Schroeder C, Back C, Koc Ü, Strassburger-Krogias K, Reinacher-Schick A, Gold R, Haghikia A. Breakthrough treatment with bortezomib for a patient with anti-NMDAR encephalitis. Clin Neurol Neurosurg. 2018 Jun 23;172:24-26. doi:10.1016/j.clineuro.2018.06.005. [Epub ahead of print]
After its discovery, anti-N-methyl-d-aspartate receptor encephalitis is now an established neuroinflammatory disorder, for which various immune-suppressive strategies have been successfully proposed. The most commonly applied therapy includes high dose cortico-steroids, as well as plasma exchange procedures (PLEX), and subsequently either oral immunosuppressants, such as azathioprine or B-cell depletion by the anti- CD20 monoclonal antibody rituximab. However, in rare cases we are faced with patients who do not respond to either oral immunosuppressants, or rituximab. Hence, we have recently described bortezomib, a proteasome inhibitor as a potentially effective treatment in patients not responding to first-line immune-therapies. Particularly, plasma cells as mature, non-dividing antibody secreting cells are highly sensitive to proteasome inhibitors. Here, we report of a patient with severe, and prolonged anti-NMDAR encephalitis despite PLEX and repeatedly applied high dose rituximab. As documented in the accompanying video that shows the different stages before, and immediately after bortezomib therapy the patient recovered swiftly.
From the article
A 22-year-old woman presented with a subacute psychosis including visual hallucinations at the emergency department of a hospital in Luxembourg in September 2016. She had developed prodromal signs with severe anorexia the weeks before. Neurological testing revealed no paresis, sensory deficit, or meningism. Cranial MRI was normal. A lumbar puncture showed 65 lymphocytes per uL. Based on these findings antibiotic and antiviral therapy including ceftriaxone, aciclovir and methylprednisolone was initiated. During follow-up, bacteriological and virological testing of the CSF showed negative results for HSV, Neisseria, haemophilus, Streptococcus, and E. coli. Additionally, serum blood test showed negative results for listeria and brucellosis. Due to blurred consciousness the patient was sedated and intubated after admission to the ICU. After occurrence of generalized epileptic seizures the patient was treated with levetiracetam and midazolam. In the further course quadruple combination of epileptic treatment was established to achieve freedom of seizures (daily: levetiracetame 2 g, topiramate 175 mg, lacosamide 200 mg, and valproate 300 mg).
Paraneoplastic antibody panel testing revealed the presence of anti-NMDAR antibodies in the CSF (1:400). Treatment was started with high dose i.v. methylprednisolone (cumulative 5 g for 5 days), 60 g intravenous immunglobulines for 6 days and four cycles of PLEX. Hereafter, rituximab with a cumulative dose of 3.6 g was initiated (600 mg once a week) over the course of following weeks. A second MRI (performed before therapy with rituximab) showed hyperintense signals in the vermis, nodulus, and both cerebellar hemispheres in fluid-attenuated inversion recovery (FLAIR) and T2-weighted MRI. Recently performed MRI showed no new lesions.
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