Age: 3.0
Sex: F
Vaccine: FLUX
Symptoms: CSF oligoclonal band absent, CSF protein increased, CSF red blood cell count, CSF test, CSF white blood cell count negative
Clinical narrative: The patient was diagnosed with GBS, most consistent with the acute bulbar palsy-plus (ABPp) variant; This literature case was received on 15-Aug-2022 and concerned a 3-year-old, female patient.  Guillain-Barre syndrome (GBS) is an acute immune-mediated polyradiculoneuropathy that clinically manifests variably, most classically as acute inflammatory demyelinating polyneuropathy with progressive, ascending limb weakness and reduced or absent reflexes in both children and adults. More rare variants include the bifacial weakness with paraesthesia, characterized by isolated facial diplegia with distal limb paresthesias, and acute bulbar palsy-plus (ABPp) syndromes, which presents with multiple cranial neuropathies and ataxia without neck or limb weakness. This is a rare case of a 3-year-old girl whose clinical presentation appeared consistent with the ABPp variant of GBS.  The patient's medical history and concomitant medications were not reported.   On an unspecified date, the patient was vaccinated with influenza vaccine (brand not specified; dose, route of administration, anatomical location and indication: not reported). The batch number was not reported. As reported, the patient was in her usual state of health, with no known recent illnesses.  On the same date, a few hours after receiving influenza vaccine, the patient's mother noticed that, while the patient cried, her left face appeared flat and emotionless with the left eye slightly open without any tears, while the right face was creased with the right eye closed and tears coming out.   On an unspecified date, reported as on the next day, she was prescribed acyclovir by her pediatrician on for suspected Bell's palsy. Two days later, the patient stopped talking and appeared as if she was gasping to breathe. The patient also had increased difficulty with eating and drinking and was no longer able to walk without assistance.  On unspecified date, the patient presented to the emergency department with worsening facial weakness and difficulty walking. At the time of her presentation, the patient's lung exam was remarkable for inspiratory stridor. On neurologic exam, the patient was awake and followed commands. The patient was nonverbal but hummed with a soft voice. The patient's pupils were equal and reactive to light, and gaze was conjugate in all directions. The patient had bilateral upper and lower facial weakness, left worse than right. When the patient laughed, her right lower face moved slightly up, while the left lower face did not move, and the left nasolabial fold remained absent. The patient's strength was full throughout, and she responded to touch in all extremities. Reflexes were absent throughout. The patient had dysmetria bilaterally when attempting to grab small items with each hand. The patient stood without assistance but displayed a staggering, cautious gait while walking. The patient was admitted to hospital.  On an unspecified date, magnetic resonance imaging (MRI) of brain with and without contrast revealed abnormal smooth enhancement of the bilateral oculomotor, trigeminal, facial, and vagus nerves. In addition, MRI of the entire spine obtained with and without contrast revealed similar smooth enhancement of spinal nerve roots at many levels, most conspicuous in the cauda equina and cervicothoracic junction. Additionally, lumbar puncture with cerebrospinal fluid (CSF) studies revealed white blood cell count of 19 cells/cm2 (normal range: 0-10) without red blood cells, glucose 81 mg/dL (normal range 45-75) and protein 116 mg/dL (normal range: 15-45). Meningitis panel, which included Escherichia coli, Haemophilus influenzae, Listeria monocytogenes, Neisseria meningitidis, Streptococcus agalactiae, Streptococcus pneumoniae, Cytomegalovirus, Enterovirus, Herpes Simplex Virus 1, Herpes Simplex Virus 2, Human herpesvirus 6, Human parechovirus, Varicella zoster virus, Cryptococcus neoformans/gattii, as well as CSF cultures were negative. Multiple sclerosis panel revealed elevated CSF immunoglobulin G (IgG) with elevated IgG synthesis rate, without oligoclonal bands. Serum autoimmune panel which included Anti-Neuronal Nuclear Ab, Type 1 (ANNA-1), CSF, CASPR2-IgG CBA, DPPX Ab IFA, GABA-B-R Ab CBA, GAD65 Ab Assay, GFAP IFA, LGI1-IgG CBA, mGluR1 Ab IFA, MOG FACS, NMDA-R Ab CBA, NMO/AQP4 FACS,  Purkinje Cell Cytoplasmic Ab Type and TR (PCA-Tr), and CSF autoimmune encephalopathy panels which included Anti-Neuronal Nuclear Ab, Type 1, (ANNA-1), CASPR2-IgG CBA, DPPX Ab IFA, GABA-B-R Ab CBA, GAD65 Ab Assay, GFAP IFA, LGI1-IgG CBA, mGluR1 Ab IFA, NMDA-R Ab CBA, NMO/AQP4 FACS, Purkinje Cell Cytoplasmic Ab Type TR (PCA-Tr) were negative. Serum acute neuropathy panel which included IgM versus GM1, IgM versus GalNAc-GD1a, IgM versus GD1b, IgM versus GM2, IgG versus GT1a, IgG versus GM1, IgG versus GQ1b, IgG versus GD1b, IgG versus GalNAc-GD1a, IgG versus Sulfatide, IgM versus ß-Tubulin, IgG versus ß-Tubulin, IgM versus Heparan Sulfate, IgM versus Histone H3, IgM versus GD1a, IgG versus Neurofascin-140, IgG versus Neurofascin-155, IgM versus Neurofascin-155, IgG versus Contactin-1, IgG versus Caspr1 was negative.   On an unspecified date, the patient was diagnosed with Guillain-Barre Syndrome (GBS), most consistent with the ABPp variant. The patient received intravenous immunoglobulin 1 mg/kg daily for two days. The patient's respiratory status was monitored and was without complication, and her symptoms steadily improved over the next ten days. By hospital discharge, the patient appeared to smile with present bilateral nasolabial folds. The patient's cry was less hoarse, and she was able to eat soft foods. Reflexes remained absent throughout, and the patient continued to have mild ataxic gait requiring intermittent assistance.   