Primary Angiitis Of The Central Nervous System Research Articles

Benign angiopathy of the central nervous system: cohort of 16 patients with clinical course and long-term followup.

Benign angiopathy of the central nervous system (BACNS) is a subset of primary angiitis of the central nervous system (PACNS) with favorable outcome, not requiring prolonged immunosuppression. We retrospectively studied the clinical characteristics and prospectively assessed long-term outcome in a cohort of BACNS patients. Patients meeting the clinical description for BACNS, evaluated and treated by a single investigator, were included. Data on demographics, signs and symptoms, laboratory studies, neuroimaging, brain biopsy, treatment, and complications were recorded. The long-term assessment included a phone interview utilizing the Barthel index and a specifically designed cognitive index. Sixteen cases met the inclusion criteria. Mean age was 40 years (range 10-66 years) with female:male ratio of 4.3:1 and a mean followup period of 35 months (0-128 months). Headache was the most common presenting symptom, seen in 88% of the cases, followed by focal symptoms (63%), and diffuse symptoms (44%). All patients had highly abnormal cerebral angiography, and magnetic resonance imaging abnormalities were present in 77% (10 of 13). Severe cerebral spinal fluid (CSF) abnormalities were present in 1 patient (7%). All followup cerebral angiography showed marked improvement. Recovery was demonstrated in 94% of the patients, 6% relapsed, and there were no deaths. Of patients assessed by the Barthel index, 71% showed no disability and 29% had mild disability. There is a PACNS subset characterized by acute presentation (most commonly headache), normal to mildly abnormal CSF findings, female predominance, and highly abnormal cerebral angiography (reversible after treatment), requiring less intensive treatment than has been traditionally used.

CADASIL Mimicking Primary Angiitis of the Central Nervous System

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and primary angiitis of the central nervous system (PACNS) share several clinical and radiological features. However, digital subtraction angiogram (DSA) is generally reported as normal in CADASIL, whereas lumen irregularities in distal cerebral arteries indicate PACNS. To describe a potential pitfall of DSA interpretation, which led to the tentative diagnosis of PACNS in a CADASIL patient. Single case observation. A 47-year-old man sustained recurrent subcortical infarcts. He had mild hypercholesterolemia and migraine. His family history was unremarkable. The underlying cause of stroke could not be elucidated. Transcranial Doppler sonography revealed decreased intracranial blood flow velocities compatible with CADASIL. Lumen irregularities of several peripheral intracranial arteries were seen on DSA, which suggested PACNS. CADASIL was confirmed by results from skin biopsy and genetic testing. First, in patients with CADASIL, DSA can show segmental lumen irregularities in distal cerebral arteries suggestive of PACNS. Second, the potential role of transcranial Doppler sonography to distinguish CADASIL from PACNS deserves further testing.

Primary angiitis of the central nervous system: serial MRI of brain and spinal cord.

MRI findings in primary angiitis of the central nervous system (PACNS) are highly variable, ranging from normal to diffusely abnormal. We describe brain and spinal cord abnormalities in patients with PACNS and changes over time, to provide criteria which could be useful for differential diagnosis. We reviewed six patients, with a final diagnosis of PACNS, who underwent serial contrast-enhanced brain and spinal MRI. Follow-up ranged from 12 to 60 months. Brain MRI showed multiple small abnormalities in all patients, giving high signal on T2-weighted images, focal or diffuse, mainly in deep and subcortical white matter; four patients had both supra- and infratentorial lesions. On the initial MRI, in five patients, almost 90% of the abnormal foci showed contrast enhancement. Virchow-Robin perivascular spaces were enlarged and simultaneously enhancing in four patients. Three patients also had spinal cord abnormalities, in the cervical and thoracic segments in two, and exclusively cervical segment in one. Two patients had brain biopsy-proven PACNS; in the remainder, the diagnosis of PACNS was presumptive, considering similarities in clinical and MRI features and MRI follow-up. On MRI, after steroid and immunosuppressive therapy, a significant decrease in the number and size of the abnormalities, enhancing and nonenhancing and of enhancing perivascular spaces was observed. Simultaneous enhancement of brain and spinal cord lesions and of perivascular spaces, at the onset of the disease, which resolves during follow-up, can therefore suggest PACNS.

