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Case 5-2012: A 39-Year-Old Man with a Recent Diagnosis of HIV Infection and Acute Psychosis
Oliver Freudenreich, M.D., Nesli Basgoz, M.D., Carlos Fernandez-Robles, M.D., Mykol Larvie, M.D., Ph.D., and Joseph Misdraji, M.D.

Pr e sen tat ion of C a se
From the Departments of Psychiatry (O.F., C.F.-R.), Radiology (M.L.), and Pathology (J.M.), and the Infectious Disease Unit (N.B.), Massachusetts General Hospital; and the Departments of Psychiatry (O.F., C.F.-R.), Medicine (N.B.), Radiology (M.L.), and Pathology (J.M.), Harvard Medical School — both in Boston. N Engl J Med 2012;366:648-57.
Copyright © 2012 Massachusetts Medical Society.

Dr. Carlos Fernandez-Robles: A 39-year-old man with a recent diagnosis of human immunodeficiency virus (HIV) infection was transferred to this hospital from another hospital because of fever, sweats, and psychosis. The patient had been well until 4 months before admission, when fevers with temperatures up to 40.6°C, night sweats, and chills developed. During the next 3 months, anorexia, nonproductive cough, and unintentional weight loss (7 to 14 kg) occurred, associated with early satiety, epigastric burning that improved with eating, and abdominal pain that was intermittent, mild, and crampy. Two courses of antibiotics were reportedly administered, without improvement. Six days before admission, the patient was seen in the emergency department at the other hospital. The evaluation was reportedly negative; a skin test for tuberculosis was administered, and he was discharged. The next day, he saw his internist. Computed tomography (CT) of the abdomen, after the administration of contrast material, revealed a thick-walled mass near the duodenum (7 cm by 2.2 cm, with air in its center), scattered lymph nodes near the porta hepatis, a thickened gallbladder wall, and mild splenomegaly (13.5 cm). The patient was admitted to the other hospital. On examination, the patient was alert, oriented, cooperative, and thin, with shaking chills. The temperature was 38.5°C, the blood pressure 135/76 mm Hg, the pulse 106 beats per minute, the respiratory rate 20 breaths per minute, and the oxygen saturation 93% while he was breathing ambient air. There was mild epigastric and right-upper-quadrant tenderness, with no induration at the site of the skin test for tuberculosis. The hematocrit was reportedly 31.9%, the white-cell count 4600 per cubic millimeter (with 75% neutrophils and 14% lymphocytes), the blood level of alkaline phosphatase 233 U per liter, and the level of aspartate aminotransferase 47 U per liter. Broad-spectrum antibiotics and intravenous pantoprazole were administered. During the next 2 days, the temperature rose to 39.4°C and the stools became black and tarry; the hematocrit was 28.3%. Magnetic resonance imaging (MRI) of the abdomen, after the administration of contrast material, revealed a thick-walled

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n engl j med 366;7  nejm.org  february 16, 2012

The New England Journal of Medicine Downloaded from nejm.org on February 25, 2014. For personal use only. No other uses without permission. Copyright © 2012 Massachusetts Medical Society. All rights reserved.

A unit of red cells was transfused. and nystatin was begun orally. There were white plaques on the tongue. Psychiatric consultation was obtained. Testing for HIV and syphilis had reportedly been negative 11 years before admission. cryptococcal antigen. retroperitoneal. including statements that he had died and was dead. He had no known allergies. MRI scans of the brain obtained before and after the administration of contrast material showed multiple punctate foci of enhancement. Testing for antibody to HIV was positive. 2012 The New England Journal of Medicine Downloaded from nejm. strongyloides antibody. in the right and left cerebral hemispheres. reporting a nightmare in which he was dying. thyrotropin. and small. although one lesion appeared extraaxial and another lesion appeared to involve cortical gray matter. mild distention of the gallbladder. Three induced-sputum specimens showed hyphae on fungal wet preparation and were negative for acid-fast bacilli. For personal use only. A bird and a turtle were in the home. and a small amount of fluid adjacent to the gallbladder wall. speaking with his teeth and fists clenched and his eyes staring ahead. other vital signs and the remainder of the physical examination were normal. On psychiatric examination later that day. His parents and siblings were healthy. the patient was awake but initially unresponsive. magnesium. The distribution of the lesions was predominantly intraaxial and involved white matter and the junction of the gray and white matter. he appeared tense. 