Late relapse of anti-N-methyl-d-aspartate receptor encephalitis with amusia and transiently reduced uptake in 123I-iomazenil single-photon emission computed tomography

IntroductionAnti-N-methyl-d-aspartate receptor (NMDAR) encephalitis has a high relapse rate at approximately 10–20%. Most relapses occur within 2 years from onset, and 5 years after onset is rare. We report a case of anti-NMDAR encephalitis relapse with amusia 10 years after the initial encephalitis and discuss the usefulness of ¹²³I-iomazenil single-photon emission computerized tomography (IMZ-SPECT) for its diagnosis.CaseA 13-year-old left-handed girl presented with a depressed level of consciousness and focal to bilateral tonic-clonic seizures. Cerebrospinal fluid (CSF) analysis showed a mildly increased white blood cell count, elevated neopterin levels, and positive oligoclonal bands. Brain MRI was normal. IMZ-SPECT revealed reduced uptake in the right frontoparietal region. She received intravenous pulse methylprednisolone (IVMP) and high-dose intravenous immunoglobulin for autoimmune encephalitis; her symptoms resolved without neurological deficits. At 23 years old, she had mild right-sided numbness, dysarthria, amusia, and tonic-clonic seizures. Although the CSF analysis and brain MRI were normal, IMZ-SPECT revealed reduced uptake, indicating a relapse of encephalitis. IVMP administration resolved the symptoms. After discharge, the initial and relapse CSF analysis revealed anti-NMDAR antibodies.ConclusionAn anti-NMDAR encephalitis relapse 10 years after onset has never been reported. IMZ-SPECT may help in the diagnosis of anti-NMDAR encephalitis.     

Novel FDG-PET findings in anti-NMDA receptor encephalitis: a case based report

The clinical manifestation and nuclear imaging findings in a 15-year-old boy with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis are described in this case report. The previously healthy patient presented with new onset hallucinations, seizure, and within a week, his mental status rapidly deteriorated to nonverbal with oro-lingual-facial dyskinesias. An extensive laboratory work-up for encephalopathy was negative. Repeated brain magnetic resonance imaging (MRI) studies were normal. On day 26 of admission, nuclear imaging using fluorodeoxyglucose positron emission tomography (FDG-PET) showed global hypometobolism with a prominent focally intense hypermetabolic lesion in the right cerebellar cortex. Diagnosis of anti-NMDAR encephalitis was confirmed with quantitative serology. The patient showed clinical signs of improvement after 2 courses of intravenous immunoglobulin therapy over 4 weeks. On day 46, repeat brain FDG-PET showed overall improvement but in contrast to the previous, the right cerebellar cortex showed focal hypometabolism. This is the first reported case of such findings using FDG-PET in anti-NMDAR encephalitis.     

晚发型抗N-甲基-D-天冬氨酸受体脑炎临床特征分析

目的分析晚发型抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎的临床特征。方法收集2010-01-01—2019-05-01于郑州大学第一附属医院住院确诊为抗NMDAR脑炎的患者临床资料,分析晚发型(≥50岁)患者数据,并与早发型(18~49岁)患者进行对比。结果18例晚发型患者中,男11例(61%),发病年龄50~84岁。晚发型患者中,9例(50%)患者出现前驱症状,精神行为异常是最常见的首发症状(44%)和临床表现(78%);头颅磁共振提示脑实质炎性病变9例(9/17,53%);脑脊液检验结果异常17例(94%);合并肿瘤4例(22%),均非畸胎瘤。相比于早发组患者,晚发组患者有更高的自主神经功能障碍比例(72%vs 45%,P=0.032),更高的岛叶病变比例(67%vs 27%,P=0.047),更高的脑脊液蛋白升高比例(56%vs 28%,P=0.023),以及更高的脑脊液鞘内IgG合成率升高比例(73%vs 44%,P=0.041)。晚发组合并肿瘤均非畸胎瘤,早发组合并肿瘤均为畸胎瘤(P=0.001)。结论相比早发型抗NMDAR脑炎患者,晚发型患者更易出现岛叶病变,更易出现脑脊液炎症反应,其发病机制可能与畸胎瘤不相关。     

Hyperammonemia in a case of herpes simplex and anti-N-methyl-d-aspartate receptor encephalitis

Herpes simplex encephalitis (HSE) is a widely accepted risk factor for anti N-methyl-d-aspartate receptor (NMDAR) encephalitis. Association of inherited metabolic disease has never been reported in a patient with HSE and anti-NMDAR encephalitis. Herein, we report a case of pediatric HSE complicated by development of anti-NMDAR encephalitis; this patient showed subsequent recurrent, unexplained episodes of encephalopathy associated with hyperammonemia. The patient was diagnosed with lysinuric protein intolerance (LPI), a rare inborn metabolic disorder. Although it would be difficult to make conclusions regarding the casual link of HSE and anti-NMDAR encephalitis with LPI from a single case, there have been many reports that autoimmune diseases and immunologic abnormalities are frequently associated with LPI. Thus, we speculate that LPI may contribute to the development of anti-NMDAR encephalitis following HSE.     

