Surgical treatment of hypothalamic hamartomas.

Hypothalamic hamartomas are aberrant masses, composed of abnormally distributed neurons and glia. Along endocrine and cognitive symptoms, they may cause epileptic seizures, including the specific gelastic and dacrystic seizures. Surgery is the treatment of drug-resistant hamartoma epilepsy, with associated positive results on endocrine, psychiatric, and cognitive symptoms. Recently, alternatives to open microsurgical treatment have been proposed. We review these techniques and compare their efficacy and safety. Open resection or disconnection of the hamartoma, either through pterional, transcallosal, or transventricular approach, leads to good epileptological control, but its high complication rate, up to 30%, limits its indications. The purely cisternal peduncular forms remain the only indication of open, pterional approach, while other strategies have been developed to overcome the neurological, endocrine, behavioral, or cognitive complications. Laser and radiofrequency thermocoagulation-based disconnection through robot-guided stereo-endoscopy has been proposed as an alternative to open microsurgical resection and stereotactic destruction. The goal is to allow safe and complete disconnection of a possibly complex attachment zone, through a single intraparenchymal trajectory which allows multiple laser or radiofrequency probe trajectory inside the ventricle. The efficacy was high, with 78% of favorable outcome, and the overall complication rate was 8%. It was especially effective in patients with isolated gelastic seizures and pure intraventricular hamartomas. Stereotactic radiosurgery has proved as efficacious and safer than open microsurgery, with around 60% of seizure control and a very low complication rate. Multiple stereotactic thermocoagulation showed very interesting results with 71% of seizure freedom and 2% of permanent complications. Stereotactic laser interstitial thermotherapy (LiTT) seems as effective as open microsurgery (from 76 to 81% of seizure freedom) but causes up to 20% of permanent complications. This technique has however been highly improved by targeting only the epileptogenic onset zone in the hamartoma, as shown on preoperative functional MRI, leading to an improvement of epilepsy control by 45% (92% of seizure freedom) with no postoperative morbidity. All these results suggest that the impact of the surgical procedure does not depend on purely technical matters (laser vs radiofrequency thermocoagulation or stereotactic vs robot-guided stereo-endoscopy) but relies on the understanding of the epileptic network, including inside the hamartoma, the aim being to plan an effective disconnection or lesion of the epileptogenic part while sparing the adjacent functional structures.

New and enlarging white matter lesions adjacent to the ventricle system and thalamic atrophy are independently associated with lateral ventricular enlargement in multiple sclerosis.

OBJECTIVE: To investigate the association between new or enlarging T2-weighted (w) white matter (WM) lesions adjacent to the ventricle wall, deep grey matter (DGM) atrophy and lateral ventricular enlargement in multiple sclerosis (MS). METHODS: Patients derived from the Genetic Multiple Sclerosis Associations study. Lateral ventricles and DGM were segmented fully automated at baseline and 5 years follow-up using Automatic Lateral Ventricle delineation (ALVIN) and Multiple Automatically Generated Templates brain segmentation algorithm (MAgeT), respectively. T2w and T1w lesions were manually segmented. To investigate the association between lesion distance to the ventricle wall and the lateral ventricle volume, we parcellated the WM into concentric periventricular bands using FMRIB Software Library. Associations between clinical and MRI parameters were assessed in generalized linear models using generalized estimating equations for repeated measures. RESULTS: We studied 127 MS patients. Lateral ventricles enlarged on average by 2.4%/year. Patients with new/enlarging T2w WM lesions between baseline and follow-up at 5 years had accelerated lateral ventricular enlargement compared with patients without (p = 0.004). This was true in a multivariable analysis adjusted for age, gender, and whole brain atrophy. When looking at the T2w lesions in different periventricular bands, we found the strongest association between new/enlarging T2w lesions and lateral ventricle enlargement for WM lesions adjacent to the ventricle system (p < 0.001). Moreover, and indepedent of new/enlarging WM lesions, DGM atrophy was associated with ventricular enlargement. In a multivariable analysis, this was driven by thalamic atrophy (p < 0.001). CONCLUSION: New/enlarging T2w lesions adjacent to the ventricle system and thalamic atrophy are independently associated with lateral ventricular enlargement in MS.

Influence of Intracerebral Hemorrhage Location on Outcomes in Patients With Severe Intraventricular Hemorrhage.