2014. Twenty-four-hour accompaniment was begun. the agitation had resolved. On the fourth day. amylase. Fevers occurred daily. and urine histoplasma antigen was negative. and ammonia were normal. Other test results are shown in Table 1. the patient appeared lucid and somber and had appropriate speech content. He had a history of alcohol abuse and did not smoke or use intravenous drugs. and extrapyramidal side effects developed. scars from zoster on the right thorax. The aspartate aminotransferase level increased to 155 U per liter. The temperature was 37. flat affect. the patient had disorganized and guarded behavior. with overlying beta activity and no evidence of epileptiform activity. with temperatures up to 40. folic acid. CT of the abdomen and pelvis obtained after the administration of contrast material showed upper abdominal. as were the results of tests of renal function and urinalysis.case records of the massachusetts gener al hospital lesion that was contiguous with the posteromedial wall of the duodenum. All rights reserved. psychiatric symptoms persisted. Copyright © 2012 Massachusetts Medical Society. splenomegaly. On the fifth day. and pelvic lymphadenopathy. bilirubin. During the next 9 days. esophagogastroduodenoscopy revealed a duodenal ulcer and gastritis.org on February 25. . CT of the chest without contrast material revealed a few nonspecific nodules and multiple supraclavicular. The maximum temperature was 40. Cultures of sputum grew Candida 649 n engl j med 366. religious delusions developed. Olanzapine and haloperidol were administered. and testing for syphilis. and upper abdominal lymph nodes. phosphorus. No other uses without permission. He became agitated and continued to have bizarre delusions. CMV antigen. He lived with his partner and her children. and olanzapine was prescribed.3°C.1°C. He had immigrated to the United States from a Caribbean country more than a decade earlier. Blood levels of platelets. and the performance of visuospatial tasks (Fig. A portable chest radiograph was normal. vitamin B12. thought blocking. up to 4 mm in diameter. mediastinal. During that night. Broad-spectrum antibiotics were stopped. a duodenal diverticulum.6°C and the blood pressure 148/81 mm Hg. Respiratory-isolation measures were instituted. anterograde memory (inability to orally recall three objects). He was not oriented to date and was found not to have the capacity to sign out against medical advice. On admission. He had biologic children who lived in his native country. the patient became agitated.7  nejm. The patient was transferred to this hospital.org  february 16. On the third day. Blood tests for IgG antibodies to toxoplasma and cytomegalovirus (CMV) was positive. Although the cog- nitive examination was limited in scope because of the patient’s lack of cooperation. On formal psychiatric examination on the second day. lipase. up to 12 mm in diameter. calcium. The patient had had herpes zoster of the thoracic dermatome 4 years before admission and again 3 months before admission. 1) in the absence of fluctuations in the level of consciousness. tests for toxic drugs and hepatitis B and C viruses were negative. with no family history of psychiatric illness. rubbery lymphadenopathy in the left axilla. with mild surrounding hyperintensity on fluid-attenuated inversion recovery (FLAIR) images. The results of portable electroencephalography were normal. CT of the brain showed no clinically significant abnormality. it revealed deficits in attention (inability to name months of the year backward). and bizarre nihilistic delusions. and gallbladder-wall thickening.

For personal use only.2 11. multiply by 0.05551. All rights reserved.1 45–115 10–40 10–55 110–210 614–1295 Negative 7.3 136 3.2 266 61 27 443 1759 Positive.0 6700 * To convert the values for glucose to millimoles per liter.9 15.0 2.0 10.1 1.5 (men) 4500–11.5–17. No other uses without permission.7  nejm.8–13.000 135–145 3.9 123 40–70 22–44 4–11 80–100 86 9 5 78 1+ Microcytes Reference Range. On the ninth day. This Hospital 32. Laboratory Data.6–4. and flow cytometry revealed T lymphocytes n engl j med 366.9 70–110 950–2967 348–1456 148–1173 21. HIV denotes human immunodeficiency virus.4 463 30 322 25.5 4. and blood for mycobacteria and fungi remained negative.8 100–108 23.7 3. The ranges used at Massachusetts General Hospital are for adults who are not pregnant and do not have medical conditions that could affect the results. Adults† 41. Copyright © 2012 Massachusetts Medical Society. albicans and normal respiratory flora.0–8.org  february 16.The n e w e ng l a n d j o u r na l of m e dic i n e Table 1. urine.000 On Admission. with no malignant cells on cytologic examination. Cultures of sputum. Lumbar puncture was performed.0–33.3 3.0 (men) 13. including the patient population and the laboratory methods used.0–31. by RT-PCR) 6.* Variable Hematocrit (%) Hemoglobin (g/dl) White-cell count (per mm3) Differential count (%) Neutrophils Lymphocytes Monocytes Mean corpuscular volume (µm3) Smear description T-cell subsets Absolute lymphocyte count (per mm3) CD4 T-cell count (per mm3) CD8 T-cell count (per mm3) Activated partial-thromboplastin time (sec) Prothrombin time (sec) International normalized ratio Sodium (mmol/liter) Potassium (mmol/liter) Chloride (mmol/liter) Carbon dioxide (mmol/liter) Glucose (mg/dl) Protein (g/dl) Total Albumin Globulin Alkaline phosphatase (U/liter) Aspartate aminotransferase (U/liter) Alanine aminotransferase (U/liter) Lactate dehydrogenase (U/liter) IgG (mg/dl) HIV antibodies (by enzyme-linked immuno­ sorbent assay) HIV nucleic acid (copies per ml of plasma. and analysis of the cerebrospinal fluid (CSF) was normal.4–4. ­ † Reference values are affected by many variables. They may therefore not be appropriate for all patients. . The HIV RNA level was 3010 650 copies per milliliter of CSF. 2012 The New England Journal of Medicine Downloaded from nejm.3–5. and RT-PCR reverse-transcriptase polymerase chain reaction.0–53. 2014.org on February 25. fine-needle aspiration of the peripancreatic lymph node showed no malignant cells.2 103 24. confirmed by Western blot analysis 893.

