Clinical characteristics, radiological findings, treatment and outcome concerning patients with CLIPPERS-mimic
| Case/Reference | Age at onset/sex/significant background | Attacks (n); follow-up (months) | PCGd+ localisation | Atypical clinical and radiological findings during attack (attack number) | mRS at the last visit | Treatment failed to prevent relapse | Free of relapse with or without treatment | CLIPPERS categories along follow-up/time to reach definitive category (months)/final diagnosis |
| 1 | 42/male/no | 2 attacks; 33 months | Brain, hindbrain, spinal cord | Axonal polyneuropathy, brain, hindbrain and spinal cord ‘on fire’, no predominance in the pons, T2 hyperintensities wider than Gd+ (1, 2) | 2 | No | Yes, 6 cycles of CYC, then CT 4 mg/day + AZT 150 mg/day | Non-CLIPPERS/NA/autoimmune GFAP astrocytopathy |
| 212 | 46/male/no | 6 attacks; 228 months | Brain, hindbrain, spinal cord | Brain ‘on fire’ involving predominantly the corpus callosum (1–6), T2 hyperintensities wider than Gd+ (6) | 0 | MTX | Yes since 192 months after AHSCT | Non-CLIPPERS/NA/CNS-LYG III† on BB |
| 316 | 56/male/no | 4 attacks; 15 months | Brain, hindbrain | Margin of the pons + fifth nerve Gd+ (1, 2, 3); relapse while on 60 mg/day of CT with pontine ring-like Gd+ and necrotic centre (4) | 6 | IVMP, CT >60 mg/day, RB, MTX | NA | Non-CLIPPERS/NA/CNS-LYG III† on second BB targeting the pons |
| 4 | 38/male/MAS-related to EBV at 37 | 1 attack; 9 months | Brain, hindbrain | Cerebellar hemisphere and frontal patchy Gd+ (1) | 1 | No | Yes without treatment since 4 months | Non-CLIPPERS/NA/CNS-LYG I† on BB |
| 5 | 75/female/no | 2 attacks; 16 months | Brain, hindbrain | Brain infarctions and multiple arterial stenosis (1, 2) | 3 | CT 14 mg/day | Yes with CT 20 mg/day | Non-CLIPPERS/NA/PACNS on DSA |
| 617 | 50/male/no | 2 attacks; 61 months | Brain, hindbrain, spinal cord | Cortical nodular Gd+ (1); relapse while on 60 mg/day of CT with large pontine Gd+ and T2* hypointense lesions matching with nodular and PCGd+ (2) | 1 | CT 60 mg/day, CYC | Yes since 56 months after RB, currently CT 8 mg/day + AZT 100 mg/day | Non-CLIPPERS/NA/PACNS on BB, DSA was normal |
| 7 | 60/female/no | 5 attacks; 40 months | Brain, hindbrain | Brain ‘on fire’ + cerebellar patchy Gd+ + T2* hypointense lesions related to calcifications matching with PCGd+ and arterial stenosis + brain infarction with aphasia (1–5) | 4 | No | NA | Non-CLIPPERS/NA/PACNS on DSA |
| 818 | 37/female/no | 4 attacks; 73 months | Brain, hindbrain | Sulci Gd+ and T2* hypointense lesions related to microaneurysms (1) | 2 | AZT 150 mg/day | Yes with MTX 15 mg/week | Non-CLIPPERS/NA/PACNS on DSA |
| 9 | 25/male/HL (IV*) at 21 | 5 attacks; 120 months | Hindbrain, spinal cord | HL relapses + T2* hypointense lesions matching with PCGd+ (1, 2, 3, 4, 5) | 0 | AHSCT, several lines of chemotherapy | Yes with CT 10 mg/day | Non-CLIPPERS/NA/HL relapse II* on nodal biopsy |
| 10 | 49/male/no | 2 attacks; 4 months | Brain, hindbrain | Relapse while on 80 mg/day of CT with large pontine Gd+ and worsening despite IVMP (2) | 6 | CT 80 mg/day | NA | Probable CLIPPERS, then non-CLIPPERS/4 months/CNS-LYG III† on BB |
| 1122 | 44/male/no | 2 attacks; 46 months | Hindbrain | T2 hyperintensities wider than Gd+, large pontine Gd+ around the fourth ventricle, T2* hypointensities matching with PCGd+ (2) | 1 | AZT 100 mg/day | Yes with CT 10 mg/day + AZT 150 mg/day | Probable CLIPPERS, then non-CLIPPERS/7 months/MOG-related disease |
| 1219 | 33/male/no | 2 attacks; 9 months | Hindbrain, spinal cord | Relapse while on 30 mg/day of CT with pontine ring-like Gd+ and necrotic centre, and worsening despite IVMP (2) | 6 | IVMP, CT 60 mg/day, PLEX, CYC | NA | Definite CLIPPERS, then non-CLIPPERS/3 months/PCNSL on second BB |
| 134 20 | 58/male/no | 3 attacks; 37 months | Brain, hindbrain | Relapse while 40 mg/day of CT, persistence of Gd+ under CT (2); large pontine and corpus callosum Gd+ (3) | 6 | CT 40 mg/day, AZT 150 mg/day | NA | Definite CLIPPERS, then non-CLIPPERS/18 months/PCNSL on second BB |
*According to Ann Arbor staging system for lymphoma.
†LYG grading (I–III) according to the WHO classification.
AHSCT, autologous haematopoietic stem cell transplant; AZT, azathioprine; BB, brain biopsy;CLIPPERS, chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids; CNS, central nervous system; CNS-LYG, CNS lymphomatoid granulomatosis; CT, corticosteroids; CYC, cyclophosphamide; DSA, digital subtraction angiography; EBV, Epstein-Barr virus;GFAP, glial fibrillar acidic protein; Gd+, gadolinium enhancement; HL, Hodgkin's lymphoma; IVMP, intravenous methylprednisolone; MAS, macrophage activation syndrome;MOG, myelin oligodendrocyte glycoprotein; mRS, modified Rankin Scale; MTX, methotrexate; NA, not applicable;PACNS, primary angiitis of the CNS; PCGd+, punctate and curvilinear gadolinium enhancement;PCNSL, primary CNS lymphoma; PLEX, plasma exchange; RB, rituximab.