On a unspecified date, the patient was discharged to inpatient rehabilitation with ongoing physical, occupational, and speech therapy.   On an unspecified date, the patient recovered from the event. As reported, on three-month follow-up, the patient was back to her normal self, with intact facial strength, fluent speech with normal pitch and no dysarthria, and normal reflexes. No ataxia was observed, as the patient was able to run, skip, and jump up and down without difficulty.  In conclusion, it was suspected that the influenza vaccine most likely contributed to the patient's development of Guillain-Barre Syndrome (GBS), given her onset of symptoms just hours after vaccine administration and lack of other known risk factors. This short latency is unusual given that the risk for GBS is expected in the eight to 21-day window after vaccinations. Compared to adults with GBS, children with GBS were found to have a more acute onset of symptoms, higher likelihood of developing cranial nerve palsies, and better prognosis, with >70% returning to ambulation by one year. The patient's clinical course also appeared to be consistent with those of other cases of GBS in children, with a more rapid onset and significant improvement following intravenous immunoglobulin (IVIg) administration.  The reporter considered the event of 'Guillain Barre syndrome' as most likely related to influenza vaccine, as the symptoms appeared just hours after vaccine administration and lack of other known risk factors.  The event of 'bulbar palsy' was considered as serious due to seriousness criteria of hospitalization. Additionally, the event of 'bulbar palsy' was considered to be medically significant by a Physician within Seqirus's Pharmacovigilance and Risk Management Department.   Company comment: A 3-year-old, female patient was vaccinated with the suspect product influenza vaccine. A few hours after vaccination, the patient's mother noticed that, while the patient cried, her left face appeared flat and emotionless with the left eye slightly open without any tears, while the right face was creased with the right eye closed and tears coming out. Symptoms progressed three days later. On neurologic exam, the patient was nonverbal but hummed with a soft voice, the patient had bilateral upper and lower facial weakness, left worse than right. The patient's strength was full throughout, and she responded to touch in all extremities. Reflexes were absent throughout. The patient had dysmetria bilaterally when attempting to grab small items with each hand. The patient stood without assistance but displayed a staggering, cautious gait while walking. Magnetic resonance imaging (MRI) of brain with and without contrast revealed abnormal smooth enhancement of the bilateral oculomotor, trigeminal, facial, and vagus nerves, while MRI of the entire spine revealed similar smooth enhancement of spinal nerve roots at many levels. Additionally, lumbar puncture with cerebrospinal fluid (CSF) studies revealed white blood cell count of 19 cells/cm2 (normal range: 0-10) without red blood cells, glucose 81 mg/dL (normal range 45-75) and protein 116 mg/dL (normal range: 15-45). Meningitis panel, Serum acute neuropathy panel, Serum autoimmune panel and CSF autoimmune encephalopathy panel all were negative. The patient was diagnosed with Guillain-Barre Syndrome (GBS), most consistent with the acute bulbar palsy-plus (ABPp) variant. Based on provide information causality is assessed as possibly related. The provided information do not fulfil Brighton Collaboration criteria for Guillain-Barre syndrome.; Reporter's Comments: The reporter considered the event of 'bulbar palsy' as most likely related to influenza vaccine, as the symptoms appeared just hours after vaccine administration and lack of other known risk factors.; Sender's Comments: A 3-year-old, female patient was vaccinated with the suspect product influenza vaccine. A few hours after vaccination, the patient's mother noticed that, while the patient cried, her left face appeared flat and emotionless with the left eye slightly open without any tears, while the right face was creased with the right eye closed and tears coming out. Symptoms progressed three days later. On neurologic exam, the patient was nonverbal but hummed with a soft voice, the patient had bilateral upper and lower facial weakness, left worse than right. The patient's strength was full throughout, and she responded to touch in all extremities. Reflexes were absent throughout. The patient had dysmetria bilaterally when attempting to grab small items with each hand. The patient stood without assistance but displayed a staggering, cautious gait while walking. Magnetic resonance imaging (MRI) of brain with and without contrast revealed abnormal smooth enhancement of the bilateral oculomotor, trigeminal, facial, and vagus nerves, while MRI of the entire spine revealed similar smooth enhancement of spinal nerve roots at many levels. Additionally, lumbar puncture with cerebrospinal fluid (CSF) studies revealed white blood cell count of 19 cells/cm2 (normal range: 0-10) without red blood cells, glucose 81 mg/dL (normal range 45-75) and protein 116 mg/dL (normal range: 15-45). Meningitis panel, Serum acute neuropathy panel, Serum autoimmune panel and CSF autoimmune encephalopathy panel all were negative. The patient was diagnosed with Guillain-Barre Syndrome (GBS), most consistent with the acute bulbar palsy-plus (ABPp) variant. Based on provide information causality is assessed as possibly related. The provided information do not fulfil Brighton Collaboration criteria for Guillain-Barre syndrome.