Hypoxic-ischaemic encephalopathy: early and late magnetic resonance imaging findings in relation to outcome

Sixteen infants with hypoxic-ischaemic encephalopathy (HIE) were studied using serial magnetic resonance imaging (MRI) up to the age of 2 years. The infants had regular neurological and developmental assessments. An nuclear magnetic resonance (NMR) score was devised to quantify the early and late MRI findings and a neurological optimality score was used to quantify abnormal neurological signs at the time of the final examination. The follow up MRI score was compared with the neonatal MRI score and the outcome of the child. There was a strong positive correlation between the neonatal and follow up MRI scores and between MRI scores and optimality score. All infants with a normal outcome had patchy white matter abnormalities. All infants with an abnormal outcome had extensive white matter abnormalities. The outcome was most severe in those infants with additional basal ganglia atrophy with or without cyst formation. Infants with mild HIE who are developmentally normal at the age of 2 years do not have normal MRI scans and may be at risk of minor neurological problems by school age. Bilateral basal ganglia abnormalities are associated with severe developmental delay, but infants with mainly white matter and cortical abnormalities have less severe problems despite extensive tissue loss.     

Temporal lobe abnormalities in dementia and depression: a study using high resolution single photon emission tomography and magnetic resonance imaging

OBJECTIVES: Perfusion SPECT and MRI were used to test the hypothesis that late onset depression is associated with brain abnormalities. METHODS: Forty depressed patients (DSM-III-R major depressive episode, not demented at two year follow up) were recruited who were either drug free, or on a stable dose of antidepressants for at least three weeks, as well as 22 demented patients (DSM-IIIR and NINCDS/ADRDA criteria for probable Alzheimer's disease). Patients were imaged at rest with a high resolution single slice 12 detector head scanner (SME-Neuro 900) and the cerebral perfusion marker 99mTc-exametazime (HM-PAO). Temporal lobe templates were fitted with brains pitched by 20 degrees-30 degrees. A subgroup of 41 patients (22 depressed) were also scanned using a Siemens Magnetron 1.0 Tesla magnetic resonance imager, using a FLAIR imaging sequence for the assessment of white matter hyperintensities, and a Turbo FLASH sequence for the measurement of medial temporal lobe width. RESULTS: Demented patients showed reduced perfusion, particularly in the left temporoparietal cortex. In these regions of interest, patients with late onset depression tended to have perfusion values intermediate between patients with early onset depression and demented patients. Differences in changes in white matter between demented and early and late onset depressive patients did not reach conventional levels of significance. Temporal lobe width differed between demented and depressed patients, but not between early and late onset depressed patients. Perfusion and temporal lobe width were not associated, but reductions of perfusion were associated with periventricular white matter changes. Mini mental state examination scores were associated with temporal perfusion in demented patients and with changes in deep white matter in depressed patients. Finally, severity of depressive symptoms was associated with decreased perfusion in frontotemporal and basal ganglia regions of interest. CONCLUSION: A cumulative effect of duration of illness on regional cerebral perfusion could not be confirmed. Late onset depression may show more abnormalities of deep white matter and of left temporoparietal perfusion than early onset depression, but the underlying pathology remains to be established.     

MRI signal hyperintensities in geriatric depression

OBJECTIVE: The authors rated periventricular and subcortical signal hyperintensities on magnetic resonance imaging (MRI) scans in elderly patients with depression and in normal subjects with similar demographic features to examine whether such changes discriminate patients with depression from normal subjects and whether they are associated with any clinical variables. METHOD: Two established hyperintensity rating systems were used to compare the MRI brain scans of 48 elderly patients with depression diagnosed according to DSM-III-R with the scans of 39 normal elderly subjects. RESULTS: Elderly depressed patients manifested significantly more severe hyperintensity ratings in the subcortical gray matter than age-matched comparison subjects. Significant differences were not identified between patients with similar current ages and cerebrovascular disease risk who had early-onset or late-onset depression. CONCLUSIONS: These findings support those of neuroimaging studies implicating the basal ganglia in depression and geriatric depression. The data suggest that the relationship observed in some reports between late-onset depression and MRI hyperintensities is most likely a function of cerebrovascular disease risk and age.     

