Relevant literature review of CNS HLH cases with brainstem or cerebellitis patterns with available MR imaging and genetic data
| Literature Review | Imaging Pattern | Genetic Variants | Age of Onset, Relation to Systemic HLH | Imaging Findings |
|---|---|---|---|---|
| Benson et al23 cases | Brainstem–predominant pattern (CLIPPERS- like) | 1 disruptive, 2 with missense mutations and absent protein expression Pt 1: PRF1 c.452A>T (p.H151L) and c.666C>A (H222Q), Perforin expression 0% Pt 2: PRF1 c.443C>G (p.A148G) and c.666C>A (H222Q), Perforin expression 0% Pt 3: UNC13D c.2346_2349delGGAG(p.R782fs), c.2588G>A (p.G863D) | 5–7 yr, all 3 CNS-restricted HLH | CLIPPERS MR imaging criteria NA |
| Taieb et al284 patients | Brainstem–predominant pattern (CLIPPERS- like) | 4 cases, all with missense mutations and retained-but-decreased protein expression Pt 1: PRF1 c.272C>T(p.A91V) homozygous, perforin expression 38% Pt 2: UNC13D c.919C>T (p.Q307*) and c.2038C>T (p.R680W), not applicable Pt 3: PRF1 c.116C>A (p.P39H) and c.272C>T (p.A91V), perforin expression 25% Pt 4: PRF1 c.82C>T (p.R28C) and c.272C>T (p.A91V), perforin expression 38% | Adults (42–73 yr), all had CNS-restricted HLH | Three-fourths had atypical MR imaging CLIPPERS features (confluent contrast-enhancing lesions) |
| Bhoopalan et al26 1 patient | Cerebellitis | 1 patient with compound heterozygous PRF1 gene mutations with at least 1 disruptive mutation PRF1: c.50delT (p.L17fs) and c.527G>A(p.C176Y)) | 8 yr, CNS-restricted HLH | Cerebellitis, tonsillar herniation, no multifocal lesions |
| Khan et al271 patient | Cerebellitis | 1 patient with homozygous missense mutation c. 173T > C (p.L58P) in STX11 (syntaxin 11) gene | 2 yr 7 months, systemic HLH already present | Cerebellitis, tonsillar herniation, diffuse-to-multifocal lesions already present |
| Astigarraga et al3 1 patient | Cerebellitis | 1 patient with compound heterozygous missense PRF mutations PRF1: c.643C>A (p.L215I) and c.785C>A (p.Ala262Asp) (perforin expression data NA) | 3 yr, preceded systemic HLH | Recurrent cerebellitis, tonsillar herniation, subsequently multifocal lesions |
| Taieb et al281 patient | Cerebellitis | Patient 3’s (in CLIPPERS series) brother’s; granddaughter, monoallelic PRF1 mutation (genetic variant NA) | Not specified, self-limited CNS-restricted presentation | NA |
| Chiapparini et al29 1 patient | Cerebellitis | 1 patient with homozygous missense PRF1 mutation c.673C>T (p.Arg225Trp) (perforin expression data NA) | 13 yr, preceded systemic HLH | Cerebellitis, tonsillar herniation followed by multifocal lesions |
Note:—NA indicates not available; Pt, patient.