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she presented with a 5-day history of behavioral change , in the form of incomprehensive talking visual and auditory hallucinations , and short attention span .
she had sleep disturbance , labile mood , and decreased appetite with loss of sphincter control .
one month prior to this episode , she had one attack of unprovoked generalized tonic - clonic brief seizure .
her father had hypothyroidism that was , well controlled on treatment . on physical examination , she was agitated , hemodynamically stable , and afebrile .
she had hallucinations and abnormal facial movements , but otherwise there was no neurological deficit .
a full work - up including metabolic screening , toxicology screening , brain mri , cerebrospinal fluid ( csf ) analysis , and septic screening were all negative .
her thyroxine ( t4 ) and thyroid stimulating hormone ( tsh ) were normal , but thyroid antibodies were elevated : thyroglobulin=383 ( normal range < 115 iu / ml ) , and thyroid peroxidase= 195 ( normal range < 34 iu / ml ) .
the working diagnosis was hashimoto thyroiditis , and she was treated with intravenous immunoglobulin ( 400 mg / kg / day for 5 days ) .
she showed a quick improvement in her condition , and returned to her baseline within 2 weeks .
electroencephalography showing diffuse slow background activity without epileptiform discharges . a 9-year - old boy presented with a history of behavioral changes associated with aggressiveness and excessive crying for one week .
he then started to develop a series of seizures and status epilepticus . on examination , he was encephalopathic , with a glasgow coma scale of 9/15 , hemodynamically stable , and afebrile .
results of brain mri were normal , and csf showed 24 cells / mm normal range < 5 , mainly mononuclear .
the anti - nmdar antibodies were high in the csf ( 1:30 ; normal range<1:1 ) and serum ( 1:160 ; normal range<1:10 ) . other work - up including septic work - up , toxicology , and metabolic screening ,
he was considered to have anti - nmdar encephalitis , and treated with intravenous immunoglobulin , steroids , rituximab , and anti - epileptics .
the outcome was good , and he returned to normal within 9 months of treatment .
a 7-year - old girl was referred because of acute psycho - behavioral changes , 2 weeks after febrile illness .
her vital signs were within normal limits . a systemic examination including neurological examination was normal .
she was diagnosed with lgi1 antibodies encephalitis and started on intravenous immunoglobulins and pulse methylprednisolone with a good outcome .
she presented with a 5-day history of behavioral change , in the form of incomprehensive talking visual and auditory hallucinations , and short attention span .
she had sleep disturbance , labile mood , and decreased appetite with loss of sphincter control .
one month prior to this episode , she had one attack of unprovoked generalized tonic - clonic brief seizure .
her father had hypothyroidism that was , well controlled on treatment . on physical examination , she was agitated , hemodynamically stable , and afebrile .
she had hallucinations and abnormal facial movements , but otherwise there was no neurological deficit .
a full work - up including metabolic screening , toxicology screening , brain mri , cerebrospinal fluid ( csf ) analysis , and septic screening were all negative .
her thyroxine ( t4 ) and thyroid stimulating hormone ( tsh ) were normal , but thyroid antibodies were elevated : thyroglobulin=383 ( normal range < 115 iu / ml ) , and thyroid peroxidase= 195 ( normal range < 34 iu / ml ) .
the working diagnosis was hashimoto thyroiditis , and she was treated with intravenous immunoglobulin ( 400 mg / kg / day for 5 days ) .
she showed a quick improvement in her condition , and returned to her baseline within 2 weeks .
a 9-year - old boy presented with a history of behavioral changes associated with aggressiveness and excessive crying for one week .
he then started to develop a series of seizures and status epilepticus . on examination , he was encephalopathic , with a glasgow coma scale of 9/15 , hemodynamically stable , and afebrile .
results of brain mri were normal , and csf showed 24 cells / mm normal range < 5 , mainly mononuclear .
the anti - nmdar antibodies were high in the csf ( 1:30 ; normal range<1:1 ) and serum ( 1:160 ; normal range<1:10 ) . other work - up including septic work - up , toxicology , and metabolic screening ,
he was considered to have anti - nmdar encephalitis , and treated with intravenous immunoglobulin , steroids , rituximab , and anti - epileptics .
