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Ron Kikinis

Publications and source records attributed to Ron Kikinis.

At least 19 recordsLinked to original sources

Anatomic and physiologic predictors of apnea severity in morbidly obese subjects.

STUDY OBJECTIVES: While obesity is the most common risk factor for the development of obstructive sleep apnea, the correlation between measures of obesity and apnea severity is only moderate. We thus attempted to identify anatomic and physiologic predictors of apnea severity. DESIGN: We combined a careful assessment of upper airway anatomy, upper airway physiology, and ventilatory control in a group of obese individuals to identify predictors of apnea severity. SETTING: Tertiary care academic medical center. PATIENTS: 14 morbidly obese subjects being evaluated for weight-reduction surgery. INTERVENTIONS: N/A MEASUREMENT AND RESULTS: We found no relationship between obesity (weight or body mass index) and apnea severity (respiratory disturbance index, RDI). However, those with severe apnea (RDI > 30) were found to have higher peak genioglossus EMG (GGEMG) (23.5 +/- 1.9 vs. 14.1 +/- 3.7 %max, p = 0.05) and greater airway collapsibility during pulses of negative pressure (7.6 +/- 0.9 vs. 4.4 -/+/-0.7 cmH2O, p =0.02). Airway collapsibility was significantly associated with RDI (r = 0.62, p < 0.01) as was peak GGEMG (r = 0.55, p < 0.05). Of the anatomic variables airway shape (A-P/lateral ratio) and volume change of the pharyngeal airway between total lung capacity and residual volume were different between those with and without severe apnea. Both correlated with RDI (A-P/lateral ratio: r = 0.70, p < 0.01 and volume change: r = 0.77, p < 0.01). CONCLUSIONS: We believe these findings suggest that specific anatomic and physiologic properties of the airway interact with obesity to predispose to the development of airway collapse during sleep.

Adult↗

Fusiform gyrus volume reduction and facial recognition in chronic schizophrenia.

BACKGROUND: The fusiform gyrus (FG), or occipitotemporal gyrus, is thought to subserve the processing and encoding of faces. Of note, several studies have reported that patients with schizophrenia show deficits in facial processing. It is thus hypothesized that the FG might be one brain region underlying abnormal facial recognition in schizophrenia. The objectives of this study were to determine whether there are abnormalities in gray matter volumes for the anterior and the posterior FG in patients with chronic schizophrenia and to investigate relationships between FG subregions and immediate and delayed memory for faces. METHODS: Patients were recruited from the Boston VA Healthcare System, Brockton Division, and control subjects were recruited through newspaper advertisement. Study participants included 21 male patients diagnosed as having chronic schizophrenia and 28 male controls. Participants underwent high-spatial-resolution magnetic resonance imaging, and facial recognition memory was evaluated. Main outcome measures included anterior and posterior FG gray matter volumes based on high-spatial-resolution magnetic resonance imaging, a detailed and reliable manual delineation using 3-dimensional information, and correlation coefficients between FG subregions and raw scores on immediate and delayed facial memory derived from the Wechsler Memory Scale III. RESULTS: Patients with chronic schizophrenia had overall smaller FG gray matter volumes (10%) than normal controls. Additionally, patients with schizophrenia performed more poorly than normal controls in both immediate and delayed facial memory tests. Moreover, the degree of poor performance on delayed memory for faces was significantly correlated with the degree of bilateral anterior FG reduction in patients with schizophrenia. CONCLUSION: These results suggest that neuroanatomic FG abnormalities underlie at least some of the deficits associated with facial recognition in schizophrenia.

Adult↗

Progressive decrease of left Heschl gyrus and planum temporale gray matter volume in first-episode schizophrenia: a longitudinal magnetic resonance imaging study.

