Cell-based assays (CBA) have increased the sensitivity of the neuromyelitis optica (NMO)-IgG/aquaporin-4-antibody detection compared to classical tissue-based indirect assays. We describe the sensitivity of an optimized immunohistochemistry (IHC-o) to detect NMO-IgG/aquaporin-4-antibody in comparison with that of two CBA: an in-house (CBA-ih) and a commercial (CBA-c) assay (Euroimmun, Germany). Coded serum from 103 patients with definite NMO and 122 inflammatory controls were studied by IHC-o, CBA-ih, and CBA-c. IHC-o used the same protocol described to detect antibodies against cell surface antigens. CBA-ih used live cells transfected with the aquaporin-4-M23-isoform. The sensitivity of the IHC-o was 74.8% (95% confidence interval [CI] 65-83) and was similar to that of the CBA-ih 75.7% (95% CI 66-84) and the CBA-c 73.8% (95% CI 64-82). The specificity of the three assays was 100% (95% CI 97-100). Interassay concordance was high, 100 of 103 samples were coincident in all techniques. The optimized immunohistochemistry proves to be as sensitive and specific as the cell-based assays. This assay extends the available tools for NMO-IgG/aquaporin-4-antibody detection.
The causes of encephalitis are numerous, and extensive investigations for infectious agents and other etiologies are often negative. The discovery that many of these encephalitis are immune mediated has changed the approach to the diagnosis and treatment of these disorders. Moreover, the broad spectrum of symptoms including, psychosis, catatonia, alterations of behavior and memory, seizures, abnormal movements, and autonomic dysregulation usually requires a multidisciplinary treatment approach. This review focuses in several forms of encephalitis that occur in children, and for which an autoimmune etiology has been demonstrated (eg, anti-N-methyl-D-aspartate receptor encephalitis) or is strongly suspected (eg, Rasmussen encephalitis, limbic encephalitis, opsoclonus-myoclonus). The authors also review several disorders that may be immune mediated, such as the rapid onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD) syndrome and some encephalopathies with fever and status epilepticus. Recognition of novel immune-mediated encephalitis is important because some of these disorders are highly responsive to immunotherapy.
autoimmune; encephalitis; limbic; anti-NMDA receptor; NMDA
Homer proteins are a family of scaffolding proteins of the postsynaptic density. Homer-3 colocalizes and modulates the activity of group I metabotropic glutamate receptors (mGluR1 and mGluR5). Cerebellitis has been reported in association with antibodies to mGluR1. We describe the second patient with cerebellitis and Homer-3 antibodies and report a novel, highly specific immunoblot assay.
A 38-year-old man had acute onset of headache, nausea, vomiting, and confusion. He developed a pancerebellar syndrome during the ensuing week. Extensive studies did not reveal any tumor. Cerebrospinal fluid analysis showed a white blood cell count of 60/µL (to convert to ×109 per liter, multiply by 0.001). Brain magnetic resonance imaging findings were normal. For 2 years, the patient was treated with intravenous immunoglobulins and steroids, with partial improvement of the cerebellar ataxia. The patient was negative for onconeural (Hu, Yo, Ri, CV2, Tr, amphiphysin, and Ma2), glutamic acid decarboxylase, and mGluR1 antibodies. Immunohistochemistry on rat brain revealed immunostaining of the cerebellar molecular layer. Homer-3 antibodies were demonstrated by immunoblot of recombinant Homer-3. The clinical features of this patient and a previously described patient with Homer-3 antibodies are similar to those of patients with mGluR1 antibodies.
Conclusions and Relevance
We report the second case of autoimmune cerebellar ataxia associated with Homer-3 antibodies. The presence of Homer-3 autoantibodies should be considered in the differential diagnosis of patients with subacute cerebellar ataxia of unknown cause.
To determine continuous EEG (cEEG) patterns that may be unique to anti-NMDA receptor (NMDAR) encephalitis in a series of adult patients with this disorder.
We evaluated the clinical and EEG data of 23 hospitalized adult patients with anti-NMDAR encephalitis who underwent cEEG monitoring between January 2005 and February 2011 at 2 large academic medical centers.
