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Primary angiitis of the central nervous system presenting with subacute and fatal course of disease: a case report
© Lukas et al; licensee BioMed Central Ltd. 2005
Received: 06 June 2005
Accepted: 14 September 2005
Published: 14 September 2005
Primary angiitis of the central nervous system is an idiopathic disorder characterized by vasculitis within the dural confines. The clinical presentation shows a wide variation and the course and the duration of disease are heterogeneous. This rare but treatable disease provides a diagnostic challenge owing to the lack of pathognomonic tests and the necessity of a histological confirmation.
A 28-year-old patient presenting with headache and fluctuating signs of encephalopathy was treated on the assumption of viral meningoencephalitis. The course of the disease led to his death 10 days after hospital admission. Postmortem examination revealed primary angiitis of the central nervous system.
Primary angiitis of the central nervous system should always be taken into consideration when suspected infectious inflammation of the central nervous system does not respond to treatment adequately. In order to confirm the diagnosis with the consequence of a modified therapy angiography and combined leptomeningeal and brain biopsy should be considered immediately.
Primary angiitis of the central nervous system (PACNS) is an idiopathic, recurrent vasculitis confined to the central nervous system and the dural reflections. It may involve small and medium-sized leptomeningeal, cortical and subcortical arteries. The most common presentation is headache with encephalopathy accompanied by multifocal symptoms . PACNS can occur at any age but there is a predominant appearance in the fourth to sixth decade . The course and the duration of this disease show a wide variation. We describe a case with rapid progression and fatal outcome.
The clinical course of PACNS shows a wide variation, progressive courses with fatal outcome as well as benign courses have been reported. In general, the course of the untreated disease is, if clinical manifestation is protean, progressive, with death occurring within 9–12 months . Shukla et al. reported on a patient with PACNS and an unusual prolonged clinical course of 8.5 years without treatment . The ante-mortem diagnosis of PACNS depends on a combination of clinical, imaging and histological findings. Major differential diagnosis of PACNS include secondary vasculitides of the CNS which can occur in collagen vascular disorders, viral and bacterial infections, in malignancies and due to drugs and substance abuse [1, 4]. Abeta-related angiitis (ABRA) that occasionally complicates cerebral amyloid angiopathy may also be taken into consideration, however, the mean age of presentation of ABRA seems to be higher than that of PACNS . Young women with a history of headaches may present with benign angiopathy of the central nervous system [6, 7]. Headache and encephalopathy are also common clinical features of posterior leukoencephalopathy. This newly recognised neurological disorder is usually seen in patients with uncontrolled hypertension, eclampsia and in patients treated with immunosuppressive drugs . As recently published, posterior leukoencephalopathy can be associated with isolated CNS angiitis .
Examination of the CSF in PACNS is abnormal in 80–90% of patients and consists of lymphocytic pleocytosis and elevated protein . MRI findings in PACNS are variable and non-specific. The most common findings are multiple bilateral asymmetrical supratentorial lesions, involving grey and white matter . In a few cases mass lesions have been described [10, 11], but nevertheless normal MRI and biopsy findings consistent with CNS vasculitis have also been found . Abnormal conventional angiography may be useful to assume cerebral vasculitis [12, 13], but many cases of PACNS have normal arteriograms while in cases with abnormal findings, such as multiple segmental narrowings of cerebral arteries, the diagnosis of PACNS could not be confirmed . Moore has suggested criteria for the diagnosis of PACNS . To fulfill these criteria systemic infections and inflammatory diseases have to be excluded. Combined leptomeningeal and brain biopsy has to confirm the presence of vascular inflammation. Biopsy should be performed prior to immunosuppressive treatment in order to exclude lesions of infectious, neoplastic or non-inflammatory etiology and to confirm a diagnosis of vasculitis. Due to the segmental nature of the lesions false-negative results can be obtained in up to 35% of biopsies [15–18]. The best established therapy is a combination of high-dose steroids with cyclophosphamide . After clinical stabilization of the patient, treatment should be continued for at least 1 year .
In our case the duration between onset of neurological symptoms and death was markedly short. Fever, that one would expect in infectious inflammation of the CNS, was not present in our patient. Nevertheless, the lack of fever is not specific enough to guide diagnostic efforts. These conditions highlight the importance of early angiography and biopsy in cases of suspected vasculitis. Unfortunately, in our case the brief and fluctuating course of the disease with final deterioration within 10 days did not lead to angiography and brain biopsy in time. In conclusion even in young patients PACNS should always be taken into consideration especially when suspected infectious inflammation of the CNS does not respond to treatment adequately. In the face of a progressive clinical course and no specific etiological diagnosis one should not continue to treat CNS inflammatory disease empirically. Since PACNS would require a modification of the therapy, angiography and a combined leptomeningeal and cortical biopsy should be performed immediately.
Written consent was obtained from the relatives of the patient for publication of the case report.
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