one of the most common types of autoimmune encephalitis ( ae ) associated with neuronal cell surface autoantibodies are mediated by antibodies against the n - methyl - d - aspartate receptor ( nmdar ) . most of the patients with nmdar encephalitis have prodromal headache , fever , or other symptoms that may resemble a viral process . patients develop psychiatric manifestations such as anxiety , insomnia , agitation , hallucinations , or delusions . these symptoms are usually followed by orofacial and limb dyskinesias , choreoathetosis , dystonia , rigidity , and opisthotonic postures in the context of catatonia , coma , and autonomic instability . this condition affects predominantly young females , in association with a tumor , most commonly an ovarian teratoma . this is an immune - mediated disorder and despite its severity , patients often recover after tumor removal and immunotherapy ( corticosteroids , intravenous immunoglobulin , or plasma exchange [ pe ] ) . approximately 25% of the patients , mainly those without a tumor , have a tendency to relapse . hiv patients have a higher incidence of systemic autoimmune diseases , even on highly active antiretroviral therapy ( haart ) . on the other hand , immunosuppressive therapy ( ist ) poses a not unreasonable fear of further immune dysfunction / immunodeficiency . in this case report , we describe the first known case of an hiv - positive individual with nmdar encephalitis with a focus on therapeutic choices and a successful outcome . a 36-year - old female in an acute confusional state was admitted to the hospital in 2014 . she had been in good health until 2 weeks prior to admission when she complained of acute - onset generalized severe headache , high fever , generalized myalgia , and anorexia . she had been prescribed analgesics to which she was unresponsive . over the past week , her family had progressively noticed more frequent episodes of a stiff posture , blank stares , and tonic movements of her arms , alongside insomnia , anxiety , and confusion . she was known to be hiv - positive under anti - retroviral therapy for the past 16 years , with a normal cd4 t - cell count , undetectable viral load , and no aids - defining diagnosis . there was no history of recreational drug use , alcohol abuse , toxin exposure , recent vaccination , or epidemiological risk factors . initially , she was conscious and obeyed simple requests but was mostly noncooperative with the neurological examination , which failed to reveal any anomaly except for generalized stiffness and an absent reflexive blink . laboratory investigations revealed a hemoglobin level of 11.6 g / dl , leucocytes 10,000  10/l ( normal differential count ) , platelets 263,000  10/l , c - reactive protein < 0.3 mg / dl , and no evidence of renal , hepatic , thyroid , or metabolic dysfunction . the antinuclear antibody test was positive ( 1/160 ) with a fine , granular pattern on hep-2 cell indirect immunofluorescence . the cerebrospinal fluid ( csf ) was clear , colorless with an increased number of cells ( 86/l , predominantly mononuclear ) , a slight increase in protein concentration ( 64 mg / dl ) , normal glucose ( 45 mg / dl ) , negative gram stain , and no evidence of cryptococcus . treatment was empirically started with acyclovir , and 2 days later , ceftriaxone and ampicillin were added . in the next 48 h , she was in mutism , with periods of motor agitation , myoclonic jerks of the hands , and her mental state progressively deteriorated . the cerebral mri showed a small number of focal t2 hyperintensities bilaterally , located in the frontal subcortical region . sedation was titrated for seizure control , reduced , and withdrawn on icu day 8 . on icu day 10 , she remained unreactive to painful stimuli , with episodes of involuntary eyelid contractions , chewing , and sucking motions . she completed 16 days of acyclovir and 14 days of antibiotics with no clinical improvement , remaining afebrile , hemodynamically stable , and without evidence of infection ( table 1 ) . an autoimmune basis for her disorder was suspected , and the presence of anti - n - methyl - d - aspartate receptor ( anti - nmdar ) antibodies ( euroimmun ) both in serum and csf clinched the diagnosis of ae . no evidence of neoplastic disease was found ( actively searched for by abdominopelvic ct and mri , thyroid and breast ultrasound , and a positron emission tomography scan ) . clinical improvement together with a reduction in the antibody titer was only apparent after 5 sessions of pe , on alternate days . pe was then performed daily over the next 7 days , after which the patient regained consciousness , there were no further seizures , and she was transferred back to the ward . she was then treated with rituximab and cyclophosphamide and maintained on mycophenolate mofetil ( mmf ) . motor status was fully normal when she was discharged after 