Vasculitis of the nervous system.

Vasculitis is inflammation of the blood vessels, which may involve either the central nervous system (CNS), or the peripheral nervous system (PNS), or both. This involvement may be primary and restricted to the CNS, and rarely to the PNS."Primary angiitis of the CNS" is the term used to describe isolated CNS involvement by vasculitis, in which neither the clinical presentation and behaviour of the disease, nor the histopathology is uniform. This heterogeneity indicates a spectrum, depending on the type and extent of the vascular involvement seen within the CNS, covering a group of disorders, rather than a single disease. This may explain the different prognosis and response to treatments. In clinical practice vasculitis of the nervous system, secondary to a known cause or underlying disease is more commonly seen than as a primary disorder. Primary systemic vasculitides and connective-tissue disorders, Behçet's Disease, lymphoproliferative diseases and other malignancies, some infections and related conditions, drugs and substance abuse are some of the conditions known to cause vasculitis in the nervous system. There is a broad variety of pathogenetic mechanisms. Both the CNS and the PNS may be involved, either separately or together.

Primary angiitis of the central nervous system: Unusual clinical presentation

Primary angiitis of the central nervous system (PACNS) is a form of vasculitis restricted to the CNS. Most patients with PACNS present with focal neurologic deficits suggesting stroke or with a syndrome of headache and confusion. Less commonly, seizures, dementia, cranial neuropathies, myelopathies and, rarely, radiculopathies are seen. We report a 14-year-old girl who presented with partial motor seizures complicating focal cerebral vasculitis of superior parietal gyrus on the left. Despite extensive evaluation, no etiology was apparent for the vasculitis. Steroid therapy was administered, and 6 months after the therapy, she remains healthy except for a mild weakness of her right leg. Follow-up brain magnetic resonance images were normal. We conclude that partial motor seizures is uncommon as a presenting complaint in PACNS and steroid therapy is successful for this patient.

Abstracts of literature

Abstracts of literature

Brain biopsy in primary angiitis of the central nervous system.

To determine the yield of brain biopsy and the predictive value of clinical features and ancillary studies, we retrospectively analyzed hospital chart data from 61 consecutive patients suspected of having primary angiitis of the CNS (PACNS). Biopsies disclosed PACNS in 22 (36%), alternative diagnoses in 24 (39%), and no diagnosis in 15 (25%). Clinical indicators and angiography were not useful predictors of PACNS. Brain biopsy should be the primary diagnostic tool in this setting because of the poor reliability of other indicators and because of the high yield of alternative diagnoses requiring different management.

Angiographically defined primary angiitis of the CNS: Is it really benign?

Angiographically defined primary angiitis of the CNS: Is it really benign?

Vasculitis of the central nervous system.

Central nervous system (CNS) involvement and management in primary vasculitis (giant cell arteritis, primary angiitis of the CNS, Takayasu's disease, periarteritis nodosa, Kawasaki disease, Churg-Strauss syndrome, Wegener's granulomatosis) and vasculitis secondary to collagen vascular diseases, Beçhet's disease and other systemic conditions (excluding those secondary to infections) and the use of illicit drugs are reviewed. Vasculitis is an infrequent cause of stroke even in the young age groups, and routine screening of stroke patients for vasculitis is not cost-effective. CNS vasculitis may present with isolated CNS symptoms and signs (headaches, meningeal signs, encephalopathy, psychiatric syndromes, dementia, cranial nerve palsies, seizures, strokes), neuropathy or muscle damage, multiorgan involvement or non-specific systemic symptoms or a combination of the above. Magnetic resonance is the most sensitive ancillary procedure to detect CNS damage. Many of the angiographic features found in vasculitis are non-specific. Autoantibodies and tissue biopsy are also useful to the diagnosis. There are few controlled studies on the treatment of vasculitis. Usually a combination of steroids and cytotoxic drugs is used, but there is considerable variation between centres on current therapeutic regimens.

Angiographically defined primary angiitis of the CNS: is it really benign?

