An 8-year-old boy presents with increasing fatigue (past 2 weeks) and new acute-onset symptoms of aphasia, ataxia, headaches, and progressive vertigo for the past 24 h. He has no personal of family history of clotting disorders, strokes or autoimmune/inflammatory disease. He has had no infections in the past year and no travel history (other than a "sore throat or sniffles here and there"), no pets, and no other symptoms.
When asked about diagnostic approaches to this specific case (Q7, N = 74 responses), respondents ranked emergency MRI of the brain including angio-MRI (90.5%) and blood tests including full blood counts, inflammatory markers and clotting tests (90.5%) as most important. These were followed by lumbar puncture to analyze the CSF (82.4%), and brain CT scan including CT angiography (23.0%). Of the respondents who considered blood tests essential (Q8, N = 74 responses), 98.6% would order full blood count including complete white cell count, 97.3% would order clotting tests including PTT, INR, fibrinogen and D dimers, and 94.6% would order immunology tests including ANA, ENA, complement factors, cardiolipin antibodies and ANCA. When asked which blood immunology tests they would order, 97.3% answered anti-phospholipid antibody testing, followed by antinuclear antibody testing (93.2%), requested anti-neutrophil cytoplasmic antibodies (89.2%), anti-dsDNA antibodies (87.8%), complement factors and activation of the complement cascade (83.8%), and anti-NMDA (N-methyl-D-aspartate) receptor and aquaporin antibodies (67.6%) (Q9, N = 74 responses). Of 74 respondents who considered performing a lumbar puncture (Q10, N = 74 responses), most (98.6%) would request cell counts, differentiation and protein quantification, followed by microbial culture (93.2%), glucose levels (90.5%), oligoclonal bands (89.1%), CSF opening pressure (86.5%), lactate (74.3%) and anti-NDMA and aquaporin antibodies (68.9%). When asked about helpful MRI techniques (Q11, N = 71 responses), 87.3% of responders requested MRI angiography, followed by fluid-attenuated inversion recovery (FLAIR; 55/71; 77.5%), diffusion-weighted MRI sequences (53/71, 74.7%), T1 with fat saturation (FS; 30/71; 42.3%), T1FS with contrast medium (38/71, 53.5%), T2FS (37/71, 52.1%), Turbo inversion recovery magnitude (TIRM)/Short tau inversion recovery (STIR; 28/71; 39.4%). Detailed results are summarized in Table 2.
Next, respondents were informed that the patient exhibited elevated ESR (30mm/h) and CRP (4mg/L). Approximately 30 h after the onset of ataxia and aphasia, Magnetic Resonance Imaging (MRI) shows alterations in proton diffusion capacity in the Cerebellum and a significant and long ranging stenosis of the distal Basilar artery in MRI angiography (Supplementary Material 1).
Based on new information provided, respondents were asked to select 5 most likely differential diagnoses (Q12, N = 73 responses). Most respondents selected progressive p-cPACNS (80.8%), followed by transient p-cPACNS (69.9%), ischaemic stoke (64.4%), congenital anatomical deformity (39.7%) and infections (38.4%). Asking indicators of likely progressive p-cPACNS (Q13, N = 73 responses), the majority of respondents suggested imaging results (87.7%), followed by clinical course with disease progression over 3 months or more (69.9%), laboratory findings suggesting systemic inflammation (46.6%), acute presentation with "systemic signs" (43.8%), and response to immune modulation (41.1%). Detailed results are summarized in Table 3.
Next, the following information was provided: Autoantibodies in CSF and blood come back negative, there's no evidence for clotting disorders or infection, including TB. Systemic inflammatory parameters remain normal. Based on the involvement of posterior arteries, the diagnosis of (likely) progressive p-cPACNS (Childhood Primary Angiitis of Central Nervous System) is made.
Participants were asked to decide which medication they consider for the induction of remission (Q14, N = 73 responses). Sixty-eight of 73 respondents would start treatment with intravenous Methylprednisolone (IVMP) over 5 days, followed by oral prednisolone (93.2%), 47/73 (64.3%) consider treatment with intravenous Cyclophosphamide every month for 4-6 months, 9/73 (12.3%) would start treatment with mycophenolate mofetil (MMF), and 3/73 (4.1%) would treat with oral prednisolone. None of the respondents chose oral cyclophosphamide or azathioprine for induction treatment.
Considering prophylaxis of thromboembolic events (Q15, N = 70 responses), most responders agreed on administering IV heparin initially (65.7%), followed by acetyl salicylic acid (ASA), and a combination of ASA and clopidogrel. Considering post-acute phase thrombosis prophylaxis (Q16, N = 70 responses), the majority of respondents would prescribe aspirin (47.1%), followed by subcutaneous heparin (22.9%), a combination of ASA and clopidogrel (14.3%), warfarin (11.4%), clopidogrel alone (5.7%), or DOACs (2.9%). Opinions on when to discontinue anticoagulation treatments (Q20, N = 70 responses) were divided and ranged between 3 and 36 months. One respondent would not administer anticoagulation treatment (1.4%) (Table 4).
Considering immune modulating maintenance treatment (Q17, N = 73 responses), the majority of respondents (72.6%) would prescribe MMF, followed by azathioprine (20.5%), oral prednisolone (17.8%), intravenous cyclophosphamide (13.7%), rituximab (9.6%), methotrexate (5.5%), oral cyclophosphamide (following Fauci scheme) or TNF inhibitors (1.4% each). Opinions on the required duration of treatment were divided (Q18, N = 73 responses) and ranged between 3 and 36 months. When asked how long to include oral corticosteroid treatment in the regimen, including slow taper (Q19, N = 72 responses), respondents responded: 3 months (20.8%), 6 months (41.7%), 12 months (15.3%), 18 months (4.2%), 24 months (5.6%), 36 months (1.4%), and 1.4% indicated no corticosteroid treatment (Table 4).
Monitoring disease activity and damage using MRI (Q21, N = 72 responses), 56/72 (77.8%) respondents suggested to repeat MRI after 3 months, 36/72 after 6 months (50.0%), 25/72 after 12 months (34.7%), 11/72 after 18 months (15.3%), 21/72 after 24 months (29.1%), and 10/72 after 36 months (13.9%) and 11/72 answered other (15.3%). When asked when to schedule clinical follow up (Q22, N = 73 responses), 59/73 respondents indicated within 3 months (80.8%), 23/73 after 6 months (31.5%), 22/73 after 12 months (30.1%), 19/73 after 18 months (26.0%), 21/73 after 24 months (28.8%) and 15/73 after 36 months (20.6%).