CLIPPERS: chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids. Review of an increasingly recognized entity within the spectrum of inflammatory central nervous system disorders.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a recently defined inflammatory central nervous system (CNS) disorder, prominently involving the brainstem and in particular the pons. The condition features a combination of clinical symptoms essentially referable to brainstem pathology and a characteristic magnetic resonance imaging (MRI) appearance with punctate and curvilinear gadolinium enhancement 'peppering' the pons. The radiological distribution is focused in the pons and adjacent rhombencephalic structures such as the cerebellar peduncles, cerebellum, medulla and the midbrain. While the lesion burden with a perivascular pattern is typically most dense in these pontine and peripontine regions, enhancing lesions may additionally extend into the spinal cord and supratentorial structures such as the thalamus, basal ganglia, capsula interna, corpus callosum and the cerebral white matter. Another core feature is clinical and radiological responsiveness to glucocorticosteroid (GCS)-based immunosuppression. As withdrawal of GCS treatment results commonly in disease exacerbation, long-term immunosuppressive therapy appears to be mandatory for sustained improvement. Diagnosis of CLIPPERS is challenging, and requires careful exclusion of alternative diagnoses. A specific serum or cerebrospinal fluid (CSF) biomarker for the disorder is currently not known. Pathogenesis of CLIPPERS remains poorly understood, and the nosological position of CLIPPERS has still to be established. Whether CLIPPERS represents an independent, actual new disorder or a syndrome that includes aetiologically heterogeneous diseases and/or their prestages remains a debated and not finally clarified issue. Clinicians and radiologists should be aware of this condition and its differential diagnoses, given that CLIPPERS constitutes a treatable condition and that patients may benefit from an early introduction of GCS ensued by long-term immunosuppression. Based on previous reports in literature - currently encompassing more than 50 reported cases of CLIPPERS - this review addresses clinical features, diagnostic criteria, differential diagnoses and therapeutic management of this peculiar disorder.

Insular stroke is associated with acute sympathetic hyperactivation and immunodepression.

BACKGROUND AND PURPOSE: Post-stroke immunodepression has been related to brain lesion size but not a specific lesion location. Here, we studied the influence of lesion location within middle cerebral artery (MCA) territory on parameters related to activation of sympathetic adrenomedullar pathway, immunodepression, and associated infection. METHODS: We analyzed clinical, brain imaging, and laboratory data of 384 patients (174 women; mean age 70.8 ± 12.9 years) consecutively admitted to the stroke unit no later than 24 h after onset of acute ischaemic stroke involving the MCA territory. RESULTS: Patients with lesion affecting >33% of MCA territory had increased serum metanephrine and normetanephrine levels, elevated neutrophil counts but decreased eosinophil, helper T lymphocyte, and cytotoxic T lymphocyte counts compared to patients with lesion in <33% of MCA territory. Patients with large infarctions had increased frequency of infections within 14 days after stroke, especially chest infections (P < 0.001). Considering only patients with non-lacunar infarction in <33% of MCA territory, those with insular lesion had significantly higher normetanephrine levels, higher neutrophil but lower eosinophil and helper T lymphocyte counts than those with non-insular lesion, despite similar lesion diameters. This coincided with an increased frequency of chest infections (P < 0.01) in patients with insular lesion. Whilst patients with right insular lesion showed decreased heart rate variability, lesion laterality had no impact on laboratory findings or infection frequency. CONCLUSION: These findings suggest a specific role of insular lesion in the pathogenesis of stroke-induced sympathetic hyperactivation and immunodepression. Neuroimaging studies applying lesion volume calculation techniques are warranted to confirm these findings.