Primary angiitis of the CNS (PACNS) is a diagnostically challenging disorder. In patients whose diagnosis is ascertained solely by cerebral angiography without histologic verification, a benign monophasic clinical course with favorable response to a brief course of immunosuppressive therapy is often reported. We performed a retrospective review of patients with PACNS seen at the Stanford Stroke Center. Patients were followed for a median of 27.5 months. Acute focal deficits (9 of 10) and headache (3 of 10) were the most frequent presenting symptoms. Significant recurrent neurologic symptoms occurred in 5 of 10 patients before the initiation of immunosuppressive treatment. Three of six patients had recurrent symptoms during prednisone therapy alone, whereas only one of seven patients had recurrent symptoms while receiving combination immunosuppressive therapy. None had recurrent stroke during immunosuppressive treatment. Dynamic arterial changes were seen in four of five patients who underwent follow-up angiography that often, but not always, correlated with disease activity. Patients with angiographically defined PACNS frequently did not have a benign outcome or monophasic course. Repeat angiography was useful in supporting the diagnosis of PACNS, but did not always correlate with disease activity. A prospective multicenter collaborative effort is required to better define the clinical course and optimal treatment of PACNS.

Diagnosis of intracranial vasculitis: a multi-disciplinary approach.

Intracranial vasculitis, or primary angiitis of the central nervous system (PACNS), is an uncommon, often fatal disorder that frequently responds to aggressive immunosuppressive therapy. Magnetic resonance imaging (MRI), cerebral angiography, and brain biopsy are diagnostic modalities that vary in invasiveness and diagnostic accuracy. The purpose of this study was to determine whether certain clinical or radiologic features were predictive of a diagnostic biopsy. Thirty consecutive patients undergoing brain biopsy to "rule out vasculitis" were studied. Nine patients demonstrated granulomatous or lymphocytic vasculitis, 1 had lymphocytic vasculitis and encephalitis secondary to arbovirus infection, 5 had thickened vessels consistent with hypertensive changes, 5 had amyloid angiopathy and/or changes of Alzheimer disease, 5 demonstrated no pathologic abnormalities, and 1 each had acute infarct, vascular malformation, aneurysm, acellular fibrinoid necrosis, and demyelination. The spectrum of MRI and angiographic changes associated with PACNS were nonspecific, overlapping extensively with changes of chronic hypertension and amyloid deposition. The predictive values of brain biopsy (90-100%) were significantly higher than those of angiography (37-50%) or MRI (43-72%). In this study, morbidity associated with aggressive immunosuppression was significantly greater than that associated with cerebral angiography or brain biopsy. Thus, wedge biopsy of cortical and leptomeningeal tissues is central to the multi-disciplinary approach to a patient with clinical suspicion of PACNS.

Central nervous system vasculitis

Vasculitis is inflammation of blood vessel walls, which produces dysfunction in both the peripheral and central nervous system (CNS). Cerebral ischemia is the major cause for neurological manifestations of CNS vasculitis. Unfortunately, a universally accepted classification of vasculitis has not emerged. Vasculitis affecting the CNS alone is referred to as primary angiitis of the CNS; secondary vasculitis occurs in association with a variety of conditions, including infections, drug abuse, lymphoproliferative disease and connective tissue diseases. The pathogenesis of vasculitis includes different immunological mechanisms. Recently, anti-neutrophil cytoplasmatic antibody (ANCA) has been demonstrated to play an active role in the immunopathogenesis of the vasculitis. Diagnosis of vasculitis depends on a combination of clinical, radiographic and pathologic features. A wide spectrum of clinical features may occur. The most typical clinical picture of CNS vasculitis is troke, encephalopathy or seizures. Assays for ANCA, serum cytokines, antibodies to endothelial cell antigens have been reported to be useful in diagnosing or monitoring the disease activity. The gold standard in diagnosis is confirmation of vasculitis in a biopsy specimen. Angiography may suggest the diagnosis but not abnormalities are pathognomonic. Ideally, the therapy of each vasculitis would focus on the specific immunologic mechanism causing the disease. Such specific interventions are not yet available. In general the most important approaches induce global immunosuppression. The goal of therapy, however, is to prevent recurrence of disease.

