# Limbic Encephalitis with HU-Antibodies in T-cell Anaplastic Lymphoma. A Case Report
###### Abstract  
Limbic encephalitis is a rare paraneoplastic neurological syndrome usually associated with small cell lung cancers, testicular and breast cancers or B-cell lymphomas. We herein report the first patients with paraneoplastic limbic encephalitis associated with HU antibodies and anaplastic T-cell lymphoma.  
T cell lymphoma; limbic encephalitis; paraneoplastic; HU antibodies +
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system (right mesh temporal lobe, insula, cingulate gyrus and hypothalamus). Laboratory findings were unremarkable, except for an LDH increase (540 U/L, n.v. \(<\) 200 U/L). A panhypopitiutarism with diabetes insipidus likely secondary to lymphoma infiltration was also diagnosed and managed successfully with desmopressin, levothyroxine, cortisone acetate and sodium replacement therapy. Taking into account CNS involvement, the patient was treated with three courses of MATRIX (methotrexate, cytarabine and thiotepa), followed by two courses of ICE (ifosfamide, carboplatin and etoposide), with resolution of neurologic symptoms, radiologic findings and lymphoma remission [6]. Soon after the second course of ICE, the patient developed confusion, memory loss, and religious delirium. Generalized seizures also recurred. A neuropsychological evaluation demonstrated a significant impairment restricted to the memory domain, whereas executive and visuospatial functions were partially involved (Mini-Mental State Exam = 26/30). Brain and spine MRI, as well as whole body positron emission tomography (PET)-MRI, while ruling out lymphoma progression, revealed recurrence of focal cerebral altered signal intensity with diffusion restriction involving the limbic system (Figure 1A). Autoantibody screening was positive for the anti-HU (antineuronal nuclear autoantibody type 1) antibody. Based on the combination of symptoms, MRI findings and paraneoplastic antibodies, a diagnosis of anti-HU limbic encephalitis was made (Table 1). A further neuropsychological evaluation revealed a more extensive impairment in anterograde amnesia, fluencies, processing speed and executive and visuo-spatial domain. After treatment with methylprednisolone (1 g IV for three days) and seven sessions of plasma exchange, the patient regained his status ante (Figure 1B). He then started steroid maintenance therapy and underwent autologous stem cell transplantation with thiotepa/carmustine as a conditioning regimen. The response to therapy, assessed by PET-MRI and brain and spine MRI, showed a complete remission of lymphoma and substantial improvement of the encephalitis MRI findings, with only few small spots of cerebral altered signal intensity with vasogenic edema being left. Brain MRI control two months later confirmed the same findings, but also revealed hippocampal atrophy as a long-term impact of limbic encephalitis (Figure 1C). The patient therefore started regular hematological follow-up. He died one year later, still in hematological remission, as a consequence of pneumonia.  
Figure 1: **Encephal MRI at encephalitis onset and during the follow-up**. Coronal T2 images at the level of the hippocampal formations at onset (**A**), +4 and (**B**) +9, (**C**) months later showing edema of the hippocampal formation (arrowhead) resulting in bilateral atrophy (arrows).