© Springer-Verlag Italia 2015
Angelo Sghirlanzoni, Giuseppe Lauria and Luisa Chiapparini (eds.)Prognosis of Neurological Diseases10.1007/978-88-470-5755-5_1515. Antibody-Mediated Encephalitis
(1)
UOC Neurologia, Ospedale “Ca’Foncello”, Azienda ULSS9, Treviso, Italy
Keywords
Autoimmune encephalitisNeural surface antibody (NSAb)NSAb syndrome (NSAS)Key Facts
Terminology and definition – Encephalitis caused by antibodies directed against antigens located on the surface of neurons
Clinical features – Acute/subacute onset of psychiatric symptoms, memory deficits, and seizures (limbic encephalitis [LE]), or more diffuse CNS involvement with movement disorders, coma, hypoventilation, and dysautonomia.
Diagnostic markers
CSF – Increased lymphocytes and protein content and intrathecal IgG in about 50 % of patients; neuronal surface antibodies (NSAb) (in serum and CSF)
MRI – Often normal or nonspecific; medial temporal lobe T2-hyperintensity in LE
Electroencephalography: Slow waves, temporal lobe epileptic activity
Pathology (variable depending on Ab association); IgG and complement deposits gliosis, neuronal loss, B cells and plasma cell infiltrates).
Top differential diagnosis – Infectious encephalitis, paraneoplastic limbic encephalitis, prion disease and degenerative disorders, temporal lobe epilepsy.
Priciples of treatment – Immuno and antineoplastic (in the presence of a tumor) therapies.
Prognosis – Anti-VGKC encephalitis often causes residual amnestic deficits. Anti-NMDR encephalitis has 80 % favorable autcome.
Abbreviations
CNS, central nervous system; DPPX, Dipeptidyl-peptidase-like protein-6; EEG, electroencephalogram; FBDS, Faciobrachial dystonic seizures; LE, Limbic encephalitis; LGI1, leucine-rich glioma-inactivated 1; mGluR5, Metabotropic glutamate receptor 5; NMDA, N-Methyl-D-aspartic acid; NSAb, neuronal surface antibodies; NSAbs, anti-neuronal surface antibodies; PERM, progressive encephalomyelitis with rigidity and myoclonus; PNS, paraneoplastic neurological syndrome; REM, rapid eye movements; VGKC, voltage-gated potassium channels
15.1 Definition
Antibody-associated encephalitis (alias: autoimmune encephalitis, central nervous system neuronal surface antibody-associated syndromes) are a group of immunotherapy-responsive diseases affecting the central nervous system (CNS) caused by antibodies against antigens located on the surface of neurons (NSAbs).
Initially recognized in the paraneoplastic context, it is now established that these diseases can occur with or without tumor association. Thus, they are distinct from diseases associated with antibodies against intracellular neuronal antigens (onconeural antigens) which invariably are markers of underlying tumor (classical paraneoplastic syndromes).
15.2 Clinical Features
Patients present with acute or subacute onset (days to weeks) of classical limbic encephalitis (psychiatric disturbances, memory deficits, and seizures) or with more diffuse involvement of the CNS. The clinical picture and the association with tumors vary according to the related antibody. Most patients with a form of antibody-associated autoimmune encephalitis harbor antibodies against the VGKC-complex protein LGI1 and NMDA-type glutamate receptor.
Anti-LGI1 (VGKC-complex) encephalitis. Less than 11 % cases are paraneoplastic (lung cancer, thymoma) [1, 2]. Male predominance. Usually typical limbic encephalitis (LE); faciobrachial dystonic seizures (FBDS) can precede the florid phase [3]; hyponatremia and REM-sleep behavior disorders are also reported.
Anti-NMDA receptor encephalitis. More frequent in the pediatric age group and in young women; 30–40 % are paraneoplastic and generally associated with ovarian teratoma, especially in young women. Multistage symptoms preceded by prodromes (e.g., cough, fever, headache): psychiatric symptoms, cognitive deficits, seizures, movement disorders, dysautonomia, stupor or coma, hypoventilation.
Less common NSAb-associated encephalitis:
Anti-GABAb receptor encephalitis. 50 % of patients harbor a small-cell lung cancer; typical LE with prominent seizures [4].
Anti-Caspr2 (VGKC complex) encephalitis. Some cases are associated with thymoma. Peripheral nerve hyperexcitability with dysautonomia, sleep disorders, psychiatric features, and seizures (e.g., Morvan syndrome) [2–5].
Anti-AMPA receptor encephalitis. Most cases are paraneoplastic (lung, breast, and thymus). Typical limbic encephalitis, with prominent memory deficits and psychiatric symptoms [6].
Further NSAb have recently been reported:
Against glycine receptor (α1 subunit): progressive encephalomyelitis with rigidity and myoclonus (PERM; variant of Stiff Person Syndrome)
Against anti-dipeptidyl-peptidase-like protein-6 (DPPX), a subunit of Kv4.2 potassium channels: encephalitis characterized by agitation, myoclonus, seizures and diarrhea at the onset
Against metabotropic glutamate receptor 5 (mGluR5): in two patients with LE and Hodgkin lymphoma (Ophelia syndrome)
Against the D2 subunit of the dopamine receptor in basal ganglia encephalitis with psychiatric disturbances and movement disorders
Anti-GAD antibodies are not directed against surface antigens but should be considered in the diagnosis of autoimmune encephalitis since they have been found in women with limbic encephalitis with prominent temporal lobe epilepsy [7].
15.3 Diagnosis
If the clinical and paraclinical features are typical of a well-defined syndrome such as LE, the presence of an NSAb in the serum and/or CSF will confirm the diagnosis. In other cases, the exclusion of other potential causes should prompt the search for NSAb and onconeural antibodies and at the same time would justify a trial of immunotherapy. A diagnosis of autoimmune encephalopathy, with variable levels of evidence, will be subsequently based on NSAb presence and/or response to treatment [8].
MRI
Is often nonspecific; T2-weighted medial temporal lobe hyperintensity is a common finding especially in anti-LGI1, GABAbR, and AMPAR; temporal lobe hyperintensity is a common finding in a post-seizure phase. In anti-NMDAR, lesions can affect futher cortical areas.
Functional nuclear images: Cortical hypermetabolism especially in the acute phase.
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