Introduction
Primary angiitis of the central nervous system (PACNS) is a rare idiopathic disorder that results in multifocal inflammation of the small and medium-sized blood vessels in the brain, which causes focal or diffuse neurological symptoms (1,2). PACNS may occur at any age, but is predominantly observed in children aged between 4 and 6 years old, with no clear gender predilection (3). PACNS is a rare disease, with incidences of 1–2.4 per million per year reported in Europe and America (4). Although PACNS is extremely rare, the number of reported cases has gradually increased since the late 1970s and after the diagnostic criteria had been devised (5). Viral infections increase the possibility of PACNS, particularly in immunocompromised patients (5). It is important to diagnose it promptly, since results on a small case series have suggested a favourable response to corticosteroids and immunosuppressive therapy (6). However, the diagnosis is often difficult due to its rarity and nonspecific clinical presentation (7). The range of differential diagnosis is broad, including infection, connective tissue diseases and systemic vasculitis, which require careful exclusion (8). Magnetic resonance imaging (MRI) is the primary neuroimaging modality for patients with suspected PACNS (9). Most PACNS patients have abnormal findings on MRI. Therapy comprises of immunosuppressants, including corticosteroids alone or, preferably, in combination with cyclophosphamide (10).
The present study performed a retrospective analysis of 19 cases of PACNS from Suqian City People's Hospital (Suqian, China) to characterise the MRI features of PACNS and to evaluate the diagnostic value and clinical significance of MRI.
Discussion
In 1959, Cravioto and Feigin (11) were the first to recognize the entity of PACNS after examination of brains on autopsy. PACNS attracted more attention when instances of successful treatment were reported in the 1980s (12). It was then referred to as ‘granulomatous angiitis of the CNS’, with the lesions mainly consisting of granulomas. In 1983, the term ‘isolated angiitis of the central nervous system’ (IACNS) was adopted for the disease. However, as certain patients presented with extracranial involvement, the term IACNS had limitations, and in recent years, the term PACNS has therefore been used in common practice (13).
According to Kelley (14), PACNS may be due to direct damage to blood vessels from infection or an immunoreaction mediated by immune complex deposits from auto-antibodies. PACNS may occur at any age. The mean age of the cohort of the present study was 42 years. The mode of onset may be acute or insidious. The prodrome usually lasts for half a year or longer, featuring chronic processes and easy recurrence. PACNS has varied clinical symptoms with headache being most common one (15), which occurred in 14 cases of the present study. Symptoms may correspond to focal or diffuse CNS involvement. Focal symptoms include hemiparesis and seizures; diffuse symptoms are headache, apathy, cognitive abnormalities and psychosis (16).
The histopathologic features of PACNS include inflammatory infiltrates composed mainly of lymphocytes accompanied by histiocytes and plasma cells, particularly involving small leptomeningeal and intracerebral arteries (17,18). Small vessels can be distinguished by bleeding of small vessels in brain parenchyma. At the acute stage, the vascular wall is infiltrated by lymphocytes, plasmatocytes, monocytes and giant cells. In the chronic stage, achroacytes and multinucleate giant cells with focal fibrosis of the vascular wall are observed. Langerhans cells are found in granulomatous arterial angiitis. At the stable stage, scar tissues develop (19).
A confirmed diagnosis of PACNS generally requires digital subtraction angiography (DSA) or biopsy, but none of them shows a high diagnostic rate (20,21). This is due to clinically suspected PACNS having a low detectability on DSA and biopsy results being subject to sampling errors and showing a variation depending on the course of the disease (22). The high proportion of negative biopsies in patients with clinical and radiographic features of PACNS may be explained as follows: i) The larger-diameter vessels of lesions may not extend to the superficial parenchyma and leptomeninges, and biopsy may not be possible and ii) vessels of lesions in the potential biopsy field may be excluded by sampling errors due to their focality (23).
The MRI manifestations of PACNS are highly varied, with a sensitivity of 90–100% (3,5). Lesions are mostly located in the subcortical and deep white matter, while they are less common below the tentorium and occasionally occur in the spinal cord (5%) (9). The lesions in the present case series presented with slightly low intensity on T1WI, slight hyperintensity on T2WI, hyperintensity on FLAIR, isointensity or slight hyperintensity on DWI and hyperintensity on ADC mapping. Restricted or normal ADC values were found in the majority of acute and sub-acute phase PACNS lesions in the present study. Lesions with restricted ADC values are thought to be ischemic (6).
Infarcted lesions had cytotoxic oedema. The lesions with normal ADC values may reflect persistence of cytotoxic oedema and development of simultaneous vasogenic oedema (24).
PACNS mainly involves small and medium-sized vessels, and most lesions do not present as a wedge shape and do not conform to the typical distribution region of a vascular territory; MRI detection has a fairly high sensitivity. DWI has been recommended for the diagnosis of PACNS (3,25), and is capable of detecting early or small-sized lesions, particularly for identifying additional lesions in different vascular distribution regions or in different stages (26). Cytotoxic oedema is thought to be one characteristic of PACNS (27). DWI is helpful in increasing the diagnostic accuracy (28). Occasionally, since microhaemorrhages may occur, petechial hypointense lesions are seen on SWI, as in our patients.
SWI is an advantageous sequence for diagnosing PACNS. SWI is a technology with generates images by using magnetic susceptibility, including phase images and magnitude images, which are blended through reprocessing and made into SWI images. Vascular imaging on SWI relies on magnetic susceptibility deviation in oxygen saturation; it is free from interference by blood flow velocity and is thus particularly advantageous for imaging of small vessels around angiitis.
Lesions may be multiple, bilateral, unilateral, symmetrical, asymmetrical and even tumour-mimicking, and may show heterogeneous, cord-like and gyral enhancement patterns (4,28). MRI contrast-enhanced scanning has a significant meaning for diagnosing PACNS through diversified enhancement of the lesion. The vascular walls of acute inflammatory lesions are thickened and enhanced, which may be regarded as a direct sign of angiitis. Enhanced scanning serves as a basis for judging old and new lesions.
With regard to differential diagnoses, PACNS requires to be differentiated from the following diseases: i) Cerebral infarction: This disease tends to appear in patients with a medical history of hypertension, arteriosclerosis or diabetes mellitus. DWI and ADC mapping are useful for diagnosing infarction. ii) Multiple sclerosis: It mostly has an acute onset and a deferred course of disease. Multiple sclerosis is generally present in the white matter. iii) Infectious lesions. Onset may be acute or sub-acute and the disease course is comparatively short. Common signs of disease include fever, cephalalgia and meningeal irritation. Cerebrospinal fluid examination may provide evidence for intracranial infection. iv) Mitochondrial encephalomyopathy: This disease mainly features epileptic seizures and increased lactic acid, presenting as a disorder of energy metabolism and more pronounced damage to the cortex.
For the treatment of PACNS, glucocorticoids are the first choice for treating PACNS. In cases of resistant disease, CTX may be added. The period of treatment is 1–2 years in general. Within the cohort of the present study, 17 patients showed evident improvement of their clinical symptoms and imaging performance. Two patients had a relapse and progression of the symptoms during ongoing steroid therapy but responded to subsequent combination treatment with CTX. Furthermore, combination of steroids with CTX produced clinical stabilization in 8 patients with severe PACNS. Analysis of the cases of the present study as well as evidence from other cases from the literature suggested that long-term remission or cure is possible, particularly when therapy is combined with CTX (29,30).