Usefulness of arterial spin labeling imaging,which contributed to the early detection of cerebellitis complicated by clinically mild encephalitis/encephalopathy with a reversible splenial lesion: Lessons from three cases

BackgroundCerebellitis is a rare complication of clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS); however, MERS with cerebellitis is associated with a higher risk of neurological sequelae in comparison to MERS alone. Although the disease is difficult to diagnose by conventional MRI in the early disease phase, arterial spin labeling (ASL), a noninvasive MRI perfusion technique using magnetically-labeled arterial blood water protons, is considered promising.Case reportWe experienced three cases of MERS with cerebellitis. Diffusion-weighted imaging showed a high-intensity lesion at the splenium of the corpus callosum. ASL showed increased blood flow in the cerebellum in all three cases, despite cerebellar symptoms being inapparent or difficult to notice in the early phase of disease in all cases. Patients received methylprednisolone pulse therapy and intravenous immunoglobulin from the early phase of the disease and recovered without neurological sequelae.DiscussionASL magnetic response imaging simultaneously showed an area of hyperperfusion in the cerebellum. At the same time, the apparent diffusion coefficient of the splenial lesion was decreased in all three cases. The successful diagnosis of cerebellitis in the acute phase led to early therapeutic intervention, which may be important for this condition. We report the usefulness of ASL and review the relevant literature on MERS with cerebellitis.     

Altered perception might be a symptom of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis

ABSTRACT

Most patients with N-methyl-D-aspartate receptor (NMDAR) encephalitis initially present with psychiatric symptoms. Although a delayed diagnosis may lead to a poor outcome, psychiatric symptoms that could differentiate anti-NMDAR encephalitis from other psychoses have not been fully investigated. We evaluated two patients with anti-NMDAR encephalitis who were observed by psychiatrists from onset throughout the course of disease. Both patients exhibited disorientation, memory deficits, perceptual disturbances, hallucinations, and mood liability. Among those, altered perceptions were most prominent - in particular, altered time perceptions without disorganization syndrome. The information obtained for these patients may help clinicians differentiate anti-NMDAR encephalitis from other psychoses, e.g., schizophrenia.     

Arterial spin labeling hyperperfusion in Rasmussen's encephalitis: Is it due to focal brain inflammation or a postictal phenomenon?

Background and purpose

The study evaluated the utility of arterial spin labeling (ASL) perfusion imaging in Rasmussen's encephalitis (RE).

Japanese encephalitis-induced anti-N-methyl-d-aspartate receptor encephalitis: A hospital-based prospective study

ObjectivesA hospital-based prospective study was performed to determine: 1) whether Japanese encephalitis (JE) normally triggers anti-N-methyl-d-aspartate receptor (NMDAR) immunoglobulin G (IgG) synthesis, especially in monophasic JE patients; and 2) the incidence of JE-induced anti-NMDAR encephalitis in pediatric patients with JE.MethodsWe detected the level of anti-NMDAR IgG in the serum and cerebral spinal fluid (CSF) of JE patients within one week of onset. If patients relapsed during the convalescence phase, we detected JE virus RNA in the CSF and anti-NMDAR IgG in both the serum and CSF. For patients who did not relapse during the convalescence phase, serum was collected and anti-NMDAR IgG was detected during the 30–60-day course of the disease.ResultsWe enrolled 65 JE patients, who were negative for anti-NMDAR IgG in the serum and CSF during the acute phase, of which 63 patients were successfully followed up. Five patients relapsed during the convalescence phase, for whom JE virus RNA in the CSF was negative and excluded latent JE reactivation. The distinctive symptoms of four younger patients were choreoathetosis, whereas the psychiatric and behavioral manifestations were the distinctive symptoms experienced by the teenager. Anti-NMDAR IgG in the CSF of three patients was positive and they were diagnosed with anti-NMDAR encephalitis. The other two patients were negative for anti-NMDAR IgG in both the serum and CSF. For the 58 patients who did not relapse during the convalescence phase, anti-NMDAR IgG was negative in the serum of all patients at 30–60 days during the course of the disease.ConclusionsJE does not typically trigger anti-NMDAR IgG synthesis. Besides anti-NMDAR IgG, other unknown autoantibodies can also cause autoimmune encephalitis in the convalescence phase of JE. The incidence of JE-induced autoimmune encephalitis in pediatric patients with JE was 7.9%, and the incidence of JE-induced anti-NMDAR encephalitis was 4.7%.     