BACKGROUND: The Heschl gyrus and planum temporale have crucial roles in auditory perception and language processing. Our previous investigation using magnetic resonance imaging (MRI) indicated smaller gray matter volumes bilaterally in the Heschl gyrus and in left planum temporale in patients with first-episode schizophrenia but not in patients with first-episode affective psychosis. We sought to determine whether there are progressive decreases in anatomically defined MRI gray matter volumes of the Heschl gyrus and planum temporale in patients with first-episode schizophrenia and also in patients with first-episode affective psychosis. METHODS: At a private psychiatric hospital, we conducted a prospective high spatial resolution MRI study that included initial scans of 28 patients at their first hospitalization (13 with schizophrenia and 15 with affective psychosis, 13 of whom had a manic psychosis) and 22 healthy control subjects. Follow-up scans occurred, on average, 1.5 years after the initial scan. RESULTS: Patients with first-episode schizophrenia showed significant decreases in gray matter volume over time in the left Heschl gyrus (6.9%) and left planum temporale (7.2%) compared with patients with first-episode affective psychosis or control subjects. CONCLUSIONS: These findings demonstrate a left-biased progressive volume reduction in the Heschl gyrus and planum temporale gray matter in patients with first-episode schizophrenia in contrast to patients with first-episode affective psychosis and control subjects. Schizophrenia but not affective psychosis seems to be characterized by a postonset progression of neocortical gray matter volume loss in the left superior temporal gyrus and thus may not be developmentally fixed.

Adolescent↗

Tumor detection in the bladder wall with a measurement of abnormal thickness in CT scans.

Virtual cystoscopy is a developing technique for bladder cancer screening. In a conventional cystoscopy, an optical probe is inserted into the bladder and an expert reviews the appearance of the bladder wall. Physical limitations of the probe place restrictions on the examination of the bladder wall. In virtual cystoscopy, a computed tomography (CT) scan of the bladder is acquired and an expert reviews the appearance of the bladder wall as shown by the CT. The task of identifying tumors in the bladder wall has often been done without extensive computational aid to the expert. We have developed an image processing algorithm that aids the expert in the detection of bladder tumors. Compared with an expert observer reading the CT, our algorithm achieves 89% sensitivity, 88% specificity, 48% positive predictive value, and 98% negative predictive value.

Anatomy, Cross-Sectional↗

Progressive decrease of left superior temporal gyrus gray matter volume in patients with first-episode schizophrenia.

OBJECTIVE: Smaller temporal lobe cortical gray matter volumes, including the left superior temporal gyrus, have been reported in magnetic resonance imaging (MRI) studies of patients with chronic schizophrenia and, more recently, in patients with first-episode schizophrenia. However, it remains unknown whether there are progressive decreases in temporal lobe cortical gray matter volumes in patients with first-episode schizophrenia and whether similarly progressive volume decreases are present in patients with affective psychosis. METHOD: High-spatial-resolution MRI scans at initial hospitalization and 1.5 years later were obtained from 13 patients with first-episode schizophrenia, 15 patients with first-episode affective psychosis (mainly manic), and 14 healthy comparison subjects. MRI volumes were calculated for gray matter of superior temporal gyrus and for the amygdala-hippocampal complex. RESULTS: Patients with first-episode schizophrenia showed significant decreases in gray matter volume over time in the left superior temporal gyrus compared with patients with first-episode affective psychosis or healthy comparison subjects. This progressive decrease was more pronounced in the posterior portion of the left superior temporal gyrus (mean=9.6%) than in the anterior portions (mean=8.4%). No group differences in the rate of change over time were present in other regions. CONCLUSIONS: These findings demonstrate a progressive volume reduction of the left posterior superior temporal gyrus gray matter in patients with first-episode schizophrenia but not in patients with first-episode affective psychosis.

Adolescent↗

The male predisposition to pharyngeal collapse: importance of airway length.

