Age: 77.0
Sex: F
Vaccine: FLUX
Symptoms: Cerebrovascular disorder, Chest X-ray normal, Computerised tomogram abnormal, Computerised tomogram head, Echocardiogram normal
Clinical narrative: Initial report received on 16 February 2012 and follow up report received on 17 February 2012, 20 February 2012 and 21 February 2012 from an investigator participating in a study. A 77-year-old female subject was diagnosed with "Admission: left side numbness. Discharge: ADEM" on 01 January 2012 i.e. 117 days after receiving a first dose of intramuscular study vaccine (FLUZONE HIGH DOSE or FLUZONE) in right deltoid region on 06 September 2011 (batch number not reported). The subject had medical history of atrial fibrillation, peripheral artery disease, peripheral neuropathy, hypercholesterolemia, hyperthyroid (values within normal limits) thyroid nodules; breast cancer (left side radical mastectomy); status post appendectomy, cholecystectomy, left side thyroidectomy and chronic headaches (multiple durations of 1.5 month, a few months, over the last year, many years reported). Concomitant medications included Propafenone, LANOXIN and baby Aspirin. As per the subject, she had been experiencing intermittent left side weakness and numbness with headache for an uncertain duration on 01 January 2012. The subject was taken to the ER on 01 January 2012 and was subsequently admitted to the hospital on the same day. At this hospital multiple tests were run and the diagnoses was made which included stroke, viral meningitis and possible seizures. The subject was discharged home on 05 January 2012 but came back to the ER on 06 January 2012 and was readmitted. The subject's daughter was not satisfied with that hospital, and hence took the subject and had her admitted to another hospital on 11 January 2012. Lab investigations were performed on an unspecified date that included lumbar puncture, CSF which was slightly bloody, no diagnosis was made; CT of head showed right frontal lobe petechial hemorrhage and MRI of brain revealed possible subarachnoid hemorrhage. Chest x-ray and echocardiogram were negative; blood work including troponin was negative. Electroencephalogram revealed a possible epileptic activity and ECG showed normal sinus rhythm. Upon admission on 11 January 2012 brain MRI was repeated, it showed subcortical vasogenic edema pattern in the lateral temporal lobes and to a lesser degree anterior frontal lobes in the high fronto-parietal region. Also, 11 January 2012 brain MRI showed right pre- and postcentral gyrus with adjacent sulcal effacement and hyperemia. Corrective treatment included Acyclovir, KEPPRA and COREG started on an unspecified date. The associated symptom left side numbness and left side weakness resolved on an unspecified date in 2012 whereas headache resolved on an unspecified date in January 2012. The stop date of event 'Admission: left side numbness. Discharge: ADEM', was reported as 13 January 2012 however the outcome of the event was reported as ongoing. The subject was discharged from the hospital on 13 January 2012. According to the investigator, the event was related to the study vaccine and not related to the trial procedure. The serious adverse event did not lead to the termination of the subject from the study. List of documents held by sender: None. MEDICAL ASSESSMENT: The subject was a 77 year-old female with a medical history of chronic headaches, atrial fibrillation, peripheral artery disease, peripheral neuropathy, hypercholesterolemia, hyperthyroidism, thyroid nodules, breast cancer (left side radical mastectomy), status post appendectomy/cholecystectomy/and left side thyroidectomy. She was receiving concomitant therapies that included Propafenone, LANOXIN and baby Aspirin. The reported start date of this event is 117 days after vaccination, when the subject was evaluated in the emergency room for headaches, intermittent left-sided weakness. The subject was later admitted to the hospital on the same day. The differential diagnoses considered at the hospital included stroke, viral meningitis and possible seizures. The subject was discharged after 4 days but readmitted next day, however was taken to another hospital after 5 days as her daughter was not satisfied with that hospital. Lab investigations included lumbar puncture with CSF described as slightly bloody; CT of head showed right frontal lobe petechial hemorrhage and MRI of brain revealed possible subarachnoid hemorrhage. Follow-up MRI reported subcortical vasogenic edema pattern in the lateral temporal lobes and to a lesser degree anterior frontal lobes (in the high right fronto-parietal region), right pre- and postcentral gyrus with adjacent sulcal effacement and hyperemia. Electroencephalogram revealed a possible epileptic activity. Treatment included Acyclovir, KEPPRA and COREG. The discharge diagnosis after 2 days was (ADEM) Acute Disseminated Encephalomyelitis. The investigator has assessed the case as "related" to the study vaccine based on the opinion provided in the hospital discharge summary. The sponsor does not agree with the investigator's causality assessment based on the long latency reported and the possibility of an alternative diagnosis. ADEM has been described after vaccination (predominantly after MMR vaccine) but the latency reported for this event (117 days, approximately 4 months) is against the causal relationship between the event and the vaccine. In addition, workup findings reported suggest the possibility of subarachnoid hemorrhage and parenquimal petechial hemorrhage as possible diagnoses, and no findings are characteristic of ADEM: ADEM usually reveals non-bloody CSF with lymphocytic pleocytosis and MRI of the brain usually reports deep high-matter changes, features not reported for this event. Also, based on a recent review by the Institute of Medicine (IOM), the committee that reviewed adverse effects of vaccines concluded that the epidemiological evidence is insufficient or absent to assess an association between influenza vaccine and ADEM.