M. Judith Donovan Post

A pilot study of cidofovir for progressive multifocal leukoencephalopathy in AIDS

ObjectiveTo assess the safety, tolerability and effect of cidofovir for HIV-1 associated progressive multifocal leukoencephalopathy. DesignProspective, open-label study in nine AIDS Clinical Trials Units. Patients and methodsTwenty-four HIV-1-infected individuals, with neuroimaging and clinical findings consistent with PML, and symptoms for 90 days or less, whose diagnosis was confirmed by the detection of JC virus DNA in the cerebrospinal fluid or brain biopsy, received cidofovir 5 mg/kg intravenously at baseline and 1 week, followed by infusions every 2 weeks with the dose adjusted for renal function. Follow-up continued to 24 weeks. The safety of cidofovir and changes in neurological examination scores between baseline and week 8 were assessed. ResultsSeventeen subjects were receiving potent antiretroviral agents. Survival at 12 weeks was 54%. The CD4 cell count at entry was significantly associated with survival (P = 0.02). Five subjects discontinued treatment because of toxicity: a 50% or greater decrease in intraocular pressure in either eye in four, and proteinuria in one. Overall, magnetic resonance imaging abnormalities and neurological examination scores worsened. Only two subjects experienced a 25% or greater improvement in neurological examination scores at week 8, which were significantly better in subjects with HIV-1-RNA levels of 500 copies/ml or less at entry compared with those with HIV-1-RNA levels over 500 copies/ml (P = 0.05). ConclusionCidofovir did not improve neurological examination scores at week 8. However, such scores were significantly better in subjects who entered with suppressed plasma HIV-1-RNA levels, which could be the result of control of HIV-1 infection itself or cidofovir.

Analysis of the utility of diffusion-weighted MRI and apparent diffusion coefficient values in distinguishing central nervous system toxoplasmosis from lymphoma

IntroductionToxoplasmosis and lymphoma are common lesions of the central nervous system in patients with AIDS. It is often difficult to distinguish between these lesions both clinically and radiographically. Previous research has demonstrated restricted diffusion within cerebral lymphomas and bacterial abscesses. However, little work has been done to evaluate the diffusion characteristics of toxoplasmosis lesions. This study was designed to explore further the utility of diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps and values in making the distinction between toxoplasmosis and lymphoma.MethodsThe magnetic resonance imaging (MRI) studies of 36 patients, including 22 with toxoplasmosis (all of whom had AIDS) and 14 with lymphoma (8 of whom had AIDS), at two institutions were reviewed retrospectively. The characteristics of the lesions on DWI were evaluated, and the ADC ratios of the lesions were calculated and compared.ResultsThere was significant overlap of the ADC ratios of toxoplasma and lymphoma, most notably in the intermediate (1.0–1.6) range. There was variability in ADC ratios even among different lesions in the same patient. In only a minority of the lymphoma patients were the ADC ratios low enough to suggest the correct diagnosis.ConclusionOur study showed that toxoplasmosis exhibits a wide spectrum of diffusion characteristics with ADC ratios which have significant overlap with those of lymphoma. Therefore, in the majority of patients, ADC ratios are not definitive in making the distinction between toxoplasmosis and lymphoma.

MR of Toxoplasma encephalitis : Signal characteristics on T2-weighted images and pathologic correlation

PURPOSE Our goal was to determine if there are any T2-weighted MR signal characteristics of Toxoplasma encephalitis that might be useful in diagnosis and/or in gauging the effectiveness of medical therapy. METHOD We retrospectively analyzed the MR, CT, thallium-201 SPECT brain scans, and medical records of 27 patients with medically proven (26) and biopsy proven (1) Toxoplasma encephalitis, supplemented by autopsy findings in 4 additional patients, 2 of whom had postmortem MR correlation. The neuropathologic literature was also reviewed. RESULTS Among the 27 patients, we discovered three distinct imaging patterns. Ten (37%) patients had predominantly T2-weighted hyperintense lesions and had been on medical therapy an average of 3 days (excluding one outlier). Ten (37%) patients had T2-weighted isointense lesions and had received medical therapy an average of 61 days. Seven (26%) patients had lesions with mixed signal on T2-weighted images and had been on treatment an average of 6 days. Analysis of autopsy material from the four additional patients revealed the presence of organizing abscesses in three and necrotizing encephalitis in one, while the patient who had a brain biopsy demonstrated both types of pathologic lesions. In both cases having postmortem MRI, organizing abscesses appeared isointense to hypointense on T2-weighted images. CONCLUSION There is a definite variation in the appearance of lesions of Toxoplasma encephalitis on T2-weighted images that precludes a definitive diagnosis based on signal characteristics alone. Pathologically, our data suggest that T2-weighted hyperintensity correlates with necrotizing encephalitis and T2-weighted isointensity with organizing abscesses. Furthermore, in patients on medical therapy the T2-weighted MR appearance may be a transition from hyperintensity to isointensity as a function of a positive response to antibiotic treatment, indicating that the signal change might be used to gauge the effectiveness of medical therapy.