Obstructive sleep apnea is an important disorder because of both its prevalence and its cardiovascular and neurocognitive sequelae. Despite the fact that male sex is a major risk factor for this disorder, the mechanisms underlying this predisposition are unclear. To understand the pathophysiologic basis of the male predisposition for pharyngeal collapse, we performed a detailed analysis of the anatomic and physiologic features of the upper airway in a cohort of normal and near-normal subjects (equal number of men and women). Although no important physiologic (genioglossal electromyogram, airflow resistance) differences were observed between sexes, a number of anatomic differences were apparent. The pharyngeal airway length was substantially longer in men compared with women. There was also an increased cross-sectional area of the soft palate and an increased airway volume in men compared with women. Using signal-averaged anatomic data from male and female subjects, we developed representative male and female finite element airway models. This model demonstrated the male airway to be substantially more collapsible than the female airway, solely on the basis of anatomic differences. This study suggests that the male predisposition to pharyngeal collapse is anatomically based, primarily as the result of an increased length of vulnerable airway as well as increased soft palate size.

Adult↗

Amygdala-hippocampal shape differences in schizophrenia: the application of 3D shape models to volumetric MR data.

Evidence suggests that some structural brain abnormalities in schizophrenia are neurodevelopmental in origin. There is also growing evidence to suggest that shape deformations in brain structure may reflect abnormalities in neurodevelopment. While many magnetic resonance (MR) imaging studies have investigated brain area and volume measures in schizophrenia, fewer have focused on shape deformations. In this MR study we used a 3D shape representation technique, based on spherical harmonic functions, to analyze left and right amygdala-hippocampus shapes in each of 15 patients with schizophrenia and 15 healthy controls matched for age, gender, handedness and parental socioeconomic status. Left/right asymmetry was also measured for both shape and volume differences. Additionally, shape and volume measurements were combined in a composite analysis. There were no differences between groups in overall volume or shape. Left/right amygdala-hippocampal asymmetry, however, was significantly larger in patients than controls for both relative volume and shape. The local brain regions responsible for the left/right asymmetry differences in patients with schizophrenia were in the tail of the hippocampus (including both the inferior aspect adjacent to parahippocampal gyrus and the superior aspect adjacent to the lateral geniculate nucleus and more anteriorly to the cerebral peduncles) and in portions of the amygdala body (including the anterior-superior aspect adjacent to the basal nucleus). Also, in patients, increased volumetric asymmetry tended to be correlated with increased left/right shape asymmetry. Furthermore, a combined analysis of volume and shape asymmetry resulted in improved differentiation between groups. Classification function analyses correctly classified 70% of cases using volume, 73.3% using shape, and 87% using combined volume and shape measures. These findings suggest that shape provides important new information toward characterizing the pathophysiology of schizophrenia, and that combining volume and shape measures provides improved group discrimination in studies investigating brain abnormalities in schizophrenia. An evaluation of shape deformations also suggests local abnormalities in the amygdala-hippocampal complex in schizophrenia.

Adult↗

Association between smaller left posterior superior temporal gyrus volume on magnetic resonance imaging and smaller left temporal P300 amplitude in first-episode schizophrenia.

BACKGROUND: In chronic schizophrenia, the P300 is broadly reduced and shows a localized left temporal deficit specifically associated with reduced gray matter volume of the left posterior superior temporal gyrus (STG). In first-episode patients, a similar left temporal P300 deficit is present in schizophrenia, but not in affective psychosis. The present study investigated whether the left temporal P300-left posterior STG volume association is selectively present in first-episode schizophrenia. METHOD: P300 was recorded as first-episode subjects with schizophrenia (n = 15) or affective psychosis (n = 18) or control subjects (n = 18) silently counted infrequent target tones amid standard tones. High-resolution spoiled gradient-recalled acquisition magnetic resonance images provided quantitative measures of temporal lobe gray matter regions of interest. RESULTS: Patients with first-episode schizophrenia displayed a reversed P300 temporal area asymmetry (smaller on the left), while magnetic resonance imaging showed smaller gray matter volumes of left posterior STG relative to control subjects and patients with affective psychosis (15.4% and 11.0%, respectively), smaller gray matter volumes of left planum temporale (21.0% relative to both), and a smaller total Heschl's gyrus volume (14.6% and 21.1%, respectively). Left posterior STG and the left planum temporale, but not other regions of interest, were specifically and positively correlated (r>0.5) with left temporal P300 voltage in patients with schizophrenia but not in patients with affective psychosis or in control subjects. CONCLUSION: These results suggest that the left temporal P300 abnormality specifically associated with left posterior STG gray matter volume reduction is present at the first hospitalization for schizophrenia but is not present at the first hospitalization for affective psychosis.

