This is a 13-year-old AIDS patient with decreased mental state and incoordination, distal sensory polyneuropathy of legs and feet, hyporeflexia, and sensory ataxia with two enhancing lesions in right basal ganglia and left periventricular WM that are not responsive to anti-protozoals.

patient is older, otherwise good

* sensory neuropathy: peripheral nerve, dorsal root ganglia
* sensory ataxia: dorsal columns or peripheral nerve
* decreased mental state, incoordination: cerebrum

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We don’t know the duration of the neurological problems or their course, but we do know that the patient was HIV infected for at least 2 years, which predisposes him to fungal CNS infections and lymphomas.

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Primary CNS lymphoma of AIDS with paraneoplastic neuropathy

very good thought; I am not aware of paraneoplastic neuropathy occurring as a complication of Primary cns lymphoma whereas it certainly can occur with systemic lymphomas. The primary cns lymphomas are usually B cell type and these make antibodies.

Differential diagnosis:
* Infectious: toxoplasmosis, cryptococcosis, CMV
* AIDS complications causing neuropathy: AIDS neuropathy, AIDS cachexia with nutritional disturbances, vacuolar myelopathy of AIDS
* metastatic carcinoma

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* Brain MRI: lymphoma is usually periventricular; multiple lesions suggestive of lymphoma, but very difficult to distinguish from toxoplasmosis

* Epstein-Barr test in CSF: if positive, diagnostic of AIDS lymphoma (80% primary CNS lymphomas are associated with EBV)

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* in AIDS, rapid progression to death in most cases, even with treatment (3-month mean survival)
* complete disability -- support for family & loved ones
* in survivors, permanent neurological deficits are common
* treatment-related complications: steroid may make AIDS patients even more susceptible to infection. Radiation can induce secondary tumors. Chemotherapy is not indicated in AIDS patients because of its toxicity--regular follow-up care is needed.

good: note early in hiv infection patients tend to get neurological complications secondary to autoimmune processes whereas later in the disease when cd4 counts are low as in this case the neurological complications are often secondary to infections or tumor.

Primary CNS lymphomas arise from periventricular parenchymal blood vessels, thus accounting for their location. The severe immunosuppressed state of AIDS contributes to the formation of lymphoma by decreasing the usual surveillance function of the immune system against tumors. Polyneuropathy has been associated with lymphomas, with a loss of dorsal root ganglion neurons and an associated inflammatory reaction. Steroids can dramatically reduce tumor mass, but can further complicate AIDS because they add to immunosuppression. Chemotherapy is considered too stressful for AIDS patients, but has been shown to be effective in patients with a normal immune system. Radiotherapy is currently the treatment of choice for AIDS patients, with a mean survival of 3 months.

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The patient is a 31 year-old male, HIV + with T4:T8 ratio of less than .1, presented with a history of multiple opportunistic infections over 2 years, mental status change, weakness, and decreased coordination over at least 5 months. Physical exam revealed decreased DTR's, muscle atrophy, reduced vibratory sense, pos. Romberg, and lesions in right basal ganglia and cerebrum on CT scan.

good; also confusion

Cortex - mental status change (confusion, oriented 1x) Lethargy(dec. alertness) - reticular activating system.

LMN - dec. muscle tone and dec. DTR (NMJ, muscle, peripheral nerve). dec. vibratory sense, pos. Romberg, and difficult tandem gate - likely to be peripheral neuropathy rather than dorsal column lesion based on its distal pattern.

good; may be both peripheral n. (note areflexia) and posterior columns (note severity of sensory ataxia)

The course is unknown but is longer than 5 months - subacute or chronic process, indicating infection, tumor, or recurrent vascular accidents.

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Primary CNS lymphoma secondary to AIDS with underlying AIDS neuropathy and dementia.