147 days of hospital admission . at the 2-year follow - up , , serial cd4 t - cell counts remained persistently above 400 cells/l , the hiv viral load was repeatedly undetectable , and there was no evidence of neoplastic disease or opportunistic infections . ae is a rare condition , recently recognized and classically described in association with ovarian teratoma and as a paraneoplastic phenomenon . it is mediated by anti - nmdar antibodies , which likely result in the loss of receptor function . recent reports suggest that ae may be triggered by herpes simplex and measles viral infection [ 7 , 8 ] . we recognize that there was a diagnostic delay as we actively sought to exclude a systemic infection or a metabolic cause for her illness ( table 1 ) . the initial symptoms with acute - onset generalized severe headache , high fever , and neurologic symptoms ( stiff posture , blank stares , tonic movements , insomnia , anxiety , and confusion ) together with the csf profile ( normal glucose , a mild increase in the protein concentration , and the presence of mononuclear cells ) were suggestive of a viral infection . even though the hiv infection was controlled by haart and herpes simplex virus 1 and 2 are most frequently associated with psychiatric symptoms , an extensive search for several causes of viral encephalitis was undertaken , namely herpes 1 , 2 , 6 , 7 , 8 ; epstein barr ; varicella ; lymphocytic choriomeningitis virus ; enterovirus ; parvovirus , and cytomegalovirus . there was also a concern as regards the need to exclude infection in the light of the need to institute ist . other infections , such as mycobacteria , borrelia , coxiella , toxoplasma , and fungi , a space - occupying lesion , or ischemia were considered less likely but were still actively searched . our patient developed a prodromal illness , and her disease was further characterized by opisthotonic postures , rigidity , orofacial , and limb dyskinesia , confusion , seizures , and coma . the beneficial response to ist and the lack of improvement to the initial empirical viral and bacterial encephalitis treatment suggested an autoimmune condition . as the hiv infection was controlled , it was not thought to contribute to the clinical picture , but detailed studies of immune function were not performed . nevertheless , there is a recognized association between hiv infection and autoimmunity as patients with hiv infection managed with haart may develop acute immune dysregulation collectively known as immune reconstitution inflammatory syndrome . once the diagnosis of ae was made , the therapy is yet another challenge because potent immunosuppression is required in a patient with an acquired immunodeficiency . the poor response to first - line treatments ( high - dose intravenous corticosteroid , intravenous immunoglobulin , and pe ) justified further therapy with rituximab and cyclophosphamide in combination . further mmf therapy was justified by several studies suggesting that prolonged ist with mycophenolate mmf or azathioprine may prevent a relapse . hiv has become a chronic disease after the advent of haart , posing a dilemma as regards ist due to a documented risk of opportunistic infections and drug - drug interactions ( haart and ist ) . of note , in our patient , there was no evidence of hiv reactivation despite ist , and she remained free of infections during the 2 years of follow - up . the present case report illustrates that ae is a severe condition reversible with appropriate therapy . this is the first report of anti - nmdar encephalitis in an hiv - infected individual , reminding us that ae should be included in the differential diagnosis of any patient in an acute confusional state . the authors declare that there are no conflicts of interest regarding the publication of this paper .
anti - n - methyl - d - aspartate receptor ( anti - nmdar ) encephalitis is a rare condition characterized by emotional and behavioral disturbances , dyskinesias , and extrapyramidal signs . 
 it occurs in young women of reproductive age and is classically described as a paraneoplastic phenomenon . 
 we present a 36-year - old , hiv - positive female who was admitted to the hospital in an acute confusional state , with a stiff posture , periods of motor agitation , and myoclonic jerks of the hands . 
 her mental state progressively deteriorated . without evidence of infection , 
 the presence of anti - nmdar antibodies both in serum and cerebrospinal fluid clinched the diagnosis of autoimmune encephalitis . 
 no evidence of neoplastic disease was found , and the beneficial response to immunosuppressive therapy was exceptional . 
 this is the first report of anti - nmdar encephalitis in an hiv - infected individual , reminding us that autoimmune encephalitis should be included in the differential diagnosis of a young patient presenting in an acute confusional state .