Response to Immunotherapy in CLIPPERS: Clinical, MRI, and MRS Follow‐Up

Abstract

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a recently defined inflammatory central nervous system disorder responsive to steroids with characteristic magnetic resonance imaging (MRI) features. We report a 69-year-old man presenting with gait ataxia with the characteristic MRI features of CLIPPERS and describe the clinical, MRI, and magnetic resonance spectroscopy (MRS) follow-up after treatment with glucocorticosteroids. Brain and spine MRI showed punctate enhancement peppering the brainstem, cerebellar peduncles, and upper cervical cord. In MRS, the ratio of N-acetyl aspartate to creatine (NAA/Cr) was significantly decreased in the pons and both thalami. An extensive evaluation found no alternative diagnoses. Treatment with steroids led to rapid clinical improvement. Repeat MRI and MRS showed complete resolution of gadolinium-enhancing lesions and recovery of NAA/Cr levels in the pons and thalami. After 1 month of tapering oral steroids, weekly oral methotrexate was started and the patient has remained stable for the past 6 months.

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

“…Clinical manifestations may be heterogeneous, multi‐faceted and variable in individual cases, but comprise essentially the following. Commonly prominent symptoms related to multi‐locular brainstem including cranial nerve and cerebellar involvement, which may present in various combinations or rarely in isolation (e.g. ataxia, dysarthria, oculomotor abnormalities, tingling of the face, vertigo) ; and Possible additional features such as: (i) symptoms referable to long tract affections and/or a spinal cord syndrome (e.g. pyramidal tract signs, spasticity, para‐/tetraparesis, altered limb superficial and deep sensation, sphincteric dysfunction) ; (ii) pseudobulbar affect (pathological crying and laugther) ; (iii) cognitive dysfunctions (e.g.…”

“…In some exceptional cases brainstem mass effect in the form of pons or middle cerebellar peduncle swelling was observed during relapses . Magnetic resonance as well as digital subtraction angiography of intracranial and neck vessels do not display specific abnormalities, in particular no changes seen in vasculitic disorders . Gadolinium enhancement decreases as the patient responds to immunosuppressive therapy .…”

“…So far, an independent benefit of GCS‐sparing therapies could not be substantiated reliably. After complete GCS withdrawal, only methotrexate and potentially rituximab were described to be effective in a few patients.…”

“…The following immunmodulatory or immunosuppressive agents have been used for long‐term therapy in hitherto published cases, either as monotherapy or as add‐on therapy. Although at least partial benefits were reported, their GCS‐independent efficacy could not been proved so far: azathioprine (as add‐on therapy ; as monotherapy in one patient not controlling recurrence ) methotrexate, weekly oral administration (as add‐on therapy ; as monotherapy ) cyclophosphamide, intravenous pulses (as add‐on therapy and as monotherapy : mainly reported to improve the clinical syndrome although presumably not protecting against subsequent relapse) rituximab (anti‐CD20 monoclonal antibody treatment) (as add‐on therapy or monotherapy possibly beneficial) Application in individual cases with undetermined efficacy: mycophenolate mofetil (as add‐on therapy ) mitoxantrone (as add‐on therapy ). …”

Síndrome CLIPPERS con distribución atípica de las lesiones en la resonancia magnética cerebral

“…Desde que Pittock et al [1] describiesen la entidad, se han publicado una veintena de casos más, ampliando el espectro clínico de este síndrome [2][3][4][5][6][7][8][9]. En ellos, las alteraciones oculomotoras y la ataxia están presentes en el diagnóstico prácticamente siempre.…”