Intracranial Lesion (Toxoplasmosis) Case File

Intracranial Lesion (Toxoplasmosis) Case File

Eugene C. Toy, MD, Ericka Simpson, MD, Pedro Mancias, MD, Erin E. Furr-Stimming, MD

CASE 31

A 25-year-old man is brought to the emergency room after experiencing a generalized tonic-clonic seizure. He was getting ready for work when he apparently fell to the floor and had the seizure. His mother, who witnessed the event, states that he lost consciousness and “shook all over.” The seizure lasted approximately 30 seconds and was associated with tongue biting as well as bladder incontinence. He returned to his baseline within 20 minutes. Over the past 6 months he has been complaining of headaches and had two previous generalized tonicclonic seizures. He has also lost approximately 6.8 kg (15 lb) over 1 month. He has been healthy otherwise, and the only other pertinent history is that he has been sexually promiscuous and experimented with intravenous (IV) cocaine. His last human immunodeficiency virus (HIV) test was 12 months ago, and he did not wait for the result. On physical examination, he is afebrile with a blood pressure of 130/68 mm Hg and a heart rate of 88 beats/min. He is awake and alert and oriented to person, time, location, and situation. His cranial nerves, sensory examination, cerebellar examination, and deep tendon reflexes are normal. His motor examination is notable for increased tone on the right with intact motor strength. His gait shows decreased arm swing on the right but otherwise is unremarkable. A computed tomography (CT) scan of the head without contrast shows that he has a solitary mass lesion measuring 15 mm over the left motor strip region with surrounding edema. Additionally, there is a 12-mm lesion in the left basal ganglia. With the administration of IV contrast, these lesions show enhancement.

▶ What is the most likely diagnosis?

▶ What is the best way to confirm the diagnosis?

▶ What is the next step in therapy?

ANSWERS TO CASE 31:

Intracranial Lesion (Toxoplasmosis)                                                    

Summary: A 25-year-old previously healthy man presents to the emergency room after experiencing a generalized tonic-clonic seizure that lasted 30 seconds. He has been experiencing headaches over the past 6 months but no other associated symptoms. His mother states she has witnessed him have two previous seizures. The history is notable for being sexually promiscuous and using IV illicit drugs. The result of his last HIV test is unknown. On neurologic examination, he is noted to have increased tone on the right and decreased right arm swing when walking. The remainder of his neurologic examination is normal. A CT scan of the head with contrast reveals that he has a ring-enhancing lesion measuring 15 mm over the left motor strip region and a 12-mm ring-enhancing lesion in the left basal ganglia.

• Most likely diagnosis: Cerebral toxoplasmosis.
• Best way to confirm diagnosis: Serum immunoglobulin M (IgM) and IgG titers for Toxoplasmosis gondii, and lumbar puncture to evaluate for polymerase chain reaction (PCR) of T. gondii.
• Next step in therapy: Start anticonvulsants to prevent further seizures and then start treatment for toxoplasmosis. Therapy consists of a combination of medications including pyrimethamine, sulfadiazine, and folinic acid.

ANALYSIS

Objectives

1. Know the diagnostic approach to toxoplasmosis, including the use of imaging studies and cerebrospinal fluid (CSF) studies.
2. Describe the clinical features of toxoplasmosis.
3. Describe how to treat toxoplasmosis and what precautions are necessary.

Considerations

This 25-year-old healthy man has been experiencing headaches for the past 6 months and just experienced his third generalized tonic-clonic seizure. His examination suggests a left-sided brain lesion, as he has right-sided motor findings (decreased right arm swing and increased tone on the right). The fact that he seems to have constitutional symptoms of weight loss and has risk factors for an HIV infection narrows the differential diagnosis significantly. This individual is most likely now HIV positive. This is based on the fact that he has been experiencing weight loss and has continued to participate in behavior placing him at high risk for HIV infection. Primary central nervous system (CNS) lymphoma, syphilitic gummas, tuberculomas, abscesses, neurocysticercosis, or metastatic brain tumors should be considered in the differential diagnosis. The presentation of headache, weight loss, generalized tonic-clonic seizures, and a focal neurologic examination suggests an intracranial lesion. An individual who is young and HIV positive should be evaluated for toxoplasmosis, primary CNS lymphoma, syphilitic gummas, tuberculomas, and brain abscesses. A CT scan of the head with and without contrast usually confirms the clinical suspicion but cannot differentiate each entity. Serologic studies in addition to CSF studies will help best determine the diagnosis. Besides the diagnostic tests described previously, other CSF studies include protein, glucose, cell count with differential, Gram stain, cytology, and Venereal Disease Research Laboratory (VDRL) testing. Other serologic studies include chemistry 20, complete blood count (CBC), HIV and CD4 count, erythrocyte sedimentation rate (ESR), rapid plasma reagin (RPR), and international normalized ratio (INR).

