Young Man With Fever, Headache, and Seizures

November 1, 2006

A 28-year-old man is hospitalized because of highfever with rigors and chills and rapid weight loss(5.4 kg [12 lb] in 2 weeks). During the past 48 hours,generalized throbbing headache, intermittent vomiting,blurry vision, and seizures have developed. The progressiveseizures started in the left hand and have becomegeneralized grand mal.

A 28-year-old man is hospitalized because of highfever with rigors and chills and rapid weight loss(5.4 kg [12 lb] in 2 weeks). During the past 48 hours,generalized throbbing headache, intermittent vomiting,blurry vision, and seizures have developed. The progressiveseizures started in the left hand and have becomegeneralized grand mal.

History. The patient has had HIV disease subgroupC3-with a low CD4 cell count (46/μL) and a high viralload (410,000 copies/mL)-for the past 4 years. His antiretroviralregimen consists of lamivudine/zidovudine andlopinavir/ritonavir, and he takes trimethoprim-sulfamethoxazole,azithromycin, and fluconazole for opportunistic infectionprophylaxis. His adherence to therapy is poor.

He denies cough, dyspnea, chest pain, and diarrhea.His left arm is somewhat weak and clumsy. He does notsmoke, abuse alcohol, or use illicit drugs. No history ofblood transfusion or foreign travel; no pets. Immunizationsare up-to-date, including tetanus and hepatitis A and B.

Examination. This pale, emaciated man appearschronically ill. Pulse rate is 140 beats per minute; respirationrate, 20 breaths per minute; temperature, 38.6oC(101.5oF); blood pressure, 106/72 mm Hg. He is well hydrated.No rashes, ankle swelling, adenopathy, or bleedingtendency. Oral thrush is noted. He has palpable small,discrete lymph nodes in the cervical chain and axillae.Thyroid is not palpable.

Skull and spine are normal; carotid arteries are equaland palpable. The patient is lethargic but arousable andgives appropriate responses. Cranial nerve function is intact.Funduscopy reveals papilledema. Grade III to IV weaknessof the left arm is noted. Sensory function and deeptendon and plantar reflexes are normal. Neck is supple; nomeningeal or cerebellar signs. Heart, lungs, and abdomenare normal. During the examination, the patient has a jacksonianseizure that culminates in grand mal convulsion.

Laboratory studies. White blood cell count, 240/μL,with 60% polymorphonuclear neutrophils, 32% lymphocytes,4% eosinophils, and 4% monocytes. Hemoglobin level is9.6 g/dL; platelet count, 156,000/μL; erythrocyte sedimentationrate, 140 mm/h. Serum sodium level is 134 mEq/L;potassium, 3.8 mEq/L; chloride, 96 mEq/L; calcium,8.4 mg/dL; blood urea nitrogen, 29 mg/dL; serum creatinine,1.1 mg/dL; blood glucose, 108 mg/dL; total bilirubin,1.2 mg/dL. Total serum protein level is 5.1 g/dL:albumin, 2.8 g/dL, and globulin, 2.3 g/dL. Liver functiontest results are normal. Blood cultures are negative. Urinalysisresults are normal. A VDRL test and serologictests for Coccidioides antibodies, Cryptococcus antigen, andToxoplasma antibodies are negative. Tuberculin skin testis negative. CD4 cell count, 32/μL; HIV load, 462,000copies/mL. Chest film is normal.

You order an emergent CT scan.

What abnormality is evident here-and to whatdiagnosis does the clinical picture point?A. Glioblastoma multiforme
B. Herpes encephalitis
C. Septic embolism
D. Cerebral lymphoma
E. Kaposi sarcoma
F. Toxoplasma abscess


The CT scan shows a ringenhancedshadow in the frontalparietal area with cerebral edemaand encroachment on the ventricularsystem (Figure). In a patientwith advanced AIDS, these CTfindings narrow the differential tocerebral lymphoma and Toxoplasmaabscess. The negative Toxoplasmatiter makes Toxoplasma abscessless likely than cerebrallymphoma,D.

Hospital course. The patient isgiven sulfadiazine, pyrimethamine,clindamycin, dexamethasone, andintravenous phenytoin. Ventilatorysupport is required to protect hisairway. His seizures continue.A neurosurgeon is consulted;stereotactic biopsy of the ring-enhancedlesion reveals non-Hodgkinlymphoma. The hematologyoncologyservice recommends intrathecalcytarabine; intravenouschemotherapy with cyclophosphamide,doxorubicin, vincristine, andprednisone (CHOP); and cranialirradiation.

Outcome. Because the patient'sclinical status is deteriorating, hisclose friend and family request thathe be given supportive care only.All medications except intravenousmorphine are discontinued. He dies6 days after hospitalization.

AIDS-related non-Hodgkin lymphoma is uncommonyet highly lethal. HIV-infected persons are at increasedrisk for lymphoma, particularly of the CNS; this elevatedrisk was noted early in the epidemic and was added to thedefinition of AIDS in 1985.

The risk of lymphoma increases as immune suppressionworsens, especially when the CD4 cell count falls below100/μL. The risk is estimated at 1.6% to 8% per yearfor patients with severe immunosuppression. Most of thelymphomas are B cell tumors and are closely associatedwith Epstein-Barr virus (EBV) infection.

Clinical features. The presentation of lymphoma inHIV-infected patients differs from that in uninfected persons;it is more likely to be extranodal in origin. Commonsites are the GI tract (25%), CNS (22%), bone marrow(22%), and liver (13%). Twenty percent to 40% of patientshave leptomeningeal involvement at the time of diagnosis.

Systemic symptoms, such as fever, night sweats, andprogressive weight loss, are common. Evidence of CNSinvolvement ranges from cognitive and personalitychanges and motor deficits to frank seizures.

Diagnosis. When seizures are predominant, the closestdifferential diagnosis is Toxoplasma abscess; both conditionsproduce characteristic low-density, ring-enhancedlesions on CT and MRI. If repeated CT scans show a reductionin the size of the lesions after a 3-week trial of anti-Toxoplasma antibiotics, Toxoplasma abscess is likely. The "gold standard" in making the diagnosis is brain biopsy,which carries its own morbidity.

Order appropriate cultures and serologic tests to ruleout other opportunistic infections, such as Mycobacteriumavium complex, cytomegalovirus, EBV, and fungal infections;syphilis; and tuberculosis.

The cerebrospinal fluid (CSF) pressure may be increased.Examination of the fluid shows an elevated proteinlevel and lymphocytic pleocytosis; CSF culture is negative.An electroencephalogram may show localized ordiffuse abnormalities. Staging of lymphoma may requireCT scanning of the abdomen, pelvis, and chest; galliumscanning; and bone marrow aspiration and biopsy.

Treatment. The management of CNS lymphomaincludes:

  • CHOP or bleomycin, doxorubicin, cyclophosphamide,vincristine, dexamethasone, and methotrexate(M-BACOD).
  • Intrathecal cytarabine or methotrexate.
  • Cranial and spinal irradiation.

Prognosis. Overall, the prognosis for patients withCNS lymphoma is poor; mean survival is 4 to 12 months.The outcome is worse if the CD4 cell count is less than100/μL and if opportunistic infections are present.


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  • Goldstein JD, Dickson DW, Moser FG, et al. Primary central nervous systemlymphoma in acquired immune deficiency syndrome. A clinical and pathologicstudy with results of treatment with radiation. Cancer. 1991;67:2756-2765.
  • Kaplan LD, Abrams DI, Feigal E, et al. AIDS-associated non-Hodgkin's lymphomain San Francisco. JAMA. 1989;261:719-724.