Jesse Sarah, Riemann Marie, Schneider Hauke, Ringelstein Marius, Melzer Nico, Vogel Niklas, Pfeffer Lena Kristina, Friese Manuel A, Sühs Kurt-Wolfram, Hudasch Dominica, Schwenkenbecher Philipp, Günther Albrecht, Geis Christian, Wickel Jonathan, Lesser Martin, Kather Annika, Leypoldt Frank, Dargvainiene Justina, Markewitz Robert, Wandinger Klaus-Peter, Thaler Franziska S, Kuchling Joseph, Wurdack Katharina, Sabater Lidia, Finke Carsten, Lewerenz Jan
Department of Neurology, University Hospital Ulm, Ulm, Germany.
Department of Neurology, Augsburg University, Augsburg, Germany.
Front Immunol. 2024 Dec 13;15:1500904. doi: 10.3389/fimmu.2024.1500904. eCollection 2024.
Very rarely, adult NMDAR antibody-associated encephalitis (NMDAR-E) leads to persistent cerebellar atrophy and ataxia. Transient cerebellar ataxia is common in pediatric NMDAR-E. Immune-mediated cerebellar ataxia may be associated with myelin oligodendrocyte glycoprotein (MOG), aquaporin-4 (AQP-4), kelch-like family member 11 (KLHL11), and glutamate kainate receptor subunit 2 (GluK2) antibodies, all of which may co-occur in NMDAR-E. Here, we aimed to investigate the frequency, long-term outcome, and immunological concomitants of ataxia in NMDAR-E.
In this observational study, patients with definite NMDAR-E with a follow-up of >12 months were recruited from the GENERATE registry. Cases with documented ataxia were analyzed in detail.
In 12 of 62 patients (19%), ataxia was documented. Bilateral cerebellar ataxia without additional focal CNS findings was found in four (one child and three adults); one of these was previously reported as a case with persistent cerebellar atrophy and ataxia. Two patients with bilateral cerebellar ataxia had additional focal neurological symptoms, optic neuritis and facial palsy. Two patients developed hemiataxia: one with diplopia suggesting brainstem dysfunction and the other probably resulting from cerebellar diaschisis due to contralateral status epilepticus. In all but the one developing cerebellar atrophy, cerebellar ataxia was transient and not associated with a worse long-term outcome. In all five patients with cerebellar ataxia tested, MOG, AQP-4, GluK2, and KLHL11 antibodies were negative. In two additional patients negative for both MOG and AQP-4 antibodies, ataxia was sensory and explained by cervical myelitis as part of multiple sclerosis (MS) manifesting temporal relation to NMDAR-E. One of the patients with bilateral ataxia with focal neurological deficits was also diagnosed with MS upon follow-up. Finally, in two patients, ataxia was explained by cerebral hypoxic damage following circulatory failure during an ICU stay with severe NMDAR-E.
Ataxia of different types is quite common in NMDAR-E. Cerebellar ataxia in NMDAR-E is mostly transient. NMDAR-E followed by persistent ataxia and cerebellar atrophy is very rare. Cerebellar ataxia in NMDAR-E may not be explained by concomitant KLHL11, MOG, AQP-4, or GluK2 autoimmunity. Of note, ataxia in NMDAR-E may result from treatment complications and, most interestingly, from MS manifesting in temporal association with NMDAR-E.
极罕见情况下，成人N-甲基-D-天冬氨酸受体（NMDAR）抗体相关脑炎（NMDAR-E）会导致持续性小脑萎缩和共济失调。短暂性小脑共济失调在儿童NMDAR-E中很常见。免疫介导的小脑共济失调可能与髓鞘少突胶质细胞糖蛋白（MOG）、水通道蛋白4（AQP-4）、kelch样家族成员11（KLHL11）和谷氨酸钾离子受体亚基2（GluK2）抗体有关，所有这些抗体都可能在NMDAR-E中同时出现。在此，我们旨在研究NMDAR-E中共济失调的发生率、长期预后及免疫相关因素。
在这项观察性研究中，从GENERATE注册库中招募了随访时间超过12个月的确诊NMDAR-E患者。对有共济失调记录的病例进行详细分析。
62例患者中有12例（19%）记录有共济失调。4例（1名儿童和3名成人）出现双侧小脑共济失调且无其他局灶性中枢神经系统表现；其中1例之前被报道为持续性小脑萎缩和共济失调病例。2例双侧小脑共济失调患者有其他局灶性神经症状，即视神经炎和面神经麻痹。2例患者出现偏瘫共济失调：1例伴有复视提示脑干功能障碍，另1例可能是由于对侧癫痫持续状态导致的小脑交叉性失联络。除1例出现小脑萎缩的患者外，所有患者的小脑共济失调都是短暂的，且与较差的长期预后无关。在所有接受检测的5例小脑共济失调患者中，MOG、AQP-4、GluK2和KLHL11抗体均为阴性。另外2例MOG和AQP-4抗体均为阴性的患者，共济失调为感觉性，由作为多发性硬化（MS）一部分的颈髓炎解释，其与NMDAR-E存在时间关联。1例伴有局灶性神经功能缺损的双侧共济失调患者在随访时也被诊断为MS。最后，2例患者的共济失调是由重症NMDAR-E入住重症监护病房期间循环衰竭后的脑缺氧损伤所致。
不同类型的共济失调在NMDAR-E中相当常见。NMDAR-E中的小脑共济失调大多是短暂的。NMDAR-E后出现持续性共济失调和小脑萎缩非常罕见。NMDAR-E中的小脑共济失调可能无法用同时存在的KLHL11、MOG、AQP-4或GluK2自身免疫来解释。值得注意的是，NMDAR-E中的共济失调可能由治疗并发症引起，最有趣的是，也可能由与NMDAR-E存在时间关联的MS引起。
