Age: 36.0
Sex: M
Vaccine: FLUX
Symptoms: CSF lymphocyte count increased, CSF myelin basic protein, CSF oligoclonal band present, CSF protein increased, CSF red blood cell count positive
Clinical narrative: Longitudinally extensive transverse myelitis; Mpox (monkeypox) infection; This literature case was received on 19-Sep-2023 and concerned a 36-year-old male patient.   This case report describes a patient with recently diagnosed mpox who developed longitudinally extensive transverse myelitis.  The patient's concurrent conditions included well-controlled HIV infection and syphilis. The patient's concomitant medications were not reported.  On an unspecified date, the patient was vaccinated with influenza vaccine, reported as trivalent inactivated influenza vaccine (brand not specified; dose, route of administration, anatomical location, and indication: not reported). The batch number was not reported.  On an unspecified date, an unknown amount of time after receiving influenza vaccine, the patient developed fevers, fatigue, and characteristic vesicular lesions on upper arms, bilateral groin, and right shin and had been diagnosed with mpox infection. The patient was unaware of any sick contacts and tecovirimat was initiated two days after diagnosis.  On an unspecified date, three days after initial diagnosis with mpox infection and one week after receiving influenza vaccine, the patient was presented to the emergency room with rapidly progressive bilateral lower extremity weakness, numbness, and abdominal pain. The patient drove himself to the emergency department for sudden onset left-sided flank pain associated with bilateral lower extremity numbness. The patient was ambulatory upon presentation, however, several hours later, the patient developed weakness of bilateral lower extremities and urinary incontinence. The numbness ascended the patient's abdomen and torso, up to the T4 spinal level. On neurologic examination the patient was awake and oriented, with good attention. Cranial nerves II-XII were intact and had 5/5 strength in the bilateral upper extremities. The patient had 0/5 strength and areflexia throughout both lower extremities and plantar responses were mute. The patient was unable to appreciate light touch, vibration, proprioception, temperature, or pinprick below the T4 spinal level. Cerebellar testing was within normal limits. Magnetic resonance imaging (MRI) scans of the cervical, thoracic, and lumbar spine, with and without contrast, demonstrated a contiguous, non-enhancing fluid-attenuated inversion recovery (FLAIR) signal abnormality, located in the centre of the cord, spanning the T1-T10 vertebral segments, with slight swelling of the cord over the same distribution. MRI brain demonstrated several discrete, no-enhancing FLAIR hyperintensities in the left external capsule, central pons, left cerebellar white matter, and right middle cerebellar peduncle. The patient had no prior brain imaging for comparison. On the evening of presentation, the patient became febrile to 101.2, and broad-spectrum antibiotics were initiated. Lumbar puncture was performed, and cerebrospinal fluid (CSF) analysis was notable for 883 nucleated cells per µL (normal range <6) with lymphocytic predominance (83%, normal range 40-80%) and an elevated protein of 241 mg/dL (normal range 15 - 45), there was 1 unique oligoclonal band too, red blood cell count (RBC) was 25 cells per µL (normal range less than three). Myelin basic protein level was slightly elevated (8.7, normal range less or equal to four), but still considered within normal limits. The remainder of CSF testing was negative. Evaluation for monkeypox in the CSF was considered, but there was no remaining fluid to send. Serological laboratory testing was notable for borderline low Vitamin B12 at 398 pg/mL (normal range 211-911), and positive HIV-1 antibody titers with an HIV viral load less than 40, HIV-1/HIV-2 AB/p24 Ag reactive and HIV1 reactive, positive rapid plasma reagin test (RPR) with decreased titers from prior evaluations. Based on the latter results it was concluded that his syphilis had been adequately treated. Other serum and urine studies were within normal limits. Computed tomogram (CT) chest with contrast did not demonstrate hilar lymphadenopathy consistent with sarcoidosis. Based on the results of the CSF analysis, broad-spectrum antibiotics were discontinued and was continued on acyclovir and tecovirimat. High dose of intravenous (IV) methylprednisolone was administered and the patient then completed treatment with intravenous immunoglobulin. However, the patient demonstrated no improvement in physical exam. The decision was then made to pursue plasma exchange for five treatments. The patient also received steroids for five days.  Extensive testing for co-morbid infectious and inflammatory disorders that could present with longitudinally extensive transverse myelitis was pursued, but the work-up was largely unrevealing. Although the patient had HIV, his titers were low, he was not lymphopenic, and the reporter found no evidence of opportunistic infections. By process of elimination, the reporter suspects that this presentation may be a direct consequence of mpox transverse myelitis.  On an unspecified date, despite aggressive treatment, discharge exam showed persistent flaccid paraplegia. The patient's sensory level had descended to the mid-thorax. Patellar reflexes were 1+ and there were bilateral positive Babinski signs. The patient was discharged to inpatient rehabilitation with a plan to follow-up in the ambulatory Neuro-immunology clinic.  On an unspecified date, at five-month follow-up, the patient remained non-ambulatory. The patient's exam revealed spastic paraplegia, 3+ patellar reflexes, clonus at both ankles, and bilateral Babinski signs. The patient had a T6 sensory level. Repeated MRI demonstrated resolution of the intramedullary signal hyperintensity and swelling.  