Primary angiitis of the central nervous system: emerging variants
ABSTRACT Primary angiitis of the central nervous system (PACNS), a serious disease, has not featured prominently in the spectrum of multi-organ disease seen in vasculitis clinics.
To evaluate the presentation, natural history and features of PACNS variants and compare to those of systemic vasculitides.
Patients (n=105) presented during 1988-2003 to a tertiary regional vasculitis clinic receiving unselected disease types. Data were collected from a clinical database, patient and laboratory records.
The frequency of PACNS presentation rose over the study period, compared with most of the other vasculitides. When PACNS was divided into small- and middle-sized vessel disease (SVD/MVD), their clinical courses differed substantially. SVD PACNS was responsive to immunosuppressive drugs, but relapsed during prolonged periods in all patients on maintenance immunosuppressives, or after withdrawal of treatment, causing recurrent, severe and irreversible CNS injury. MVD PACNS had isolated episodes at presentation, with a paucity of relapses during prolonged follow-up.
Similarities between SVD PACNS and microscopic polyarteritis suggest the former may represent a limited form of the latter. MVD PACNS has a distinctly more benign relapse pattern than its multisystem counterpart polyarteritis nodosa. Acute-phase serology was useful in designating inflammatory processes at presentation of patients presenting with encephalopathy caused by SVD only, but were unhelpful in defining relapses in this form of PACNS, the definition of which in all cases rested on clinical assessment and MR scanning. Direct cerebral angiography was not diagnostic in any case of SVD PACNS; positive brain biopsy is diagnostically unequivocal, but the total clinical syndrome with imaging may establish a diagnosis with highest probability. In MVD PACNS, angiography with MR scan proved diagnostic. We suggest an algorithm for a rational, minimally invasive approach to investigation. In PACNS, SVD and MVD are important variants, and decisions about therapy should incorporate these distinctions.
- SourceAvailable from: Thomas RobertClinical Neurology and Neurosurgery 08/2013;
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ABSTRACT: Vasculitides are characterized by inflammation and necrosis of the blood vessel wall. Large vessels including the aorta are affected in giant-cell arteritis, medium-size arteries in classic polyarteritis nodosa. The small-vessel vasculitides are separated in those with antineutrophil cytoplasm antibodies (ANCA) and those without. The primary angiitis of the central nervous system (PACNS) is a rare disorder affecting both medium- and small-sized vessels. Major symptoms of cerebral vasculitis are stroke, headache and encephalopathy. Diagnosis is based on laboratory and imaging findings. When cerebral affection occurs in systemic vasculitis an acute inflammatory response with raised erythrocyte sedimentation rate and increased values of C-reactive protein is present. In many cerebral vasculitides including PACNS, CSF studies reveal inflammatory findings. Magnetic resonance imaging, including ADC maps, diffusion and gradient echo sequences, is the investigation of choice to detect and monitor cerebral involvement. Certain MRI techniques and 18-fluorodeoxyglucose positron emission tomography allow the visualization of vessel wall inflammation when the lumen is still unaffected on angiography. The treatment recommendations for cerebral angitis are derived from protocols for systemic vasculitides. In general, a combination of steroids and pulse cyclophosphamide (CYC) is recommended for induction treatment. An alternative option is the use of the anti- CD20 antibody rituximab. Methotrexate, azathioprine and mycophenolate mofetil are recommended as alternatives to CYC once remission is achieved.Therapeutic Advances in Neurological Disorders 01/2010; 3(1):29-42. DOI:10.1177/1756285609347123
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ABSTRACT: We are conducting nanosecond time-resolved crystallographic studies at the ID9 beamline of the ESRF on two heme proteins: sperm whale myoglobin (Mb) and dimeric hemoglobin (HbI) from the clam Scapharca inaequivalvis. The goals of these studies are to understand the evolution of the photo-induced structural changes and their propagation from the active site through the protein and to determine the trajectories and the docking sites of the photo-dissociated ligand and how they are affected by mutations of side chains known to affect ligand binding properties. We use intense, focused, white, 150-ps and 1-μs X-ray pulses in a pump-probe type of measurement to investigate structural changes in carbonmonoxy complexes of Mb and HbI. Changes are photo-initiated by 10-ns laser pulses. The complete reversibility of the reaction simplifies the use of the signal averaging to improve the data quality and allows us to obtain complete and even multiple data sets from one crystal. Departure of the CO ligand upon photolysis and its subsequent rebinding, and the iron atom displacement from the heme plane are clearly observed in both molecules. We also identify a possible docking site for the photo-dissociated CO molecule in the MbCO heme pocket