Differential diagnosis: Mass lesion - toxoplasma abscess, metastatic Kaposi's sarcoma. Peripheral neuropathy - CMV neuropathy, Guillain-Barre, herpes zoster radiculopathy.

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Ventricular tap - pos. cytology in primary CNS lymphoma.

Biopsy of the R. cerebral mass - expect to see sleeves of primitive reticular cells extending outward from the blood vessels.

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Mass in the brain - hydrocephalus, herniation, metastasis of lymphoma (CT scan). AIDS - opportunistic infections, especially pneumonia (Chest x-ray and prophylactic treatment).

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CD-4 molecule is a high-affinity receptor for HIV, resulting in the selective infection of CD4+ T cells and macrophages. Extensive viral replication leads to CD4+ cell lysis and immunosuppression. Patients with AIDS have a high incidence of certain tumors. The basis of the increased risk of malignancy includes profound deficiency in T-cell immunity, dysregulated B-cell and monocytic functions, and multiple infections with viruses such as EBV and HPV. Especially immune deficiency is implicated as the central predisposing factor for primary CNS lymphoma; patients with CD4+ cell count below 50/ul incur an extremely high risk of AIDS-associated lymphoma. The pathogenesis of AIDS-associated lymphoma probably involves sustained polyclonal B-cell activation followed by the emergence of monoclonal B-cell population. Thus, it is critical to increase the CD4 count and reduce the viral load by giving anti-HIV medication in managing patients with AIDS-associated primary CNS lymphoma.

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Patient is a 31 y/o known HIV positive male presenting with new onset mental status changes and decreased coordination (time course not specified). Pt. has no other current complaints and has a hx of varied viral, bacterial, and fungal infections, consistent with AIDS.

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Physical Exam of the patient yielded non-focal results.
á Cortical involvement is suggested by the altered mental status changes and disorientation. Positive Romberg test (eyes closed) indicates a sensory ataxia, implicating damage of the dorsal columns or a proprioceptive defect. This sensory ataxia may also explain the patient's inability for tandem gait. However, the patient does not manifest any UMN signs indicating spinal cord damage.
á Muscle tone and power are normal, but decreased in bulk, most likely due to atrophy. (Note that the patient had complained of weakness, but the PE results showed normal power, indicating a normal motor function.) LMN lesion is ruled out on this basis.
á Loss of vibratory sensation again points to a possible dorsal column etiology, but may be due to a sensory neuropathy of large fibers as well. Loss of proprioception will lead to decreased coordination and ataxia.
á Absence of DTR's in the ankles with 1+ reflexes elsewhere is also suggestive of a peripheral neuropathy.

Conclusion: This patient most likely has more than one disease process occurring. He has diffuse cortical involvement, causing his altered mental status. In addn, he likely has a peripheral sensory neuropathy, causing a loss of vibratory sensation and proprioception, presenting as ataxia.

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á The patient's immune status as an AIDS patient, combined with the chronic, progressive nature of his disease suggests a degenerative or infectious process or cancer. It should be noted that the chronic progressive course refers to the patients course once admitted to the hospital. The actual onset of the altered mental status and decreased coordination is not ascertainable from the given history.

the question really asks how does the clinical course provide clues to the underlying pathogenesis. the answer is that the time course is not necessarily clear and that consequently it is not clear on the time course whether you are dealing with an acute process eg trauma or stroke, subacute course eg inflammatory process or tumor or a chronic process eg degenerative

á CT shows evidence of a rt. basal ganglia enhancing lesion. á Etiology of Rt. BG lesion- CNS Non-Hodgkins Lymphoma Alternative dx: Toxoplasmosis (typically occur in BG and are multiple lesions); Abscess (Tuberculoma, etc.)

good, your hypothesis is that the right basal ganglia lesion is responsible for the patient's presentation and that the nature of this lesion is that it might be a primary brain lymphoma.

