Age: 73.0
Sex: F
Vaccine: FLU3
Symptoms: Cystitis, Diplopia, Dizziness, Dysphagia, Dyspnoea
Clinical narrative: Initial report received from a health care professional (PEI2010008243) on 27 Apr 2010: This patient with a history of previous vaccination with MUTAGRIP was vaccinated with GRIPPE-IMPFSTOFF N-HEXAL (batch no: 095903B), (dose: unknown) subcutaneously in the left upper arm for immunisation on 14 Oct 2009. On 30 Nov 2009 the patient presented with Miller Fisher syndrome (special form of Guillain Barre syndrome) and was hospitalized. The patient also experienced ophthalmoplegia, ptosis, mydriasis, dysphagia, areflexia, ataxia, quadriparesis and dyspnea. G11A lgM + lgG, GQ1B lgM antibodies and dissociation of lgG antibodies were positive. Tests for cerebrospinal fluid were normal, with no cytoalbumin and tensilon test was negative. The outcomes of the events were reported as not recovered. The seriousness criterion was reported as life threatening that required hospitalization. Follow up information received on 03 May 2010: No additional information was provided. Follow-up report received from the health authority (PEI) on 18 May 2010: The patient had relevant history of CNS-vascular and cardiac arterial hypertension, hyperlipoproteinemia, intracerebral bleeding left temporoparietal (in 1994) consecutive to hypertensive crisis with dysarthria as sequel, Tako-tsubo cardiomyopathy (stress induces cardiomyopathy) in April 2009 for which coronary heart disease had subsequently been disregarded based on coronarography result. Further, adiposity, diabetes mellitus type II so far controlled by diet, and food allergies were also reported as part of medical history. The patient experienced marked dizziness with nausea, repeated vomiting, double vision and gait disturbances in the morning of 30 Nov 2009 and then the patient was admitted to the neurology intensive care department (NIC). Neurological examination at admission showed that the patient was alert, cooperative, presenting with non-continuous visual processing (i.e. interrupted flow in movements); visual paresis to the right side: left-sided deficit in abduction; anisocoria (right more than left side); round pupils; bilateral, decreased reaction to light, both direct and indirect; left-sided ptosis. There were no sign of meningismus; sensory abnormalities in face and extremities, facial paresis and hypoaccusia. Pronation drift test bilateral was normal. Barre's pyramidal sign showed maintained leg position with no evident paresis in extremities; weak monosynaptic reflex in all extremities and triggering of patellar tendon reflex was not possible. Plantar reflexes negative. There was discrimination between sharp and blunt objects and temperature discrimination (both intact). Finger-to-nose coordination test showed bilaterally dysmetria. Cardiac and pulmonary auscultation was unremarkable in agreement with later on performed ECG, continuous-recording ECG and chest x-ray. Brain stem ischemia was suspected. Intracerebral bleeding was disregarded based on native CT scan of had performed on 30 Nov 2009. Diffusion MRI of brain in the evening of 30 Nov 2009 revealed from hemodynamic point of view, neither signs of a recently occurred pathology nor relevant stenosis. There were visible known alterations in the frame of above left-sided, temporoparietal intracerebral bleeding and areas with substance loss were filled out with cerebrospinal fluid. Additional changes assessed as being compatible with microvascular encephalopathy impacting both subcortical white substance and pons (multiple lacunar lesions). On 01 Dec 2009, the patient presented with ophthalmoplegia, mydriasis with pupillary areflexia, marked ataxia of predominantly spinal origin with absent monosynaptic reflexes, and tetraparesis. Based on these symptoms, diagnosis of suspected Miller-Fisher syndrome was made. Cerebrospinal fluid showed unremarkable findings. Electromyography performed on an unknown date revealed normal results except slight alteration in N. tibialis function. On 01 Dec 2009, Anti-ganglioside antibodies showed positivity for GT1A both lgM and lgG and for GQ1B lgM, whilst GQ1B lgG was negative. The patient was started on therapy with i.v. immunoglobulins at 0.4 g/kg BW. The patient received two courses from 01 Dec 2009 to 05 Dec 2009 and from 19 Dec to 21 Dec 2009. Campylobacter jejuni lgG antibody performed on non-reported date was positive but no numerical value was provided. Due to vomiting-induced aspiration pneumonia (evidently dysphagia-related) with acute respiratory insufficiency, the patient was transferred to IM ICU on 01 Dec 2009 