Anti-N-Methyl-D-Aspartate Encephalitis With Ovarian Cystadenofibroma

We report the case of an adolescent girl with anti-N-methyl-D-aspartate-receptor (NMDAR) encephalitis who presented with focal seizures and hemichorea, followed by agitation, speech disturbance, mutism, and autonomic dysfunction. The institution of immunotherapy and removal of an ovarian cystadenofibroma led to full resolution of her symptoms with disappearance of serum NMDAR antibodies. This is the first report linking ovarian cystadenofibroma to anti-NMDAR encephalitis.     

Gray matter atrophy and corresponding impairments in connectivity in patients with anti-N-methyl-D-aspartate receptor encephalitis

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe autoimmune disease that is commonly accompanied by cognitive impairment and various neurological and psychiatric symptoms, advanced image analyses help explore the pathogenesis of this disease. Therefore, this study aimed to explore specific structural and functional alterations and their relationship with the clinical symptoms of anti-NMDAR encephalitis. In this study, twenty-two patients with anti-NMDAR encephalitis after the acute stage and 29 controls received cognitive assessments and magnetic resonance imaging. Grey matter atrophy was measured using voxel-based morphometry, and functional alterations in abnormal regions were subsequently investigated using resting state functional connectivity (RSFC). Finally, correlation analyses were performed to explore the associations between imaging alterations and cognitive assessments. The patients demonstrated significant gray matter atrophy in the bilateral triangle part of the inferior frontal gyrus (triIFG.L and triIFG.R) and right precuneus, decreased RSFC between triIFG.L and bilateral Heschl gyrus (HES), decreased RSFC between triIFG.R and HES.R, decreased RSFC between right precuneus and left cerebellum, and increased RSFC between triIFG.R and left superior frontal gyrus. Further correlation analyses showed that the gray matter volume in triIFG.R and decreased RSFC between triIFG.L and HES.R were associated with decreased memory scores, whereas decreased RSFC between triIFG.R and HES.R was marginally correlated with the disease course in patients. In conclusion, this study suggests that cognitive impairments in patients with anti-NMDAR encephalitis may be mainly associated with gray matter atrophy and abnormal RSFC in the triIFG. These findings provide new insights into anti-NMDAR encephalitis pathogenesis and help explore potential treatments.

     

抗NMDAR脑炎临床特点及影像表现分析

目的 探讨抗NMDAR脑炎的临床特点、影像表现及意义.方法 回顾性分析陕西省人医院2014-01—2020-08确诊的11例抗NMDAR脑炎患者的临床及影像资料.结果 11例患者为急性或亚急性起病,首发症状表现为精神症状2例,认知功能损害2例,痫性发作4例,非特异性症状3例.11例患者的脑脊液抗NMDAR抗体均为阳性,...     

抗NMDA受体脑炎45例特点和临床转归分析

目的探讨本组抗NMDA受体脑炎患者的临床特点。方法收集北京丰台右安门医院和北京宣武医院神经内科2012年10月至2015年4月收治的45例抗NMDA受体脑炎患者的临床资料,分析病例特点,随访病情转归。结果本组的45例患者年龄为14~61岁,平均年龄32.2±13.24岁;男性27例,其中3例(11%)合并肿瘤。女性18例,其中5例(28%)合并卵巢畸胎瘤。23例(51%)出现前驱症状。本组45例临床症状表现为精神症状(91%)、癫痫发作(76%)、不自主运动(42%)、中枢性低通气(24%)、意识水平下降(47%)及自主神经功能障碍(40%)。脑脊液(CSF)常规、生化检查阳性率为89%,所有患者CSF抗NMDA受体抗体阳性。脑电图(EEG)多表现为双额、颞、中央导联为主的轻度(21%)至中度(59%)慢波。53%患者头颅CT平扫或MRI检查有异常表现,多见于额颞叶T2-Flair异常信号。所有患者均给予激素和丙种球蛋白治疗,6例患者接受环磷酰胺或吗替麦考酚治疗。除1例失访,44例患者预后良好(MRS评分0-2分)者占86%。结论抗NMDAR脑炎发病男性并不少见,肿瘤合并率低。以精神行为异常、癫痫发作、CSF抗NMDA受体抗体阳性为其主要临床特点。绝大部分患者EEG异常,并与病情严重程度相关。79%患者一线免疫治疗效果良好。8例合并肿瘤患者病情严重且预后不良,畸胎瘤摘除术不能完全预防该病发生,但能减轻病情严重程度。     