atazanavir. and numbers continued past the number 12.1. omission and repetition of numbers. such as delirium.7  nejm. DELIRIUM The first question we must ask is whether this patient’s new-onset psychosis is caused by an underlying. there is no gross evidence of hemorrhage or abscess. Clock Drawing.org on February 25. For personal use only. psychosis itself.5 A delirium can be easily missed if ancillary features such as psychosis overshadow the core problem of inattention.2 Psychosis is a symptom. a normal EEG is not sensitive enough to reliably rule out a delirium. including aortocaval and periaortic nodes (Fig. . with no evidence of mass effect. and can be organized into primary and secondary (organic) psychoses. enhancing. Also. numbers written inaccurately.5 The clinical diagnosis of delirium hinges on the presence of two cardinal features: disruption of attention and disruption of the sleep–wake cycle. not a diagnosis. Ophthalmologic examination showed retinal lesions. Although the images are degraded by motion artifact.4 and assessment of the overall clinical situation is very important in narrowing the differential diagnosis and determining the degree of urgency. May we review the imaging studies? Dr. including one focus in the right medial temporal lobe and another in the inferior left frontal lobe. a diagnostic procedure was performed. Transthoracic echocardiography was normal. Freudenreich: This patient has new-onset psychosis. The gallbladder wall is thickened with a small amount of pericholecystic fluid. which occur when the self becomes unfamiliar. including superficial whitening and fluffy white infiltrate. although there are two distinguishable hands. Haloperidol was stopped. which leads to fluctuation in symptoms over the course of a day. visuospatial skills were assessed by having the patient draw a clock. evidencing deficits in abstract thinking and in the ability to translate the concept of time into a drawing. Unfortunately. 2014. A tiny punctate intraaxial calcification was a nonspecific and nonacute finding. 2012 The New England Journal of Medicine Downloaded from nejm. On the second hospital day. An electroencephalogram (EEG) that shows diffuse slowing is suggestive of a delirium. Differ en t i a l Di agnosis Dr. He also made repeated statements about having died and being dead that are consistent with nihilistic delusions (termed the Cotard syndrome).6 The sudden onset of psychosis in a patient with fluctuating mental status and fevers is a delirium 651 n engl j med 366. Mykol Larvie: The abdominal CT scan (Fig. tenofovir. and olanzapine and lorazepam were administered as needed for agitation. All rights reserved. there is no easy way to reliably differentiate primary from secondary psychoses on the basis of the characteristics of the Figure 1. MRI of the brain (Fig. low-density lymph nodes. either inflammatory or malignant. 2B). No other uses without permission. the time is not identified correctly. leading to a delusion of being dead. CT of the brain revealed no clinically significant abnormality.case records of the massachusetts gener al hospital with an inverted ratio of CD4 T cells to CD8 T cells and no monoclonal B cells. although it initially raised concern for a mass. and ritonavir) and prophylactic trimethoprim–sulfamethoxazole was begun. Severe visuospatial disorganization is evidenced by the poor spacing between the numbers. life-threatening medical condition. Dr. hyperintense foci on T2-weighted images. 2A) shows a structure posterior to the second part of the duodenum that is typical in appearance for a duodenal diverticulum. some of which were originally worrisome for a parapancreatic mass. Psychosis is common in patients with delirium. Copyright © 2012 Massachusetts Medical Society. Oliver Freudenreich: I am aware of the diagnosis in this case.org  february 16. findings consistent with retinopathy from CMV or HIV. but as in this patient. There are enlarged. 3) revealed multiple predominantly punctate. Treatment with antiretroviral medications (emtricitabine.3. On the 12th day.

