R.J.S. Chinn

A longitudinal study of anticardiolipin antibody levels and cognitive functioning in systemic lupus erythematosus

OBJECTIVE To determine the relationship between persistently raised anticardiolipin antibody (aCL) levels and neuropsychological performance in patients with systemic lupus erythematosus (SLE). METHODS Forty-five patients with SLE underwent a detailed neuropsychological assessment on 2 occasions 12-18 months apart. Serum samples stored since the time of previous assessments as well as samples obtained 6 months to 2 years before the first neuropsychological assessment were tested for IgG aCL levels. Patients were divided into 4 groups according to the number of times their aCL levels were elevated (never, once, twice, 3 times). A wide-ranging battery of new neuropsychological tests was utilized, and the results were compared with double-stranded DNA (dsDNA) antibody levels, C3 levels, and results of magnetic resonance imaging (MRI). RESULTS Analysis of variance revealed that the group with persistently elevated aCL levels performed less well than the other groups. At the first neuropsychological assessment, poorer performance by this group was noted for letter cancellation (P = 0.02), trail making task B (P = 0.04), and digit span (P = 0.03). At the second assessment, letter cancellation (P = 0.01), trail making task A (P = 0.03), trail making task B (P = 0.01), word fluency (P = 0.01), and reaction time (P = 0.05) were impaired. In contrast, no significant differences in neuropsychological test results were identified with respect to DNA antibody or C3 levels. MRI abnormalities were associated with both persistent elevation of aCL levels and low C3 levels. CONCLUSION Levels of IgG aCL that were persistently elevated over a 2-3-year period (as opposed to never or occasionally elevated) were associated with significantly poorer performance in cognitive function by patients with SLE. Tasks requiring speed of attention and concentration appear to be particularly affected.

Proton MRS and quantitative MRI assessment of the short term neurological response to antiretroviral therapy in AIDS

OBJECTIVE To investigate MRI and proton spectroscopy changes in five patients with HIV associated dementia complex (HADC) treated with antiretroviral therapy. METHODS Three markers were evaluated: (1) CSF/intracranial volume ratio; (2) T2 weighted signal ratio between parieto-occipital white and subcortical grey matter; and (3) metabolite ratios from long echo time (TE=135 ms) single voxel proton spectra of parieto-occipital white matter. RESULTS Spectroscopic changes indicated initial increases in N-acetyl/(N-acetyl + choline + creatine) ratio (NA/(NA+ Cho+Cr)) and progression of atrophy after initiation of antiretroviral therapy in four of five patients. When the neurological status of the patients subsequently deteriorated (two of five patients), the NA/(NA+Cho+Cr) ratio also declined. CONCLUSIONS spectroscopic changes mirror reversible neuronal dysfunction. These objective, non-invasive techniques may be used for monitoring the neurological effects of antiretroviral drug therapy in patients with HADC.

Cerebral proton magnetic resonance spectroscopy in asymptomatic HIV infection.

Objective:To determine whether proton magnetic resonance spectroscopy (MRS) demonstrates central nervous system abnormalities in asymptomatic HIV-1-infected individuals. Design:Both prospective and retrospective cross-sectional analyses of MRS in asymptomatic HIV-infected individuals. Setting:Two specialist HIV/AIDS outpatient facilities in London. Participants:Eighty-four HIV-1-seropositive asymptomatic men; 29 HIV-1 antibody-negative homosexual men at high-risk for HIV infection and 48 HIV-1 antibody-negative men at low-risk for HIV infection as controls. Main outcome measures:Single voxel, gradient-localized proton MRS performed at 1.5 T with a 135 msec echo-time and 1600 msec repeat-time in an 8 ml volume of interest positioned in the parieto-occipital white matter. Spectroscopic results were expressed as ratios between the areas under the N-acetyl (NA), creatine (Cr) and choline (Cho) resonance peaks. Results:There were no differences between those controls at high and those at low-risk for HIV infection. Comparing the combined control groups with the asymptomatic seropositive patients there were statistically significant differences in NA/Cho, NA/Cr (both P< 0.05) and NA/(NA + Cho + Cr) (P < 0.01). Conclusion:Abnormalities in cerebral biochemistry may be demonstrated by proton MRS during asymptomatic HIV-1 infection.

Comparison of magnetic resonance imaging with neuropathological findings in the diagnosis of HIV and CMV associated CNS disease in AIDS.

OBJECTIVES: To compare the results of clinical assessment and MRI with neuropathological findings in the diagnosis of HIV and cytomegalovirus (CMV) associated CNS disease. METHODS: A retrospective study of 35 patients infected with HIV who were examined at necropsy between four and 70 (median 20) days after neurological assessment and MRI. RESULTS: Of the 35 patients, 19 had diffuse white matter hyperintensity on T2 weighted MRI, six of whom also had focal lesions. Nine other patients had focal white matter lesions and seven had changes in cortical atrophy only. Necropsy in the 19 with diffuse white matter hyperintensity showed HIV leukoencephalopathy (HIVLEP) with encephalitis in 10, CMV encephalitis in three, both HIVLEP/HIV encephalitis and CMV encephalitis in one, lymphoma in three, and non-specific inflammation in two. Necropsy in the 16 other patients without diffuse white matter hyperintensity showed CMV encephalitis in six, HIV encephalitis (without HIVLEP) in two, CMV encephalitis and HIVLEP/HIV encephalitis in one, non-HIV associated abnormalities in five, herpes simplex encephalitis in one, and lymphoma in one. CMV DNA was detected in CSF of five of seven patients with CMV encephalitis and in two of two with CMV associated polyradiculopathy but without CMV encephalitis. Diffuse white matter hyperintensity on MRI had a sensitivity of 100%, a specificity of 66.6%, and a positive predictive value of 58% for diagnosis of HIVLEP. CONCLUSION: Diffuse white matter hyperintensity on MRI can be due to either HIV or CMV associated pathology or non-specific abnormalities.