Twenty-three patients with anti-NMDAR encephalitis underwent a median of 7 (range 1−123) days of cEEG monitoring. The median length of hospitalization was 44 (range 2−200) days. Personality or behavioral changes (100%), movement disorders (82.6%), and seizures (78.3%) were the most common symptoms. Seven of 23 patients (30.4%) had a unique electrographic pattern, which we named “extreme delta brush” because of its resemblance to waveforms seen in premature infants. The presence of extreme delta brush was associated with a more prolonged hospitalization (mean 128.3 ± 47.5 vs 43.2 ± 39.0 days, p = 0.008) and increased days of cEEG monitoring (mean 27.6 ± 42.3 vs 6.2 ± 5.6 days, p = 0.012). The modified Rankin Scale score showed a trend toward worse scores in patients with the extreme delta brush pattern (mean 4.0 ± 0.8 vs 3.1 ± 1.1, p = 0.089).
Extreme delta brush is a novel EEG finding seen in many patients with anti-NMDAR encephalitis. The presence of this pattern is associated with a more prolonged illness. Although the specificity of this pattern is unclear, its presence should raise consideration of this syndrome.
Immune-mediated paraneoplastic neurologic disorders (PND) may affect any part of the nervous system, and can mimic many non-cancer associated disorders. The availability of diagnostic tests based on the presence of specific anti-neuronal antibodies facilitates diagnosis and can suggest treatment strategies. Once thought to be poorly responsive to therapies, it is now recognized that there is a subgroup of PND, mostly associated with antibodies to antigens on the neuronal cell surface that are highly treatment responsive. For all PND, identification and treatment of the underlying tumor is the most effective step in the potential control or stabilization of the neurological disorder.
paraneoplastic; neurologic; autoimmunity; antibodies
We review novel findings in paraneoplastic syndromes including the Lambert-Eaton myasthenic syndrome, and then focus on the novel disorders associated with antibodies against cell surface antigens, discussing the importance and caveats of antibody testing, and providing an algorithm for interpretation of results. In anti-NMDAR encephalitis 2 novel findings include the recognition of a characteristic EEG pattern (“extreme delta brush”) in 30% of patients and the demonstration of a fronto-temporo-occipital gradient of glucose metabolism that correlates with disease activity. In limbic encephalitis, antibodies to GABA(B) receptor are the most frequently detected in patients with small-cell lung cancer who are anti-Hu negative, and antibodies to mGluR5 distinctively associate with Hodgkin lymphoma (Ophelia syndrome). We also address the syndromes associated with “VGKC-complex antibodies,” a problematic term that groups well-characterized immune-mediated disorders (LGI1, Caspr2) with others that lack syndrome specificity, are less responsive to treatment, and for which the target antigens are unknown.
Tumor resection is recommended in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, however it is often difficult during an early stage of the disease. We report here the efficacy of early tumor removal in a patient with anti-NMDAR encephalitis. This 21-year-old woman was admitted to another hospital with rapidly progressive psychiatric symptoms, a decreased level of consciousness, and seizures. Abdominal CT showed a pelvic mass. On day 1 of admission to our center, she developed hypoventilation requiring mechanical support. She had orofacial dyskinesias with well-coordinated, pseudo-piano playing involuntary finger movements. Based on these clinical features, she was immediately scheduled for tumor resection on day 3. While awaiting surgery, she began to receive high-dose intravenous methylprednisolone. After tumor removal, she received plasma exchange, followed by intravenous immunoglobulin and additional high-dose methylprednisolone. Two weeks after tumor removal, she started following simple commands and progressive improvement, although she remained on mechanical ventilation for 10 weeks due to nocturnal central hypoventilation. Anti-NMDAR antibodies in serum/CSF were detected. Pathological examination showed immature teratoma with foci of infiltrates of B- and T-cells. Early tumor resection with immunotherapy facilitates recovery from this disease, but central hypoventilation may require long mechanical support. Non-jerky elaborate finger movements suggest antibody-mediated disinhibition of the cortico-striatal systems.
paraneoplastic; encephalitis; ovarian tumor; NMDA receptor; early treatment
Patients with encephalitis associated with antibodies against N-methyl-D-aspartate-receptor antibody (NMDAR-ab) encephalitis frequently show psychotic symptoms, amnesia, seizures and movement disorders. While brain MRI in NMDAR-ab encephalitis is often normal, abnormalities of cerebral glucose metabolism have been demonstrated by positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) in a few usually isolated case reports. However, a common pattern of FDG-PET abnormalities has not been reported.
