Page 157 - Read Online

Table 1: Details of NSAS encephalitis in adults and children
Target Antigen Adult forms Pediatric forms
Patients Clinical signs Neuroimaging EEG pattern Tumor association (%) Outcome Incidence Peculiar symptoms
Glutamate-N-methyl-D-aspartate receptor (NMDA-R)
Glutamate- GluNR1/ F 80% Psychosis or epileptic seizures Normal (50%) -GS and FIED Age dependent Monophasic (75%): excellent if 40% Seizures > psychosis
N-methyl- GluNR2/ Age:1-80 y followed by insomnia, amnesia, Non specific -Extreme delta -OT (10-50% > 18 y) [11] early treated (good response to of the total [14] occurrence
D-aspartate (median 20 y) MD, catatonia, AI, coma [11-13] pattern or DMN brush (25%) - ADC (rare) IM/tumor removal). (age dependent)
receptor involvement (50%) Relapsing-remitting (25%): EEG: Rarely extreme
subunits normal in between delta brush. [11-13]
Voltage-gated potassium channel (VGK)
VGKC- VGKC M 60% Peripheral nerve LE, possible GS/FS (temporal) Age dependant Variable response to IM F = M Broad clinical
complex undefined Age:1-86 hyperexcitability, Morvan’s atrophy at MRI and bilateral Thymoma, SCLC/ADC/ Age: 1-16 y spectrum: fever
targets (median 55) syndrome, encephalopathy, follow-up (temporal) FIED HM (rare) (< 50 cases) followed by SE,
(intracellular behavioural changes, seizures, encephalopathy, GDR,
epitope? short term memory loss. MD (Cho, My, Tr,
interacting Possible coexistence with MT), CA, AI, RS,TLE;
proteins?) LEMS. [1,17] RE. [18-20]
Leucine- LGi1 M 65% Prodromal faciobrachial LE generally -GS/FS (temporal) -Thymoma (< 10%) Monophasic with complete Not reported Not reported
rich glioma Age: 30-80 y seizures, short term memory progressing to and bilateral -SCLC/ADC/HM (rare) recovery (rare) or relapsing
inactivated-1 (median 60 y) loss, psycosis, hyponatremia hippocampal/whole (temporal) FIED desease course evolving to
component (60%), tonic seizures/ brain atrophy memory impairment, TLE,
myoclonus. [21] psychiatric disorders.
contactin- CASPR2 M 85% Morvan’s syndrome; -Normal (especially -GS/FS Thymoma (0-40%) Generally monophasic with good M * GBS without
associated Age: 45-80 y psychosis, seizures, memory in Morvan’s and GED/FIED SCLC/ADC/HM (rare) outcome (good response to IM). Age: 2 y,6 y encephalitis. [23]
protein-like 2 (median 60 y) impairment syndrome) Relapses may occur. (2 cases) Complete recover
hyponatremia (60%). [22] -aspecific T2/FLAIR
abnormalities
-LE (25%)
No progression
to hippocampal
atrophy/sclerosis
Alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid- glutamate receptor (AMPA-R)
GluA1/2 F 90% Seizures, short term memory LE GS or FS Lung (70%), Monophasic (50%) good Not reported Not described (GluA3).
Age: 40-80 y loss, disorientation, psychosis. and GED/FIED breast, thymoma (rare) response to IM/tumor removal RE (occasional reports)
(median 60 y) Frequent coexisting Relapsing remitting disease doubt pathogenicity [25]
autoimmunities. [24] course (50%).
Metabotropic gutamate receptors
Type 1 mGluR1 F 100%* Cerebellitis. [26] -Normal (generally) Normal HL (70%) Monophasic or chronic disease Not reported Not reported
Age: 20-50 y* -cerebellar course (correlation with titer).
T2/FLAIR Good response to IM
abnormalities
evolving in atrophy
-LE (rare)
Type 5 mGluR5 F 50%* Ophelia syndrome LE FS (bi-temporal) HL (70%) Monophasic or chronic disease M Confusion,
Age: 15-45 y* or FIED; FED or course (correlation with titer). 15 y anxiety, fear, extreme
GED Generally good response to IM (1 case) agitation, auditory/
visual
hallucination, GS.
