Leighton P. Mark

Heterogeneity in 1H-MRS profiles of presymptomatic and early manifest Huntington's disease

OBJECTIVE To evaluate (1)H-MRS profiles of the putamen in presymptomatic and manifest Huntingtons disease (HD) patients for spectroscopic markers that are reliable, consistent signs of early pathology and to look for hemispheric differences as signs of use activation in an accelerated degradative process of the dominant hemisphere. METHODS A short echo time Point RESolved Spectroscopy (PRESS) spectroscopic imaging study was performed at low field (0.5 Tesla, T) on 27 right-handed patients (17 presymptomatic gene carriers and 10 manifest patients of less than 3 years from clinical onset) and 10 right-handed normal volunteers. Spectra from individual voxels (0.56 cm(3)) in the putamen were selected for analysis. Resonance areas of peaks were normalized to water as a concentration standard. Interhemispheric comparisons were made in individuals in all three groups to look for hemispheric differences. RESULTS Two presymptomatic patients showed normal spectra but all other HD patients displayed some combination of reduced N-acetylaspartate (NAA), enhanced glutamate/glutamine (Glx) activity, and lactate (Lac) elevations or reduced creatine (Cr). Rather than showing any one metabolite as pathognomonic of early change, spectroscopic profiles showed heterogeneity between HD patients. Low creatine was common in the presymptomatic but not in the manifest group. Hemispheric ratios of abnormal metabolites showed lower values of NAA and Glx in the dominant hemisphere in all three groups but values of creatine were selectively lower in the dominant hemisphere of only the presymptomatic patients. Lac was elevated in both hemispheres but less so in the dominant hemisphere in all HD patients. CONCLUSIONS (1)H-MRS profiles from the putamen of presymptomatic and manifest patients reflect heterogeneity in pathophysiology. With the possible exception of low creatine in presymptomatic patients (1)H-MRS spectra are not suggestive of hemispheric differences supportive of an overall accelerated degradative process in the dominant hemisphere.

Cortical activation response to acoustic echo planar scanner noise.

PURPOSE Our goal was to determine the distribution of auditory and language cortex activation in response to acoustic echo planar scanner noise with functional MRI (fMRI). METHOD Acoustic scanner noise and spoken text, reproduced on high output cassette tape, were separately delivered at equivalent intensities to six normal hearing adult volunteers through earphones during fMRI data acquisition. In nine other subjects, taped scanner noise was delivered in five successive iterations of the task to assess the consistency of cortical activation to the noise stimulus. Gyri of the auditory and language system were divided into 10 different subregions for analysis of cortical activation. The number of activated pixels and proportion of volunteers activating each cortical subregion were determined using a cross-correlation analysis. RESULTS Cortical activation to taped acoustic scanner noise was present within the transverse temporal gyrus (primary auditory cortex) in all subjects, but activation was highly variable between subjects in auditory association and language relevant cortex. Auditory association cortex activation was seen in the planum polari, planum temporali, and middle temporal gyrus/superior temporal sulcus regions in one-half to two-thirds of the volunteers. There was no significant difference in the distribution of cortical activation within individual subjects across five successive iterations of the scanner noise task. Listening to spoken text consistently activated primary and association auditory cortex bilaterally as well as language relevant cortex in some cases. The mean number of activated pixels was significantly greater for text listening than acoustic scanner noise in auditory association and language relevant cortical subregions (p < 0.01), although the distribution of activity was similar between the two tasks. CONCLUSION This preliminary investigation suggests that the complex sounds produced by the echo planar pulse sequence can activate relatively large regions of auditory and language cortex bilaterally, with the extent of activation outside the primary auditory cortex being variable between subjects. However, the distribution of activation within individual subjects was relatively constant across several iterations of the scanner noise stimulus.

Magnetization transfer imaging of skeletal muscle in autosomal recessive limb girdle muscular dystrophy.