Biochemical alterations in multiple sclerosis lesions and normal-appearing white matter detected by in vivo 31P and 1H spectroscopic imaging

The goals of the current study were threefold: first, to confirm previous single volume proton (1H) magnetic resonance spectroscopy results of reduced N-acetyl aspartate (NAA, a putative marker of neurons) in multiple sclerosis (MS) white matter lesions using multiple volume 1H magnetic resonance spectroscopic imaging (MRSI); second, to measure the phospholipid metabolites phosphomonoesters and phosphodiesters in such lesions using phosphorus (31P) MRSI; and third, to test the hypothesis that biochemical changes occur in the normal-appearing (on spin echo T2-weighted magnetic resonance images) white matter in patients with MS. Thirteen subjects with clinically definite MS were studied with both 1H and 31P MRSI, and 19 controls were studied with either 1H MRSI, 31P MRSI, or both. MS lesion, MS normal-appearing white matter, and region-matched control spectra from the centrum semiovale were analyzed. The major findings of this study were that in both white matter lesions and normal-appearing white matter in patients with MS, the metabolite ratio NAA/creatine and the total 31P peak integrals were significantly reduced compared with controls. In addition, in MS lesions NAA/choline and phosphodiesters/total 31P were significantly reduced compared with controls, and in MS normal-appearing white matter there was a trend for NAA/choline to be reduced compared with controls. In normal-appearing white matter in patients with MS, total creatine and phosphocreatine were significantly increased compared to controls, as detected with both 1H (total creatine peak integrals) and 31P (phosphocreatine/total 31P) MRSI techniques. These results suggest reduced neuronal density and altered phospholipid metabolites in white matter lesions in patients with MS.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evolution in coronary stenting: use of ticlopidine with and without oral anticoagulants

We have investigated proton magnetic resonance spectra of the basal ganglia in 41 medication-free outpatients with major depression, prior to starting an 8-week standardized trial of open-label fluoxetine, and 22 matched comparison subjects. Upon completing the trial, depressed subjects were classified as treatment responders (n = 18) or nonresponders (n = 23), based on changes in the Hamilton Depression Rating Scale. Depressed subjects had a lower area ratio of the choline resonance to the creatine resonance (Cho/Cr) than comparison subjects. This statistically significant difference between the depressed subjects and comparison subjects was more pronounced in the treatment responders than in the nonresponders. There were no differences in the relative volumes of gray matter or white matter in the voxel used for proton spectroscopy in depressed subjects relative to comparison subjects. These results are consistent with an alteration in the metabolism of cytosolic choline compounds in the basal ganglia of depressed subjects and, in particular, those who are responsive to fluoxetine.     

1997 IPA/Bayer Research Awards in Psychogeriatrics. Subcortical hyperintensities in late-life depression: acute response to treatment and neuropsychological impairment

Subcortical hyperintensities are easily visualized areas of signal abnormality that are seen on T2-weighted magnetic resonance imaging (MRI). Characteristically they occur in the white matter of the brain and are more common in elderly people. In depression, little is known of the clinical significance of subcortical hyperintensities or their contribution to the prognosis. Fifty-eight consecutive patients with DSM-III-R depression and an age range of 65 to 85 years were prospectively collected from an old-age psychiatry service. Response to treatment was assessed with a clinical global outcome measure. A neuropsychology battery was completed on all patients after treatment. Forty-four patients completed MRI scanning. The scans were scored using a regional rating system for hyperintensities. Forty-eight percent of patients had a favorable response to treatment on the clinical global outcome scale. Poor outcome was associated with female sex (p = .07), poor physical health (p = .040), diabetes (p = .018), psychosis (p = .026), and an early age at onset of first episode of depression (p = .036). Even after adjustment for confounding effects, there were significant neuropsychological associations with the regional hyperintensities. Distribution in the periventricular area correlated with delayed recall after distraction (p = .025), and punctate lesions in the basal ganglia correlated with impaired category production (p = .020). Pontine reticular formation hyperintensities were related to impaired psychomotor speed (p = .04). Location in the frontal deep-white matter (p = .024), basal ganglia (p = .03), and pontine reticular formation (p = .02) was associated with a poor acute response to treatment. However, the response to treatment was not related to total cerebral white-matter hyperintensity load. A logistic regression equation included all the significant prognostic features and found four independent predictors of poor outcome: More than five punctate lesions of the basal ganglia, diabetes, lower mean arterial pressure, and hyperintensity of the pontine reticular formation significantly predicted outcome. These four factors correctly predicted 95.6% of patients with a poor outcome and 85.7% with a favorable outcome. In late-life depression, subcortical hyperintensities are common. Lesions in the cerebral white matter are predominantly associated with memory disturbance, and those in deeper infratentorial areas, with psychomotor slowing and executive deficits. Total white-matter load has no prognostic value, and although some subcortical regions are associated with poor response, individually they have little specificity. However, a combination of involvement in three areas (basal ganglia, pons, and frontal lobe) is clinically relevant and predicts outcome with great accuracy (91%). Patients with lesions in the basal ganglia and deep white matter had an especially poor response to pharmacotherapy.     

