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anti n - methyl - d - aspartate receptor encephalitis ( anmdare ) , also known as limbic encephalitis , is a rare disorder characterized by quintet of psychiatric manifestations like seizures , unresponsiveness , dysautonomia and movement disorders .
it is of clinical interest as it is a paraneoplastic debilitating syndrome , which is curable when the underlying malignancy is removed .
most of the times , a combination of symptoms , magnetic resonance imaging ( mri ) findings and paraneoplastic antibodies establish the diagnosis of paraneoplastic syndrome ( pns ) .
our patient , a 13-year - old girl , presented initially with acute behavioral changes and rapid deterioration in academic performance .
the patient was treated with phenargan , haloperidol , put on intubation and mechanical ventilation due to oxygen desaturation .
lumbar puncture revealed clear fluid with a total count of 32 cells , all lymphocytes , 52 mg% of protein and normal sugar .
csf evaluations for encephalitis were negative [ herpes simplex virus ( hsv ) 1/ii , cytomegalovirus ( cmv ) , varicella zoster virus ( vzv ) , measles , mumps , rubella , enterovirus , mycobacterium tuberculosis , cryptococcus , toxoplasma gondii and streptococcus pneumoniae ] .
fatty acid oxidation defects , organic acid disorders , amino acid disorders and urea cycle disorders were excluded . nevertheless , she was put on a low - protein diet .
twenty days after admission , she developed oro - facial grimacing movement ( like chewing , vacant smiling , bruxism and facial twitching ) with oculogyric deviation and twisting choreic movements of the left leg .
the patient continued to have episodic hyperventilation , tachy / brady arrhythmias and blood pressure variations .
clinically anmdare was suspected and antineuronal antibodies were found to be positive . due to her overall poor general condition , an ictal and interictal study was not performed , but she was referred to us for fluorine-18 fluorodeoxyglucose positron emission tomography - computed tomography ( f fdg pet / ct ) imaging .
both brain and whole body images up to mid thigh were acquired using an 8-slice pet / ct camera in euglycemic , ictal free status .
patient was under continuous eeg monitoring , especially at the time of fdg injection , to rule out an ictal or peri ictal phase .
diffuse fdg uptake was noted in bilateral lungs with consolidation in bilateral upper , lower lobes apical , posterior segments , and diffuse ground - glass opacities were also noted in ct images .
pet images also showed moderate diffuse fdg uptake in bone marrow ( seen in mip image ) and spleen ( no splenomegaly ) [ figure 3 ] .
associated minimally fdg avid multiple supra and infradiaphragmatic lymph nodes were reported ( i.e. standard uptake value suv between 2.5 and 4 g / ml in bilateral level 2 , right upper paratracheal , subcarinal , right axillary , left para - aortic , left external iliac and right external iliac lymph nodes ) which were given importance in this clinical setting to rule out a lymphoproliferative disorder , but with no evidence of a teratoma .
however , usg - guided cervical node biopsies ruled out lymphoma and suggested reactive lymphadenitis .
thus , a non - paraneoplastic type of anmdare with no detectable malignancy was suspected .
thus , in such cases a whole body pet / ct is warranted to confirm or rule out teratoma or other possible malignancies apart from confirming the cerebral involvement .
treatment of choice is usually removal of the underlying neoplasm , combined with immunotherapy ( plasma exchange , iv immunoglobulin , steroids ) .
our patient was finally considered to be a case of idiopathic anmdare and she was treated with only iv steroids due to financial constraints . at the last follow - up , she was minimally conscious .
fdg pet / ct brain transaxial images showing hypometabolism in left temporal and occipital cortex f fdg pet / ct images of thorax show diffuse fdg avid bilateral lungs with consolidation in bilateral upper , lower lobes apical , posterior segments and diffuse ground - glass opacities .
findings were attributed to aspiration pneumonitis pet / ct transaxial images of abdomen show moderate diffuse fdg uptake in bone marrow ( in mip image ) and spleen ( no splenomegaly ) with associated minimally fdg avid multiple supra and infradiaphragmatic lymph nodes present ( i.e. suv between 2.5 and 4 g / ml in bilateral level 2 , right upper paratracheal , subcarinal , right axillary , left para - aortic , left external iliac and right external iliac lymph nodes ) , raising the possibility of a lymphoproliferative disorder , but no evidence of a teratoma .