which some of the patients cited in the literature might have had.10 although it cannot be distinguished from a first episode of schizophrenia. including aortocaval and periaortic nodes (Panel B. until proved otherwise. it is char652 n engl j med 366. Abdominal CT Scan. No other uses without permission.org The New England Journal of Medicine Downloaded from nejm. When psychosis occurs in patients with HIV-associated dementia. This patient almost certainly has some degree of brain involvement by HIV infection. Most likely. All rights reserved. Since this patient has advanced HIV infection.7 The typical presentation is a progressive dementia with subcortical features (apathy. HIV-associated dementia Psychosis can occur in patients with delirium and in those with dementia. Primary Psychiatric Disorders Delirium often occurs in patients with cognitive impairment and dementia. had children.The n e w e ng l a n d j o u r na l of m e dic i n e A B acterized by prominent agitation.7 A primary psychiatric disorder such as schizophrenia. without HIV as a causative factor. hallucinations (61%). neurologic findings are typically limited and CT findings are nonspecific. The extent of his cognitive impairment will require reexamination with a full battery of neuropsychological tests after his acute illness has resolved. Psychosis due to general medical conditions Figure 2. inattention.12 Since substance abuse is a common coexisting disorder in HIV-infected patients and can further impair cognition. which was a common problem before the introduction of highly active antiretroviral therapy (HAART). and mood symptoms (81%). It may also occur as a direct manifestation of an underlying medical condition. since he did not have focal findings and his history showed no cognitive decline. .” HIV-associated dementia is a diagnosis of exclusion. develops in some patients who have established HIV infection. he is in an early stage of HIV-associated dementia. The common clinical features of HIV-associated psychosis include sudden onset without prodrome. Therefore. since the onset of schizophrenia is typically not sudden but instead involves a prodromal period of several years. delusions (87% of patients). he is at risk for HIV-associated dementia. and loss of retentive memory) and abnormalities of motor function.org on February 25. There are enlarged.13 I would not diagnose HIV-associated psychosis in a patient with a delirium. since men typically february 16. and delusions8 (all of which were present in this patient) and is often part of a manic syndrome that has been called “AIDS mania. For personal use only. EEGs are abnormal in 50% of cases. Copyright © 2012 Massachusetts Medical Society. a thorough evaluation involving CSF analysis and MRI is warranted for ruling out infection and a malignant condition of the central nervous system. and at the age of 39 years would be unusually old to be having a first episode of schizophrenia. In this patient. however.9 In HIV-associated psychosis.14 This patient was married. 2012 nejm. it is important to rule out the use of alcohol or other drugs as a contributing cause. A structure posterior to the second part of the duodenum (Panel A) has an appearance typical of a duodenal diverticulum (arrow). 2014. our differential diagnosis and evaluation must focus on his advanced HIV infection.9 Cognitive impairment has consistently been described as a feature of HIV-associated psychosis. In this patient. such as HIV infection. irritability. with gradual loss of function and social competence. such as psychomotor slowing. as suggested by the severe immunosuppression and presence of HIV RNA in the CSF. a first episode of schizophrenia is unlikely. supported by findings on CSF analysis and MRI.9.11. arrow). low-density lymph nodes.

org february 16. For example. enhancing foci throughout the brain on T2 -weighted imaging. The absence of cryptococcal antigen in the CSF of this patient makes this diagnosis unlikely.leukoencephalopathy or lymphoma associated with n engl j med 366. making this diagnosis unlikely. Cryptococcal meningitis is another possibility. no brain abscess was identified on MRI. Testing for CMV in the Late Diagnosis of HIV infection blood and CSF was negative. it is not particularly sensitive for the detection of invasion of the central nervous system. This patient does not have evidence of tuberculous meningitis or a tuberculoma. since the organism may not elicit a robust inflammatory response. psychosis is a feature of other psychiatric disorders besides schizophrenia. To summarize. There are scattered hyperintense.case records of the massachusetts gener al hospital A B C Figure 3. dition of the central nervous system must be considered.patient is also at risk for progressive multifocal es in mental status. However. For personal use only. Results of CSF analysis are often bland in cryptococcal meningitis. the very sudden onset of psychosis during the course of a day or so has been called “reactive psychosis.” in response to stressors. infection or a malignant con. and T2 -weighted (Panel C). and this makes CMV Dr. Shown are corresponding axial images — T1-weighted (Panel A). In this patient with HIV infection and a low CD4 T-cell count. Copyright © 2012 Massachusetts Medical Society. . The small lesions seen on MRI are not sufficient to explain this patient’s psychosis. Cerebral toxoplasmosis is possible. particularly given the clear evidence that he had a delirium.15 This patient’s delirium is a sufficient explanation for his psychosis. In any patient with fever and sudden chang. therefore. and disorientation at times) suggest a delirium in this patient with AIDS and severe immune suppression. All rights reserved. T1-weighted after the administration of contrast material (Panel B). and may occur in patients with HIV infection. The nonspecific MRI findings and the lumbar puncture that showed HIV viral replication but no other infection suggest one of the HIV-associated neurocognitive disorders as a vulnerability factor for the delirium. since the patient has serologic evidence of past infection.7 nejm. our differential diagnosis has to include processes that cause central nervous system disease in immunosuppressed hosts. the clinical history (sudden onset of psychosis in a patient with constitutional symptoms and fevers) and results of the serial mental status examination (characterized by delusions. Nesli Basgoz: I am aware of the diagnosis in this encephalitis unlikely although not impossible. most likely from systemic infection. especially given the abnormalities seen on retinal examination. No other uses without permission. and psychiatric causation does not need to be invoked. Infection with Mycobacterium tuberculosis may cause chronic central nervous system disease. attentional problems. 2014. CMV infection should also be considered. This case.org on February 25. 2012 653 The New England Journal of Medicine Downloaded from nejm. Arrows identify lesions in the left inferior frontal lobe and in the junction of the right temporal lobe and insula. become ill in their 20s. tuberculosis affecting the central nervous system cannot be ruled out. MRI Scans of the Brain. Although MRI may reveal gross disease. However.

All rights reserved. most likely superimposed on a mild HIV-associated neurocognitive disorder. Ol i v er Fr eudenr eich a nd Dr . Pathol o gic a l Discussion Dr. blood. but there is no imaging evidence to support these diagnoses. Some of the granulomas show central amorphous necrotic debris (Panel B. His fever. and urine. hematoxylin and eosin). peripancreatic lymph-node aspirate. area between the arrows. tuberculosis was confirmed. The two most important predictive factors in this case are the CD4 T-cell count of 30 per cubic millimeter and the fact that the patient comes from an island in the Caribbean where tuberculosis is endemic. the final anatomical diagnosis is disseminated M. cough. Therefore. The diagnosis was mycobacterial infection of the liver with necrotizing granulomatous inflammation. sweats. Ne sl i B a sg oz’s Di agnose s C Acute psychosis with Cotard’s delusion. Ziehl–Neelsen stain).org The New England Journal of Medicine Downloaded from nejm. Dr . we took another look at the peripancrefebruary 16. and lymphadenopathy are all consistent with disseminated tuberculosis. tuberculosis complex. Epstein–Barr virus. Panel A (hematoxylin and eosin) shows an epithelioid granuloma with a cuff of lymphocytes. Since the initial review of the lymph-node aspirate did not show acid-fast bacilli or fungi. tuberculosis. 4A and 4B). The large number of bacilli and the somewhat looser arrangement of the histiocytes are features consistent with the immunodeficient status of the patient. but most disease is caused by a relatively small number of organisms. . During the patient’s hospital course. 2012 Figure 4. including histoplasmosis. Histochemical staining for acid-fast organisms revealed numerous acid-fast bacilli (Fig. The range of possible opportunistic infections is vast. For personal use only. various cultures were reported as positive for M. In this profoundly immunosuppressed patient. arrows. chills.The n e w e ng l a n d j o u r na l of m e dic i n e A B to patients with low CD4 T-cell counts. he had a persistently high aspartate aminotransferase level. Although he had a negative purified protein derivative skin test for tuberculosis. Copyright © 2012 Massachusetts Medical Society. Liver-Biopsy Specimen. most likely M. some of them necrotizing (Fig. No other uses without permission. sputum. this test lacks sensitivity in normal hosts and is likely to be uninformative in this patient with a low CD4 T-cell count. 2014. tuberculosis infection.org on February 25.7 nejm. Joseph Misdraji: Examination of the liver-biopsy specimen revealed several epithelioid granulomas. the next step was a liver biopsy. Numerous acid-fast bacilli are present (Panel C. since the laws of medical parsimony do not apply 654 n engl j med 366. multiple opportunistic infections may be involved. After the diagnosis of M. 4C). We also need to consider fungal infections that behave like tuberculosis. Shortly after the diagnosis was made. including the liver biopsy. Delirium due to the systemic effects of an opportunistic infection or malignant condition.

