Cyclophosphamide-responsive Lgi1-related limbic encephalitis with basal ganglia hypermetabolism

Excerpt

An 80-year-old man presented with progressive drowsiness, weight loss, memory impairment [Mini Mental State (MMS) 24/30 and cognitive testing showed essentially limbic system dysfunction], and repetitive right-sided faciobrachial dystonic movements since 1 month. MRI revealed a left mesial temporal lobe FLAIR hyperintensity (Fig. 1). One month later, mesial temporal involvement was seen bilaterally on MRI (Fig. 1), in the absence of basal ganglia signal changes. At that time, FDG-PET showed hypermetabolism in both mesial temporal lobes and putamina (Fig. 1). Despite the absence of epileptic activity (only temporal slowing was seen) on repeated electroencephalograms during the first month after admission, antiepileptic treatment (combined oral valproic acid 1000 mg bid and levetiracetam 750 mg bid) was tried in order to treat repetitive dystonic movements. These antiepileptic drugs had effect neither on the patient’s general state nor on the dystonic movements. Since autoimmune encephalitis was suspected, a course of five sessions of plasmapheresis was started 6 weeks after symptom onset. Two weeks after the end of plasmapheresis treatment, anti-leucine-rich glioma inactivated-1 [Lgi1, a voltage-gated potassium channel (VGKC) complex antibody] antibodies were found positive, in the absence of other autoimmune/paraneoplastic antibodies. Whole body FDG-PET, thoraco-abdominal-pelvic CT, and testicular echography were normal. A diagnosis of autoimmune Lgi1-antibody-related limbic encephalitis was made and dystonic movements were interpreted as faciobrachial dystonic seizures (FBDS). After positive Lgi1 antibody results, oral prednisolone 60 mg od was started. Because of the lack of clinical improvement after 5 weeks after the end of plasmapheresis treatment and 3 weeks of oral prednisolone therapy, intravenous immunoglobulins (0.4 g/kg/day during 5 days) were added (while prednisolone was reduced to 40 mg) and repeated monthly. Partial clinical improvement on FBDS (frequency of FBDS reduced by more than 50 %) was seen during the following months while confusion and amnesia continued. FDG-PET was repeated, showing less pronounced hypermetabolism in the temporal lobes whereas putaminal hypermetabolism persisted, together with diffuse brain hypometabolism (and the rest of the whole body FDG-PET was normal). After 4 months, because of progressive worsening of the patient’s cognitive deficit (the patient became bedridden and MMS decreased to 18/30), intravenous immunoglobulins were stopped and replaced by monthly intravenous cyclophosphamide 700 mg/m² therapy (while continuing prednisolone 40 mg od). After 3 months, progressive clinical (FBDS frequency dropped to only 1/day) and cognitive improvement (MMS 27/30) was seen, stabilizing after 8 months. At that time, Lgi1 antibodies were absent and both mesial temporal lobes became hypometabolic on brain FDG-PET. Cyclophosphamide was stopped and replaced by mycophenolate mofetil 500 mg bid, and prednisolone was tapered and stopped after 5 months.

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