Focal EEG slowing and chorea: electroclinical clues to the diagnosis of anti‐NMDAR encephalitis

Variations in clinical presentation can lead to delays in the diagnosis and initiation of treatment of anti‐N‐methyl‐D‐aspartate receptor encephalitis. Most patients have an EEG study performed early in the course of their illness. Although not specific, there may be clues in the electroclinical features that should alert clinicians and electroencephalographers to the possibility of this diagnosis. This case is a reminder that anti‐ anti‐N‐methyl‐D‐aspartate receptor encephalitis may present initially with a movement disorder as the sole symptom, without features of an encephalopathy. In addition, it adds to the growing body of evidence that recognition of certain electroclinical clues may shorten the time to diagnosis. [Published with video sequence]     

Movement disorders in children with anti‐NMDAR encephalitis and other autoimmune encephalopathies

Accurate recognition of movement disorder phenomenology may differentiate children with anti‐N‐methyl D‐aspartate receptor (NMDAR) encephalitis, autoimmune basal ganglia encephalitis (BGE), and Sydenham's chorea (SC). Three neurologists blinded to the diagnoses recorded dominant and associated movement disorders seen on videos of 31 patients with anti‐NMDAR encephalitis (n = 10), BGE (n = 12), and SC (n = 9). Stereotypy was only seen in anti‐NMDAR encephalitis (8/10) and not in BGE and SC (P < 0.001). Perseveration was only seen in anti‐NMDAR encephalitis (5/10) and not in BGE and SC (P < 0.001). Akinesia was more commonly seen in BGE (5/12) than in anti‐NMDAR encephalitis (1/10, P = 0.097). Tremor was more commonly seen in BGE (5/12) than in anti‐NMDAR encephalitis (1/10, P = 0.097). Chorea was seen in all groups: anti‐NMDAR encephalitis (4/10), BGE (3/12), and SC (9/9). Likewise, dystonia was seen in all groups: anti‐NMDAR encephalitis (6/10), BGE (7/12), and SC (2/9). Stereotypies or perseveration are suggestive of anti‐NMDAR encephalitis, whereas their absence and the presence of akinesia and tremor is more suggestive of BGE. Chorea and dystonia are least discriminating. © 2014 International Parkinson and Movement Disorder Society     

Serial EEG findings in anti‐NMDA receptor encephalitis: correlation between clinical course and EEG

Anti‐NMDA receptor encephalitis is a paraneoplastic encephalitis characterised by psychiatric features, involuntary movement, and autonomic instability. Various EEG findings in patients with anti‐NMDA receptor encephalitis have been reported, however, the correlation between the EEG findings and clinical course of anti‐NMDA receptor encephalitis remains unclear. We describe a patient with anti‐NMDA receptor encephalitis with a focus on EEG findings, which included: status epilepticus, generalised rhythmic delta activity, excess beta activity, extreme delta brush, and paroxysmal alpha activity upon arousal from sleep, which we term“arousal alpha pattern”. Initially, status epilepticus was observed on the EEG when the patient was comatose with conjugate deviation. The EEG then indicated excess beta activity, followed by the emergence of continuous slow activity, including generalised rhythmic delta activity and extreme delta brush, in the most severe phase. Slow activity gradually faded in parallel with clinical amelioration. Excess beta activity persisted, even after the patient became almost independent in daily activities, and finally disappeared with full recovery. In summary, our patient with anti‐NMDA receptor encephalitis demonstrated slow activity on the EEG, including extreme delta brush during the most severe phase, which gradually faded in parallel with clinical amelioration, with excess beta activity persisting into the recovery phase.     

PET‐positive extralimbic presentation of anti‐glutamic acid decarboxylase antibody‐associated encephalitis

Anti‐glutamic acid decarboxylase (GAD) antibody‐associated autoimmune encephalitis has been reported mostly as limbic encephalitis. Only few cases with extralimbic involvement are reported with limited investigation. Here, we report an extensive investigation with MRI, PET, and pathological examination. A 66‐year‐old Japanese female with a history of hypothyroidism, colon cancer, pheochromocytoma, and thymoma‐associated myasthenia gravis presented with generalised tonic‐clonic seizures. MRI showed multiple hyperintense lesions and PET showed hypermetabolic lesions in the brain. Biopsy showed non‐specific gliosis, microglial proliferation, and perivascular lymphohistiocytic infiltrates. Various neuronal antibodies were negative, except for anti‐GAD antibody. Anti‐GAD antibody‐associated encephalitis is an increasingly recognised CNS disease. Pathophysiology of this encephalitis is unclear. While PET showed hypermetabolic lesions, the biopsy showed non‐specific changes. The treatments may include immunosuppressants, IVIg, and plasma exchange. One should consider to measure this antibody, in addition to others, when autoimmune encephalitis is suspected [Published with video sequences].     