The authors retrospectively identified six patients with NMDAR-ab encephalitis in two large German centres who underwent at least one whole-body FDG-PET for tumour screening between January 2007 and July 2010. They analysed the pattern of cerebral uptake derived from whole-body PET data for characteristic changes of glucose metabolism compared with controls, and the changes of this pattern during the course of the disease.
Groupwise analysis revealed that patients with NMDAR-ab encephalitis showed relative frontal and temporal glucose hypermetabolism associated with occipital hypometabolism. Cross-sectional analysis of the group demonstrated that the extent of these changes is positively associated with clinical disease severity. Longitudinal analysis of two cases showed normalisation of the pattern of cerebral glucose metabolism with recovery.
A characteristic change in cerebral glucose metabolism during NMDAR-ab encephalitis is an increased frontotemporal-to-occipital gradient. This pattern correlates with disease severity. Similar changes have been observed in psychosis induced by NMDAR antagonists. Thus, this pattern might be a consequence of impaired NMDAR function.
To determine the presence and kinetics of antibodies against synaptic proteins in patients with herpes simplex virus encephalitis (HSE).
Retrospective analysis of 44 patients with polymerase chain reaction-proven HSE for the presence of a large panel of onconeuronal and synaptic receptor antibodies. The effect of patients’ serum was studied in cultures of primary mouse hippocampal neurons.
N-Methyl-d-aspartate receptor (NMDAR) antibodies of the immunoglobulin (Ig) subtypes IgA, IgG, or IgM were detected in 13 of 44 patients (30%) in the course of HSE, suggesting secondary autoimmune mechanisms. NMDAR antibodies were often present at hospital admission, but in some patients developed after the first week of HSE. Antibody-positive sera resulted in downregulation of synaptic marker proteins in hippocampal neurons.
Some patients with HSE develop IgA, IgG, or IgM autoantibodies against NMDAR. Sera from these patients alter the density of neuronal synaptic markers, suggesting a potential pathogenic disease-modifying effect. These findings have implications for the understanding of autoimmunity in infectious diseases, and prospective studies should reveal whether the subgroup of patients with HSE and NMDAR antibodies may benefit from immunotherapy.
To determine whether glycine receptor α1 subunit-specific autoantibodies (GlyRα1-IgG) occur in a broader spectrum of brainstem and spinal hyperexcitability disorders than the progressive encephalomyelitis with rigidity and myoclonus phenotype recognized to date, and to ascertain disease specificity.
Retrospective, case-control study.
Mayo Clinic, Rochester, Minnesota, and University of Barcelona, Spain.
Eighty-one patients with stiff-man syndrome phenotype, 80 neurologic control subjects, and 20 healthy control subjects.
Glycine receptor α1–transfected cells to test serum or cerebrospinal fluid from cases and control subjects.
Main Outcome Measures
Frequency of GlyRα1-IgG positivity among stiff-man syndrome phenotype cases and control subjects. Comparison of GlyRα1-IgG seropositive and seronegative cases.
Seropositive cases (12% of cases) included 9 with stiff-man syndrome (4 classic; 5 variant; 66% were glutamic acid decarboxylase 65–IgG positive) and 1 with progressive encephalomyelitis with rigidity and myoclonus. Immunotherapy responses were noted more frequently in GlyRα1-IgG–positive cases (6 of 7 improved) than in seronegative cases (7 of 25 improved; P=.02). The single seropositive control patient had steroid-responsive vision loss and optic atrophy with inflammatory cerebrospinal fluid.
Glycine receptor α1–IgG aids identification of autoimmune brainstem/spinal cord hyperexcitability disorders and may extend to the glycinergic visual system.
Anti-NMDA receptor (NMDAR) encephalitis is a recently characterised
autoimmune disorder mainly affecting young women. Although the clinical
features of the acute disease are well characterised, cognitive long-term
outcome has not been examined in detail.
The authors investigated cognitive performance in nine patients with
proven anti-NMDAR encephalitis after recovery from the acute disease period
(median 43 months after disease onset, range 23 to 69). Patients underwent a
comprehensive neuropsychological assessment, including memory tasks that
have previously been shown to be sensitive for hippocampal dysfunction.
Substantial persistent cognitive impairments were observed in eight
out of nine patients that mainly consisted of deficits in executive
functions and memory. The severity of these deficits varied
inter-individually. Patients with early immunotherapy performed
significantly better. The most severe deficits were observed with
inefficient or delayed initial treatment.