Adolescent↗

Fusiform gyrus volume reduction in first-episode schizophrenia: a magnetic resonance imaging study.

BACKGROUND: The fusiform gyrus (occipitotemporal gyrus) is thought to be critical for face recognition and may possibly be associated with impaired facial recognition and interpretation of facial expression in schizophrenia. of postmortem studies have suggested that fusiform gyrus volume is reduced in schizophrenia, but there have been no in vivo structural studies of the fusiform gyrus in schizophrenia using magnetic resonance imaging. METHODS: High-spatial resolution magnetic resonance images were used to measure the gray matter volume of the fusiform gyrus in 22 patients with first-episode schizophrenia (first hospitalization), 20 with first-episode affective psychosis (mainly manic), and 24 control subjects. RESULTS: Patients with first-episode schizophrenia had overall smaller relative volumes (absolute volume/intracranial contents) of fusiform gyrus gray matter compared with controls (9%) and patients with affective psychosis (7%). For the left fusiform gyrus, patients with schizophrenia showed an 11% reduction compared with controls and patients with affective psychosis. Right fusiform gyrus volume differed in patients with schizophrenia only compared with controls (8%). CONCLUSION: Schizophrenia is associated with a bilateral reduction in fusiform gyrus gray matter volume that is evident at the time of first hospitalization and is different from the presentation of affective psychosis.

Adolescent↗

Tumor detection by virtual cystoscopy with color mapping of bladder wall thickness.

PURPOSE: We determine the value of color mapping of bladder wall thickness for detection of tumor as a component of virtual cystoscopy. MATERIALS AND METHODS: A total of 31 subjects with hematuria and/or a history of bladder tumor underwent helical computerized tomography of the pelvis after distention of the bladder with air. Three-dimensional (D) models were constructed, and thickness of the wall was color mapped according to a fixed and validated mm. scale. Axial source images and 3-D models were reviewed and graded for the presence of wall thickening. A comparison was made with findings on conventional cystoscopy in 31 patients and pathological specimen in 13. RESULTS: Compared with conventional cystoscopy, the analysis of axial image yielded a sensitivity of 0.80, specificity 0.90, positive predictive value 0.80 and negative predictive value 0.90 for the presence of tumor. Examination of color mapped 3-D renderings resulted in 0.83, 0.36, 0.42 and 0.71, respectively. CONCLUSIONS: Thin axial computerized tomography of the air distended bladder shows promise as a potential screening tool for bladder cancer. The low specificity of color mapped 3-D renderings makes the technique inappropriate for screening. It may valuable for guiding urologists to additional suspicious sites in a patient with a known tumor.

Aged↗

Quantitative MR imaging assessment of prostate gland deformation before and during MR imaging-guided brachytherapy.

RATIONALE AND OBJECTIVES: The authors performed this study to document the deformations that occur between pretreatment magnetic resonance (MR) imaging and intraoperative MR imaging during brachytherapy. MATERIALS AND METHODS: MR images obtained at 1.5 and 0.5 T in 10 patients with prostate cancer were analyzed for changes in the shape and substructure of the prostate. Three-dimensional models of the prostate were obtained. The authors measured anteroposterior dimension; total gland, peripheral zone, and central gland volumes; transverse dimension; and superoinferior height. RESULTS: Gland deformations were seen at visual inspection of the three-dimensional models. The anteroposterior dimension of the total gland, central gland, and peripheral zone increased from 1.5- to 0.5-T imaging (median dimension, 4.9, 1.5, and 1.8 mm, respectively), and the increase was greatest in the peripheral zone (P < .05, all comparisons). There was a decrease in the transverse dimension from 1.5- to 0.5-T imaging (median, 4.5 mm; P < .005). The total gland volume and the superoinferior height did not show a statistically significant change. CONCLUSION: There were significant deformations in the shape of the prostate, especially in the peripheral zone, between the two imaging studies. The likely causes of the shape change are differences in rectal filling (endorectal coil used in 1.5-T studies vs obturator in 0.5-T studies) and/or changes in patient position (supine vs lithotomy). These findings suggest that pretreatment images alone may not be reliable for accurate therapy planning. It may be useful to integrate pre-and intraoperative data.