The distinct movement disorder in anti‐NMDA receptor encephalitis may be related to status dissociatus: A hypothesis

The majority of patients with anti‐N‐methyl‐D‐aspartate‐receptor encephalitis (NMDAE) present a characteristic movement disorder, which consists of complex bilateral stereotyped movements of the arms, with perioral and eye movements, and less frequently involvement of the legs. We have observed striking similarities in the characteristics of the abnormal movements observed in NMDAE and those described in Status Dissociatus, which is characterized by a complete breakdown of state‐determining boundaries (wakefulness, REM and NREM sleep) and can result from pathophysiologically diverse disorders (e.g. fatal familial insomnia, delirium tremens, Morvan's syndrome). Here, we suggest that the state of paradoxical responsiveness in which NMDAE patients present these stereotyped movements may be that of Status Dissociatus and discuss the clinical similarities and pathophysiological explanations that support such a suggestion. This hypothesis explains why patients that seem to be unconscious have a movement disorder that is not epileptic and may have management implications, since many patients with NMDAE‐related movement disorder are treated with anticonvulsants that may not be indicated. © 2012 Movement Disorder Society     

A case of anti‐NMDA receptor encephalitis revealed by insular epilepsy

Anti‐N‐methyl‐D‐aspartate receptor (NMDAR) encephalitis is an autoimmune disorder of the central nervous system that typically manifests predominantly as a psychiatric disorder. However, other manifestations such as epileptic seizures, abnormal movements, and memory or language complications are not unusual. Here, we report the case of a young man who presented with a new‐onset epilepsy, with ictal semiology suggestive of insular involvement; this hypothesis was supported by a PET‐CT study. Anti‐NMDAR antibodies were found in the CSF, confirming the diagnosis of anti‐NMDAR encephalitis. A review of the literature reveals that epilepsy can be the first manifestation of NMDAR encephalitis, with a clear male predominance. Despite its rarity, neurologists should consider this diagnosis for any young patient developing a new‐onset epilepsy with temporal or insular features, particularly if the patient is male. Other cognitive or behavioural signs, even very subtle, should also prompt diagnosis.     

Brain immunohistopathological study in a patient with anti‐NMDAR encephalitis

Background and purpose: Anti‐N‐methyl‐d ‐asparate (NMDA) receptor encephalitis is thought to be antibody‐mediated. To perform an immunohistopathological study of the inflammatory reaction in a brain biopsy performed before immunomodulatory treatments in a patient with anti‐NMDA receptor encephalitis. Methods: An immunohistochemical study was performed using CD3, CD68, CD20, CD138 and CD1a antibodies. Results: Prominent B‐cell cuffing was present around brain vessels accompanied by some plasma cells, while macrophages and T cells were scattered throughout the brain parenchyma. Conclusion: These findings suggest that the B cells interact with the T cells and are involved in antibody secretion by the plasma cells.     

Possible induction of multiple seizure foci due to parietal tumour and anti‐NMDAR antibody

“Formes frustes” of encephalopathy associated with anti‐NMDAR antibody have been recently described in cases of chronic epilepsy. We report a young woman with a parietal lesion and anti‐NMDAR antibody who acquired bilateral, secondary epileptogenesis in the temporal lobes within a period as short as six years. Removal of the primary epileptogenic lesion of oligoastrocytoma in the right parietal lobe resulted in seizure freedom, disappearance of secondary foci, and substantial decrease of the antibody titre. Chronic exposure to anti‐NMDAR antibody, albeit at a low titre, may have resulted in a smoldering chronic course and relatively early acquisition of “reversible” secondary foci without development of a high degree of epileptogenicity and structural changes.