Clinical and magnetic resonance imaging correlates of hypothalamic-pituitary-adrenal axis function in depression and Alzheimer's disease

BACKGROUND: An age-related dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is well recognised in animals, but still remains controversial in humans. There is increasing interest that raised corticosteroid levels, due to activation of the HPA axis, may cause both depressive symptoms and cognitive impairments. Steroid effects on cognition may be via the hippocampus, a major site of corticosteroid action and an important structure involved in learning and memory. METHOD: To investigate this further, we examined the relationship between the dexamethasone suppression test, cognitive function, depressive symptoms and hippocampal atrophy on magnetic resonance imaging (MRI) in 32 normal controls, 49 subjects with NINCDS/ADRDA Alzheimer's disease and 51 patients with DSM-III-R Major Depression. RESULTS: Controlling for differences in dexamethasone concentrations, post-dexamethasone cortisol levels were related to advancing age in controls and depressed subjects. However, among subjects with Alzheimer's disease, post-dexamethasone cortisol levels were independently associated with both minor depressive symptoms and hippocampal atrophy on MRI. CONCLUSION: An association between advancing age and increased HPA axis dysregulation is supported for controls and depressed subjects. In Alzheimer's disease, HPA axis changes were associated with depressive symptoms and hippocampal atrophy. Longitudinal studies are now needed to determine the causal direction of these associations.     

Some methodological issues in neuroradiological research in psychiatry

An outline is given of some of the methodological issues discussed in neuroradiological research on psychiatric illness. Strengths and shortcomings of magnetic resonance imaging (MRI) in depicting and quantifying brain structures are described. Temporal lobe anatomy and pathology are easily accessible to MRI, whereas limits on anatomical delineation hamper approaches to frontal lobe study. White matter hyperintense lesions are sensitively depicted by MRI, but specificity is limited. Distinction of vascular and primary degenerative dementia is considerably improved by CT and MRI analysis. Computed tomography (CT) and MRI have enhanced the understanding of treatable organic psychiatric disorders, e.g., normal pressure hydrocephalus. Subcortical and white matter pathology has been replicated in CT and MRI studies of late-onset psychiatric disorders, clinical overlap with cerebrovascular disease or neurodegeneration may be of import. Transcranial sonography findings of brainstem structural change specific to unipolar depression may contribute to the understanding of affective psychoses. Magnetic resonance spectroscopy and functional MRI are likely to stimulate psychiatric research in the future.     

MR diffusion imaging in Pelizaeus-Merzbacher disease

A case of classical type Pelizaeus-Merzbacher disease was reported. This patient exhibited marked motor and mental developmental delay, and nystagmus, with a positive familial history. Electrophysiological studies, such as on brainstem auditory evoked potentials, blink reflex and somatosensory evoked potentials, suggested marked disturbance of nerve conduction in CNS. T2-weighted magnetic resonance (MR) images revealed non-progressive diffuse T2 prolongation of cerebral white matter after a 2-year interval, indicating congenital hypomyelination in CNS. A newly developed magnetic resonance diffusion imaging method demonstrated the existence of diffusional anisotropy in the corpus callosum, internal capsule, and white matter of the frontal lobe. Although the diffusional anisotropy was considered to depend on the well-developed multiple layers of myelin around the axons, the imaging data of this patient demonstrated that the diffusional anisotropy did not necessarily depend on those multiple layers. These results may indicate the potential usefulness of MR diffusion imaging, combined with electrophysiological studies and conventional MR imaging, for analyzing the lesions of the cerebral white matter.     

