clinical features are acute limbic encephalitis with personality and behavioral change , catatonia , memory loss , seizures , dyskinesia , and autonomic dysfunction [ 2 , 3 , 4 , 5 ] .
however , 40% of patients do not have a detectable tumor , and men are also affected .
the clinical manifestation of nonparaneoplastic anti - nmdar encephalitis ( without ovarian teratoma ) is similar to that of paraneoplastic anti - nmdar encephalitis ( with ovarian teratoma ) . in many cases ,
the medial temporal lobes and cerebral cortex are affected on mri . on the other hand , patients with anti - glutamate receptor ( glur ) 2 ( nr2b ) antibody have been reported to show an association with nonherpetic acute limbic encephalitis ( nhale ) , rasmussen 's encephalitis , and chronic forms of epilepsia partialis continua [ 7 , 8 ] .
although anti - nmdar antibody and anti - glur 2 antibody could be simultaneously detected in nhale [ 6 , 9 ] , some patients had anti - nmdar antibody but did not have anti - glur antibody , and others vice versa .
little is known about the clinical difference between anti - nmdar antibody - only encephalitis and anti - glur antibody - only encephalitis .
we herein report a man with anti - glur antibody but without anti - nmdar antibody , presenting with predominantly frontal lobar encephalitis , and discuss the clinical significance of this type of non - paraneoplastic anti - glur encephalitis .
a left - handed , 33-year - old man , an office worker who had graduated from university , presented with progressive speech disturbance in february 2013 .
he was noted to have difficulty finding words in the office and made grammatical errors on writing e - mails .
he was referred to and admitted to our hospital 2 days after disease onset . on neurological examination
, the patient exhibited fluctuating consciousness disturbance and difficulty saying words : he could only say  yes. he did not obey some simple verbal commands such as eye closing or tongue protrusion . when asked to perform dictation , he repeatedly wrote down a character that was a part of our oral command .
once he had raised his arms , he kept them raised until we forced him to stop ( catalepsy ) .
lumbar puncture showed cerebrospinal fluid ( csf ) lymphocytic pleocytosis ( cells : 51/mm , protein : 35 mg / dl ) , and an elevated igg index ( 1.32 , normal < 0.7 ) .
antibodies to n - terminals of nmda - type glur including glun2b ( 2 , nr2b ) and glun1 ( 1 , nr1 ) , and those to the n - terminal of glud2 ( 2 ) were all positive , and the antibody to the nmdar nr1/nr2 complex ( dalmau 's method )   was negative in both the csf and serum . magnetic resonance imaging ( mri ) performed 2 weeks after onset revealed hyperintensity in diffusion - weighted images in the bilateral frontal and left parietal cortices ( fig .
1 ) . electroencephalography ( eeg ) showed diffuse semirhythmic 1- to 2-hz  waves with a small amount of 10-hz  waves superimposed on the  waves in p - o , which was similar to the  extreme delta brush in anti - nmdar encephalitis . on admission ,
however , oral intake decreased gradually , and he could not swallow purposely at 6 days after onset . even if the patient put water in his mouth , the swallowing reflex did not occur , and water finally leaked out through the corners of his mouth . although sialorrhea was not noted , he choked on his saliva at 10 days after onset , suggesting that voluntary oral transport of the trapped saliva was interrupted . as a result , he was dehydrated and required an intravenous drip .
the patient exhibited bulging eyes , became mute and inattentive ( he sometimes turned his eyes away while the doctor talked to him ) , with forced grasping that was more pronounced in the left hand .
he was restless in the evening , and tried to leave the bed despite the infusion tube , and so required sedation with intravenous haloperidol .
suspecting herpetic encephalitis , we first administered intravenous acyclovir ( 1,500 mg / day ) from 5 to 7 days after onset , which was ineffective and discontinued because of drug - induced acute renal injury . from 7 to 9 days after onset , he developed a transient partial seizure on the right side of his face and extremities .