however , usg - guided cervical node biopsies ruled out lymphoma and suggested reactive lymphadenitis .
our patient was treated with only iv steroids due to financial constraints . at the last follow - up
pns is a disabling but rare disease caused by autoimmune processes triggered by cancer and directed against antigens common to both the cancer and nervous system .
n - methyl - d - aspartate - selective glutamate receptor ( nr ) , predominantly involved in synaptic plasticity and memory function , gets deranged in this form of encephalitis .
these antibodies bind to the nr2b and , to a lesser extent , the nr2a subunits of nmdar .
nr2b binds to glutamate and is avidly expressed in the hippocampal and forebrain neurons of human beings .
there is a reduction in gamma - aminobutyric acid ( gaba ) release , leading to disinhibition of postsynaptic glutamatergic transmission and secondarily excessive release of glutamate in the prefrontal / subcortical structures , and glutamate and dopamine dysregulation .
the initial prodromal phase , manifests like a viral flu . in the 2 phase ,
patients develop intractable seizures , are often unresponsive and require multiple anticonvulsants and often mechanical ventilation . in the 4 phase ,
other peculiar features of this autoimmune encephalitis are central hypoventilation and dysautonomia with severe oro - facial dyskinesias .
brain pet findings can be variable depending on the course and timing of the scan .
patients in acute phase of illness can have cerebral hypermetabolism , while relapsing cases have demonstrated reduced fdg uptake in the cerebral cortex , with the temporal regions being most affected .
eaton myasthenic syndrome ) , testicular in 20% , and breast in 8% of cases .
its associations with teratoma , lymphoma and , rarely , gastric malignancies have also been reported . during the neurological manifestation phase underlying cancers are not clinically overt and whole
body pet / ct is a turning point to establish pns and in guiding cancer treatment .
antineuronal antibodies positive in descending order of prevalence are anti - hu , anti - ta and anti - ma .
reports have shown anti - hu antibodies to be associated with small - cell lung cancer in 94% cases and have a poor neurological outcome .
patients with anti - ta ( also called anti - ma2 ) antibodies were invariably associated with testicular tumors .
literature review shows diverse presentation of anti - hu or anti - ta antibody negative patients , with cancer of the lung being the most common ( 36% ) .
mri of the brain can be normal or show hyperintensities in the medial temporal lobes or may exhibit mild leptomeningeal enhancement .
thus , anmdare may be associated with variable pet findings , possibly dependent upon the timing of the study and other factors like phase of encephalitis , i.e. relapsing course . however , clinically , the presence of oro - facial dyskinesias and absence of residual post - encephalitic parkinsonism are the features in favor of anmdare . role of pet / ct in these cases is to confirm or rule out the presence of teratoma or any other possible sites of malignancy . as
brain pet findings can be variable , patients in acute phase of illness can have cerebral hypermetabolism while relapsing cases can show hypometabolism in the cerebral cortex , with the temporal regions being most affected .
the treatment of choice for anmdare is removal of the underlying neoplasm , combined with immunotherapy ( plasma exchange , intravenous immunoglobulin , corticosteroids ) .
it is worth to consider this rare anmdare in every non - herpetic syndrome as it is potentially diagnosable and treatable .
anti n - methyl - d - aspartate receptor encephalitis ( anmdare ) , also known as limbic encephalitis ( le ) , is a treatable rare disorder characterized by personality changes , irritability , depression , seizures , memory loss and sometimes dementia . 
 it is classified under paraneoplastic syndrome ( pns ) and produces antibodies against nr1 and nr2 subunits of glutamate aspartate receptor . 
 it is thought to be closely related with malignancies like small cell lung cancer , ovarian teratoma and hodgkin 's lymphoma , apart from testis , breast and rarely gastric malignancies . 
 non - paraneoplastic encephalitis cases are the ones with no detectable malignancy and may be triggered by severe infection . 
 as nuclear medicine physicians , we must be aware of the diverse presentation of anmdare or le and should include a whole body positron emission tomography / computed tomography ( pet / ct ) and not just brain petct during imaging . 
 we describe the first case of pet / ct in an idiopathic anmdare indian adolescent girl .