Brachytherapy↗

Serial registration of intraoperative MR images of the brain.

The increased use of image-guided surgery systems during neurosurgery has brought to prominence the inaccuracies of conventional intraoperative navigation systems caused by shape changes such as those due to brain shift. We propose a method to track the deformation of the brain and update preoperative images using intraoperative MR images acquired at different crucial time points during surgery. We use a deformable surface matching algorithm to capture the deformation of boundaries of key structures (cortical surface, ventricles and tumor) throughout the neurosurgical procedure, and a linear finite element elastic model to infer a volumetric deformation. The boundary data are extracted from intraoperative MR images using a real-time intraoperative segmentation algorithm. The algorithm has been applied to a sequence of intraoperative MR images of the brain exhibiting brain shift and tumor resection. Our results characterize the brain shift after opening of the dura and at the different stages of tumor resection, and brain swelling afterwards. Analysis of the average deformation capture was assessed by comparing landmarks identified manually and the results indicate an accuracy of 0.7+/-0.6 mm (mean+/-S.D.) for boundary surface landmarks, of 0.9+/-0.6 mm for landmarks inside the boundary surfaces, and 1.6+/-0.9 mm for landmarks in the vicinity of the tumor.

Algorithms↗

3D modeling and virtual endoscopy of the small bowel based on magnetic resonance imaging in patients with inflammatory bowel disease.

RATIONALE AND OBJECTIVES: Small bowel MRI (MR imaging) is a new imaging modality that excellently depicts small intestine pathology in patients with inflammatory bowel disease. Virtual endoscopy based on sectional imaging is a recently introduced technique to create endoscopy like views. The aim of this study was to evaluate the feasibility of virtual small bowel endoscopy based on MR imaging in patients with Crohn disease. MATERIALS AND METHODS: Thirty consecutive patients with Crohn disease were scanned after oral application of pineapple juice for contrasting the small bowel. Dedicated high resolution T1 weighted 3D-FLASH sequences with fat suppression were used for volume scanning. Volume-rendered 3D models of the small bowel were created and virtual endoscopy was performed. The feasibility and quality of this new visualization method was assessed. RESULTS: In nine of 30 patients virtual endoscopy was considered as good quality (flight through the entire small bowel was possible, typical folds were revealed). In 18 patients fair quality (at least 4/5 of the small bowel were depicted adequately) was assessed. In three of 30 patients virtual endoscopy was not sufficiently possible because of inadequate bowel filling or breathing artifacts. Three fistulae diagnosed on 2D MRI were visualized on the virtual endoscopic view. CONCLUSION: Virtual endoscopy of the small bowel is feasible based on high resolution MR imaging. Vivid insight views and 3D models provide an interesting addition to sectional MR findings.

Adolescent↗

Uncinate fasciculus findings in schizophrenia: a magnetic resonance diffusion tensor imaging study.