taking the possibility of an autoimmune mechanism into account , we then administered a total of 3 courses of intravenous corticosteroid pulse therapy ( methylprednisolone at 1,000 mg / day for 3 days ) from 10 to 25 days after onset , and subsequently gave him oral prednisolone at 30 mg / day that was tapered and discontinued for 6 weeks .
immediately after the first pulse therapy , the patient was able to repeat a syllable following the doctor 's example and responded properly to yes - no questions , such as  are you mr . ( patient 's name)? he was able to take meals by himself 16 days after onset and spoke some sentences correctly 20 days after onset .
eeg performed 23 days after onset showed a moderate amount of 10-hz  waves with occasional 6- to 7-hz  waves .
spect with a tc - ethylcysteinate dimer ( ecd - spect ) performed 3 weeks after onset revealed , for the mean cerebral blood flow ( cbf ) , a reduced blood flow in both hemispheres [ early picture ( ep ) method , left 32.8 , right 32.2 ml/100 g / min ] with the patlak plot method and , for the regional cbf , significant hypoperfusion ( uncorrected p < 0.001 , by statistical parametric mapping version 2 ) in the bilateral frontal convexity and mesial frontal gyri , and the left supramarginal gyrus ( fig .
the patient 's cognitive function was evaluated for the first time 21 days after onset . the mini - mental state examination ( mmse )
score was 24.7/30 : mental arithmetic ( serial 7 ) and auditory comprehension ( 3-step command ) were impaired .
the western aphasia battery ( japanese edition ) conducted 27 days after onset revealed that spontaneous speech was dysfluent ( 5/10 ) , with stuttering , halting , and occasional phonemic paraphasia and phonetic distortion ( e.g. , [ handan ]  [ hannan ] ) , suggesting slight apraxia of speech .
auditory comprehension ( 9.35/10 ) , repetition ( 9.2/10 ) , naming ( 9.3/10 ) , reading ( 9.2/10 ) , and writing ( 9.85/10 ) were minimally impaired .
overall , his language profile was rated as slight boca 's aphasia with apraxia of speech .
the wechsler adult intelligence scale - iii conducted 4 weeks after onset revealed a nearly normal cognitive function : verbal iq 84 , performance iq 80 , and working memory 76 .
the wechsler memory scale - revised conducted 33 days after onset revealed a normal memory function ( verbal memory 110 , visual memory 101 )
the mmse score at this time was 29/30 , the fab score was 16/18 with word fluency of 7 words / min .
stuttering , halting speech , phonemic paraphasia , and phonetic distortion disappeared 3 months after onset .
however , the working memory remained lower ( digit span forward , 5 ) after 1 year .
mri performed 7 months after onset revealed a small area of hyperintensity in the left parietal cortex ( fig .
performed 13 months after onset , the reduced blood flow recovered to the normal range ( ep , left 46.9 , right 46.9 ml/100 g / min ) and the regional hypoperfusion was restricted to the diffuse areas of the frontal lobe ( fig .
the patient 's cognitive function was evaluated for the first time 21 days after onset . the mini - mental state examination ( mmse )
score was 24.7/30 : mental arithmetic ( serial 7 ) and auditory comprehension ( 3-step command ) were impaired .
the western aphasia battery ( japanese edition ) conducted 27 days after onset revealed that spontaneous speech was dysfluent ( 5/10 ) , with stuttering , halting , and occasional phonemic paraphasia and phonetic distortion ( e.g. , [ handan ]  [ hannan ] ) , suggesting slight apraxia of speech .
auditory comprehension ( 9.35/10 ) , repetition ( 9.2/10 ) , naming ( 9.3/10 ) , reading ( 9.2/10 ) , and writing ( 9.85/10 ) were minimally impaired .
overall , his language profile was rated as slight boca 's aphasia with apraxia of speech .
the wechsler adult intelligence scale - iii conducted 4 weeks after onset revealed a nearly normal cognitive function : verbal iq 84 , performance iq 80 , and working memory 76 .
the wechsler memory scale - revised conducted 33 days after onset revealed a normal memory function ( verbal memory 110 , visual memory 101 )
the mmse score at this time was 29/30 , the fab score was 16/18 with word fluency of 7 words / min .