where the patient was intubated. Tracheal secretion culture on 02 Dec 2009 revealed E. coli and beta-hemolytic streptococci and unspecified antibiotic therapy NOS (apparently ciprofloxacin) was started. On 14 Dec 2009, the patient underwent tracheotomy. On the same day, coagulase-negative staphylococci were found in tracheal secretion culture. Tensilon test (myasthenia gravis) performed on non-reported date was negative. On 18 Dec 2009, the patient was transferred back to NIC department. Unchanged neurological condition was assessed with tetraparesis, truncal and extremities ataxia, ophthalmoplegia with bilateral both mydriasis and ptosis and dysphagia. Ciprobay therapy was again started on 21 Dec 2009 unto 30 Dec 2009. Due to urinary tract infection (UTI) including isolation/identification of Candida glabrata, DIFLUCAN was added on 29 Dec 2009. Because of persisting aspiration risk consecutive to marked dysphagia, percutaneous endoscopic gastrostomy (PEG) was performed on 29 Dec 2009. The patient's cardiac situation during the whole course showed 5 second lasting atrio-ventricular black (AV block) on 30 Nov 2009 followed by marked bradycardia of 40 bpm lasting 15 sec. Atrial fibrillation induced high frequency arrhythmia occurred on 03 Dec 2009 which was regarded to be associated to aspiration pneumonia. Therefore, no anticoagulation therapy was started. Both on 22 Dec 2009 and 29 Dec 2009, bradycardia of 30 and respectively 25 bpm occurred following carvedilol dosing for which this treatment was stopped. As a consequence, systolic blood pressure increased up to 180 mmHg. Microbiological tests performed on 01 Dec 2009 showed syphilis serology negative (less than 1:80). Borrelia serology showed borderline titer compatible with either beginning of borreliosis or cross-reaction with other antibodies. Mycoplasma pneumoniae (Mp) serology was negative (less than 1:40), thus no hint for Mp-acute infection. Native CT of neck, thorax, abdomen and pelvis with contrast medium performed 08 Dec 2009 showed no clear signs of lung infiltration and malignancy. Atelectasis was seen at the lung bases and cystitis was suspected. Chest x-ray on 02 Dec 2009 showed progression of parenchymal infiltrates with right-sided predominance. Repeat chest x-ray on 24 Dec 2009 showed regression of infiltrates compared to previous findings. There were no signs of either acute congestion or relevant effusion. Electromyoneurography on 01 Dec 2009 showed essentially normal findings except right-sided reduction of compound muscle action potential (CMAP) amplitude in N. tibialis. Electromyoneurography on 08 Dec 2009 showed electrophysiological evidence of axonal and clearly predominant sensory polyneuropathy. Compared to 01 Dec 2009, there were worsening of findings with absence of sensory nerve action potential (SNAP) of N. radialis and N. suralis and further reduction on CMAP amplitude of left N. tibialis and right N. ulnaris. Electromyoneurography on 22 Dec 2009 compared to 08 Dec 2009 showed more accentuated findings of the predominantly sensory polyneuropathy and also worsening regarding previous CMAP amplitude of left N. tibialis which was now accompanied by pathologic spontaneous activity in left M. tibialis anterior. According to hospital discharge report on 30 Dec 2009, the patient was diagnosed with Miller-Fisher syndrome symptomatically manifested as ophthalmoplegia, ptosis, mydriasis, dysphagia, dyspnoea, areflexia, ataxia, tetraparesis and further characterized as GT1A both lgM and lgG and GQ1B lgM antibodies positive in serum, normal cerebrospinal fluid findings, (i.e. without cyto-albumin dissociation), Campylobacter jejuni lgG antibodies positive, sensory axonal polyneuropathy based on nerve condition velocity test of 08 Dec 2009 and tensilon test negative. The patient was also presented with acute renal failure on an unspecified date. Arterial hypertension and hyperlipoproteinemia were reported as cardiovascular risk factors. The patient was discharged to geriatric, social medicine and rehabilitation department on 30 Dec 2009. At the time of discharge, there was slightly improved both ptosis and tetraparesis (especially proximal and more accentuated in arms). Mydriasis remained unchanged with moderate anisocoria (more in left side than right side). There was still marked ataxia, ophthalmoplegia; dysphagia and dyspnoea partially counteracted by respectively PEG and tracheotomy. The patient presented with both urinary and faecal incontinence. The patient was evidently bearing an indwelling bladder catheter. At transfer, partial pressure of oxygen was 68 mmHg and partial pressure of