Neuroimaging in the Brain in HIV-1–Infected Patients

The brain may be affected by a variety of abnormalities in association with HIV infection. Knowledge of these abnormalities and their characteristic imaging features is important to neuroradiologists for the detection, diagnosis, and initiation of appropriate treatment. This review attempts to describe the imaging findings associated with brain disorders in HIV-seropositive patients and the rationales for integrating neuroradiologic techniques.

Computed Tomographic Evaluation of the Cavernous Sinus

In evaluating over 300 patients with sellar and parasellar lesions, the computed tomographic (CT) appearance of the cavernous sinus was studied. Optimal visualization of the cavernous sinus was obtained with continuous contrast enhancement of both axial and coronal tomograms. The coronal projection and reformatted views provided imaging of the cranial nerves within the cavernous sinus. In addition to the physiologic CT appearance of the cavernous sinus, a variety of pathologic conditions are illustrated. CT criteria suggesting an abnormal cavernous sinus are: (1) asymmetry of size; (2) asymmetry of shape, particularly the lateral wall; and (3) focal areas of abnormal density within the sinus.

The radiographic recognition of two clinically elusive mass lesions of the cavernous sinus: Meningiomas and aneurysms

SummaryCavernous sinus syndromes secondary to chronic mass lesions, although a relatively rare cause of ophthalmoplegia, represent a distinct challenge in neuroradiologic diagnosis. Puzzling neuro-ophthalmologic signs and often subtle radiologic changes consistently lead to erroneous and delayed diagnoses as exemplified by a review of 20 patients; a correct clinical or radiographic diagnosis was initially not made in any individual.

Progressive cytomegalovirus encephalopathy following congenital infection in an infant with acquired immunodeficiency syndrome

Congenital central nervous system infection with cytomegalovirus (CMV) usually results in a nonprogressive encephalopathy. Ninety percent of patients with clinically apparent infections at birth have a permanent neurological disability. It has been suggested that some infants may have persistent infection manifested by progressive encephalopathy during infancy. In the present case, clinical and pathological findings suggest the reactivation of a prior intrauterine CMV infection in a child with human T-lymphotrophic virus type III (HTLV-III) infection. The presence of HTLV-III may have reduced the immune surveillance of this infant, allowing the CMV to reactivate.

Rare presentation of BK encephalitis in a child: imaging and pathological findings

Clinically apparent BK virus infections mostly involve the genitourinary system of immunocompromised patients, particularly those who have undergone renal or bone marrow transplantations. Central nervous system involvement is extremely rare. In this report, we describe the pathologic and MR findings of BK encephalitis in a child. Initial involvement of the brainstem and the cervicomedullary junction was noted that later rapidly progressed to involve other regions of the supratentorial brain parenchyma including the basal ganglia and the thalami as well as the cerebellum.

Leber congenital amaurosis in siblings with diffuse dysmyelination

Two brothers are described with the previously unrecognized combination of Leber amaurosis and abnormal myelin detected by magnetic resonance imaging. Both have evidence of delayed psychomotor development and one has autistic features. A possible relationship with infantile autism or a peroxisomal dysfunction syndrome is explored. No peroxisomal defect was found in these patients.

Computed tomography in gunshot wounds to the neck: Can we predict vascular injury?

The purpose of this study was to evaluate the ability of helical computed tomography (CT) to detect arterial injuries in gunshot wounds to the neck. In a blinded retrospective review, 54 helical CT scans of the cervical spine were evaluated for bullet/bone fragments, subcutaneous air, bullet path, hematoma, spine fractures, and pharyngoesophageal compromise. The distance of fragments to a major vessel was calculated. CT findings that correlated significantly with major arterial injury included the presence of fragments (bullet/bone) close to a major vessel (2.5 mm) and spine fractures. Visualizing fragments <5 mm from a vessel or a transcervical bullet trajectory predicted 12 of 13 major arterial injuries. We conclude that CT clearly depicts anatomic damage. Specific findings, such as the location of fragments and bullet trajectory adjacent to a vessel and spine fractures, indicate a higher probability of vascular damage, thus directing more definitive evaluation.