OBJECTIVE: Disruptions in connectivity between the frontal and temporal lobes may explain some of the symptoms observed in schizophrenia. Conventional magnetic resonance imaging (MRI) studies, however, have not shown compelling evidence for white matter abnormalities, because white matter fiber tracts cannot be visualized by conventional MRI. Diffusion tensor imaging is a relatively new technique that can detect subtle white matter abnormalities in vivo by assessing the degree to which directionally organized fibers have lost their normal integrity. The first three diffusion tensor imaging studies in schizophrenia showed lower anisotropic diffusion, relative to comparison subjects, in whole-brain white matter, prefrontal and temporal white matter, and the corpus callosum, respectively. Here the authors focus on fiber tracts forming temporal-frontal connections. METHOD: Anisotropic diffusion was assessed in the uncinate fasciculus, the most prominent white matter tract connecting temporal and frontal brain regions, in 15 patients with chronic schizophrenia and 18 normal comparison subjects. A 1.5-T GE Echospeed system was used to acquire 4-mm-thick coronal line-scan diffusion tensor images. Maps of the fractional anisotropy were generated to quantify the water diffusion within the uncinate fasciculus. RESULTS: Findings revealed a group-by-side interaction for fractional anisotropy and for uncinate fasciculus area, derived from automatic segmentation. The patients with schizophrenia showed a lack of normal left-greater-than-right asymmetry seen in the comparison subjects. CONCLUSIONS: These findings demonstrate the importance of investigating white matter tracts in vivo in schizophrenia and support the hypothesis of a disruption in the normal pattern of connectivity between temporal and frontal brain regions in schizophrenia.

Adult↗

Shape differences in the corpus callosum in first-episode schizophrenia and first-episode psychotic affective disorder.

OBJECTIVE: The corpus callosum, the largest white matter tract in the brain, is a midline structure associated with the formation of the hippocampus, septum pellucidum, and cingulate cortex, which have been implicated in the pathogenesis of schizophrenia. Corpus callosum shape deformation, therefore, may reflect a midline neurodevelopmental abnormality. METHOD: Corpus callosum area and shape were analyzed in 14 first-episode psychotic patients with schizophrenia, 19 first-episode psychotic patients with affective disorder, and 18 normal comparison subjects. RESULTS: No statistically significant corpus callosum area differences between groups were found, but there were differences in the structure's shape between the patients with schizophrenia and the comparison subjects. A correlation between width and angle of the corpus callosum was found in patients with affective disorder. CONCLUSIONS: Corpus callosum shape abnormalities in first-episode psychotic patients with schizophrenia may reflect a midline neurodevelopmental abnormality.

Adult↗

MRI study of caudate nucleus volume and its cognitive correlates in neuroleptic-naive patients with schizotypal personality disorder.

OBJECTIVE: "Cognitive" circuits anatomically link the frontal lobe to subcortical structures; therefore, pathology in any of the core components of these circuits, such as in the caudate nucleus, may result in neurobehavioral syndromes similar to those of the frontal lobe. Neuroleptic medication, however, affects the size of the caudate nucleus. For this reason, individuals diagnosed with schizotypal personality disorder offer an ideal group for the measurement of the caudate nucleus because they may be genetically related to individuals with schizophrenia but do not require neuroleptic treatment because of their less severe symptoms. METHOD: Magnetic resonance imagining (MRI) scans obtained on a 1.5-T magnet with 1.5-mm contiguous slices were used to measure the caudate nucleus and lateral ventricles in 15 right-handed male subjects with schizotypal personality disorder who had no previous neuroleptic exposure and in 14 normal comparison subjects. Subjects were group matched for parental socioeconomic status, handedness, and gender. RESULTS: First, the authors found significantly lower left and right absolute (13.1%, 13.2%) and relative (9.1%, 9.2%) caudate nucleus volumes in never-medicated subjects with schizotypal personality disorder than in normal subjects. Second, they found significant, inverse correlations between caudate nucleus volume and the severity of perseveration in two distinct working memory tasks in these neuroleptic-naive subjects with schizotypal personality disorder. CONCLUSIONS: These data are consistent with the findings of reduced caudate nucleus volume reported in studies of neuroleptic-naive patients experiencing their first episode of schizophrenia and support the association of intrinsic pathology in the caudate nucleus with abnormalities in working memory in the schizophrenia spectrum.

Adult↗

High-resolution line scan diffusion tensor MR imaging of white matter fiber tract anatomy.