Our results suggest that cognitive deficits constitute a major
long-term morbidity of anti-NMDAR encephalitis. These deficits relate to the
distribution of NMDARs in the human brain and their functional role in
normal cognition. Good cognitive long-term outcome may depend on early and
The discovery of disorders that are associated with antibodies to neuronal cell-surface proteins has led to a paradigm shift in our understanding of CNS autoimmunity. These disorders can occur in patients with or without cancer—often children or young adults who develop psychosis, catatonic or autistic features, memory problems, abnormal movements, or seizures that were previously considered idiopathic. The autoantigens in such cases have crucial roles in synaptic transmission, plasticity and peripheral nerve excitability. Patients can be comatose or encephalopathic for months and yet fully recover with supportive care and immunotherapy. By contrast, disorders in which the antibodies target intracellular antigens, and in which T-cell-mediated irreversible neuronal degeneration occurs, show a considerably poorer response to treatment. In this article, we review the various targets of neuronal antibodies, focusing predominantly on autoantigens located on the cell surface or synapses—namely, N-methyl-d-aspartate receptors, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, γ-aminobutyric acid receptors, leucine-rich glioma-inactivated protein 1, contactin-associated protein-like 2, and metabotropic glutamate receptors. We also provide an algorithm to identify and assess antibodies that bind to cell-surface and synaptic antigens.
In recent years there is an increasing description of novel anti-neuronal antibodies that are associated with paraneoplastic and non-paraneoplastic neurological syndromes. These antibodies are useful in clinical practice to confirm the immunmediated origin of the neurological disorder and are helpful in tumor search. Currently, antineuronal antibodies can be classified according to the location of the recognized antigen into two groups, 1.) intraneuronal antigens and 2.) antigens located in the cell membrane. Different techniques are established for detecting these antibodies: tissue-based assay (TBA), cell-based assay (CBA), immunoblot, immunoprecipitation assay (IP), and ELISA. TBA detect most of the antibodies, however, different pretreatment methods of rat brain are necessary to visualize either Group 1 or 2 antibodies. Higher specificity is provided by immunoblots, applicable for Group 1 antibodies, and CBA, suitable for Group 2 antibodies. IP and ELISA may be useful for the detection of specific antibodies or to solve particular issues such as antibody titers. Diagnosis of paraneoplastic and non-paraneoplastic neurological syndromes has important implications on treatment and follow-up of patients. Selection and proper combination of test systems and appropriate knowledge of the clinical information will provide a maximum of sensitivity and specificity in identifying the associated antibody.
anti-neuronal antibodies; diagnosis; tissue-based assay; cell-based assay; immunoblot; sensitivity; specificity
Psychiatric symptoms combined with neurological disturbances should always arouse suspicion that the cause may be organic. We describe a young patient whose examination revealed a recently described condition for which there are precise diagnostics and in many cases effective treatment.
Anti–N-methyl-d-aspartate receptor (NMDAR) encephalitis is a severe autoimmune disorder characterized by high intrathecal antibody synthesis. Little is known about the long-term follow-up of the cerebrospinal fluid antibody status.
To describe persistent intrathecal antibody synthesis in a clinically healthy person 15 years after recovering from anti-NMDAR encephalitis.
Academic medical center.
A 40-year-old woman who had been diagnosed as having encephalitis of unknown origin in 1995.
Main Outcome Measures
Clinical evaluation and NMDAR antibody testing.
On reexamination in 2011, the patient had fully recovered. Investigation of archived as well as follow-up serum and cerebrospinal fluid samples revealed intrathecal synthesis of NMDAR antibodies.
This is the longest follow-up on a patient with anti-NMDAR encephalitis. Our findings emphasize that intrathecal antibody synthesis does not necessarily reflect disease activity and that the significance of NMDAR antibody titers needs to be interpreted for each patient according to the clinical context.
Purpose of review
The most relevant advances in immune-mediated movement disorders are described, with emphasis on the clinical–immunological associations, novel antigens, and treatment.
