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Granulomatous angiitis (GANS) of the CNS is a rare, idiopathic vasculitis confined largely to the small blood vessels of the CNS. It has also been referred to as “isolated”,1“primary”, and “idiopathic”2 angiitis of the nervous system. Clinical manifestations are usually the result of multifocal ischaemia and infarction and patients with GANS typically present with a chronic and relapsing but ultimately progressive encephalopathy, characterised by cognitive impairment and multifocal deficits. Less commonly, haemorrhage can occur as a result of infarction, focal necrosis of a vessel wall, or aneurysm rupture and the presentation may therefore be primarily neurosurgical.3 4 It is important to recognise this condition because long term clinical remission is possible with immunotherapy. In this letter we present a case which serves as a reminder to neurosurgeons to include GANS in the differential diagnosis of spontaneous intracerebral haemorrhage and emphasises the importance of leptomeningeal biopsy.
A forty six year old woman was admitted to our unit with a 24 hour history of confusion, vomiting, dysphasia, and a generalised seizure. The patient also had a 30 month history of deteriorating work performance and had had episodes of nausea, vertigo, and headache lasting 1 to 2 days. After one of these episodes she was investigated by one of us (SM). Neurological examination and a CT were normal. Diagnoses of migraine and Ménière’s disease were considered. Four months before admission, she had experienced transient mild dysphasia and left hemianaesthesia.
On admission to our unit, she was drowsy but opened her eyes to voice and obeyed simple commands. She had a left retinal haemorrhage and an expressive dysphasia. She was afebrile, there was no meningism, and general examination was normal. Brain CT showed an extensive area of low density involving both grey and white matter of the left frontal lobe, with three separate areas of intraparenchymal haemorrhage and mild mass effect. She was started on dexamethasone, phenytoin, and acyclovir and arrangements were made for MRI and MR angiography to be performed the following day.
An improvement was noted overnight, but the next day her clinical condition deteriorated. Urgent CT was performed and this showed further haemorrhage into the left frontal lobe with appreciable midline shift (figure). Immediately after the scan her left pupil became fixed and dilated. An urgent left frontal lobectomy was performed.
Macroscopically the left frontal lobe was swollen, with multiple small areas of haemorrhage in the cortex and white matter, and thrombosis of superficial cortical veins. Histological examination disclosed a coexistant pattern of granulomatous and necrotising non-granulomatous vasculitis affecting the small leptomeningeal and intracerebral blood vessels. Occasional leptomeningeal vessels were occluded by thrombus.The granulomatous lesions featured an infiltrate of lymphocytes and histocytes within blood vessel walls. The vascular intima was variably thickened by a fibrocellular proliferation and small numbers of Langhans and foreign body type giant cells were scattered individually within the media of some vessels.The leptomeninges contained a dense infiltrate of mononuclear inflammatory cells. The cerebral tissues were oedematous with extensive extravasation of erythrocytes and diffuse hypoxic neuronal changes but there was no evidence of a discrete area of infarction. Special stains for organisms (zinc, gram, PAS, PAS-D, Giemsa and GMS) were negative. Viral inclusions were not seen.
Haematological investigation disclosed a mild neutrophil leucocytosis, but haemoglobin, platelet count, and erythrocyte sedimentation rate were all in the normal range as were serological investigations including C reactive protein, complement assays, antinuclear antibodies, double and single stranded DNA antibodies, and rheumatoid antibodies.
The patient was treated intensively with a combination of oral cyclophosphamide and intravenous methyl prednisolone for one week followed by oral cyclophosphamide and prednisone. Treatment was complicated by haemorrhagic cystitis (for which oral cyclophosphamide was changed to pulsed intravenous cyclophosphamide), and organic psychosis. At 2 years the patient is clinically stable. Immunotherapy is being gradually reduced. She has a fixed frontal lobe deficit consisting of impulsivity, a loss of control of emotions, reduced verbal fluency, and impaired insight. Serial CT and MRI show only postsurgical change in the left frontal lobe.
The importance of this case is firstly that it draws attention to the protean manifestations of this rare but treatable condition. Other reported presentations include recurrent intracerebral haemorrhage, radiculomyelopathy, cerebral and spinal aneurysms, subarachnoid haemorrhage, seizures, and mass lesions.1 2 5
Secondly, this case emphasises the fact that the disease mostly affects small vessels of the leptomeninges. Neurosurgeons are most likely to encounter this disease in the setting of a request by their neurology colleagues for a diagnostic brain biopsy. Moore suggested that the ideal biopsy in these patients is a 1 cm wedge of cortex including leptomeninges and preferably containing a cortical vessel.1
Our patient ultimately required urgent decompressive frontal lobectomy. The diagnosis of GANS was not suspected preoperatively and the inclusion of leptomeninges in the surgical specimen was fortuitous. We would advise others undertaking the evacuation of an intracerebral haematoma of uncertain aetiology to obtain a leptomeningeal biopsy at the same time, particularly when there is a background of neurological symptoms.
Other investigations may not be helpful. Brain CT and MRI are abnormal in 30%-65% and 75%-100% of cases respectively and may show a wide variety of lesions. Angiographic abnormalities are present in 50%-90% of cases but are not specific for GANS. The CSF may be normal.1 2 It is essential to differentiate GANS, from the many secondary causes of cerebral vasculitis such as giant cell arteritis. The presence of markers of systemic, inflammatory, or autoimmune disease should suggest an alternative diagnosis.
Because GANS is rare, our knowledge of its natural history and optimum management is incomplete. Early reported cases of GANS were invariably fatal5 but immunotherapy has now been shown to improve symptoms and result in sustained remission in some cases. The results with corticosteroids alone have been disappointing and the combination of prednisone with cyclophosphamide is the mainstay of treatment.1 3 5