Postperceptual effects and P300 latency

BACKGROUND: Structural and functional brain changes have been described in elderly patients with unipolar affective disorder. Changes appear to be more marked in patients with late-onset depression, but the reversibility of such changes after clinical recovery is not known. METHODS: Magnetic resonance imaging, electroencephalography (EEG), and cognitive tests were performed in 23 elderly patients (mean age 66.5 years) clinically recovered from major depression. Twelve had late-onset depression (first episode over 55 years of age); 11 had early onset (first episode before 50 years). EEG and cognitive testing were also performed on 15 control subjects. RESULTS: Patients with late-onset depression had larger third and lateral ventricles, increased ventricular-brain ratio, and greater frequency and severity of subcortical white matter lesions than those with early onset. There was no difference between early- and late-onset patients in EEG and cognitive measures, but compared with controls patients showed significant changes in EEG evoked potentials and increased slow-wave activity, slowed reaction times, and global impairments in cognitive function. CONCLUSIONS: These results suggest that structural changes are greater in patients with late-onset depression, and that EEG and cognitive impairments persist after recovery, regardless of age of onset of depression, and are independent of structural changes.     

von Willebrand factor, tissue plasminogen activator, and dehydroepiandrosterone sulphate predict cardiovascular death in a 10 year follow up of survivors of acute myocardial infarction

Earlier reports on T2-weighted magnetic resonance imaging (MRI) in the classical form of Pelizaeus-Merzbacher disease seemed to divide the patterns of the high-intensity lesions in the white matter into three subtypes: type I, diffusely hemispheric and corticospinal; type II, diffusely hemispheric without brainstem lesions; and type III, patchy in the hemispheres. The four boys presented in our study, between 10 and 17 years of age, with classical Pelizaeus-Merzbacher disease, who all had a duplicated proteolipid protein gene, invariably manifested type I despite their various clinical severities. Follow-up MRI after an interval of 5 years and proton magnetic resonance spectroscopy was performed in three of the patients. The white matter on the last MRI was unchanged in volume and the distribution of high-intense areas. Proton magnetic resonance spectroscopy revealed no abnormal peaks. These results were consistent with the lack of definite neurologic regression in the last 5 years and with the pathologic characteristics of well-preserved axons and the absence of sclerosis. Further study is required to precisely determine whether the patterns of MRI findings can be divided into subtypes corresponding to those of proteolipid protein gene abnormalities.     

1H-MRS differentiates white matter hyperintensities in subcortical arteriosclerotic encephalopathy from those in normal elderly

BACKGROUND AND PURPOSE: White matter hyperintensities in MRI of the brain are often seen in normal elderly subjects. Radiologically, these hyperintense regions are similar to those in symptomatic patients with subcortical arteriosclerotic encephalopathy (SAE). Our aim was to discriminate white matter hyperintensities (WMH) on MRI in patients with SAE from similar appearing changes in normal elderly. METHODS: Three groups of elderly patients were studied: symptomatic patients with WMH of SAE (n = 5); asymptomatic subjects with diffuse, confluent WMH (n = 4); and elderly control subjects (n = 5). Proton density images revealed WMH in the occipital lobes. Proton magnetic resonance spectroscopy (1H-MRS) was used to acquire spectra in these hyperintensities. Metabolite concentrations were calculated from peak areas of N-acetylaspartate (NAA), creatine (Cre), and choline (Cho). RESULTS: The NAA/Cre and NAA/Cho ratios were reduced in the SAE group compared with the two asymptomatic groups (P < .05). NAA was decreased and Cho elevated in SAE compared with control subjects (P < .05). The average volumes of WMH in the SAE group (65.5 cm3) and in asymptomatic control subjects (59.4 cm3) were similar, and greater than those of the normal control group (4.0 cm3). CONCLUSIONS: Proton MRS discriminates WMH in SAE patients from those in asymptomatic elderly, suggesting differing causes of the hyperintensities.     

