Age: 44.0
Sex: M
Vaccine: FLUX
Symptoms: Anorectal manometry, Anti-GAD antibody positive, Anti-islet cell antibody positive, Bladder catheterisation, Computerised tomogram abdomen normal
Clinical narrative: This Literature - Spontaneous case, initially received on 17-Jan-2017, was reported by a health professional and concerns a 44-year-old male patient. Weight: not provided; Height: not provided. Past medical history includes obstructive sleep apnea. Concomitant medication: not reported. Administration of company suspect drug(s): On an unknown date, the patient received Influenza Virus Vaccine (INN) for indication not reported. Dose regimen: Not reported, Route of administration: Not Reported. Batch number: Not reported. No additional suspect drugs. Adverse reactions/events and outcomes: On an unknown date two weeks following influenza vaccination, the patient experienced stiff person syndrome (SPS) (medically significant, outcome: not recovered / not resolved). Associated symptoms included: abnormal relaxation of the lower and upper esophageal sphincters, antibodies to pancreatic islet cells were found to be elevated, diplopia, fourth [and sixth] nerve palsies, hyperreflexia in the lower extremities, increased tone in the lower extremities, intermittent urinary retention, outlet obstruction (anorectal), progressive cramping and spasms in the lower extremities, sensation of the urge to defecate was felt at lower volumes (100 ml) than normal (120 ml), serum anti-GAD65 (glutamic acid decarboxylase) antibody titer was highly elevated at 250 units/ml, severe constipation, sixth nerve palsies, spastic gait, toe walking, wheelchair-bound state. The patient presented with intermittent urinary retention and constipation for approximately 2 months, followed by progressive cramping and spasms in the lower extremities that were triggered by startle, stress, loud noises, and tactile stimulation. Initial symptoms started 2 weeks after influenza vaccination. On examination, increased tone and hyperreflexia in the lower extremities were accompanied by spastic gait and toe walking. Symptoms progressed to a wheelchair-bound state, complicated by severe constipation. The urologist determined the need for suprapubic bladder catheterization for urinary retention management. The patient experienced 2 self-limiting episodes of diplopia and was diagnosed with fourth and, respectively, sixth nerves palsies. Urinary retention and constipation resolved after 2 months of IVIG (intravenous immunoglobulin) therapy. Lower extremity spasms and gait impairment improved with IVIG, baclofen and diazepam; maintenance therapy was required to assure fully ambulatory state, return to full-time job and cardio exercises. Urodynamic studies were not performed in the patient despite obtaining urological consultations. The urologists felt confident that the tightness of the urethral sphincter caused urinary retention based on extremely difficult catheterization and therefore advanced catheterization techniques were applied. Manometry studies were not repeated after immunomodulation therapies, given symptoms resolved completely. Persistent elevation of anti-GAD65 antibodies despite successful immunotherapy was seen in the patient. Serologic monitoring is not recommended and the optimal therapy duration is unclear. The patient had recurrence of symptoms with discontinuing IVIG and has remained on it. Relevant tests: Serum anti-GAD65 antibody titer was highly elevated at 250 units/mL and antibodies to pancreatic islet cells were found elevated as well. Serologic workup for infections, autoimmune and paraneoplastic conditions, brain and spine MR (magnetic resonance) imaging, CT (computed tomography) chest, abdomen, and pelvis was unrevealing. Esophageal manometry revealed a prolonged refractory phase of esophageal peristalsis and abnormal relaxation of the lower and upper esophageal sphincters. The high-resolution anorectal manometry interpretation was consistent with outlet obstruction because internal anal sphincter did not relax with balloon distension during normal values and sensation of the urge to defecate was felt at lower volumes (100 mL) than normal (120 mL). In addition, elevated maximum resting sphincter pressure (117 mm Hg in our case, with normal value being less than 98 mm Hg) and maximum sphincter squeeze pressure (323 mm Hg in our case compared with normal less than 254 mm Hg) were observed. Reporter comments: Based on the observed internal anal sphincter abnormalities, autonomic nervous system involvement is implicated in this presentation. Further research into the elucidation of the mechanism involved and potential therapies targeting autonomic nervous system dysfunction should be contemplated. Sender's Comments: Listedness: Brand of Influenza vaccine not specified. Assessment according to the CCSI for CSL's Inactivated Influenza Virus Vaccine, Stiff person syndrome (SPS) is unlisted. Causality: Related. Time to event onset is 2 weeks following vaccination. Clinical presentation and elevated serum anti-GAD (glutamic acid decarboxylase) antibody were consistent with diagnosis of SPS. Serologic tests, brain imaging (MRI), CT chest, abdomen, and pelvis did not identify infections, autoimmune and or paraneoplastic conditions which are known to be associated with SPS. The pathophysiology of SPS is autoimmune with a pathologic correlation of positive anti GAD antibodies; In the absence of other risk/associated diseases (diabetes thyroiditis) and a plausible temporal association, causality is consider related to Influenza vaccination.