Age: 59.0
Sex: F
Vaccine: COVID19, FLUX
Symptoms: Aphasia, Biopsy brain, Body temperature, CSF protein, CSF white blood cell count
Clinical narrative: Neuronal intranuclear inclusion disease; Acute-onset encephalopathy; Global aphasia; This literature-non-study case was reported in a literature article and describes the occurrence of NEURONAL INTRANUCLEAR INCLUSION DISEASE (Neuronal intranuclear inclusion disease), ENCEPHALOPATHY (Acute-onset encephalopathy) and APHASIA (Global aphasia) in a 59-year-old female patient who received SPIKEVAX NOS (SPIKEVAX NOS) for COVID-19 prophylaxis.   LITERATURE REFERENCE.   Co-suspect product included non-company product INFLUENZA VACCINE (INFLUENZA) for an unknown indication.    The patient's past medical history included Middle cerebral artery stroke, Focal epilepsy and Systemic sclerosis.   On an unknown date, the patient received first dose of SPIKEVAX NOS (SPIKEVAX NOS) (unknown route) 1 dosage form and dose of INFLUENZA VACCINE (INFLUENZA) (unknown route) 1 dosage form. On an unknown date, the patient experienced NEURONAL INTRANUCLEAR INCLUSION DISEASE (Neuronal intranuclear inclusion disease) (seriousness criteria hospitalization and medically significant), ENCEPHALOPATHY (Acute-onset encephalopathy) (seriousness criteria hospitalization and medically significant) and APHASIA (Global aphasia) (seriousness criteria hospitalization and medically significant). The patient was treated with ACYCLOVIR [ACICLOVIR] (intravenous use) at a dose of 450 milligram every eight hours; AMPICILLIN at a dose of 2 gram every four hours; CEFTRIAXONE at a dose of 2 gram once a day; LEVETIRACETAM for Seizures, at a dose of 2 gram twice a day; LACOSAMIDE for Seizure, at a dose of 200 milligram twice a day; ARGININE (intravenous use) for MELAS syndrome, at a dose of 500 milligram/kilogram, for 5 days; ALPHA LIPOIC ACID for MELAS syndrome, at a dose of 600 milligram once a day; TAURINE for MELAS syndrome, at a dose of 1 gram once a day; LEVOCARNITINE for MELAS syndrome, at a dose of 330 milligram three times a day; VITAMIN C [ASCORBIC ACID] for MELAS syndrome, at a dose of 500 milligram twice a day; COENZYME Q10 [UBIDECARENONE] for MELAS syndrome, at a dose of 400 milligram once a day and IMMUNOGLOBULINS NOS (IMMUNOGLOBULIN I.V) (intravenous use) at a dose of 2 milligram/kilogram. At the time of the report, NEURONAL INTRANUCLEAR INCLUSION DISEASE (Neuronal intranuclear inclusion disease), ENCEPHALOPATHY (Acute-onset encephalopathy) and APHASIA (Global aphasia) had resolved.      DIAGNOSTIC RESULTS (normal ranges are provided in parenthesis if available): On an unknown date, Biopsy brain: On hospital day 13, which showed neuronal eosinophilic intranuclear inclusions, immunoreactive for ubiquitin, consistent with NIID. On an unknown date, Body temperature: 101.2 degree Fahrenheit. On an unknown date, CSF protein: 55 mg/dl. On an unknown date, CSF white blood cell count: less than 5 WBCs per mm3. On an unknown date, Cytokine test: 29.2 picogram per millilitre. On an unknown date, Electroencephalogram: showed diffuse slowing and epileptiform discharges over the right posterior quadrant without seizures.. On an unknown date, Interleukin level: 67.6 pg/ml. On an unknown date, Laboratory test: largely unremarkable for toxic, metabolic, and infectious etiologies. On an unknown date, Lumbar puncture: showed mildly increased protein at 55 mg/dL, <5 WBCs per mm3, matching oligoclonal bands between the CSF and serum, and normal cytopathology and flow cytometry, but elevated CSF IL-6 to 67.6 pg/mL and soluble IL-2R cytokines to 29.2 pg/ml. and on hospital day 22 was notable for normalized cytokines and protein. On an unknown date, Magnetic resonance imaging: did not show acute changes, negative for acute infarct, On hospital day 8,new left hemispheric gyral swelling and edema involving the occipital, parietal, temporal, and posterior frontal lobes with cortical/pial enhancement and marked hyperperfusion throughout that region., on hospital day 12 found worsened left hemispheric gyral swelling and enhancement but decreased hyperperfusion. Clinically, there was a concern for possible adult-onset mitochondrial encephalopathy, lactic acidosis, and strokelike episodes (MELAS)., on hospital 14 showed persistent gyral swelling and edema but the resolution of enhancement and normalized perfusion and 6 months after the acute episode revealed resolved cortical swelling with residual encephalomalacia and gliosis.. On an unknown date, Magnetic resonance imaging head: On hospital day 8, patient underwent a repeat MRI brain demonstrating new left hemispheric gyral swelling and edema involving the occipital, parietal, temporal, and posterior frontal lobes with cortical/pial enhancement and marked hyper perfusion throughout that region..     For SPIKEVAX NOS (SPIKEVAX NOS) (Unknown), the reporter did not provide any causality assessments.   