In mid-January 2010, a 49-year-old male with pulmonary asthma and a prior history of nasal polyps woke up at 00.30 at night with a feeling of tongue swollenness. Upon standing up, he noticed paraesthesia of the left hand and a left facial droop. When the emergency medical staff arrived, he was sitting, his speech was blurred, and the muscle strength of his extremities was unaffected. Due to the wake-up nature of the mild hemiparesis, he was not considered a candidate for thrombolysis treatment when he was pre-notified to the neurological emergency by the emergency medical staff.
The patient had never smoked, and his previous medical history was free of cardiac symptoms, hypertension, hyperlipidaemia, diabetes, or migraine. He was in excellent physical condition and had done a 10-km cross-country skiing trip 2 days before. In addition, he had previously run several marathons. Physical examination at the emergency department revealed a slight pronation of the left arm and a mild slowness of the diadochokinesia of the left hand together with a residual paresis and paraesthesia of the lower facial area. The head CT scan showed no findings, and neither did the plain chest X-ray. The patient was admitted to a neurological ward with a working hypothesis of brain stem infarction, and acetylsalicylic acid was administered at a loading dose of 250 mg orally, which was continued at a dose of 100 mg daily.
The next day, a head MRI and MR angiography (MRA) revealed a fresh minor infarction at the corona radiata on a FLAIR sequence (fig. 1a), with a diffusion-weighted image showing restricted diffusion of the lesion, consistent with an infarct (fig. 1b), as well as a 3-mm hemosiderin ring at the right putamen (fig. 1c). The MRA of the intracranial and neck vessels was unremarkable. The left hemiparesis progressed to sensory-motor hemiplegia on the 4th day. The head CT scan showed an expansive right-sided intracerebral haemorrhage in the basal ganglia extending to the corona radiata (fig. 1d).
The ancillary aetiological studies of the haemorrhagic infarction included transcranial Doppler sonography, which showed right-sided microemboli that were increased after a Valsalva manoeuvre. Correspondingly, a minor atrial septal defect (ASD) with shunting was suspected at transthoracic echocardiography. The patient had a heterozygotic clotting factor V R506Q mutation, i.e. activated protein C (APC) resistance.
On admission, the blood chemistry showed mild leucocytosis of 9.2 E9/l and the C-reactive protein (CRP) level was 7 mg/l. Head CT scan revealed asymptomatic pansinusitis of the frontal, ethmoidal, and left sphenoidal cavities, and the patient was given oral amoxycillin. However, during the first 10 days, the CRP level rose up to 185 mg/l, and the leucocyte count up to 20.7 E9/l. Chest X-ray remained normal. Maxillary puncture was performed, and the bacterial cultures of the pus grew coliforms and local normal flora, susceptible to the antimicrobials being used. The empiric antimicrobial therapy was changed to cefuroxime and metronidazole and then piperacillin plus tazobactam, without any response in the inflammatory parameters. The patient had high fever (up to 38.8 C) and intense muscle pain, but blood cultures were negative. Consequently, contrast-enhanced body CT was performed and showed wide-spread bilateral nodular chest infiltrates in all pulmonary lobes and reactive lymph nodes in the upper mediastinal area. Bronchoalveolar lavage was not possible due to the haemorrhagic brain infarction.
An infectious diseases specialist was consulted, and further diagnostic work-up showed a remarkable blood eosinophilia of 4.89-9.8 E9/l (30-42%) (fig. 2), positive anti-neutrophilic cytoplasmic antibodies (P-ANCA) antibody titer (200; reference value <20), a high serum myeloperoxidase antibody level (63.4 IU/ml; reference value <6) and slightly positive serum proteinase 3 antibodies (9.9 IU/ml; reference value <4), slightly decreased levels of serum IgA (0.74 g/l; reference value 0.88-4.84), normal IgG, but elevated IgG4 (4.45 g/l; reference value 0.08-1.4) (table 1). The patient had never visited the tropics. Also, stool examinations were negative for parasites including amoeba staining and Strongyloides culture, and the patient did not show serum antibodies against Trypanosoma, Toxocara, Echinococcus, Fasciola, schistosoma, Filaria, Strongyloides or Toxoplasma. Additionally, serologic tests for HIV, cytomegalovirus, Epstein-Barr virus, human herpes virus 1 and 2, and for hepatitis A, B and C were all negative. The patient did not have anti-phospholipid antibodies. HLA typing showed HLA-B*35 allele (heterozygous mutation).
The bone marrow aspirate revealed normal morphology and relatively strong eosinophilia, and the chromosomal investigation was unremarkable. Interferon gamma release assay for M. tuberculosis was negative.
The combination of asthma, sinusitis, history of nasal polyps, and eosinophilia, together with the detection of antinuclear and anti-neutrophilic antibodies evoked the suspicion of Churg-Strauss syndrome, leading to the treatment decision of a 3-day therapy with intravenous pulse methylprednisolone (1 g/day). The blood eosinophils and ANCA antibodies were undetectable 3 days and 1 month after treatment onset, respectively (fig. 2). Beta-lactam antimicrobials were changed to clindamycin together with ciprofloxacin. There were no skin or joint manifestations, cardiac dysfunction or signs of peripheral neuropathy at the time of the diagnosis, nor did the head MRA demonstrate findings that would have confirmed the CNS vasculitis as aetiology of the haemorrhagic brain infarction. The cerebrospinal fluid was not investigated, nor was a brain biopsy taken to confirm the CNS vasculitis, because of the urgent need to start immunomodulatory therapy due to the suspicion of Churg-Strauss syndrome with a cytotoxically high eosinophil level. Nasal mucous membrane biopsy did not confirm vasculitis either. No renal biopsy was performed; however, the CT scan showed wedge-like lesions, suggesting renal infarcts. In addition, urine examination showed slight microscopic haematuria and proteinuria (834 mg/l). Alanine aminotransferase temporarily increased to 509 U/l.
After treatment with high-dose corticosteroids i.v. for 3 days, the patient was first given cyclophosphamide for 2 weeks together with oral prednisolone, until he developed prolonged neutropenia and fever. During that time, he also developed ileus, which was managed conservatively. Later, a colonoscopy was performed which showed a rectal tubular polyp but no ischaemia or inflammatory lesions. At that time, he was started on immunoglobulins (0.4 g/kg i.v.) given every 3 weeks as an additive immunomodulatory treatment together with oral corticosteroids (fig. 2).
Three months after the start of the immunosuppressive treatment, while on oral corticosteroids (prednisolone 20 + 10 mg) and azathioprine (100 mg), the patient suddenly and unfortunately developed peritonitis. A laparoscopy showed an ileal perforation, but there were no histological changes suggesting vasculitis. Though taken during immunosuppressive treatment, electroneuromyography (ENMG) suggested vasculitis-like neuropathic changes, but an undiagnostic muscle biopsy from the right vastus lateralis muscle contained only subcutaneous tissue with no signs of necrotizing vasculitis or eosinophils.
The left-sided sensory-motor hemiplegia and the neuropsychological symptoms indicated physio- and ergotherapeutic as well as neuropsychological rehabilitation, which was actively continued after the initial complications. The patient was still in a neurological rehabilitation institution almost 7 months after the ictus.