LAUSR

Dear Editor: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS), which was first described 10 years ago, is considered to be a steroidresponsive relapsing-remitting brainstem inflammatory disorder of unknown origin [1]. Extrapontine manifestations are often present and can affect both the spinal cord and other brain regions [2]. Neuropathological studies have shown predominantly lymphocytic perivascular and parenchymal infiltration. Inflammatory infiltrates consist mainly of lymphocytes (particularly CD3 T cells) as well as a variable number of macrophages and B cells [1]. CLIPPERS pathogenesis remains unclear, due to the rarity of the disease. Based on case reports, it is hypothesized to represent a pre-malignant or paraneoplastic disorder. T cell–mediated autoimmunity is considered to underlie CLIPPERS. A diagnostic biomarker for CLIPPERS is lacking. Herein, we present a 66-year-old woman, with an unremarkable past medical history, who developed a rapidly progressive gait disorder, with recurrent falls due to postural instability, along with tingling and numbness in the periphery of the upper and lower extremities, over a 3-month period before admission to our neurology department. During the week before admission, she had intractable hiccup and dizziness, which did not respond to symptomatic therapy. The patient did not report any systemic symptoms (e.g., fever, rush, arthritis, uveitis, serositis, oral/genital ulcers). On neurological examination, the patient had a cerebellar syndrome, with ataxic gait, appendicular ataxia with dysmetria, decomposition of movement, dysdiadochokinesia, intention tremor, and gaze-evoked nystagmus. Her reflexes were brisk and plantar response was extensor bilaterally. Muscle strength and tone, vibration/position sense, and sphincter function were normal. Physical examination was unremarkable, with no systemic/constitutional symptoms, lymphadenopathy, or rash. Routine blood biochemistry and immunological tests (including antinuclear, antiphospholipid antibodies, complement, serum angiotensin enzyme levels, erythrocyte sedimentation rate, C-reactive protein, and protein electrophoresis) were normal. Brain magnetic resonance imaging (MRI) revealed multiple punctate pontine lesions, with high signal intensity in T2weighted sequences (Fig. 1, onset). Lesions were also evident in cerebellar hemispheres, vermis, as well as cerebral hemispheres, predominantly in the parietal lobes and to a lesser extent in the frontal and occipital lobes. Diffusion restriction was only present in a small number of pontine and quadrate lobule lesions. Lesions indicative of hemorrhage or ischemia were not evident. Gadolinium administration revealed a pepper-like enhancement pattern in the brainstem and cerebellum, with enhancing-lesion diameter < 3 mm (Fig. 1, onset). Interestingly, lesions were located in the area postrema (Fig. 1, onset). Spinal cord MRI revealed multiple hyperintense T2weighted punctate lesions with contrast enhancement, extending from the cervical to the thoracic cord, with conus medullaris involvement (Figs. 1, onset and 2a–c). Electrophysiological studies were normal. Routine CSF analysis revealed elevated protein levels, with normal white cell count. CSF cytology was negative for malignant cells. IgG index was normal and CSF oligoclonal bands were negative. CSF immunophenotypic analysis by flow cytometry revealed that T lymphocytes were the predominant cell type, comprising of 76.3% CD3 (+) CD4 (+) and 20.3% CD3 (+) Aigli Vakrakou and Vasilios Constantinides share first authorship, and they contributed equally to this manuscript.