Use and misuse of syringes in anaesthesia

OBJECTIVE: To assess whether the cerebral gray and white matter volume deficits described in patients with anorexia nervosa (AN) are fully reversible with weight rehabilitation. DESIGN: A prospective cohort study using magnetic resonance imaging to examine the brains of female adolescents after weight recovery from AN. SETTING: An adolescent eating disorder program located in a tertiary care children's hospital. PARTICIPANTS: Of 13 patients who underwent a previous magnetic resonance imaging study at a low weight, 6 patients were weight recovered and underwent rescanning. All brain measures were corrected for the effects of intracranial volume and age, based on a regression analysis of a group of 34 healthy female control subjects. Scans from the patients with AN were also compared with scans from an age-matched subset of 16 healthy female controls. MAIN OUTCOME MEASURES: White matter volumes, gray matter volumes, and cerebrospinal fluid volumes in the weight-recovered AN group. RESULTS: Quantitative analysis showed that white matter and ventricular cerebrospinal fluid volumes changed significantly (P = .03 for both) on weight recovery from AN. The weight-recovered patients had significant gray matter volume deficits (P = .01) and elevated cerebrospinal fluid volumes (P = .005) compared with those of the age-matched controls. They no longer had significant (P = .30) white matter volume deficits. CONCLUSION: The finding of persistent gray matter volume deficits in patients who have recovered their weight after AN suggests an irreversible component to the structural brain changes associated with AN, in addition to a component that resolves on weight recovery.     

Magnetic resonance in HTL-I associated myelopathy. Leukoencephalopathy and spinal cord atrophy

Cerebral white matter lesions and spinal cord atrophy have been frequently reported in patients with HTLV-I associated myelopathy (HAM). The exact frequency and the clinical relevance of these findings still remain to be elucidated. Twenty-nine patients with HAM were studied by magnetic resonance imaging of the brain and spine. Cerebral white matter lesions equal or over 3 mm in diameter were considered abnormal. The spinal cord size was evaluated using an index we have called "spinal cord index". The radiological findings were correlated to the clinical features of the myelopathy. Cerebral white matter lesions occurred in 52% of the patients, and spinal cord atrophy in 74%. There was no significant correlation between these abnormalities and the clinical features studied. These findings suggest that the resonance imaging is a useful method for detection of cerebral and spinal cord abnormalities in HAM patients. The absence of correlation between cerebral white matter lesions and either patient age or risk factors for cardiovascular disease suggests a possible association between the leukoencephalopathy and the infection.     

Elbow valgus stress radiography in an uninjured population

OBJECTIVE: The purpose of this study was to determine if P300 latency is prolonged in geriatric depression and if longer P300 latency and deficits in initiation and errors of perseveration in depressed elderly patients are related to risk factors for vascular disease. METHOD: Geriatric patients with unipolar depression (N = 43) and elderly comparison subjects (N = 24) were assessed for depressive symptoms, cognitive functions, risk factors for vascular disease, and P300 latency. RESULTS: Depressed elderly patients had longer P300 latency than normal elderly subjects. In the depressed patients, P300 latency was related to deficits in initiation and errors in perseveration. Risk factors for vascular disease were associated not only with P300 latency but also with deficits in initiation and errors in perseveration. CONCLUSIONS: Functional impairment of the cortico-striato-pallido-thalamo-cortical pathways from vascular disease, implicated in late-life depressive disorders, may explain not only deficits in initiation and errors in perseveration but also longer P300 latency in depressed elderly patients. These results are preliminary and need further examination with brain imaging and more sensitive neuropsychological measures.     

Nature of life events and difficulties in depressed adolescents

OBJECTIVE: To examine the significance of acute life events and ongoing difficulties in adolescents with a recent major depressive disorder. METHOD: Adolescents (aged 13-18 years) with a recent episode of major depressive disorder based on DSM-III-R (n = 26) and normal controls free of any Axis I lifetime psychiatric disorder (n = 15) were assessed using the investigator-based Life Events and Difficulties Schedule (LEDS). RESULTS: Traditionally defined severe events were more likely to occur in the year prior to onset among depressed adolescents (46%) than in a comparable period among normal controls (20%), but these differences did not reach statistical significance. Expanding the definition of severe events to include those events focused on others important to the adolescent resulted in a significantly higher percentage of depressed adolescents having one or more refined "severe" events in the year prior to onset (62%) compared with normal controls (27%) (p < or = .02). It is interesting that one half of the depressed adolescents had two or more refined severe events occur during the year prior to onset compared with none of the normal controls (p < or = .01). Further analyses showed that depressed adolescents were significantly more likely to have a major difficulty precede the onset of their depression (27%) compared with normal controls (0%) (p < or = .04). CONCLUSIONS: The results suggest that depressed adolescents are exposed to high levels of stress prior to becoming depressed. Future investigations might benefit from using the LEDS with adolescents to assess acute and ongoing stressors.     