the outcome was good , and he returned to normal within 9 months of treatment .
a 7-year - old girl was referred because of acute psycho - behavioral changes , 2 weeks after febrile illness .
peri - oral movements were also observed . there was no history of headache , vomiting or drug ingestion .
her vital signs were within normal limits . a systemic examination including neurological examination was normal .
she was diagnosed with lgi1 antibodies encephalitis and started on intravenous immunoglobulins and pulse methylprednisolone with a good outcome .
we describe 3 patients with immune - mediated encephalopathy / encephalitis who presented in the initial phase with predominant psychiatric symptoms . the presenting symptoms included mainly psycho - behavior changes , aggressivity and hallucinations .
immune - mediated encephalopathies / encephalitis are increasingly being recognized in children with antibodies , mainly to nmdar , but also to lgi1 , caspr2 ( previously attributed to voltage- gated potassium channel antibodies complex ) or other cns antigens.5,7 most of the patients present with a combination of recurrent seizures / status epilepticus , decreased level of consciousness , and motor neurological deficits .
a recent large cohort - based study of patients with immune - mediated encephalitis revealed that 4% of patients presented with isolated psychiatric episodes.8 support for this paradigm comes from another study involving 43 children with a first episode of acute psychosis .
antibodies to the dopamine d2 receptor were identified in 3 children , and to the nr1 subunit of the nmdar in 6 children , whereas no such antibodies were found in a group of 43 healthy control children.9 the mechanisms of psychiatric manifestations in antibodies mediated encephalitis are still not clear .
the nmda - receptor blockade in vivo produces schizophrenia - like symptoms in healthy individuals .
ion channel disturbance and hyponatremia have also been described as features of schizophrenia , previously attributed to medication - induced or psychogenic polydipsia.8,9 the findings from this study have several practical implications .
there is growing evidence that a proportion of psychosis / psychiatric manifestations in children may be immune - mediated , and psychiatrists should consider this etiology in each presentation of first - episode psychosis . if positive , these patients should be considered for treatment with immunotherapy . on the other hand , several antipsychotic drugs , such as haloperidol ,
must be used with caution in these conditions , as they have been observed to exacerbate motor symptoms in patients with anti - nmdar encephalitis .
we therefore recommend that all patients with a new - onset psychosis , or neuropsychiatric manifestations including seizures , autonomic dysfunction , movement disorders , or rapid deterioration of the level of consciousness should be evaluated for a possible antibody - associated encephalitis .
this assessment should include , as a minimum , a neurological examination and early testing for antibodies against the nmdar , lgi1 , caspr2 , ampa , gad , gabab antibodies , and thyroid antibodies .
the eeg can be useful : and encephalopathic pattern or extreme delta brushes pattern should prompt early referral .
mri of the brain may be normal ( although the finding of temporal lobe or limbic system signal changes is very suggestive of an immune - mediated encephalopathy ) .
the aim of these recommendations is the early identification and improved treatment for patients with this disorder . in conclusion ,
autoimmune mechanisms have been recently implicated in a number of neuropsychiatric disorders , classically linked to a pure psychiatric disease .
delay in diagnosis and treatment with immunomodulatory drugs can lead to permanent sequelae . in cases of acute psychosis in children ,
new - onset psychosis in children represents a complex presenting symptom . 
 psychosis can be attributable to a combination of factors and etiologies , and all possible causes must be systematically examined . 
 there is growing evidence that a proportion of psychosis / psychiatric manifestations in children may be immune - mediated , and physicians should consider this etiology in each presentation of first - episode psychosis . 
 immune - mediated encephalopathies / encephalitis are increasingly being recognized in children with antibodies to n - methyl - d - aspartate receptor , leucine - rich glioma - inactivated 1 or other central nervous system antigens such as contactin - associated protein - like 2 , glutamic acid decarboxylase , alpha - amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid or gamma - aminobutyric acid b. in this study , we describe 3 cases of immune - mediated encephalopathy / encephalitis with prominent psychiatric symptoms at presentation , and suggest a practical diagnostic and treatment approach for children with acute psychosis of an immune - mediated cause .