On Razor's edge: Managing analgosedation during severe anti-NMDA receptor encephalitis

Case Summary

A 23-year-old Caucasian woman presented with a 10-day history of nonverbal acoustic hallucinations and insomnia. Neurologic examination only showed psychomotor slowing. Cerebral MRI was normal (figure, A, first column). CSF showed 73 leukocytes/μL, isolated oligoclonal bands, and slightly increased lactate (2.3 mmol/L, normal <2.1 mmol/L). NMDAR antibodies in serum and CSF were positive (1:100), and other antineural/onconeural antibodies were negative. No ovarian teratoma was detected. Although 1,000 mg methylprednisolone and immunoglobulins 0.4 g/kg were administered IV for 5 days, followed by oral prednisolone 1 mg/kg and tapering (20 mg every second day), her condition worsened. Dyskinesias, dysautonomia, and respiratory insufficiency required analgosedation and artificial ventilation. Multidrug analgosedation (propofol, midazolam, esketamine, sufentanil, alpha-2 receptor agonists, and 4-hydroxybutyrate) failed to alleviate dyskinesias and dysautonomia (>160 bpm, systolic blood pressure 200 mm Hg) but led to laboratory signs of drug-induced hepatotoxicity (transaminases 36-fold of normal). However, all these subsided after switching to isoflurane. Rituximab (1,000 mg IV, 2 doses 2 weeks apart) was administered followed by immunoadsorption. As dyskinesias reappeared on isoflurane reduction, high concentrations (1.2 end-tidal volume%) were maintained for 72 days. MRI now showed symmetrical striatal and dentate nuclei T2-weighted hyperintensities (figure A, second column, arrows) and mesiotemporal atrophy. Otherwise unchanged CSF now showed prominently increased lactate (4.2 mmol/L). CSF neurofilament light chain levels, a neuronal damage marker,³ were dramatically increased (15.796 pg/mL) compared with CSF obtained 4 weeks (798 pg/mL) and 16 weeks (174 pg/mL) earlier. Suspecting an adverse reaction to isoflurane,⁴ IV analgosedation was reinstated. Arterial hypertension soon reappeared. Upon follow-up MRI, striatal and dentate nucleus hyperintensities had dissolved. However, now features typical for posterior reversible encephalopathy syndrome had appeared (figure, A, third column, arrows) and made switching to isoflurane inevitable. At 5 months, the patient became alert and adequately oriented but suffered from severe flaccid tetraparesis and hypoesthesias, clinically and electrophysiologically consistent with critical illness polyneuropathy/myopathy (CIP/CIM). While only minimal cognitive impairment was noted at 9 months, she was still seriously handicapped, now rather by cerebellar ataxia than residual CIP/CIM. MRI showed reversible forebrain atrophy hardly affecting the putamen and progressive cerebellar atrophy (figure, A, forth column) that was confirmed by MRI volumetry (figure, B). At 36 months, cerebellar ataxia showed mild improvement but still persisted in everyday relevance.

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Figure Multiple MRI abnormalities as correlates of diverse adverse events and neurologic impairment during the course of severe NMDAR-E

(A) Transaxial T2w MRIs at levels depicting the basal ganglia (A.a–A.d), the mesiotemporal structures (A.e–A.h), and the cerebellum (A.i–A.l) are shown. MRI at initial presentation showed no abnormalities (A.a, A.e, and A.i). After 72 days of isoflurane, T2w signal hyperintensities in the lateral striatum and the deep cerebellar nuclei developed (A.b and A.j, arrows). Temporomesial atrophy became evident (A.f, stars). Remission of the T2w signal hyperintensities after discontinuation of isoflurane while after therapy-refractory arterial hypertension, PRES with typical vasogenic edema developed in bilateral occipital regions areas (A.c, arrows). Mesiotemporal atrophy proceeded. Nine months after disease onset, signal abnormalities associated with PRES were in full remission while severe cerebellar atrophy had occurred (A.l, arrows). (B) MRI volumetry performed using the FMRIB Software Library (FSL, Version 5.0.9, fmrib.ox.ac.uk/fsl, for details see ref. 13) demonstrates a mesiotemporally pronounced reversible atrophy hardly affecting the putamen and progressive cerebellar atrophy. Volumes of the different structures were normalized to the volume of the initial MRI. NMDAR-E = NMDA receptor encephalitis; PRES = posterior reversible encephalopathy syndrome; T2w = T2-weighted.