Auto-immune limbische encefalitis
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Belang van tijdige diagnostiek en behandeling
Klinische les
12-04-2012
Judith van Vliet, Jan Meulstee, Erwin G.T.M. Hartong en Wim M. Mulleners

Autoimmune limbic encephalitis: importance of early diagnosis and treatment

This supplementary information is presented as submitted by the corresponding author. It has not been copy-edited by NTvG.

Introduction

Limbic encephalitis is a rare disorder, characterized by the subacute onset of seizures, short-term memory loss and psychiatric and behavioural symptoms. Initially it was recognized as a paraneoplastic disorder, but recently a subgroup of patients is found to have an autoimmune encephalitis, often without systemic cancer. This entity is associated with voltage-gated potassium channel antibodies (VGKC Abs) and N-methyl-D-aspartate-receptor (NMDAR) antibodies.

Case description

A 69-year-old man with peritoneal dialysis presented with two generalized tonic-clonic seizures. For a few weeks he had progressive insomnia, and the last days he demonstrated confused and aggressive behaviour. He showed severe postictal confusion, neurological examination was otherwise normal. Laboratory investigation and cerebrospinal fluid examination were uneventful, creatinine was 958 µmol/l, BUN was 14.3 mmol/l, comparable to previous values. Contrast-enhanced brain Computed Tomography (CT) was normal. He was treated with phenytoin, on the assumption of uraemic encephalopathy as the cause of his seizures. In a few weeks, he developed a third generalized tonic-clonic seizure, symptoms of depression, visual hallucinations, worsening insomnia and increasing memory deficits.

Brain MRI with gadolinium was normal. EEG showed disorganization of the background, with bilateral frontal and temporal intermittent rhythmic delta activity (FIRDA and TIRDA). Remarkably, during 24 hours, sleep was nearly absent. Taken together the clinical signs and the EEG pattern limbic encephalitis was suspected, confirmed by positive VGKC-Abs. CT thorax/abdomen showed no abnormalities. He was treated with high doses of prednisolon (60mg/day) and intravenous immunoglobulins. There was complete resolution of hallucinations and confusion in a week. Over the next weeks, his insomnia improved markedly. The prednisolon and intravenous immunoglobulins were phased out. For 18 months, he was in complete remission. Unfortunately, he developed peritonitis carcinomatosa as a result of metastasis of his renal cell carcinoma and is deceased in a short time.

A 22-year old woman presented with complex partial seizures. She developed dysphasia in a few weeks, and showed progressive inappropriate behaviour. Brain MRI was normal, cerebrospinal fluid examination showed a pleiocytosis (20 x 106). EEG demonstrated diffuse slow activity, most pronounced left temporal, with epileptiform discharges. NMDAR Abs appeared to be positive, and autoimmune encephalitis was confirmed. CT thorax/abdomen was normal, no ovarian teratoma was found. She was treated with prednisolon 50mg/day and intravenous immunoglobulins. She showed marked improvement in a few weeks.

Conclusion

These case descriptions demonstrate the typical symptoms of VGKC and NMDAR Abs limbic encephalitis, consisting of subacute onset of partial or generalized epileptic seizures, short term memory deficits and psychiatric symptoms (depressive mood, visual hallucinations, inappropriate behaviour). In both cases, brain MRI was normal, while EEG demonstrated disorganization of the background with generalized slow activity, eventually leading to the diagnosis of limbic encephalitis. VGKC Abs limbic encephalitis is in only 20% paraneoplastic, usually associated with small cell lungcarcinoma or thymoma. NMDAR Abs limbic encephalitis is in 50% paraneoplastic, most frequently associated with ovarian teratoma. Both respond remarkably well to immunosuppressive therapy, consisting of prednisolon and intravenous immunoglobulins. The earlier this therapy is initiated, the better the prognosis seems to be. We want to emphasize the importance of early diagnosing autoimmune encephalitis. Not only is it important to rule out systemic cancer, moreover this potential lifethreating disorder responds very well to immunosuppressive therapy.