4 mmol per liter). 655 n engl j med 366. which has been well documented to occur in patients with HIV. most of the patient’s psychotic symptoms had resolved. we added prednisone to the patient’s regimen. Because of the development of extrapyramidal symptoms. both of which require complex treatment regimens. persistent high fever. We closely followed the creatine kinase levels. Basgoz: This patient has at least two life-threatening infections. with calcium levels measured as high as 13. except for a persistently flat affect and mildly monotonous speech. 2012 The New England Journal of Medicine Downloaded from nejm. Review of the aspirate revealed lymphocytes and small amounts of amorphous granular debris in which acid-fast bacilli were identified. Hypercalcemia is much more commonly seen in other granulomatous diseases. there was also an increase in the alkaline phosphatase level. This constellation of findings is consistent with the immune reconstitution inflammatory syndrome (IRIS). cough.16-19 This sensitivity is thought to be related to HIV-associated damage to the dopaminergic basal ganglia system and to increased plasma levels of antipsychotic agents because of interactions with antiretroviral drugs. After discontinuation of prednisone. therapy directed against tuberculosis was initiated. from 185 U per liter to 722 U per liter.org  february 16. We assumed that this was caused by a parathyroid-hormone–independent mechanism related to the production of 1. However. it is important to notify the pathologist so that extra time can be spent reviewing the slide stained for acid-fast bacilli. We restarted low-dose prednisone.23-29 This patient was initially started on a standard four-drug antiretroviral regimen. All rights reserved.22 On day 5. when there is a high clinical suspicion of mycobacterial disease. with a decrease in alkaline phosphatase levels and an improvement in fever. The patient looked and felt well. tenderness. Severe scrotal pain also developed. This patient had markedly less agitation after 2 days of treatment with olanzapine. we became concerned about the possibility of neuroleptic malignant syndrome. which was part of his antimycobacterial regimen. On discharge. For personal use only. Copyright © 2012 Massachusetts Medical Society. and tachypnea developed. lacking the normal diurnal variation that is typical of infection. We discontinued rifabutin. and changes in mental status. As we tapered the dose of prednisone. For treatment of IRIS. No other uses without permission. . and organisms can be overlooked. which remained normal. This case underscores the fact that the identification of acid-fast bacilli is challenging. and the fever resolved.case records of the massachusetts gener al hospital atic lymph-node aspirate to see whether we could find acid-fast bacilli. probably directed against antigens liberated from dead or dying mycobacteria. During this time. fever recurred.7  nejm. than in tuberculosis. asymptomatic hypercalcemia developed. but the pattern of fever was relatively constant. with worsening malaise. and induration. requiring the administration of lorazepam and a reduction in the dose of olanzapine.20. which suggested that the fever might be medication-related.21 Dysfunction of the basal ganglia also heightens the risk for neuroleptic malignant syndrome. high temperature. His subsequent clinical course highlights an unresolved clinical question regarding the timing of the initiation of antiretroviral therapy in patients with a low CD4 T-cell count and concurrent opportunistic infection.org on February 25. and approximately 1 week later. Ultrasound examination of the scrotum showed a complex testicular mass with epididymal enlargement that was thought to be consistent with involvement by disseminated tuberculosis. Fernandez-Robles: Reversal of organic psychosis involves treatment of the underlying disorder and symptomatic treatment with antipsychotic agents.25-­ dihydroxyvitamin D by the macrophages in reaction to the tuberculosis infection. 2014. He had a rapid clinical response. As his immune function started to recover. Within 6 days after the initiation of antituberculous therapy. with swelling. he had reactivation of a latent CMV infection and required treatment with ganciclovir. extrapyramidal symptoms developed. such as sarcoidosis. HIV and tuberculosis. This drug was initially chosen because of its proven efficacy and relatively low risk of causing extrapyramidal symptoms and tardive dyskinesia. Management of Tuberculosis and HIV infection Dr. Discussion of M a nagemen t Management of HIV-associated psychosis Dr. which are highly prevalent among patients with HIV. the patient mounted an exuberant inflammatory response. a paradoxical worsening of inflammation caused by the reconstitution of immune function while on antiretroviral therapy. an antipsychotic agent. suggesting worsening of the patient’s liver disease.5 mg per deciliter (3. Therefore.