Anti-NMDAR autoimmune encephalitis

The N-methyl-d-aspartate receptor (NMDAR) is involved in normal physiological and pathological states in the brain. Anti-NMDAR encephalitis is characterized by memory deficits, seizures, confusion, and psychological disturbances in males and females of all ages. This type of encephalitis is often associated with ovarian teratoma in young women, but children are less likely to have tumors. Anti-NMDAR encephalitis is a neuroimmune syndrome in patients with autoantibodies recognizing extracellular epitopes of NMDAR, and the autoantibodies attenuate NMDAR function through the internalization of NMDAR. Following the initial symptoms of inflammation, the patients show the various symptoms such as memory loss, confusion, emotional disturbances, psychosis, dyskinesis, decrease in speech intelligibility, and seizures. About half of these patients improved with immunotherapy including high-dose intravenous corticosteroids and intravenous immunoglobulins is administrated to these patients, but the patients who had no improvement with these therapy require further treatments with rituximab or cyclophosphamide. It is necessary to detect anti-NMDAR antibodies at early stages, because the prognosis of these patients may be improved by early treatment. Recovery is slow, and the patients may have some disturbances in their motor function and cognition. The pathologic mechanism underlying the development of anti-NMDAR encephalitis has been elucidated gradually, but the optimal treatment has not yet been clarified. Further studies are required to clarify in detail the mechanism underlying anti-NMDA encephalitis and to develop effective treatments.     

Anti-NMDA receptor encephalitis presenting with focal non-convulsive status epilepticus in a child

A previously healthy 9-year-old girl presented to an emergency department (ED) with headache, dizziness, blurry vision, and abnormal visual perceptions. She was diagnosed with migraine, treated symptomatically, and discharged. Over the course of days, she became progressively somnolent, and returned to the ED, where she was found to have a right inferior quadrantanopsia and sixth nerve palsy. Magnetic resonance imaging (MRI) of the brain showed gyral swelling of the left parieto-occipital lobe. Continuous electroencephalogram (EEG) monitoring revealed focal non-convulsive status epilepticus (NCSE) in the left occipital region. Cerebrospinal fluid (CSF) was positive for antibodies directed against the N-methyl-d-aspartate receptor (NMDAR). This case is the first report of anti-NMDAR encephalitis presenting with focal non-convulsive status epilepticus (NCSE).     

Anti-N-methyl-d-aspartate receptor encephalitis with minimal cortical impairment

Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis has been recently identified as a fulminant encephalopathy, presenting with a variety of symptoms including behavioral change, amnesia and seizures suggesting cortical gray matter involvement. A 42-year-old woman presented with acute-onset clinical and magnetic resonance imaging (MRI) findings indicating brainstem and diencephalon involvement. Her neuropsychological examination revealed mild frontal dysfunction with no memory impairment. Detailed diagnostic workup proved negative except for serum/cerebrospinal fluid (CSF) NMDAR-antibodies and increased activity in inguinal and pelvic lymph nodes on positron-emission tomography (PET) examination. The symptoms and MRI findings completely resolved following steroid treatment. A 38-year-old woman presented with migraine-type headache and episodes of forgetfulness. Her brain MRI and neuropsychological examination were normal and diagnostic workup was unremarkable. N-methyl-d-aspartate receptor antibodies were identified in her sera and her symptoms spontaneously resolved within few months. Our cases suggest that anti-NMDAR encephalitis might present with minimal cognitive impairment, no apparent cortical gray matter involvement, a mild clinical course and without the classical clinical features of the disease.     

Anti-NMDA receptor encephalitis associated with ictal asystole

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis usually presents with psychiatric symptoms, behavioural changes, impaired consciousness, seizures and autonomic instability. Ictal asystole is a rare phenomenon associated with complex partial seizures. It is implicated as a potential cause of sudden unexpected death in epilepsy. We report a 41-year-old woman who presented with anti-NMDAR encephalitis. During continuous video electroencephalogram and cardiac monitoring, an episode of ictal asystole was detected. We discuss the potential link between anti-NMDAR encephalitis and ictal asystole. Treatment options for ictal asystole in the setting of anti-NMDAR encephalitis are also discussed.     

