LETTER TO THE EDITORS Response to immunotherapy in CLIPPERS syndrome In ˜ igo Gabilondo • Albert Saiz • Francesc Graus • Pablo Villoslada Received: 17 January 2011 / Revised: 11 April 2011 / Accepted: 19 April 2011 Ó Springer-Verlag 2011 Dear Sirs, Chronic lymphocytic inflammation with pontine perivas- cular enhancement responsive to steroids (CLIPPERS) is a recently described treatable, brainstem-predominant, clin- ical and radiological entity [1]. Patients with this condition present with an episodic brainstem syndrome and show characteristic scattered and punctate gadolinium (Gd) enhancement in the pons and adjacent CNS structures. They prototypically respond to high dose glucocorticos- teroids and may require chronic steroid or immunosup- pressive treatment, although the effect of intravenous immunoglobulins (IVIG) in this disease is unknown. Here we report a patient with CLIPPERS that experienced a clinical rebound of the disease after a short pulse of IVIG. A 28-year-old woman with subacute gait ataxia and diplopia was admitted to the hospital. Neurological examination revealed internuclear ophthalmoplegia, hori- zontal bidirectional nystagmus and gait and four-limb ataxia. Brain and spinal MRI showed multiple punctate Gd enhancing lesions in the mesencephalon, cerebellum and cervical spinal cord. The patient was tested for the presence of systemic auto-antibodies, anti-neuronal antibodies, infectious pathogens (HIV, T. Pallidum, Brucella spp., B. burgdorferi) and tumoral serum biomarkers. CSF analysis included standard biochemistry, cytology and bacteriolog- ical cultures, oligoclonal bands and tests for Tropheryma whippelii and Herpesviridae, with no significant findings except for mildly raised CSF protein. Body-CT and body and brain PET-CT were also normal. The patient was treated with intravenous methylprednisolone for 3 days (1 g/day) followed by oral prednisone tapering starting from a dose of 60 mg/day. One week after starting meth- ylprednisolone, she had completely recovered and was continued on a slow reduction of oral steroid dose. How- ever, any attempt to taper the oral steroid dose below 12.5 mg/day led to neurological relapse of the symptoms and, therefore this dose was maintained for the next 6 months. After this period (1 year after disease onset), she was asymptomatic and physical examination was normal, and therefore treatment discontinuation was reassessed. After she stopped steroids for a few days she suffered a rebound of her symptoms: she had new onset mild gait ataxia and brisk symmetric ankle- and knee-jerks. New brain and spinal cord MRI disclosed multiple scattered punctuate and non-confluent enhancing lesions of a maxi- mum diameter of 0.7 cm visible mainly in the white matter of both cerebellar hemispheres, cerebellar peduncles and in the cervical spinal cord. (Fig. 1a). At that moment, pontine Gd enhancement was relatively scarce compared with the cerebellar hemispheres. Additionally, mild but appreciable amount of diffuse Gd peppering was visible in the white matter of the whole brain adjacent to the cortico-subcor- tical border. Prednisone dose was increased to 30 mg/day and the patient recovered to normal in 3 days. Thereafter, a 12.5 mg/day dose was maintained for the following 9 months and the patient remained asymptomatic. A new MRI 3 months after restoration of steroid therapy showed clear improvement of Gd lesions (Fig. 1b). Notwithstand- ing, steroid side-effects became evident with amenorrhea, hirsutism, mild weight gain and acne. Any attempt to taper steroid dose below 10 mg/day resulted in a blooming of neurological symptoms. After assuring 2 weeks of clinical stability, a short attack pulse of intravenous immunoglob- ulins (IVIG) was administered (0.4 g/kg/day for 5 days) I. Gabilondo Á A. Saiz Á F. Graus Á P. Villoslada (&) Department of Neurology, Center for Neuroimmunology, IDIBAPS, Hospital Clinic of Barcelona, Villarroel 170, 08036 Barcelona, Spain e-mail: pvilloslada@clinic.ub.es 123 J Neurol DOI 10.1007/s00415-011-6068-z