PURPOSE The purpose of this work was to characterize magnetization transfer (MT) contrast of skeletal muscles in limb girdle muscular dystrophy (LGMD). METHOD The calf muscles of five LGMD patients and 10 normal volunteers were imaged with an off-resonance MT suppression pulse applied to T1-weighted images. MT suppression ratios were calculated for anterior tibialis, posterior tibialis, soleus, and gastrocnemius muscles in the LGMD and control groups. The relationship between MT of individual muscles and the duration of LGMD symptoms was determined. RESULTS Strong MT contrast was observed in normal calf muscles, with mean (+/-SD) suppression ratios ranging from 37.9% (+/-3.0) to 41.1% (+/-2.1). In diseased muscle, MT signal suppression ranged from 11 to 38%, demonstrating an inverse relationship between symptom duration and suppression ratios. MT contrast in the LGMD patients, as a reflection of muscle tissue integrity, was preserved in posterior or anterior tibialis, soleus, and gastrocnemius muscles, respectively. Suppression ratios were dramatically reduced in muscles with gross fatty infiltration but also were reduced in muscle tissues without visual evidence of fatty infiltration. CONCLUSION MT imaging provides a quantitative measure of pathologic changes occurring within the skeletal muscles of patients with LGMD relative to normal and may be useful in evaluating disease extent, progression, and response to new therapies as they become available.

Acoustic echoplanar scanner noise and pure tone hearing thresholds: The effects of sequence repetition times and acoustic noise rates

PURPOSE Our goal was to determine the effects of acoustic echoplanar scanner noise on pure tone hearing thresholds in normal volunteers and to determine the influence of echoplanar sequence repetition time on threshold effects. METHOD With use of a calibrated audiometer, pure tones ranging from 125 to 8,000 Hz were delivered monaurally to 10 normal-hearing volunteers in a quiet MR scanner suite and in the presence of acoustic scanner noise produced by three separate single shot blipped echoplanar pulse sequences varying only in repetition time (TR = 1,000, 2,000, or 3,000 ms), with all other parameters including the number of slices held constant. The magnitude of noise-induced threshold changes and the slopes of the threshold curves produced by each of the three echoplanar pulse sequences were then analyzed using multiple comparisons and a least significant difference method. The shapes of the threshold curves produced in each background state were best fit using a quadratic effect for frequency in a mixed effects linear model and compared using F test statistics. RESULTS All of the volunteers demonstrated entirely normal hearing thresholds throughout the full range of tonal frequencies tested (< 25 dB) when no acoustic scanner noise was present in the scanner suite. Pure tone hearing thresholds significantly increased (p < 0.01) in the presence of acoustic scanner noise, with the magnitude of change inversely proportional to the repetition time and therefore the rate of periodic noise production by the echoplanar sequence used. The shape of the threshold curve in the presence of noise produced by the 1,000 ms TR sequence was not equivalent across the frequency spectrum tested but had a quadratic distribution with peak effects at 750-2,000 Hz. As the repetition time was increased and the periodic noise rate decreased, the magnitude of the noise-induced threshold changes significantly lessened (p < 0.01) and the quadratic distributions of the threshold curves changed significantly (p < 0.01), tending toward a more planar configuration. CONCLUSION Background acoustic echoplanar scanner noise can significantly increase pure tone thresholds in the optimal frequency hearing range (125-8,000 Hz). However, the threshold effects are not equivalent across the frequency spectrum, and the magnitude of threshold changes is dependent on the rate at which periodic acoustic scanner noises are produced for a given sequence repetition time.