Multiple appearing and vanishing aneurysms: primary angiitis of the central nervous system

The authors present the case of a patient with ischemic episodes and recurrent intracerebral hemorrhages probably caused by primary angiitis of the central nervous system (CNS). An initial angiogram revealed multiple cerebral artery aneurysms as well as vascular wall irregularity; a second angiogram obtained 2 years later, however, did not demonstrate the previous aneurysms but instead showed new ones together with stenosis. Based on the histopathological findings and clinical course in this case, the multiple aneurysms appear to have been induced by vascular wall fragility and subsequent self-repair resulting from primary angiitis of the CNS. The authors present the histological and clinical characteristics of this unusual case of granulomatous, necrotizing CNS vasculitis.

VASCULITIS OF THE CENTRAL NERVOUS SYSTEM

Angiitis of the CNS remains a poorly understood form of vascular inflammatory disease. Primary angiitis of the CNS or PACNS, a disease once considered extremely rare, recently has been reported more frequently. Traditional views of PACNS held it to be a relentless and uniformly fatal disease if untreated, but it is now viewed as more heterogeneous, with some relatively benign subsets. Its pathophysiology is poorly understood. Secondary vasculitis of the CNS can occur with a variety of other conditions and diseases; each requires a different diagnostic and therapeutic approach. Regardless of whether primary or secondary CNS vasculitis is considered, an understanding of the limitations of currently available neurodiagnostic investigations is essential.

Primary angiitis of the CNS diagnosed by angiography

Sixteen patients (8 female, 8 male) with primary angiitis of the CNS (PACNS), were followed prospectively in a vasculitis clinic. Diagnosis was by angiography in patients without underlying disease. Median age at diagnosis was 36.5 years, and median duration of follow-up was 28 months. Onset was acute in 14 patients (88%), with 3.5 weeks (median) from onset symptoms to diagnosis. Three women developed symptoms within 3 weeks postpartum. The most frequent symptoms were severe headaches (12, 75%), stroke (6, 30%), transient ischaemic attack (TIA) (4, 28%), seizures (7, 44%), visual aberration (3, 19%), and cognitive impairment (5, 31%). Laboratory data included high ESR (2, 13%), leucocytosis (8, 80%), thrombocytosis (1, 6%), positive antinuclear antibody titre (3, 15%), and high levels of complement (5, 31%). Lumbar puncture was performed in 12 patients (75%). CSF analysis was abnormal in five patients (42%). EEG was abnormal in 5/9 patients. The major CT/MRI scan findings were cerebral haemorrhage (4, 25%), brain infarcts (5, 31%), brain atrophy (2, 13%) and non-specific lesions (2, 13%). Four patients had normal studies. All patients received corticosteroids (CS), and five were treated with oral cyclophosphamide. Two patients relapsed despite CS and cyclophosphamide therapy. All patients are alive, and at the last assessment, eight had a permanent neurological deficit, which included paresis (3, 19%), neurocognitive abnormalities (2, 13%), visual loss (2, 13%) and seizure activity (5, 31%). Our data suggest a non-progressive, non-fatal course in those PACNS patients diagnosed angiographically and treated with CS with or without cyclophosphamide.

Cerebral vasculitis: MR imaging and angiographic correlation.

Cerebral vasculitis is an unusual disorder with numerous causes. One such entity, noninfectious granulomatous angiitis of the nervous system (GANS), is an extremely rare disease with a predilection for leptomeningeal and parenchymal arteries and veins. Isolated involvement of the central nervous system is characteristic of GANS, which has also been referred to as primary angiitis of the central nervous system (PACNS). The results of magnetic resonance (MR) imaging and angiography in seven patients with presumed PACNS were retrospectively analyzed and correlated. MR images were positive in every case. Characteristically, lesions were multiple, bilateral, and supratentorial. Both gray- and white-matter infarcts were identified in four of seven patients; infarcts were most common in the deep white matter. PACNS can also appear as primary parenchymal hemorrhage or simulate low-grade glioma. All lesions identified on MR images were associated with positive angiographic findings of cerebral vasculitis in the corresponding vascular distribution. However, for 12 of 33 vascular distributions with angiographic evidence of cerebral vasculitis, no lesions were identified on MR images. These correlative observations suggest that some patients with proved PACNS may have normal MR imaging results.