Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an autoimmune disorder mediated by antibodies against the NR1 subunits of the NMDA receptors in the brain [1]. It is predominantly described in young females in association with ovarian teratoma. Ovarian teratomas account for 94% of all neoplasms; however, neuroblastoma, lymphoma, lung, breast, thymic, testicular, and ovarian carcinoma have also been described [2, 3]. It is increasingly recognized as an important cause of autoimmune encephalitis. It is especially important to consider because most often, it is dismissed initially as a psychiatric symptom or viral encephalitis, and patients are initially referred for psychiatric evaluation [4]. This disorder is severe, yet potentially treatable. The best outcome depends on prompt immunotherapy and complete tumor removal if present. However, its diverse presentations and the low awareness among clinicians often cause delay in its diagnosis and treatment [5].

Such as with this patient, we need to suspect the possibility of Anti-NMDA Encephalitis, as the patients with anti-NMDAR encephalitis present clinically with several recognized stages. An initial prodromal phase occurs in almost 70% of patients consisting of headache, fever, nausea, vomiting or upper respiratory symptoms. Then, psychiatric symptoms develop, including; anxiety, insomnia, delusions, paranoia, mania, or social withdrawal [6]. The final stage presents with dyskinesia, extrapyramidal signs, motor automatisms and autonomic instability [2]. Complex seizures can develop early in the course of the disease. The frequency and intensity of seizures decrease with disease progression; however, they may recur at any time [2]. Our patient followed these stereotypical clinical stages.

The diagnosis of anti-NMDAR encephalitis is often difficult and requires exclusion of other similar conditions including; infectious, endocrine and other immune-mediated etiologies. The typical CSF analysis for anti-NMDAR encephalitis is lymphocytic pleocytosis with either normal or elevated protein. Demonstration of oligoclonal bands and anti-NMDAR autoantibodies in the CSF and the serum confirms the diagnosis [1, 7]. Our case showed all the previously described CSF findings.

EEG is abnormal in most cases, usually showing generalized slowing activities which do not correlate with the abnormal movements, as presented in our case [2]. In some cases, it may show extreme delta brushes.

Brain MRI is often inconclusive, although some patients may have T2/FLAIR hyperintensity in regions, especially the hippocampi. These findings, however, correlate poorly with the symptoms [1]. In our case, the patient’s MRI, during the acute stage of the disease, initially showed left hippocampal involvement.

Treatment strategies consist of tumor removal, corticosteroid and IVIG or plasmapheresis as first-line therapy, and rituximab and cyclophosphamide as second-line therapy [3]. Relapse of encephalitis occurs in 20–25% of patients within 3 months up to 9 years; often in those with undetectable or without tumor [8].

Cerebral venous sinus thrombosis (CVST) may present with variable symptoms. The onset can be acute, subacute, or chronic. It mostly presents with headache, and additional symptoms including focal neurological deficits, seizures, and encephalopathy [9].

Antiphospholipid syndrome (APS) is a primary or secondary autoimmune disease, whose patients become more prone to vascular thrombosis. It may develop in patients after exposure to infectious agents or with rheumatic diseases [10].

APS with cerebral venous thrombosis can be an associated comorbidity with anti-NMDAR encephalitis. Therefore, patients with anti-NMDAR encephalitis and a thrombotic event should be screened for APS.

There was a previous report of a similar case with APS associated with anti NMDA encephalitis [11]. Another study also found that high serum titers of NMDAR1-abs are related to unfavorable functional outcome after stroke and are associated with increased cardiovascular recurrent event [12].

Khan and his colleagues [13] also reported a case that was diagnosed as cerebral venous sinus thrombosis (CVST), and was started on anticoagulation then developed new movement abnormalities and was found to have anti-NMDA receptor antibody positive in cerebrospinal fluid. They explained that it may be a possibility that there is an inflammatory or autoimmune process that led to the formation of cerebral venous thrombosis along with anti-NMDA receptor antibodies.

Similarly Yang and Zhang [14] reported a boy who was initially diagnosed with Labbe vein thrombosis and later tested positive for both NMDA and GABA (B) receptors. Vasculitis and endothelial cell impairment caused by autoantibodies are the pathological mechanisms of thrombosis in some of systemic diseases as behcet and antiphospholipid syndrome. Therefore, they propose that the brain tissue damage caused by venous thrombosis triggered an immune response and produced the two different autoimmune antibodies.

In our patient, laboratory tests were negative for APS, so the possible explanations of these findings are that: (a) over activity of NMDA receptors can result in excitotoxicity and acute neuronal injury through excessive presynaptic glutamate release and reversal of calcium uptake by astrocytes [15, 16], (b) regional inflammation can trigger arterial or venous thrombosis [17], (c) studies indicate that NMDARs contribute to the functional mechanisms of the vasculature and to the blood flow characteristics [18, 19] and (d) NMDAR1-abs may critically impair vessel diameter adaptions to metabolic demand, by antagonizing NMDA-receptors in brain endothelial cells [18].