Joshua Roffman (Psychiatry) for assistance with organizing the conference. grant money from Pfizer. I do not think it is possible to establish causality between this patient’s lesion in the temporal lobe and his psychosis. the patient is doing exceptionally well medically.190:135-41. Norman LR. New-onset psychosis in HIVinfected patients. How should DSM-V criteria for schizophrenia include cognitive impairment? Schizophr Bull 2007. 6. Disclosure forms provided by the authors are available with the full text of this article at NEJM. Seidman LJ. 10. Giuliano AJ. Johnstone EC. McArthur JC. particularly in processing speed. 2. et al. His clock drawing was intact. HIV-associated psychosis: a study of 20 cases. Neurology 1993. recall memory. Freudenreich: An EEG was obtained to rule out seizures and was normal in this patient. Approximately 14 months after discharge. Atkinson JH. Dr. sputum. Gleghorn A. Basso M. Jeste DV. Br J Psychiatry 1988. Theodore A. We thank Dr. He continued therapy for tuberculosis and HIV. Mesholam-Gately RI. He had made a remarkable recovery but had residual cognitive problems. the eye lesions were quiescent and there was no evidence of active retinitis. Copyright © 2012 Massachusetts Medical Society. Cotard’s delusion or syndrome? A conceptual history. Brenner RP. Hoover DR.The n e w e ng l a n d j o u r na l of m e dic i n e and the hypercalcemia rapidly resolved with ketoconazole. Katabira E.153:770-6. there was a focal area of chorioretinitis in the left eye that was not considered typical of CMV retinitis and was thought to possibly be a granulomatous lesion from tuberculosis. feels strong. 13. De Ronchi D. Freudenreich: I saw the patient in outpatient psychiatry for follow-up 6 months after his acute illnesses had resolved. Owens DG. Frith CD. For personal use only. . 9.32 Dr. Keefe RS. Am J Psychiatry 1994. et al. peripancreatic lymph node.org on February 25. Early diagnosis and treatment of HIV infection may help to limit brain disease. Int Psychogeriatr 1991. Portzky M. Therefore. Primary mania versus HIV-related secondary mania in Uganda.org  february 16. 3. Sewell DD. Nakimuli-Mpungu E. Curr Psychiatry Rep 2009. Malow R. at the time of his last eye examination. Stern (Psychiatry): In light of the patient’s episodic belief that he was dead. Goff KP. Kumar A. Am J Psychiatry 2006. and urine. at which time he was medically stable and had a markedly improved mental status.36:218-23. and plasma HIV RNA was not detected. 656 n engl j med 366. and honoraria from Reed Medical Education. Sewell DD. the patient was noted to have bilateral retinopathy. Neurocognition in first-episode schizophrenia: a meta-analytic review.23:315-36. Mpungu SK. Raju B. Audenaert K. and frontal-lobe functions. Of note.30 This case exemplifies the effect that HIV infection may have on the brain. Cremante G. Neuropsychological consequences of HIV and substance abuse: a literature review and implications for treatment and future research. Psychopathology of first-episode psychosis in HIV-positive persons in comparison to first-episode schizophrenia: a neglected issue. I consider HIV testing in any patient presenting with psychosis14 or with cognitive problems.33:912-20. et al.43:224552. Crow TJ. Cooling NJ. His last CD4 T-cell count was 231 per cubic millimeter. Musisi S. 12. Cotard’s syndrome: a review. Freudenreich reports receiving consulting fees from Beacon Health Strategies and Transcept Pharmaceuticals.18:872-8. 4. Curr Drug Abuse Rev 2009. blood. AIDS Care 2006. Eynde F. All rights reserved. Harris MJ. Bacellar H. Dr. Thirty months after discharge.3:211-29. Phenomenology of delirium: assessment of 100 adult cases using standardised measures.163:1349-54. No other uses without permission. and exercises frequently. all of which might have functional ramifications. with delirium and acute psychosis with Cotard’s delusion. Faraone SV. FINA L DI AGNOSE S Disseminated infection with Mycobacterium tuberculosis. Compr Psychiatry 1995. Berrios GE. Dr.25-dihydroxyvitamin D.7  nejm. Jeste DV. Basgoz reports receiving stock options and income for board membership from Forest Laboratories. should we consider the possibility that this thought or feeling was derived from a complex partial seizure in the temporal lobe? The theme of death in complex partial seizures has been described in the literature. However. particularly late in References 1. The patient was discharged after 4 weeks in the hospital.11:197202. 2014. Br J Psychiatry 2007.org. Luque R. Mild HIV-associated neurocognitive disorder. 52:369-76. he scored 7 out of 16 on the HIV Dementia Scale (with scores of 10 or less indicating HIV-associated dementia). et al. 8. J Clin Psychiatry 1991.31 Dr. Meagher DJ. On examination by the retina service. 2012 The New England Journal of Medicine Downloaded from nejm. which inhibits a step in the production of 1. 7. including the liver. 5. Fenton WS.2:143-56. which was considered to be due to CMV or HIV. Phenomenology of organic and functional psychoses and the overlap between them.151:237-42. Van den the course of infection. Debruyne H. Dementia in AIDS patients: incidence and risk factors. Bellini F. Moran M. No other potential conflict of interest relevant to this article was reported. Presented at the Psychiatry Grand Rounds. Neuropsychology 2009. Utility of EEG in delirium: past views and current practice. 11.