carbon-dioxide was 65 mmHg in supine position. Values were markedly improved in seated position and oxygen supply was ongoing. UTI was still ongoing and both arterial hypertension and cardiac rhythm abnormalities were not fully controlled yet. At an unclear time point (prior or subsequently to transfer), use of insulin for treating diabetes became necessary. The patient's rehabilitation treatment involved an intensive, multiple program including physiotherapy, ergotherapy, and logopedics besides both active self-training and medical care. Electromyoneurography findings of 02 Mar 2010 were compatible with axonal demyelinating motor sensory polyneuropathy. Determination of somatosensory evoked potentials on the same day revealed pathologic result on the right-side for N. medianus (damaged sensory fibers with significantly decreased amplitude) and not elicitable response for N. tibialis. Insulin therapy for diabetes was adjusted during the rehabilitation phase due to increased blood glucose levels. UTI accompanied by fever occurred in mid of March 2010 and was successfully treated with cefuroxime. However, urine culture on 30 mar 2010 revealed E. coli and Pseudomonas aeruginosa. Hypopotassemia of 3.3 mmol/l occurred on 30 Mar 2010 and was corrected to 4.1 mmol/l. A marked improvement was reached during rehabilitation so that at the beginning of April 2010, the patient was able to move the wheel-chair by her over a few meters. Transference from bed to wheel-chair was possible with the help of a care-person, and patient was able under supervision to seat free for short time-periods. Muscular strength and coordination of extremities sufficiently improved for permitting simple steps like washing herself (face, thorax) and grasping objects) like bread during breakfast); however, this was only possible in a very slow motion. Verbal communication became gradually possible without relevant restrictions. Improvement in motor function of both mouth and tongue and in deglution function permitted whole food and fluid intake since 01 Apr 2010. Oxygen supply was gradually restricted to the nights only and then ceased. The tracheotomy tube was eventually withdrawn. Neurological examination on 07 Apr 2010 showed that the patient was alert, orientated and in good mood. There was neither aphasia nor dysarthria. Meningismus was absent. Oculo-motor function was not impacted. Size of pupil was average. Reaction to light showed slight positivity on left side and negativity on right side with convergence pupil reaction and bilateral dysmetria. N. facialis bilaterally and tongue motor function remained unremarkable. Sensitivity in mouth was equivalent on both sides. During pronation drift test, it was possible to maintain arm position, but for only 5 seconds on the left side. Barre's pyramidal sign showed that it was possible to maintain leg position, bilaterally. Finger-to-nose coordination test showed bilateral dysmetria which was more marked on the left side. There was bilateral ataxia. Generalized muscular weakness was observed. Monosynaptic reflexes were absent and there was no pyramidal tract signs. There was hyperpathy in hands and feet at distal end. Distal symmetric hypoesthesia of lower extremities up to mid-calf was also observed. Proprioception reduced regarding hands and feet and it was more in left side than right side. Reduced or abolished vibration perception were observed in upper and lower extremities which were more marked distally and abolished in distal fingers and toes (more on left side than right side). The patient was still presenting with both urinary and faecal incontinence. On 08 Apr 2010, the patient was internally transferred to another rehabilitation section for further 3 weeks until 29 Apr 2010. At the time of discharge, following additional diagnosis were made: dysphagia and aspiration pneumonia involving need of respiratory support from 01 Jan 2010 because of hypoxemia and final weaning up to 10 Mar 2010; intermittently, blockade of tracheotomy (tube withdrawn on 15 Mar 2010); AV-block grade III on 30 Nov 2009 lasting 5 seconds with subsequent bradycardia; intermittent, self-limiting bradycardia primarily attributed to Miller-Fisher syndrome; Chronic renal failure, stage II; diabetes mellitus type 2; urinary tract infection with isolation of E. coli and pseudomonas measure was 30 to 35 points. Motor functions were severely impacted as the value for Barthel index was 0 to 15 points and score for motor functional independence measure was 13 to 30 points. Value of Barthel Index was 200 to -76 points for abilities-rehabilitation (daily routine functions, self-care).