No concomitant medications reported Patient was admitted to the hospital for acute onset encephalopathy and global aphasia. Before 15 days, she received her first Moderna vaccine followed by the seasonal influenza vaccine. Empiric antibiotics and antiviral medications were started for presumed meningitis or encephalitis. After 4 days, she was found to have a right facial droop involving the forehead and right upper extremity hemiparesis. On hospital day 8, MRI of her brain demonstrating new left hemispheric gyral swelling and edema involving the occipital, parietal, temporal, and posterior frontal lobes with cortical/pial enhancement and marked hyperperfusion throughout that region. She was treated with a course of IV immunoglobulin and antiepileptic medications. There was no clinical improvement and a repeat MRI on day 12 found worsened left hemispheric gyral swelling and enhancement but decreased hyperperfusion. Clinically, there was a concern for possible adult MELAS, and she was treated with intravenous arginine, alpha lipoic acid, taurine, levocarnitine, vitamin C, and coenzyme Q10. Ultimately, she underwent a brain biopsy on hospital day 13, which showed neuronal eosinophilic intranuclear inclusions, immunoreactive for ubiquitin, consistent with NIID. Additionally noted on biopsy was prominent neuronal central chromatolysis, where neurons appeared enlarged with Nissl substance pushed to the cytoplasmic periphery. MRI on 14 showed persistent gyral swelling and edema but the resolution of enhancement and normalized perfusion. Repeat lumbar puncture on hospital day 22 was notable for normalized cytokines and protein. On day 25 in the hospital, she was speaking in three- to five-word sentences. Upon follow-up, 3 months after discharge, there was a significant improvement in her aphasia and encephalopathy with only minor residual deficits. A follow-up MRI 6 months after the acute episode revealed resolved cortical swelling with residual encephalomalacia and gliosis  Company comment: This literature non study case concerns a 59-year-old, female patient with medical history of Middle cerebral artery stroke, Focal epilepsy and Systemic sclerosis, who experienced the unexpected serious (hospitalization and medically significant) events of neuronal intranuclear inclusion disease (NIID), acute encephalopathy and aphasia. The events occurred approximately 15 days after the first dose of Spikevax NOS. As reported, patient was admitted to the hospital for acute onset encephalopathy and global aphasia. Empiric antibiotics and antiviral medications were started for presumed meningitis or encephalitis. After 4 days, patient was found to have a right facial droop involving the forehead and right upper extremity hemiparesis. On hospital day 8, MRI of her brain demonstrated new left hemispheric gyral swelling and edema involving the occipital, parietal, temporal, and posterior frontal lobes with cortical/pial enhancement and marked hyperperfusion throughout that region. Patient was treated with a course of IV immunoglobulin and antiepileptic medications. There was no clinical improvement and a repeat MRI on day 12 found worsened left hemispheric gyral swelling and enhancement but decreased hyperperfusion. Ultimately, she underwent a brain biopsy on hospital day 13, which showed neuronal eosinophilic intranuclear inclusions, immunoreactive for ubiquitin, consistent with NIID. Additionally noted on biopsy was prominent neuronal central chromatolysis, where neurons appeared enlarged with Nissl substance pushed to the cytoplasmic periphery. MRI on 14 showed persistent gyral swelling and edema but the resolution of enhancement and normalized perfusion. Repeat lumbar puncture on hospital day 22 was notable for normalized cytokines and protein. On day 25 in the hospital, patient was speaking in three- to five-word sentences. Upon follow-up, 3 months after discharge, there was a significant improvement in patient's aphasia and encephalopathy with only minor residual deficits. A follow-up MRI 6 months after the acute episode revealed resolved cortical swelling with residual encephalomalacia and gliosis. Per authors it is not clear what provoked the attack, but stated the patient had recently received COVID-19 and influenza vaccinations prior to presentation and immunological stress may be related to patient's presentation. Considering the nature of the event of NIID with origin in genetic mutation (either hereditary or sporadic) and mentioned event as the likely underlying cause of encephalopathy and aphasia with lack of biological plausibility for causality, the events are assessed as not etiologically associated with Spikevax NOS, however, recent vaccination may have contributed to manifestation of the disease. The benefit-risk relationship of Spikevax NOS is not affected by this report.