Piggott DA.50:1539-41. Boston. 23. Am J Psychiatry 1984.5:61-9. neurologic.16:663-8. not only those published in the Journal. Power C. and cardiac studies. 15. HIV infection with immunodeficiency presenting with subacute cognitive decline: recent illustrative cases. Clin Dev Immunol 2011. N Engl J Med 2011. 2012 657 The New England Journal of Medicine Downloaded from nejm.44:7 91-4. Homosexual erotomania and HIV infection. Cahn P. Kendall MA. 20. Havlir DV. may be obtained from the Lantern Slides Service. J Acquir Immune Defic Syndr Hum Retrovirol 1995. Herrán A. Differential sensitivities to risperidone and olanzapine in a human immunodeficiency virus patient.org  february 16. Naidoo K. as well as unpublished text slides.org. Postgrad Med J 1997. et al. 32. Meintjes G. Kelly DV. and photomicrographs.13:684-9. Radiographic. Blanc FX.35:147-8. Thompson MA. Massachusetts General Hospital. Sok T.case records of the massachusetts gener al hospital 14. Coid J. Greenberg DB. The cost of an annual subscription is $600. Optimum timing of antiretroviral therapy for HIVinfected patients with concurrent serious opportunistic infections. Clin Infect Dis 2010.304:321-33. Davis J. Mirsattari SM. Ive P.3:10-8. Rapidly progressive tardive dyskinesia in AIDS. 18. All rights reserved. Extrapyramidal symptoms due to dopamine-blocking agents in patients with AIDS encephalopathy. Meintjes G.73:779-84. 16. Echevarría S. McArthur JC. Biol Psychiatry 1994. averaging 50-60 slides per set. Lantern Slides Updated: Complete PowerPoint Slide Sets from the Clinicopathological Conferences Any reader of the Journal who uses the Case Records of the Massachusetts General Hospital as a teaching exercise or reference material is now eligible to receive a complete set of PowerPoint slides. Murray GB. Cohen K. Ex27. trapyramidal symptoms with ritonavir/ indinavir plus risperidone. Nath A. pathogenesis and management. 12:842-50. Each set is supplied on a compact disc and is mailed to coincide with the publication of the Case Record. Timing of antiretroviral therapy for HIV in the setting of TB treatment. Simpson G. HIV-related movement disorders: epidemiology. CNS Drugs 2002. Riancho JA. Power C. 30. 2014.141: 1587-9. Hernández JL. Cardoso F. Masdeu JC.7  nejm.36:827-30. Grim JA. Copyright © 2012 Massachusetts Medical Society. with identifying legends.365:1471-81.org on February 25. Aberg JA. are included. Boast N. . Goff DC. Integration of antiretroviral therapy with tuberculosis treatment. This slide set contains all of the images from the CPC. 25. JAMA 2010. CNS Spectr 2007. A. Hriso E. Neuroleptic malignant syndrome in the acquired immunodeficiency syndrome. Parkinsonism with HIV infection. No other uses without permission. Palacios-Araus L. N Engl J Med 2011. Grobler Initial medical work-up of first-episode psychosis: a conceptual review. Earlier versus later start of antiretroviral therapy in HIV-infected adults with tuberculosis. Department of Pathology.8:273-8. Freudenreich O. Selnes OA. Application forms for the current subscription year. Schulz SC. Soldato-Couture C. Campo JF. 17. Meyer JM. Antiretroviral treatment of adult HIV infection: 2010 recommendations of the International AIDS Society–USA panel. Béïque LC. Karakousis PC. Mov Disord 1998. Am J Psychiatry 1991. which began in January. 19. Timing of antiretroviral therapy for HIV-1 infection and tuberculosis. 28.365:1492-501.365:1482-91. Marsh J. MA 02114 (telephone 617-726-2974) or e-mail Pathphotoslides@partners. 31. tables. Management of individuals requiring antiretroviral therapy and TB treatment. Venna N. Grundman M. 29.148:1558-61. Ann Pharmacother 2002. Kuhn T. Biol Psychiatry 1998. HIV Dementia Scale: a rapid screening test. gross specimens. et al. N Engl J Med 2011. 26. 21. Wilkinson RJ. The theme of death in complex partial seizures. Br J Psychiatry 1994.2011:103917. Copyright © 2012 Massachusetts Medical Society. Every year 40 sets are produced. Bowmer MI. and diagrams. or individual sets may be purchased for $50 each. et al. Shedlack KJ. et al. Early Interv Psychiatry 2009.164:842-6. Curr Opin HIV AIDS 2010. Costello D. shown at the live Clinicopathological Conference (CPC) that is the basis of the Case Record. 24. including digital images. 22. Hochberg FH. Abdool Karim SS. Laureillard D. Swanson CL Jr. For personal use only. n engl j med 366.