Relevant papers were identified through PubMed searches of articles published in English up to Nov 23, 2015, using the search terms (alone or in combination): “autoimmune encephalitis”, “limbic encephalitis”, “anti-NMDA receptor encephalitis”, “ acute disseminated encephalomyelitis”, “brainstem encephalitis”, “basal ganglia encephalitis”, “Hashimoto encephalopathy”, “Rasmussen encephalitis”, “primary CNS angiitis”, “primary CNS vaculitis”, “Susac syndrome”, “Morvan syndrome”, and “neuronal
Position PaperA clinical approach to diagnosis of autoimmune encephalitis
Introduction
Acute encephalitis is a debilitating neurological disorder that develops as a rapidly progressive encephalopathy (usually in less than 6 weeks) caused by brain inflammation.1 The estimated incidence of encephalitis in high-income countries is about 5–10 per 100 000 inhabitants per year; encephalitis affects patients of all ages and represents a significant burden to patients, families, and society.2, 3
Because the most frequently recognised causes of encephalitis are infectious, existing diagnostic criteria and consensus guidelines for encephalitis assume an infectious origin.1, 4, 5, 6 However, in the past 10 years an increasing number of non-infectious, mostly autoimmune, encephalitis cases have been identified and some of them do not meet existing criteria.7 These newly identified forms of autoimmune encephalitis might be associated with antibodies against neuronal cell-surface or synaptic proteins (table)8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 and can develop with core symptoms resembling infectious encephalitis, and also with neurological and psychiatric manifestations without fever or CSF pleocytosis.7 To improve the recognition of these disorders, in this Position Paper, we aim to provide a practical clinical approach to diagnosis that should be accessible to most physicians.
Section snippets
General scope and objectives
These guidelines focus on autoimmune encephalitis that presents with subacute onset of memory deficits or altered mental status, accompanied or not by other symptoms and manifestations, with the goal of helping to establish a prompt diagnosis. These guidelines do not address the clinical approach to other CNS autoimmune disorders (stiff person syndrome,24 progressive encephalomyelitis with rigidity and myoclonus,25 or autoimmune cerebellopathies26) that usually present with a clinical profile
Methods
An initial draft of these guidelines was developed by two authors (FG and JD) and subsequently underwent three rounds of reviews and updates by a panel of investigators who have expertise in autoimmune encephalitis. In the first stage, we reviewed previously published guidelines and diagnostic criteria for encephalitis (of any cause or idiopathic). This review along with clinical experience with forms of autoimmune encephalitis described in the past 10 years (eg, some of them not necessarily
Initial clinical assessment: possible autoimmune encephalitis
We regard a patient with new-onset encephalitis as having possible autoimmune encephalitis if the criteria shown in panel 1 are met. These criteria differ from those previously proposed for encephalitis (any cause or idiopathic) in which changes in the level of consciousness, fever, CSF pleocytosis, and EEG alterations are more often needed.1, 4, 5, 6 These criteria needed to be adapted for autoimmune encephalitis because patients with autoimmune encephalitis could present with memory or
Approach to patients with clinically recognisable syndromes
A substantial number of patients with autoimmune encephalitis do not present with a well defined syndrome. In some of these patients, demographic information and some comorbidities (eg, diarrhoea, ovarian teratoma, faciobrachial dystonic seizures) might initially suggest the underlying disorder (anti-dipeptidyl-peptidase-like protein-6 [DPPX], anti-NMDA receptor, anti-leucine-rich, glioma-inactivated 1 [LGI1] encephalitis), but these features are not pathognomonic and might be absent in some
Antibody testing: clinical considerations and caveats
The detection of specific autoantibodies (table, figure 1) establishes a definitive diagnosis of autoimmune encephalitis, identifies immunological subtypes of limbic encephalitis, and assists in the differential diagnosis of atypical clinical cases. Therefore, measurement of antibodies is a crucial step in the definite diagnosis of many types of autoimmune encephalitis and clinicians must be aware of potential pitfalls in the interpretation of results.
Several concepts that apply to classic
Approach to patients without recognisable syndromes or autoantibodies
After excluding all well characterised syndromes of autoimmune encephalitis (with or without autoantibodies) and other syndromes accompanied by well defined autoantibodies, a group of patients who have possible autoimmune encephalitis will remain (panel 1). Patients in this group can be regarded as having probable autoimmune encephalitis if they satisfy criteria for Hashimoto's encephalopathy (panel 6)101 or the criteria proposed in panel 7.
The definition of Hashimoto's encephalopathy has been
Implications and directions for future research
We have shown that it is possible to proceed through a logical differential diagnosis of autoimmune encephalitis using criteria based on conventional clinical neurological assessment and standard diagnostic tests (MRI, EEG, and CSF studies). Through this approach, levels of evidence of probable and definite autoimmune encephalitis can be achieved early and therapies implemented quickly, with the possibility of fine-tuning the diagnosis and treatment when antibody results become available.
Search strategy and selection criteria
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