Rosai-Dorman Disease Causing Cervical Myelopathy

STUDY DESIGN A case report of a rare disease entity and review of the literature. OBJECTIVES To illustrate the occurrence of an unusual disease affecting the spine and spinal canal. SUMMARY OF BACKGROUND DATA Rosai-Dorman disease is considered an idiopathic benign lymphoproliferative disease that typically occurs in the earlier decades of life. The usual manifestation is painless massive cervical lymphadenopathy, although involvement of many extra nodal sites is common. This case illustrates Rosai-Dorman disease occurring in an elderly man with myelopathy and mass lesions of the cervical, thoracic, and lumbar spinal canal without typical lymphadenopathy.- METHODS Case report illustrating clinical presentation as well as radiographic and pathologic findings, including comparisons to cases previously reported. RESULTS Surgical decompression with incomplete resection of the lesion was performed, providing diagnosis and treatment guidance. The patient experienced significant neurologic improvement of myelopathy. CONCLUSIONS Recognizing clinical and laboratory features of this disease may permit earlier diagnosis and limit or avoid surgical intervention in some cases.

MR-spectroscopic findings in juvenile-onset Huntington's disease.

Seven HD gene positive individuals under the age of 21 years are described with clinical examination and proton‐MR‐spectroscopy (1H‐MRS) profiles of the putamen. Despite clinical variability, the predominate 1H‐MRS abnormality is elevated glutamate, expressed well beyond the confines of the basal ganglia, and low striatal creatine.

Proton magnetic resonance spectroscopy of the hippocampus in patients with mild cognitive impairment: a pilot study.

Objective: To assess the brain metabolites in the hippocampus of patients with mild cognitive impairment (MCI) using proton magnetic resonance spectroscopy at 0.5 T. Methods: Absolute concentrations and ratios to creatine of N-acetyl aspartate, myoinositol, glutamate + glutamine, and choline were measured in the right and left hippocampus of 5 MCI patients and 5 control subjects. Results: In MCI subjects, reduced N-acetyl aspartate was found in the right hippocampus (P = 0.01), and increased myoinositol was found in the left hippocampus (P = 0.02). Myoinositol/N-acetyl aspartate ratios were higher in the right (P = 0.03) and left (P = 0.01) hippocampus of MCI subjects. No significant difference in the concentration of glutamate + glutamine was observed between the control and MCI groups. Conclusions: An increase in myoinositol and a decrease in N-acetyl aspartate may be observed in the preclinical stages of dementia. Ratio measurements of these metabolites may serve as a biomarker for MCI.

Gradient recalled echo MR imaging of superior sagittal sinus occlusion

SummaryWith T1-weighted gradient recalled echo (GRE) MR images and flow compensation, we studied the superior sagittal sinus in 3 normal volunteers and 3 patients with sinus occlusion. In these images, sites of patency of the superior sagittal sinus were identified due to the high signal intensity of the normal sinus. Tumor invading the sinus was nearly isointense with cerebral gray matter. T1-weighted GRE imaging proves to be an effective technique to evaluate sinus blood flow.

Lacrimal collecting system lymphomas: Integration of magnetic resonance imaging and therapeutic irradiation

Lymphomas arising within the lacrimal collecting system are rare tumours and unusual causes of lacrimal obstructive symptoms. The presentation, diagnosis, and treatment of this disease in five patients are described, as well as a review of the existing literature. Emphasized in this series is the efficacy of magnetic resonance imaging of these presentations and the importance of irradiation in their treatment.

Single photon emission computerized tomography (SPECT) in detecting neurodegeneration in Huntington's disease

Single photon emission computerized tomography (SPECT) studies were performed on 34 manifest Huntingtons disease (HD) patients at various stages of clinical pathology ranging from early chorea to late dystonia with or without signs of dementia and 12 pre-symptomatic patients with abnormal terminal CAG expansions. Thirty HD patients with obvious clinical signs and seven pre-symptomatic patients without signs or symptoms of HD displayed selective caudate hypoperfusion by direct visual inspection. Such qualitative, selective striatal hypoperfusion patterns can be indicative of early and persistent metabolic changes in striatal neuropathology. SPECT studies can be useful in documenting early pre-clinical changes in patients with abnormal terminal CAG expansions and in confirming the presence of caudate pathology in patients with clinical signs of HD.