Cerebral volumes and spectroscopic proton metabolites on MR: Is sex important?

One of the factors that may influence the selection of appropriate controls for MR studies of the brain is gender. This study compared calculated intracranial volumes and proton spectroscopic metabolite ratios obtained from male and female volunteers. Thirty-two males (mean age = 36; range = 30-53 yr) and 19 females (mean age = 39; range = 26-53 yr) underwent investigation at 1.5T. Brain, cerebrospinal fluid (CSF), and intracranial (ICV = brain + CSF) volumes were measured by the CLASS technique on data acquired using an axial dual spin-echo imaging sequence (TE = 20/90 ms, TR = 3500 ms). Proton spectra (TE = 135 ms, TR = 1600 ms) were acquired from an 8 ml cubic region placed in parieto-occipital white matter. The mean male and female brain, CSF and ICV were significantly different (p < .005). However, the mean CSF/ICV ratios of the two groups were not significantly different. The N-acetyl/choline and choline/creatine metabolite ratios of the two groups were significantly different (p < .05). When comparing proton metabolite ratios and absolute brain volumes between groups, gender is an important factor. CSF/ ICV ratios do not appear to depend on gender.

Short echo time proton spectroscopy of the brain in HIV infection/AIDS

Short echo time proton spectra have been acquired from the brains of 30 male homosexual Acquired Immunodeficiency Syndrome (AIDS) patients and 12 age-matched control subjects on a 1.5 T MR system. The acquisition protocol used stimulated acquisition voxel localisation with a voxel size of 8 ml and repeat, echo, and mixing times of 5000, 20, and 30 ms, respectively. A single 25.6-ms Gaussian water suppression pulse was used with 128 spectral acquisitions and the data were eddy current corrected using a water reference. Baseline-corrected spectra were nonlinearly least squares fitted to a model function consisting of Gaussian functions representing the major metabolites reported in short echo proton spectra. Results indicate that the N-acetyl/creatine (NA/Cr) ratio is significantly reduced by 20% in AIDS patients [NA/Cr = 1.91 (0.51)] compared to control subjects [NA/Cr = 2.37 (0.25)] at short echo times.

Cerebral magnetic resonance relaxometry in HIV infection

A prospective, cross-sectional study was designed to determine the magnetic resonance relaxation times of cerebral white matter in human immunodeficiency virus (HIV) infected individuals. T1 and T2 were estimated at 1.5 T using four-point methods. Seventy-five HIV-1 seropositive subjects, 48 seronegative blood donors, and 17 seronegative homosexual men were studied. Associations between relaxometry and clinical classification, neurological status, immunological status, and qualitative MRI were investigated. Statistically significant differences in white matter T1 relaxation time were found comparing low-risk control and AIDS groups (p < .005), seropositive subjects with neurological signs and those without (p < .005), and subjects with low (CD4 < or = 200 x 10(6)/l) and high (CD4 > 200 x 10(6)/1) CD4 cell counts (p < .05). These findings add to the body of information that reveals no HIV-related change in the brain before the onset of symptomatic immunosuppression and go someway to validating the previous visually rated, qualitative findings. Statistically significant difference in white matter T2 relaxation time were also found comparing the two control groups (p < .005) highlighting the need for appropriate controls.

Internuclear ophthalmoplegia following African tick bite fever

A 29-year-old previously healthy man presented with a diarrhoeal illness, headache and malaise while in South Africa where he had been living for 6 months. Two weeks later, he developed diplopia and incoordination. Neurological examination revealed a left internuclear ophthalmoplegia (INO) and limb ataxia. The rest of his cranial nerve examination was normal as was tone, power, reflexes and sensation in his limbs. His general systemic examination was unremarkable; in particular, there were no skin lesions. …

Sub-cortical White-grey Matter Contrast on MRI as a Quantitative Marker of Diffuse HIV-related Parenchymal Abnormality

White matter change occurs in human immunodeficiency virus (HIV) encephalopathy, which may be difficult to assess subjectively especially in the early stages of disease. This study applies a quantitative approach to the assessment of this finding. Sixty-three HIV seropositive subjects, 47 seronegative blood donors and 17 seronegative homosexual men underwent axial T2 weighted MRI of the brain at 1.5T. Quantitative analysis was performed by obtaining the pixel contrast between parieto-occipital white matter and head of caudate grey matter (Cwg). Highest values of Cwg were found in a subgroup of subjects with AIDS who had diffuse/patchy white matter abnormalities and atrophy on qualitative image assessment. Statistically significant differences were found in Cwg between subjects with high (> or = 200 x 10(6)/I) and low (< 200 x 10(6)/I) CD4 lymphocyte counts (P < 0.05) and between subjects with and without HIV-1 associated cognitive/motor complex (P < 0.05). This technique provides an objective measure of diffuse HIV-related parenchymal abnormality seen on T2 weighted MRI.

Subacute combined degeneration of the spinal cord due to vitamin B12 deficiency

A previously healthy 82-year-old lady presented with abnormal sensation in her fingers which she described as ‘feeling like bananas’. There was an additional history of deteriorating handwriting and a sense of imbalance when walking dating back 6 months. She obtained a score of 26 out of 30 on the mini mental state examination. She had gait ataxia, being unable to perform tandem gait. There was no convincing pseudoathetosis of the outstretched hands. She had slow, clumsy fine finger movements and her diary entries had become progressively illegible. Proprioception was abnormal in the toes and vibration sense was lost to …