Neurochemical alterations in asymptomatic abstinent cocaine users: a proton magnetic resonance spectroscopy study

Cocaine can cause a variety of neuropsychiatric and neurobehavioral complications; however, it is uncertain whether cocaine causes persistent cerebral structural and neurochemical abnormalities in asymptomatic users. We studied 52 African-American men (26 human immunodeficiency virus-negative asymptomatic heavy cocaine users and 26 normal subjects). Ventricle-to-brain ratio (VBR) and white matter lesions (WML) were quantified on magnetic resonance imaging. N-acetyl-containing compounds (NA), total creatine, choline-containing compounds, myo-inositol, and glutamate + glutamine were measured with in vivo proton magnetic resonance spectroscopy, VBR and WML were not significantly different in the cocaine users compared to the normal controls. Elevated creatine (+7%; p = .05) and myo-inositol (+18%; p = .01) in the white matter were associated with cocaine use. NA, primarily a measure of N-acetyl aspartate and neuronal content, was normal. Normal NA suggest no neuronal loss or damage in the brain regions examined in these cocaine users. Therefore, we conclude that neurochemical abnormalities observed might result from alterations in nonneuronal brain tissue.     

Cognitive attributes of depression in children and adolescents.

This study explores whether cognitive attributes differentiate depressed children from those with other psychiatric disorders. The subjects were 108 children from 7 to 17 years of age. Forty-seven children were diagnosed as currently depressed, 30 as having had an episode of major depression within the last year (depressed-resolved), and 31 with diagnoses other than depression (nondepressed). The subjects completed the Piers-Harris Children's Self-Concept Scale, the Children's Hopelessness Scale, the Nowicki-Strickland Children's Locus of Control Scale, the Children's Attributional Styles Questionnaire, and the Children's Depression Inventory. The depressed children endorsed significantly lower self-esteem, more hopelessness, a more externalized locus of control, and a more depressive attributional style than the depressed-resolved or the nondepressed children. Thus, a depressive cognitive style can be documented in clinically depressed young people. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Establishing norms for age-related changes in proton T1 of human brain tissue in vivo

The goal of this study was to determine the expected normal range of variation in spin-lattice relaxation time (T1) of brain tissue in vivo, as a function of age. A previously validated precise and accurate inversion recovery method was used to map T1 transversely, at the level of the basal ganglia, in a study population of 115 healthy subjects (ages 4 to 72; 57 male and 58 female). Least-squares regression analysis shows that T1 varied as a function of age in pulvinar nucleus (R2 = 56%), anterior thalamus (R2 = 51%), caudate (R2 = 50%), frontal white matter (R2 = 47%), optic radiation (R2 = 39%), putamen (R2 = 36%), genu (R2 = 22%), occipital white matter (R2 = 20%) (all p < 0.0001), and cortical gray matter (R2 = 53%) (p < 0.001). There were no significant differences in T1 between men and women. T1 declines throughout adolescence and early adulthood, to achieve a minimum value in the fourth to sixth decade of life, then T1 begins to increase. Quantitative magnetic resonance imaging provides evidence that brain tissue continues to change throughout the lifespan among healthy subjects with no neurologic deficits. Age-related changes follow a strikingly different schedule in different brain tissues; white matter tracts tend to reach a minimum T1 value, and to increase again, sooner than do gray matter tracts. Such normative data may prove useful for the early detection of brain pathology in patients.     

Intellectual impairment and brain MRI findings in myotonic dystrophy: with a special reference to hippocampal atrophy and white matter lesions

We performed a correlative study between intellectual impairment, CTG repeat expansion and magnetic resonance imaging (MRI) abnormalities, including hippocampal atrophy, white matter lesions and ventricular dilatation in 15 patients with myotonic dystrophy (MD). They included 4 males and 11 females aged from 20 to 66 years, averaging 43 years of age and 15 years of duration of illness. Nine patients had intellectual impairment (WAIS-R<80). Negative correlations were found between full scale IQ (FSIQ), duration of illness (p<0.05) and CTG repeat expansion (p<0.05). Compared with normal controls, the patients with MD showed a significant reduction in size of the hippocampal head (p<0.01), which was positively correlated to FSIQ, verbal IQ and performance IQ levels (p<0.05). Ten patients had white matter lesions. Severer white matter lesions tended to be recognized in patients with longer duration of illness and with decreased FSIQ level. These results suggest that hippocampal atrophy and white matter lesions are related to intellectual impairment in patients with MD.