Chorea-acanthocytosis: Time-dependent changes of symptoms and imaging findings

Background and purposeChorea-acanthocytosis, a rare neurodegenerative disease, affects both the striatum and the medial temporal lobe which may cause involuntary movements and epilepsy, respectively. We examined the imaging changes of the hippocampus/amygdala and the striatum as well as clinical symptoms.Materials and methodsWe retrospectively reviewed 29 MRI and 13 SPECT studies and the clinical findings of seven genetically confirmed chorea-acanthocytosis patients. We evaluated the time-dependent imaging changes of the hippocampus/amygdala and striatum and examined the relationships among these images and symptoms.ResultsThe initial symptom was epilepsy in four patients and involuntary movements in three patients. These symptoms were eventually noted in five and all seven patients, respectively. On MRI, most patients showed striatum atrophy before a hippocampus/amygdala abnormality emerged, but one patient showed a hippocampus/amygdala abnormality before striatum atrophy. Abnormal MRI findings of hippocampus/amygdala were noted in five patients and atrophy of striatum in all seven patients. SPECT demonstrated hypoperfusion of hippocampus/amygdala in three patients and that of striatum in all five available patients. Four patients demonstrated hypoperfusion of striatum earlier than that of hippocampus/amygdala and one patient showed hypoperfusion of both simultaneously. Many imaging abnormal lesions were accompanied by their corresponding symptoms, but not always so.ConclusionStriatum abnormalities were the initial imaging findings in many chorea-acanthocytosis patients, but epilepsy or hippocampus/amygdala imaging abnormalities may be the only findings at the early stage. It is important to understand the detailed clinical and imaging time courses for the diagnosis of chorea-acanthocytosis.     

抗N-甲基-D-天冬氨酸受体脑炎的抗体检测及临床意义

目的探讨抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎的抗体检测意义及临床特征。方法选取本院收治的脑炎病人35例及对照组30例,分析临床资料,采用转染细胞间接免疫荧光法检测两组患者其血清及脑脊液抗NMDAR机体结果抗NMDAR抗体检测仅1例边缘叶脑炎患者结果阳性,该患者腑脊液细胞数增多、蛋白轻度升高、脑电图见双侧慢波、其余检查无异常。精神症状及意识水平障碍明显,免疫治疗有效。结论抗NMDAR脑炎发病率低,临床表现复杂多样,怀疑该病时需行抗NMDAR抗体检测。     

Relapsing Anti-NMDAR Encephalitis after a gap of eight years in a girl from North-East India

It has been just 7 years since the discovery of anti-NMDAR encephalitis as distinct immune-mediated encephalitis and we have such cases being reported from our country. Herein, we describe a case of a 13-year-old girl who had relapsing encephalitis consisting of multiple types of difficult-to-control seizures, abnormal behavior, language disintegration, memory loss and abnormal movements eight years after the first clinical attack. In 2005, when she was 5 yearsold, anti-NMDAR encephalitis was not yet discovered and she was provisionally diagnosed as a case of viral encephalitis. During her second attack in 2013, antibodies against NMDAR were demonstrated by immunofluoresence in serum (1:10). This is the first report from our country of a case of relapsing anti-NMDAR encephalitis of such a long duration, successfully treated by immunotherapy.     

自身免疫性脑炎临床表现与MRI特征分析

目的对自身免疫性脑炎的临床症状与MRI特征进行分析,提高临床医师对自身免疫性脑炎的临床特征及MRI表现的认识。方法纳入自身免疫性脑炎33例,收集一般临床资料,采用MRI观察颅内病变情况,分析其主要症状及影像学特征。结果本组自身免疫性脑炎的主要症状为精神行为异常27例(81.8%),癫痫发作26例(78.8%),18例(54.5%),发热11例(33.3%),中枢性低通气9例(27.3%)等,其中不自主运动和发热发生率LE组较NMDA组低。MRI阳性者10例,脑实质受累8例,脑膜受累3例,脑实质依次累及枕叶、双侧海马、额叶、顶叶、颞叶及丘脑、小脑等部位。结论精神行为异常及癫痫发作为自身免疫性脑炎最常见的两个症状,MRI可发现边缘系统异常信号,其中FLAIR序列最为敏感。