A man in his 40s with headache and blurred vision

The patient had had recurrent otitis and episodes of treatment-resistant sinusitis. Apart from that, he was previously healthy. During a flight to Spain he developed left-sided earache and was treated for suspected otitis at a local medical office. After a few days he had increasing global headache, dysarthria and paresthesias in the right half of his body, later also secretion from the left ear. MRI of the head taken at a hospital in Spain revealed fluid in mastoid cells and a rim over the left hemisphere interpreted as chronic subdural haematoma. The patient was treated conservatively.

After his return to Norway, three weeks after the onset of symptoms, the patient developed blurred vision in the right eye, and was hospitalised at the University Hospital of North Norway. On admission he was in a slightly reduced general condition. The patient had significantly reduced right eye vision, tinnitus in the left ear and slight dysarthria. Extensive blood screening showed a sedimentation rate of 74 mm/h (2 – 12 mm/h), CRP of 83 mg/l (< 5 mg/l) and slightly elevated c-ANCA (S-Anti-PR3) of 12 U/ml (negative: 0 – 10 U/ml, positive: 11 – 530 U/ml), but otherwise normal findings. Spinal fluid analysis revealed slight pleocytosis with white blood cells of 29 · 10⁶/l (< 5 · 10⁶/l) and total protein of 686 mg/1 (< 500 mg/l). The opening pressure of the lumbar puncture was normal. The ophthalmologist’s conclusion was infarction of the right optic nerve. The ear, nose throat specialist found crust formation in the left nasal cavity, and there was suspected leakage of cerebrospinal fluid from the left ear. No infectious agent was detected in any of the body fluids (blood, cerebrospinal fluid, ear secretion, nasopharynx or urine). MRI of the head revealed a fluid rim with swelling and contrast enhancement in the meninges over the left hemisphere and fluid in the mastoid area on the left side (Figs 1 a – c). This was interpreted as probable meningeal effusion. The conclusion was bacterial meningitis, and the patient was put on antibiotics.

It was assumed that the low cell count in the spinal fluid was due to the patient having previously been treated for otitis with oral antibiotics. The patient was also examined by a neurologist, whose conclusion was atypical subacute meningitis, which could give rise to suspicion of autoimmune meningitis syndromes, for example hypertrophic pachymeningitis. Antibiotic treatment for suspected bacterial meningitis arising from otitis (or possibly mastoiditis) was nevertheless resumed. The patient was also treated with dexamethasone and had a ventilation tube implanted in his left ear. After two and a half weeks in hospital and a considerable improvement in his condition, he was discharged to home.

Further episodes of global headache with pressure features, CRP rise and sensory symptoms in the right half of the body as well as epileptic seizures in the next three weeks led to two rehospitalisations with new antibiotics and the introduction of antiepileptic medication. Repeated cerebrospinal fluid analyses showed unchanged findings. No infectious agent was found in the cerebrospinal fluid or other body fluids. MRI revealed increasing left-sided cortical brain oedema. Exploratory craniotomy with meningeal biopsy was performed, considering the possibility of epi- or subdural empyema. There were macroscopic findings of a normal coloured, but hard, thick dura, and easily bleeding subdural granulation tissue. Histology revealed a thickened dura with fibrosis and non-specific inflammatory infiltrate (Fig. 2). Microbiological test results were normal. At an interdisciplinary meeting attended by an infection specialist, neurologist, ear, nose, throat specialist, ophthalmologist, rheumatologist, neurosurgeon, neuroradiologist and neuropathologist, it was concluded that the patient’s symptoms were most likely due to intracranial hypertrophic pachymeningitis.

The patient was given a thorough examination. Differential diagnostic possibilities as mentioned in the literature (Fig. 3) were eliminated, with the exception of Wegener’s granulomatosis, which could not be excluded with certainty. Further studies were therefore focused on this. The sole positive finding was c-ANCA, which was weakly positive initially, but subsequently within the reference range. Blood tests were otherwise normal. No skin changes or heart or kidney affection were found. CT of the temporal bone showed fluid and soft tissue thickening in the middle ear and denser mastoid cells on the left side. CT of the sinuses showed a hypoplastic left maxillary sinus with thickening of the mucous membrane and an air-fluid level, but no granuloma. The conclusion of a biopsy of the respiratory mucous membrane was non-specific chronic infection, and no vasculitis or granuloma. CT of the thorax showed possible progression of one of the small non-specific nodular opacities found in the left upper lobe at the onset of the illness, but the change was not accessible for biopsy (Fig. 4).

Thus no clear evidence was found of underlying disease, either Wegener’s granulomatosis or any other condition, and the patient was treated for assumed idiopathic intracranial hypertrophic pachymeningitis. High-dose Solu-Medrol was administered for five days followed by peroral administration of 80 mg × 1 for six weeks, with slow down-titration. This treatment led to regression of both symptoms and changes on the MRI.

During down-titration of steroid treatment to 30 mg daily, the patient developed symptoms again, including diplopia. Right-side external ophthalmoplegia was found with affection of the oculomotor-, trochlear- and abducens-innervated musculature.

The patient had also complained of numbness corresponding to the ophthalmic branch of the trigeminal nerve over the affected eye. The headache was now located mainly in the right temple region up towards the forehead. A further MRI of the head and re-examination of the previous scan retrospectively revealed fluid and soft-tissue congestion around the left internal carotid artery and the jugular vein below the skull base (Fig. 1c). The condition was interpreted as being Wegener’s granulamatosis, with weakly positive c-ANCA, thickening of the mucous membrane in the sinuses, small nodular opacities in the lungs, external ophthalmoplegia with affection of several eye muscles and numbness of the forehead – even though no biopsy findings confirmed the diagnosis. The patient was transferred to the Department of Rheumatology. Because of the severity of the disease, he was treated with intravenous cyclophosphamide for six months with plans for a transition to methotrexate as maintenance treatment. However, at the evaluation after the treatment with cyclophosphamide, a further MRI head scan showed increased thickness of the meninges, and the patient was given rituximab. He has responded well to this treatment. Up to now, three rounds of therapy have been administered. The disease is in remission, the patient is free of symptoms and back in full-time work.