stuttering , halting speech , phonemic paraphasia , and phonetic distortion disappeared 3 months after onset .
however , the working memory remained lower ( digit span forward , 5 ) after 1 year .
mri performed 7 months after onset revealed a small area of hyperintensity in the left parietal cortex ( fig .
performed 13 months after onset , the reduced blood flow recovered to the normal range ( ep , left 46.9 , right 46.9 ml/100 g / min ) and the regional hypoperfusion was restricted to the diffuse areas of the frontal lobe ( fig .
the patient presented with global aphasia , swallowing disturbance , abnormal behavior [ catalepsy ( maintaining a forced posture ) and nocturnal delirium ] , and partial seizure .
global aphasia was characterized by scanty speech and motor perseveration in writing , which resolved to apraxia of speech a few days after corticosteroid pulse therapy .
the swallowing disturbance was voluntary in nature : he had difficulty transporting food to the pharyngeal cavity .
in contrast , he swallowed saliva automatically ; therefore , he did not exhibit sialorrhea .
it was clear that the patient did not initiate bolus transfer with a lack of lingual movement during the oral stage .
as described earlier , nonherpetic anti - nmdar encephalitis usually involves the limbic cortex and is associated with several psychiatric symptoms [ 2 , 3 , 4 , 5 ] . on the other hand ,
the clinical features of anti - glur antibody - positive encephalitis ( glur encephalitis ) are similar to those of nmdar encephalitis with ovarian tumor , except that paraneoplastic nmdar encephalitis necessitates a longer hospitalization period .
it is suggested that in these patients with glur encephalitis , anti - nmdar antibody was also positive .
one problem is that in many reported cases of nonparaneoplastic anti - glur encephalitis , anti - nmdar antibody was not examined .
thus , the clinical difference between anti - nmdar encephalitis and anti - glur encephalitis remains unknown .
it is suggested that our patient with lobar encephalitis without medial temporal involvement , marked cognitive impairment with a relatively preserved level of consciousness , and a favorable response to corticosteroid therapy , with nearly reversible cortical damage , characterizes anti - glur antibody - only encephalitis .
it should also be noted that the lesion was difficult to detect on mri , whereas the extent of the lesion was easily identifiable on spect .
this discrepancy suggests that neuronal damage was too mild to produce cytotoxic edema , and only a small area of the left supramarginal gyrus remained permanently injured
. this reversible cortical damage may be another characteristic of anti - glur antibody - only encephalitis .
 backgroundlittle is known about the difference between anti - n - methyl - d - aspartate receptor ( nmdar ) antibody - positive encephalitis and anti - glutamate receptor ( glur ) antibody - positive encephalitis.objectivesto characterize anti - glur antibody - positive encephalitis.methodswe report a 33-year - old man with nonparaneoplastic anti - glur 2 , 1 and 2 antibody - positive and anti - nmdar antibody - negative encephalitis , using neuropsychological tests and imaging studies including magnetic resonance imaging and single photon emission computed tomography ( spect ) with a 99mtc - ethylcysteinate dimer.resultsthe patient exhibited global aphasia and swallowing apraxia ( inability to transfer food to the pharyngeal cavity without sialorrhea ) . 
 he was treated with 3 courses of corticosteroid pulse therapy and had recovered markedly 3 weeks after onset . 
 magnetic resonance diffusion - weighted images revealed hyperintensity in the bilateral frontal and left parietal cortices . 
 seven months later , a small area of hyperintensity in the left supramarginal gyrus remained . 
 spect revealed hypoperfusion in extensive regions of the bilateral frontal lobes and left supramarginal gyrus . 
 thirteen months later , blood flow reduction was restricted to diffuse areas in the frontal lobes.conclusionsfrontal lobar encephalitis without medial temporal involvement , marked cognitive impairment with a relatively preserved level of consciousness , and a favorable response to corticosteroid therapy , with nearly reversible cortical damage , may characterize anti - glur antibody - positive encephalitis . 