Complete spontaneous
recovery. [27]
Gamma-aminobutyric acid receptors (GABA A -R and GABA B -R)
GABA A -R GABARAP, M 60% SE/RES, encephalopathy, RS, LE FS or GS + FED None Variable Age: 2-16 y SE/RES,
associated α1/β3 Age: 2-74 y SPS, CA and FIED (7 cases ) encephalopathy,
protein (median 22 y)* Refractory seizures,
(clustering SPS (rare). [28]
and anchoring Association with HL
receptors) (1 case)
GABA B -R GABAB1 F 50% Prominent seizures (FS, LE (often FS or GS + FED SCLC/thymus/NET (50%) Monophasic or chronic disease Age: 3 y, Lethargy, MD,
subunit 1/2 GABAB2 Age: 25-75 y GS), short term memory loss, asymmetric) and FIED course: good response to IM. 16 y opsoclonus, ataxia,
(median 60 y) psychosis Occasional relapses. (2 cases) seizures. Variable
outcome
MRI: diffuse changes in
cortical and subcortical
structures. [29-31]
Dopamine receptor
Type 2 D2-R M 50% SydCho, PANDAS, TS, T2/FLAIR Generally GS Exceptional Monophasic or relapsing F = M Comparable to adult
Age: 6-31 y encephalopathy, psychosis, Basal ganglia remitting; good response Age: 2-17 y forms
(median 20 y) sleep disorders abnormalities to IM. (median 7 y) Relapsing remitting
course. [32]
Glycine receptor (Gly-R)
Gly-R subunit Gly-Rα1 M 80% Prominent PERM and SPS; Normal (ca. 70%) Normal Typically none; Monophasic or chronic F 80% -PERM, hyperekplexia
α1 Age: 30-60 y hyperekplexia, spinal My, CA, LE or unspecific thymoma/lung (exceptional) disease course: good Age:14 rigidity, My, no
(median 50 y) encephalitis, FS, brainstem (rare) response to IM. M-5 y, consciousness
disfunction (rare) Occasional relapses. (3 cases) impairment;
-explosive-
onset epileptic
encephalopathy;
RFS, speech
and behavioural
disturbance.
Variable outcome. [33,34]
Dipeptidyl-peptidase-like protein 6
Cell surface DPPX M 80% Prodromal severe -Normal Normal None Good response to IM but One case Comparable to adult
auxiliary Age: 13-75 y gastrointestinal dysfunction, -Aspecific T2/FLAIR generally relapsing reported forms. [35]
subunit of (median 53 y) encephalopathy, agitation, abnormalities (rare) (13 y)
the Kv4.2 hallucinations, tremor, PERM,
potassium My, startle with muscle rigidity,
channel sleep disturbances, AI seizures
(rare)
Neuronal cell adhesion molecule IgLON5
Neuronal cell IgLON5 M 50% Prominent sleep dysfunction, Normal Normal None Chronic disease course Not reported Not reported
adhesion Age: 52-76 y abnormal sleep movements, refractory to IM
protein IgLON5 (median 59 y)* OSAS, Cho, CA, progressive
memory loss, mild gait
imbalance. [36]
Glutamic-acid-decarboxylase
Glutamic-acid- GAD65 F 80% Neurocognitive disorders, LE, -Normal -Normal Thymoma, lung, colon, Chronic disease course: M = F Comparable to adult
decarboxylase Age:15-80 y TLE with RE, SPS, PERM, CA; -LE or mesio- -GS or FS, FED pancreas, breast, thyroid, usually poor response to IM Age: 5-16 y forms
isoenzime65 (median 60 y) DM1 (if titer < 20 temporal, brain (SE) and/or GED renal cell carcinoma (rare) (more resistant than those (median10 y) Variable response. [38]
U/ml)-Frequent coexisting stem, cerebellum with cell
autoimmunities; [37] and spinal surface antibodies)
EMG abnormalities cord T2/FLAIR
abnormalities
evolving into
atrophy.
F: female; M: male; y: years; m: months; *: less than 20 cases reported; IM: immunotherapy. NMD: default mode network; LE: limbic encephalitis; GS: generalized slowing; FS: focal
slowing; FIED: focal interictal epileptic discharges; FED, GED: generalized epileptic discharges; OT: ovarian teratoma; SCLC: small cell lung carcinoma; ADC: adenocarcinomas;
HM: hematological malignancies; HL: Hodgkin Lymphoma; NET: neuroendocrine tumor; LEMS: Lambert Eaton myastenic syndrome; RE: Rasmussen’s; RSE: refractory status
epilepticus; SE: status epilepticus; RS: refractory seizures; RFS: refractory focal seizures; TLE: temporal lobe epilepsy, SydCho: Sydenham chorea, TS: Tourette’s syndrome. GDR:
global developmental regression, AI: autonomic instability; MD: movement disorders; Cho: chorea; My: myoclonus; Tr: tremor; MT: motor tics; CA: cerebellar ataxia; SPS: Stiff-person
syndrome; PERM: progressive encephalomyelitis with rigdity and myoclonus; DM1: diabetes mellitus type 1; OSAS: obstruction sleep apnea syndrome.
148 Neuroimmunol Neuroinflammation | Volume 3 | July 8, 2016