The outcome of the events 'monkeypox' and 'longitudinal extensive transverse myelitis' was not reported.   The reporter did not provide a causality assessment. It was reported that the patient received his seasonal influenza vaccine one week prior to admission, but the reporter feel the patient's clinical picture was unlikely related to the influenza vaccination.  The events of 'monkeypox' and 'longitudinal extensive transverse myelitis' were considered to be serious due to seriousness criteria of hospitalization and medically significant by a Physician within CSL Seqirus's Pharmacovigilance Department.  In conclusion, this case underscores that despite promptly identifying the viral cause and administering optimal treatment, patients may face unfavourable neurological outcomes. This highlights the importance of preventive measures, particularly the vaccination of at-risk individuals, to mitigate such occurrences.  The literature citation is report.  Company comment: A 36-year-old patient experienced fever, fatigue, and characteristic vesicular lesions on upper arms, bilateral groin, and right shin and had been diagnosed with monkeypox infection within seven days after receiving the suspect product influenza vaccine. During the same period, the patient was presented to the emergency room with rapidly progressive bilateral lower extremity weakness, numbness, and abdominal pain. The patient also developed urinary incontinence and numbness ascended the patient's abdomen and torso, up to the T4 spinal level. Neurologic examination showed that the patient had 0/5 strength and areflexia throughout both lower extremities, plantar responses were mute, inability to appreciate light touch, vibration, proprioception, temperature, or pinprick below the T4 spinal level. Magnetic resonance imaging scans of the cervical, thoracic, and lumbar spine, with and without contrast, demonstrated a contiguous, non-enhancing fluid-attenuated inversion recovery signal abnormality, located in the centre of the cord, spanning the T1-T10 vertebral segments, with slight swelling of the cord over the same distribution. Magnetic resonance imaging scans of the brain demonstrated several discrete, no-enhancing fluid-attenuated inversion recovery hyperintensities in the left external capsule, central pons, left cerebellar white matter, and right middle cerebellar peduncle. Thereafter, the patient became febrile. Lumbar puncture was performed, and cerebrospinal fluid analysis showed elevated nucleated cells per µL with lymphocytic predominance, elevated protein, and elevated red blood cell count. The reporter suspected that the patient's presentation may be a direct consequence of monkeypox transverse myelitis. The patient's significant concurrent conditions included well-controlled HIV infection and syphilis. Based on biological implausibility, causal role of the suspect vaccine for the event monkeypox is assessed as not related. Although the reported event of transverse myelitis could potentially be a consequence of monkeypox infection, there remains a probability that this event is linked to vaccination. Therefore, causality between the suspect vaccine and the event transverse myelitis is assessed as unlikely related, due to plausible temporal relationship (defaults to 'related' in the safety database for reporting purposes). Per Brighton collaboration criteria, presented information correspond to level 1 diagnostic certainty for myelitis.; Sender's Comments: A 36-year-old patient experienced fever, fatigue, and characteristic vesicular lesions on upper arms, bilateral groin, and right shin and had been diagnosed with monkeypox infection within seven days after receiving the suspect product influenza vaccine. During the same period, the patient was presented to the emergency room with rapidly progressive bilateral lower extremity weakness, numbness, and abdominal pain. The patient also developed urinary incontinence and numbness ascended the patient's abdomen and torso, up to the T4 spinal level. Neurologic examination showed that the patient had 0/5 strength and areflexia throughout both lower extremities, plantar responses were mute, inability to appreciate light touch, vibration, proprioception, temperature, or pinprick below the T4 spinal level. Magnetic resonance imaging scans of the cervical, thoracic, and lumbar spine, with and without contrast, demonstrated a contiguous, non-enhancing fluid-attenuated inversion recovery signal abnormality, located in the centre of the cord, spanning the T1-T10 vertebral segments, with slight swelling of the cord over the same distribution. Magnetic resonance imaging scans of the brain demonstrated several discrete, no-enhancing fluid-attenuated inversion recovery hyperintensities in the left external capsule, central pons, left cerebellar white matter, and right middle cerebellar peduncle. Thereafter, the patient became febrile. Lumbar puncture was performed, and cerebrospinal fluid analysis showed elevated nucleated cells per µL with lymphocytic predominance, elevated protein, and elevated red blood cell count. The reporter suspected that the patient's presentation may be a direct consequence of monkeypox transverse myelitis. The patient's significant concurrent conditions included well-controlled HIV infection and syphilis. Based on biological implausibility, causal role of the suspect vaccine for the event monkeypox is assessed as not related. Although the reported event of transverse myelitis could potentially be a consequence of monkeypox infection, there remains a probability that this event is linked to vaccination. Therefore, causality between the suspect vaccine and the event transverse myelitis is assessed as unlikely related, due to plausible temporal relationship (defaults to 'related' in the safety database for reporting purposes). Per Brighton collaboration criteria, presented information correspond to level 1 diagnostic certainty for myelitis.