APPROACH TO:

Infections in Immunocompromised Hosts: Toxoplasmosis                                       

DEFINITIONS

GENERALIZED TONIC-CLONIC SEIZURE: It is often referred to as a grand mal seizure and involves loss of consciousness, violent muscle contractions, and rigidity.

FOLINIC ACID: The reduced form of folic acid that does not require reduction reaction by enzyme for activation.

RADICULOMYELOPATHY: A process affecting the nerve root and spinal cord.

RING-ENHANCING LESION: A lesion that shows peripheral enhancement with central hypodensity on CT imaging after IV contrast is administered, unlike other lesions that have uniform/homogeneous enhancement.

CLINICAL APPROACH

Toxoplasmosis is caused by the single-celled parasite, T. gondii, which is found throughout the world. It was discovered in 1908 in the gondi, a small rat-like animal from North Africa, and causes CNS toxoplasmosis in immunocompromised hosts. Toxoplasmosis has multiple hosts including humans, cats, and other warm-blooded animals. Toxoplasmosis is a common opportunistic infection in the HIV population. In fact, it is the leading cause of focal CNS disease in AIDS patients and is most frequently seen during the later phases of the disease. It is a fairly common infection, with approximately 33% of all humans having come in contact with this parasite during their lifetime. In immunocompetent adults, exposure to toxoplasmosis is asymptomatic; however, in immunocompromised patients, it can lead to severe disease and death. Toxoplasmosis acquired in pregnancy can cause various congenital anomalies in the fetus including hydrocephalus, intracerebral calcification, retardation, chorioretinitis, hearing loss, and even death.

Toxoplasmosis is frequently seen in advanced AIDS when the CD4+ counts are less than 200 cells/mm3. Up to 5% of patients initially diagnosed with AIDS in the United States will present with toxoplasmosis. Fortunately, the incidence of toxoplasmosis has significantly declined because of the use of highly active antiretroviral therapy (HAART). In Africa and Europe as many as 50% of patients with AIDS will develop CNS toxoplasmosis.

TRANSMISSION

There are three primary ways of transmission: by ingesting uncooked meat containing cysts, ingesting food and water contaminated with oocysts from infected cat feces, and by vertical transmission. The parasite can also be transmitted by transplantation of infected organs and blood transfusions. Although CNS toxoplasmosis occasionally results from a primary infection, it is more commonly caused by hematogenous spread of a previous infection.

Clinical Presentation and Diagnosis

The most common clinical presentation in HIV-infected patients is encephalitis as a result of multiple brain lesions (Table 31–1). Usually, the patient experiences a deterioration in mentation over days to weeks, including headaches, seizures, or cognitive impairment; motor or sensory deficits can also be seen. T. gondii can also affect other organs such as the eyes or lungs.

Diagnostic studies used to diagnose CNS toxoplasmosis include T. gondii IgG and IgM titers. An IgM antibody response is associated with newly acquired toxoplasmosis. However, antibody levels can be very low in AIDS patients. It has been reported that up to 22% of patients diagnosed with toxoplasmosis by histologic confirmation had absent antibody levels. If there are no signs of increased intracranial pressure, then a lumbar puncture may be obtained. CSF studies consistently show an elevated protein level. There is a great degree of variability when it comes to other CSF studies. PCR for T. gondii in CSF has moderate sensitivity and high specificity.

The typical findings on CT scan of the brain are single or multiple hypodense lesions in the white matter and occasionally in the basal ganglia with mass effect. Lesions are usually ring enhancing. Typically, patients will present with multiple rather than solitary lesions (Figure 31–1). In fact, a solitary lesion favors CNS lymphoma over toxoplasmosis.

Brain biopsy that reveals the organism should only be performed if there is no response to empiric treatment within 2 weeks or if there is a solitary lesion and negative serologic studies. Microscopic examination is notable if it shows lymphocytic vasculitis, microglial nodules, and astroglial nodules. Cases that show marked increased intracranial pressure and herniation are best handled with the aid of neurosurgeons.

Figure 31–1. CT brain image with ring-enhancing toxoplasmosis. (Reproduced, with permission, from Roos KL. Principles of Neurologic Infectious Diseases. New York, NY: McGraw-Hill; 2005:80.)

