Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a relatively recently identified disease entity of paraneoplastic limbic encephalitis, first described by Dalmau et al. [1, 2]. Although the incidence of this disorder is still unknown [3], there has been recent interest in the recognition of immune-mediated central nervous system disorders including anti-NMDAR encephalitis [4].
In two large multicenter studies of herpes simplex encephalitis (HSE) mimics, Whitley et al. looked at 432 patients with encephalitis in the period 1973 to 1988 and found that the etiologies of the encephalitis that was experienced by 45 % of the patients were due to herpes simplex virus (HSV), 22 % were due to non-HSV etiologies and 33 % remained without a diagnosis [5]. Chow et al. examined 251 patients with encephalitis in the period 1998 to 2012 and concluded that 24 % of cases were due to HSV and 35 % were due to non-HSV encephalitis, including other infections (bacterial, fungal abscess, mycoplasma, varicella zoster virus, tuberculosis) and non-infectious causes such as vasculitis, malignancy, and anti-NMDAR encephalitis [4]. A substantial number of non-HSV etiologies, such as anti-NMDAR encephalitis, were identified in the Chow et al. cohort [4], but not in the Whitley et al. cohort [5].
Anti-NMDAR encephalitis is a serious yet treatable condition if recognized and treated early [3]. In almost 80 % of cases young females are affected [6]. Patients with this disorder present with rapidly progressive neuropsychiatric symptoms including behavioral disturbance, psychosis, memory deficits, and seizures at onset; patients’ symptoms progress to dyskinesia, autonomic instability, hypoventilation, and coma [1–3].
In 58 % of cases an associated ovarian teratoma is identified [7]. The teratoma contains neuronal cells that result in immunologic sensitization against the NMDA receptors [1, 2, 7]. NMDA receptors are present in high density in the frontotemporal region of the brain and are named after their selective agonist N-methyl-D-aspartate [8, 9]. They are involved in a number of cognitive processes including behavior, memory, learning, and synaptic spasticity [9].
It has been shown that early diagnosis and management is a critical prognostic factor in anti-NMDAR encephalitis [1, 2, 6]. Optimal management of this disorder involves a multidisciplinary team, and the use of aggressive immunotherapy, chemotherapy, surgical removal of the ovarian teratoma, and intensive care unit (ICU) support for hypoventilation and autonomic instability [10]. In 75 % of cases, patients achieve a full recovery or are left with mild deficits; in 25 % of cases, severe residual deficits or death occurs [1–3, 11]. The risk of relapse is reported to be 12 %, which is higher in cases when the tumor is not detected [10]. The mortality rate of this condition is 7 % at 2 years, and is usually secondary to neurological or autonomic dysfunction [6, 10].
In a systemic review of 100 cases of anti-NMDAR encephalitis, early surgical removal of the teratoma with immunotherapy (within 4 months of symptoms onset) showed a better neurological outcome, a lower chance of relapse, and a reduced time to recovery than late or no tumor treatment [11] (Fig. 1).
Acién et al., in their systematic review of 174 cases of anti-NMDAR encephalitis between the years of 2007 and 2013, reported that even small teratomas containing nervous tissue may result in severe complications secondary to anti-NMDAR encephalitis and, given these might be difficult to diagnose, it is very likely that prompt intervention is necessary [12]. Although an exploratory laparotomy has been suggested when a teratoma is not identified by imaging, the benefit of this procedure remains uncertain [12]. A case series review by Dalmau et al. showed that out of seven patients who underwent exploratory laparotomy, only one case was found to have a teratoma [11].
It has also been described that the teratoma might only be detected several years following the presentation of anti-NMDAR encephalitis [10], or it may only be identified microscopically following oophorectomy or at autopsy several months after admission [12]. However, only a few cases of patients with imaging-negative ovarian teratoma who have had a life-saving oophorectomy have been reported, and for this reason we present our patient.