Many movement disorders previously considered idiopathic or degenerative are now recognized as immune-mediated. Some disorders are paraneoplastic, such as anti-CRMP5-associated chorea, anti-Ma2 hypokinesis and rigidity, anti-Yo cerebellar ataxia and tremor, and anti-Hu ataxia and pesudoathetosis. Other disorders such as Sydenham's chorea, or chorea related to systemic lupus erythematosus and antiphospholipid syndrome occur in association with multiple antibodies, are not paraneoplastic, and are triggered by molecular mimicry or unknown mechanisms. Recent studies have revealed a new category of disorders that can be paraneoplastic or not, and associate with antibodies against cell-surface or synaptic proteins. They include anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis, which may cause dyskinesias, chorea, ballismus or dystonia (NMDAR antibodies), the spectrum of Stiff-person syndrome/muscle rigidity (glutamic acid decarboxylase, amphiphysin, GABAA-receptor-associated protein, or glycine receptor antibodies), neuromyotonia (Caspr2 antibodies), and opsoclonus–myoclonus–ataxia (unknown antigens).
Neurologists should be aware that many movement disorders are immune-mediated. Recognition of these disorders is important because it may lead to the diagnosis of an occult cancer, and a substantial number of patients, mainly those with antibodies to cell-surface or synaptic proteins, respond to immunotherapy.
antibodies; ataxia; autoimmune; chorea; dyskinesia; dystonia; encephalitis; immunotherapy; movement disorders; paraneoplastic
Purpose of review
This review describes relevant advances in paraneoplastic neurological syndromes (PNS) with emphasis on particular syndromes and the impact of antibodies against surface antigens in their management.
PNS may present with symptoms that do not raise the suspicion of a paraneoplastic origin. The best example is anti-N-methyl-D-aspartate receptor encephalitis that in adult women frequently associates with ovarian teratoma. An electroencephalogram pattern described as ‘extreme delta brush’ was recently identified in 30% of patients with this disorder. Isolated myelopathy may have a paraneoplastic origin associated with amphiphysin or CV2 (CRMP5) antibodies. Jaw dystonia and laryngospasm can be the predominant symptom of the brainstem encephalitis associated with Ri antibodies. γ-Aminobutyric acid (GABA)B receptor antibodies are the most common antibodies found in patients with limbic encephalitis and small cell lung cancer, and contactin-associated protein 2 antibodies in patients with Morvan’s syndrome and thymoma. Lastly, a recent study identified delta/notch-like epidermal growth factor-related receptor (DNER) as the target antigen of Tr antibodies, a marker of cerebellar ataxia and Hodgkin’s lymphoma.
The number of antibodies relevant to PNS is now expanded to those against surface antigens. These antibodies do not confirm the paraneoplastic origin of the syndrome but predict a better response to immunotherapy.
antibodies; cancer; cerebellar degeneration; Lambert–Eaton myasthenic syndrome; limbic encephalitis; paraneoplastic
Synaptic autoimmunity may result in a wide variety of symptoms, including catatonia, psychosis, movement disorders, short-term memory deficits, and refractory seizures, so these patients are seen by a wide spectrum of practitioners, who need to be aware of these disorders. In some cases, these disorders occur as a paraneoplastic manifestation of an associated cancer. However, in contrast to the well-known paraneoplastic neurologic disorders of the central nervous system that predominate in older individuals, these novel disorders often affect children and young adults. Additionally, for some syndromes, the presence of a tumor does not necessarily indicate a poor prognosis. Successful treatment of the tumor and immunotherapy often result in recovery, supporting the use of surgery for severely ill patients. In all syndromes, deficits may be reversible despite the duration or severity of symptoms. For example, patients with anti–NMDA-receptor encephalitis who had been in a coma or ventilated for 6–10 months have had full recovery after appropriate treatment.
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a newly recognized anti-neuronal antibody-mediated inflammatory brain disease causing severe psychiatric and neurological deficits in previously healthy children. The aim of this study was to report characteristic clinical features and outcomes of children diagnosed with anti-NMDAR encephalitis.
Consecutive children presenting with newly acquired psychiatric and/or neurologic deficits consistent with anti-NMDAR encephalitis and evidence of CNS inflammation were screened over a 12-month period. Children were included in the study if they had confirmatory evidence of anti-NMDAR antibodies in the serum and/or cerebrospinal fluid (CSF). Details of clinical presentation and results of investigations were reported. Type and duration of treatment and outcomes at last follow-up were documented.
Seven children were screened and three children with anti-NMDAR encephalitis were identified. All patients presented with neurological or psychiatric (‘neuropsychiatric’) abnormalities, seizures, speech disorder, sleep disturbance, and fluctuating level of consciousness. The two older patients also had more prominent psychiatric features, while the younger child had significant autonomic instability and prominent involuntary movement disorder. None had an underlying tumor. Immunosuppressive therapies resulted in near or complete recovery; however, two of the patients had early relapse requiring re-treatment.