BACKGROUND AND PURPOSE: MR diffusion tensor imaging permits detailed visualization of white matter fiber tracts. This technique, unlike T2-weighted imaging, also provides information about fiber direction. We present findings of normal white matter fiber tract anatomy at high resolution obtained by using line scan diffusion tensor imaging. METHODS: Diffusion tensor images in axial, coronal, and sagittal sections covering the entire brain volume were obtained with line scan diffusion imaging in six healthy volunteers. Images were acquired for b factors 5 and 1000 s/mm(2) at an imaging resolution of 1.7 x 1.7 x 4 mm. For selected regions, images were obtained at a reduced field of view with a spatial resolution of 0.9 x 0.9 x 3 mm. For each pixel, the direction of maximum diffusivity was computed and used to display the course of white matter fibers. RESULTS: Fiber directions derived from diffusion tensor imaging were consistent with known white matter fiber anatomy. The principal fiber tracts were well observed in all cases. The tracts that were visualized included the following: the arcuate fasciculus; superior and inferior longitudinal fasciculus; uncinate fasciculus; cingulum; external and extreme capsule; internal capsule; corona radiata; auditory and optic radiation; anterior commissure; corpus callosum; pyramidal tract; gracile and cuneatus fasciculus; medial longitudinal fasciculus; rubrospinal, tectospinal, central tegmental, and dorsal trigeminothalamic tract; superior, inferior, and middle cerebellar peduncle; pallidonigral and strionigral fibers; and root fibers of the oculomotor and trigeminal nerve. CONCLUSION: We obtained a complete set of detailed white matter fiber anatomy maps of the normal brain by means of line scan diffusion tensor imaging at high resolution. Near large bone structures, line scan produces images with minimal susceptibility artifacts.

Adult↗

A chronic illness characterized by fatigue, neurologic and immunologic disorders, and active human herpesvirus type 6 infection.

OBJECTIVE: To conduct neurologic, immunologic, and virologic studies in patients with a chronic debilitating illness of acute onset. DESIGN: Cohort study with comparison to matched, healthy control subjects. PATIENTS: We studied 259 patients who sought care in one medical practice; 29% of the patients were regularly bedridden or shut-in. MAIN OUTCOME MEASURES: Detailed medical history, physical examination, conventional hematologic and chemistry testing, magnetic resonance imaging (MRI) studies, lymphocyte phenotyping studies, and assays for active infection of patients' lymphocytes with human herpesvirus type 6 (HHV-6). MAIN RESULTS: Patients had a higher mean (+/- SD) CD4/CD8 T-cell ratio than matched healthy controls (3.16 +/- 1.5 compared with 2.3 +/- 1.0, respectively; P less than 0.003). Magnetic resonance scans of the brain showed punctate, subcortical areas of high signal intensity consistent with edema or demyelination in 78% of patients (95% CI, 72% to 86%) and in 21% of controls (CI, 11% to 36%) (P less than 10(-9)). Primary cell culture of lymphocytes showed active replication of HHV-6 in 79 of 113 patients (70%; CI, 61% to 78%) and in 8 of 40 controls (20%; CI, 9% to 36%) (P less than 10(-8], a finding confirmed by assays using monoclonal antibodies specific for HHV-6 proteins and by polymerase chain reaction assays specific for HHV-6 DNA. CONCLUSIONS: Neurologic symptoms, MRI findings, and lymphocyte phenotyping studies suggest that the patients may have been experiencing a chronic, immunologically mediated inflammatory process of the central nervous system. The active replication of HHV-6 most likely represents reactivation of latent infection, perhaps due to immunologic dysfunction. Our study did not directly address whether HHV-6, a lymphotropic and gliotropic virus, plays a role in producing the symptoms or the immunologic and neurologic dysfunction seen in this illness. Whether the findings in our patients, who came from a relatively small geographic area, will be generalizable to other patients with a similar syndrome remains to be seen.

Adult↗