, bilateral finger and toe paresthesia, dehydration, metastatic melanoma, guillain-barre syndrome, respiratory distress, tachycardia, hypotension, acute inflammatory demyelinating polyneuropathy (aidp), guillain barre syndrome, bradycardic, sepsis, paraneoplastic neuropathy and dysautonomia, while he received vaccine INFLUENZA VACCINE.  The patient's past medical history included Cancer surgery with three years ago. The patient's past medical treatment(s), vaccination(s) and family history were not provided.   On an unknown date, the patient received a dose of suspect INFLUENZA VACCINE produced by unknown manufacturer lot number not reported via unknown route in unknown administration site.  On an unknown date, the patient experienced a serious weakness of the lower and upper limbs (muscular weakness), bilateral finger and toe paresthesia (paraesthesia), dehydration, metastatic melanoma (metastatic malignant melanoma), Guillain-Barre Syndrome, acute inflammatory demyelinating polyneuropathy, respiratory distress on day 2 of hospitalization, tachycardia, hypotension, (aidp), guillain barre syndrome (demyelinating polyneuropathy), bradycardic (bradycardia), sepsis, paraneoplastic neuropathy,  (polyneuropathy in malignant disease), lost the ability to walk  and dysautonomia (autonomic nervous system imbalance) (Unknown latency) following the administration of INFLUENZA VACCINE. These events was leading to death. Patient was also hospitalized for these events.  Relevant laboratory test results included: Lymphocyte count - On an unknown date: 44 % Monocyte count - On an unknown date: 56 % Protein total - On an unknown date: 37 mg/dL, on an unknown date: 91 mg/dL. Red blood cell count - On an unknown date: [21], on an unknown date: [0]. White blood cell count - On an unknown date: [7], on an unknown date: [0].  (Other relevant tests included 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 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. Brain MRI showed a 4 3 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. 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.  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 score4 during the course of his disease starting with administration of influenza vaccine  The patient was treated with 2 g/kg IMMUNOGLOBULINS NOS (IMMUNOGLOBULIN I.V) over a period of 5 days for Guillain-Barre syndrome, 60 mg/kg PREDNISONE (PREDNISONE) for 2 daysand 240 mg NIVOLUMAB (NIVOLUMAB) which was repeated after 13 days.  Final diagnosis was (fatal) dysautonomia, (fatal) paraneoplastic neuropathy, (fatal) sepsis, (fatal) bradycardic, (fatal) acute inflammatory demyelinating polyneuropathy (aidp), guillain barre syndrome, (fatal) Severe hypotension, (fatal) tachycardia, (fatal) respiratory distress, (fatal) guillain-barre syndrome, (fatal) metastatic melanoma, (fatal) dehydration, (fatal) bilateral finger and toe paresthesia and (fatal) weakness of the lower and upper limbs.  The patient outcome was reported as fatal for all the event.  The cause of death was reported conservatively captured as Muscular weakness, Paraesthesia, Demyelinating polyneuropathy, Polyneuropathy in malignant disease, Respiratory distress, Hypotension, Autonomic nervous system imbalance, Sepsis, Tachycardia, Dehydration, Metastatic malignant melanoma, Guillain-Barre syndrome and Metastatic malignant melanoma as it was unknown if an autopsy was done.  List of document held by sender: none.; Sender's Comments: This literature case concerns a 66 years old male patient died due to exacerbation of post influenza vaccination GBS after treatment with Nivolumab for metastatic melanoma. The time to onset is unknown. Moreover, patient's medical condition and lab test at the time of vaccination were not reported. Based upon the reported information, the role of vaccine cannot be assessed.; Reported Cause(s) of Death: weakness of the lower and upper limbs; bilateral finger and toe paresthesia; acute inflammatory demyelinating polyneuropathy (AIDP), Guillain Barre syndrome; paraneoplastic neuropathy; respiratory distress; hypotension; dysautonomia; Sepsis; tachycar