á Etiology of mental changes Likely d/t edema from cortical lesion viewed on CT Alternative Dx: AIDS Dementia Complex comment: good á Etiology of peripheral neuropathy Degenerative sensory ataxic neuropathy Alternative dx: CMV Radiculopathy

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Of the varied neurological findings, the patient's most urgent pathology is clearly the brain lesion. MRI may be done to pick up any additional lesions not imaged with CT. This may help to distinguish betn. T. gondii and CNS lymphoma, as Toxoplasmosis often has multiple lesions, and lymphoma is typically a solitary lesion. Serology for T. gondii Ab titers is not reliable for confirmation, since 30% of infected pts will have negative titers. Brain biopsy will give the most definitive diagnosis, and should be attempted, especially since identification of lymphoma will direct treatment to radiation therapy, which has good success.

good; the reason the pathology is urgent to identify is because only by knowing the mechanism of disease in this patient can you be in a position to treat him (ie anti fungal meds if it is a fungal abscess, brain irradiation if it is a primary brain tumor)

á Death. The enhancing lesion of a CNS lymphoma will cause diffuse edema, and eventually lead to increased ICP, with further complications such as seizures or uncal herniation, and ultimately, a ceasing of respiration and autonomic function in general as the brain stem becomes affected.

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Once a diagnosis of lymphoma has been established, radiaion therapy can be initiated to stop/slow the abberant growth of the malignant cells. In this case, therapy can induce a remission, but death usually occures within 6 months.

ok; note the most important insight into the pathophysiology in this patient is to determine if it is a lymphoma or an infection as only by knowing this mechanism of disease (pathophysiology) can you treat the patient.

Also there are several possible reasons why patients with immunocompromise develop tumors; the immune system is designed to protect us against infections and tumors. Furthermore some opportunistic infections eg ebstein barr are known to induce B cell tumors, the usual type of primary cns lymphoma.

31 y.o. male AIDS patient with a hx of opportunistic infx presents iwht alterd LOC, generalized weakness and decreased coordination. Nonfocal physical exam reveals cachexia, lethargy with decreased sensory findings, hyporeflexia, ataxia and CT shows an enhancing lesion involving the right basal ganglia.

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Multifocal: dorsal column involvement, polyneuropathy, space occupying cerebral mass.

ok; note confusion may represent dysfunction of cortex or cortical connections;

Acute to subacute onset although not clear from history. AIDS is a chronic disease that invites opportunistic infx or certain neoplasms that could lead to symptoms. By itself, AIDS can cause dementia.

ok, course is unclear, ergo the process may be acute, subacute or chronic

Non-Hodgkin's lymphoma Ddx: toxoplasmosis, cryptococcosis,, AIDS related dementia, CMV, candidiasis

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Tissue biopsy: lymphoma or infectious organisms Lumbar tap: infectious organisms

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Weakened immune system: CBC showing decreased CD4 count Opportunistic infections: biopsies showing infectious organisms (bronchiolar lavage for infections affecting lungs--PCP, sputum culture--TB, lumbar tap for meningeal infx, cytopath for viral infx, molecular bio assays for viral infx) Neoplasms: skin bx for Kaposi's sarcoma, tissue bx for lymphomas Death

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HIV affects immune system and provides excellent opportunity for neoplasms to take root and flourish. The most common space occupuying lesions in AIDS patients are caused by Toxoplasmosis reactivation. Usually a two week trial of antibiotics with observation is attempted before more invasive measures are taken (like brain bx). Titers from blood are unreliable since positive titers are ubiquitous even among the general populous. Lymphomas in the CNS escape the weakened immune system if tumor compression of parenchymal tissue in brain leads to symptoms. Unfortunately, the interventions for the neoplasms are complicated by the immunocompromised status of the individual. Chemotherapy is considered taxing in AIDS patients, steroids which could reduce the tumor exacerbate the immunosuppression, radiation therapy is more likely to be the intervention of choice even though overall outcomes are poor as a complication of the underlying disease.

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