TREATMENT

The main treatment for CNS toxoplasmosis consists of pyrimethamine at a dose of 100 mg orally twice a day on the first day followed by 25 to 100 mg/d, usually continued for 6 weeks. Because of its selective activity against dihydrofolate reductase, it is imperative that folic acid be given concomitantly. This is often in the form of folinic acid. Sulfadiazine, which acts synergistically with pyrimethamine, should be given concomitantly at a dose of 1 to 2 g orally four times a day. If there is significant cerebral edema, corticosteroids such as dexamethasone (Decadron) should be given. Almost 75% of patients will improve within 1 week of receiving antibiotic therapy. The prognosis for full recovery is guarded, as there may be frequent relapses.

Prophylaxis

Trimethoprim/sulfamethoxazole is effective prophylaxis against T. gondii and is indicated for HIV-infected individuals with CD4 counts less than 200 cells/mm3. Precautions include cooking meats completely, hygiene when handling uncooked or undercooked meat, and avoiding exposure to cat feces, such as cleaning litter boxes.

CASE CORRELATION

• See also Case 30 (Tabes Dorsalis)

COMPREHENSION QUESTIONS

31.1 A 22-year-old man is suspected to be infected by T. gondii. In which of the following routes is he most likely to have been infected?

A. Ingesting uncooked vegetables

B. Congenital

C. Fecal-oral route

D. Inhalation of spores

31.2 A 34-year-old HIV-infected man is being evaluated by his physician. His findings are suspicious for CNS toxoplasmosis. Which of the following clinical feature would support that diagnosis?

A. Bladder retention

B. Aortic dilation

C. Argyll Robertson pupil

D. Hemiparesis

31.3 Which of the following is true regarding CNS toxoplasmosis?

A. Brain biopsy is the only reliable method of diagnosis.

B. It is frequently seen in early cases of AIDS.

C. Treatment consists of penicillin.

D. Multiple ring-enhancing lesions as opposed to solitary lesions are suggestive of CNS toxoplasmosis.

ANSWERS

31.1 C. Spores are not part of the life cycle of T. gondii; instead, cysts can be spread via airborne contact. The documented routes of being infected by toxoplasmosis include ingesting uncooked or undercooked meats, vertical transmission (congenital) infection, and the fecal-oral route. Ingestion of uncooked meat (especially pork, lamb, and venison) is much more common than uncooked vegetables.

31.2 D. Only 10% to 20% of toxoplasmosis-infected patients are symptomatic; however, immunocompromised patients have up to a 50% incidence of CNS involvement. The most common manifestations are seizures, cranial nerve defects, altered mental status, headache, and focal neurologic deficits such as hemiparesis. Argyll Robertson pupil has not been reported with CNS toxoplasmosis. Bladder incontinence, although uncommon, is part of an underlying myelopathy. Aortic root dilation is seen in syphilis but not toxoplasmosis.

31.3 D. Brain biopsies are deferred unless patients are not responsive to empiric therapy or if serologic studies are negative, and there is a solitary lesion on imaging studies.

    CLINICAL PEARLS    

▶ Imaging studies suggestive of CNS toxoplasmosis show multiple ring-enhancing lesions as opposed to a solitary ring-enhancing lesion, which is more suggestive of CNS lymphoma. ▶ The diagnosis of CNS toxoplasmosis can be made by positive serologic studies, although these may be undetectable in patients with AIDS. ▶ One-fourth to one-half of the world’s population is infected (most are asymptomatic), and infection is most common in places with warm, moist climates. ▶ Infection in the unborn child, called congenital toxoplasmosis, is the result of an acute, usually asymptomatic infection acquired by the mother in pregnancy and transmitted in utero.

REFERENCES

Agarwal A, Banderudrappagari R. Intracranial lesion with fever and headaches. Toxoplasmic encephalitis. Am Fam Physician. 2013;87(12):877-879. 

Garcia LS, Bruckner DA. Diagnostic Medical Parasitology. 3rd ed. Washington, DC: American Society of Microbiology; 1997:111-121; 423-424; 577-589. 

Jones JL, Kruszon-Moran D, Wilson M, McQuillan G, Navin T, McAuley JB. Toxoplasma gondii infection in the United States: seroprevalence and risk factors. Am J Epidemiol. 2001;154:357-365. 

Remington JS, Thulliez P, Montoya JG. Recent developments for diagnosis of toxoplasmosis. J Clin Microbiol. 2004;42(3):941-945.

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