Anti-NMDAR encephalitis is an important cause of neuropsychiatric deficits in children that must be included in the differential diagnosis of CNS vasculitis and other inflammatory brain diseases. Early diagnosis and treatment are essential for neurologic recovery.
Classic herpes simplex virus encephalitis (HSVE) is an acute viral infection that usually follows a monophasic disease course; however some patients, mainly children, experience a relapse within weeks or months after the initial event. In a subset of these patients a viral reactivation is unlikely because the CSF PCR for HSV is negative, repeated MRI does not show new necrotic lesions, and the symptoms are refractory to antiviral therapy. These patients often develop choreoathetosis variably accompanied by behavioral changes and seizures, and a postinfectious immune-mechanism has been postulated. Recent studies demonstrated that 7% of patients with HSVE harbor NR1 N-methyl-D-aspartate receptor (NMDAR) IgG antibodies. Moreover, a child with post-HSVE choreoathetosis was found to have NMDAR antibodies; the patient did not improve with antiviral therapy but recovered after aggressive immunotherapy. Based on these findings, evidence is increasing that a subgroup of post-HSVE represents a separate disease entity, which in fact is anti-NMDAR encephalitis. Patients with relapsing HSVE or prolonged atypical symptoms, who have negative CSF PCR for HSV should routinely be tested for NMDAR IgG antibodies in CSF and serum. It is important to be aware of this differential diagnosis because patients respond to immunotherapy.
NMDAR antibodies; herpes simplex encephalitis; choreoathethosis; post-herpes simplex encephalitis
Anti-NMDA receptor encephalitis is a recently described potentially lethal but treatable disorder that often occurs as a paraneoplastic manifestation of ovarian teratomas. We report three women with this disorder who presented with subacute onset of delirium, seizures and autonomic instability. Anti-NMDA receptor antibodies were detectable in the serum or CSF of each patient. Ovarian masses were detected in two patients, and subsequently excised. In the third patient, an empiric bilateral salpingo-oophorectomy was performed and revealed a microscopic neoplasm. All patients experienced slow reversal of the neurological symptoms following surgery and immunotherapy. Our experience supports that prompt syndrome recognition followed by tumor removal and immunotherapy usually results in neurological recovery.
Anti-NMDA receptor encephalitis; ovarian tumors; dermoid; paraneoplastic encephalitis
Anti-N-methyl-D-aspartic acid receptor encephalitis rivals viral etiologies as a cause of encephalitis within the California Encephalitis Project cohort. Thus it merits a prominent place on the differential diagnosis of encephalitis, allowing for prompt treatment and recovery.
Background. In 2007, the California Encephalitis Project (CEP), which was established to study the epidemiology of encephalitis, began identifying cases of anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. Increasing numbers of anti-NMDAR encephalitis cases have been identified at the CEP, and this form rivals commonly known viral etiologies as a causal agent. We report here the relative frequency and differences among encephalitides caused by anti-NMDAR and viral etiologies within the CEP experience.
Methods. Demographic, frequency, and clinical data from patients with anti-NMDAR encephalitis are compared with those with viral encephalitic agents: enterovirus, herpes simplex virus type 1 (HSV-1), varicella-zoster virus (VZV), and West Nile virus (WNV). All examined cases presented to the CEP between September 2007 and February 2011 and are limited to individuals aged ≤30 years because of the predominance of anti-NMDAR encephalitis in this group. The diagnostic costs incurred in a single case are also included.
Results. Anti-NMDAR encephalitis was identified >4 times as frequently as HSV-1, WNV, or VZV and was the leading entity identified in our cohort. We found that 65% of anti-NMDAR encephalitis occurred in patients aged ≤18 years. This disorder demonstrated a predilection, which was not observed with viral etiologies, for females (P < .01). Seizures, language dysfunction, psychosis, and electroencephalographic abnormalities were significantly more frequent in patients with anti-NMDAR encephalitis (P < .05), and autonomic instability occurred exclusively in this group.
Discussion. Anti-NMDAR encephalitis rivals viral etiologies as a cause of encephalitis within the CEP cohort. This entity deserves a prominent place on the encephalitic differential diagnosis to avoid unnecessary diagnostic and treatment costs, and to permit a more timely treatment.