Background and Purpose- We investigated the prognostic significance of spontaneous intracerebral hemorrhage location in presence of severe intraventricular hemorrhage. Methods- We analyzed diagnostic computed tomography scans from 467/500 (excluding primary intraventricular hemorrhage) subjects from the CLEAR (Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage) III trial. We measured intracerebral hemorrhage engagement with specific anatomic regions, and estimated association of each region with blinded assessment of dichotomized poor stroke outcomes: mortality, modified Rankin Scale score of 4 to 6, National Institutes of Health Stroke Scale score of >4, stroke impact scale score of <60, Barthel Index <86, and EuroQol visual analogue scale score of <50 and <70 at days 30 and 180, respectively, using logistic regression models. Results- Frequency of anatomic region involvement consisted of thalamus (332 lesions, 71.1% of subjects), caudate (219, 46.9%), posterior limb internal capsule (188, 40.3%), globus pallidus/putamen (127, 27.2%), anterior limb internal capsule (108, 23.1%), and lobar (29, 6.2%). Thalamic location was independently associated with mortality (days 30 and 180) and with poor outcomes on most stroke scales at day 180 on adjusted analysis. Posterior limb internal capsule and globus pallidus/putamen involvement was associated with increased odds of worse disability at days 30 and 180. Anterior limb internal capsule and caudate locations were associated with decreased mortality on days 30 and 180. Anterior limb internal capsule lesions were associated with decreased long-term morbidity. Conclusions- Acute intracerebral hemorrhage lesion topography provides important insights into anatomic correlates of mortality and functional outcomes even in severe intraventricular hemorrhage causing obstructive hydrocephalus. Models accounting for intracerebral hemorrhage location in addition to volumes may improve outcome prediction and permit stratification of benefit from aggressive acute interventions. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT00784134.

Thalamic and ventricular volumes predict motor response to deep brain stimulation for Parkinson's disease.

BACKGROUND: Brain atrophy frequently occurs with Parkinson's disease (PD) and relates to increased motor symptoms of PD. The predictive value of neuroimaging-based measures of global and regional brain volume on motor outcomes in deep brain stimulation (DBS) remains unclear but potentially could improve patient selection and targeting. OBJECTIVES: To determine the predictive value of preoperative volumetric MRI measures of cortical and subcortical brain volume on motor outcomes of subthalamic nucleus (STN) DBS in PD. METHODS: Preoperative T1 3D MP-RAGE structural brain MRI images were analyzed for each participant to determine subcortical, ventricular, and cortical volume and thickness. Change in Unified Parkinson's Disease Rating Scale (UPDRS) scores for subsection 3, representing motor outcomes, was computed preoperatively and postoperatively following DBS programming in 86 participants. A multiple linear regression analysis was performed to investigate the relationship between volumetric data and the effect of DBS on UPDRS 3 scores. RESULTS: Larger ventricular and smaller thalamic volumes predicted significantly less improvement of UPDRS 3 scores after STN DBS. CONCLUSIONS: Our findings demonstrate in PD that regional brain volumes, in particular thalamic and ventricular volumes, predict motor outcomes after DBS. Differences in regional brain volumes may alter electrode targeting, reflect a specific disease trait such as postoperative progression of subclinical dementia, or directly interfere with the action of DBS.

Consequence of intraventricular hemorrhage on neurovascular coupling evoked by speech syllables in preterm neonates.

Intraventricular Hemorrhage (IVH) is the leading cause of neurological and cognitive impairment in preterm neonates with an incidence that increases with increasing prematurity. In the present study, we tested how preterm neonates with IVH react to external stimulation (i.e. speech syllables). We compared their neural responses measured by electroencephalography (EEG), and hemodynamic responses measured by functional near-infrared spectroscopy (fNIRS), with those of healthy preterms. A neural response to syllables was observed in these infants, but did not induce a vascular response in contrast with healthy neonates. These results clearly demonstrate that the cerebral vascular network in IVH preterm neonates was unable to compensate for the increased metabolism resulting from neuronal activation in response to external stimulation. Optical imaging is thus a sensitive tool to identify altered cerebral hemodynamic in critically ill preterms before behavioral changes are manifested or when only minor abnormalities on other functional monitoring techniques such as EEG are visible. We propose that a multi-modal approach provides unique opportunities for early monitoring of cognitive functions and opens up new possibilities for clinical care and recommended practices by studying the difficulties of the premature brain to adapt to its environment.

Infant brain structures, executive function, and attention deficit/hyperactivity problems at preschool age. A prospective study.

BACKGROUND: Neuroimaging findings have provided evidence for a relation between variations in brain structures and attention deficit/hyperactivity disorder (ADHD). However, longitudinal neuroimaging studies are typically confined to children who have already been diagnosed with ADHD. In a population-based study, we aimed to characterize the prospective association between brain structures measured during infancy and executive function and attention deficit/hyperactivity problems assessed at preschool age. METHODS: In the Generation R Study, the corpus callosum length, the gangliothalamic ovoid diameter (encompassing the basal ganglia and thalamus), and the ventricular volume were measured in 784 6-week-old children using cranial postnatal ultrasounds. Parents rated executive functioning at 4 years using the behavior rating inventory of executive function-preschool version in five dimensions: inhibition, shifting, emotional control, working memory, and planning/organizing. Attention deficit/hyperactivity problems were assessed at ages 3 and 5 years using the child behavior checklist. RESULTS: A smaller corpus callosum length during infancy was associated with greater deficits in executive functioning at 4 years. This was accounted for by higher problem scores on inhibition and emotional control. The corpus callosum length during infancy did not predict attention deficit/hyperactivity problem at 3 and 5 years, when controlling for the confounders. We did not find any relation between gangliothalamic ovoid diameter and executive function or Attention deficit/hyperactivity problem. CONCLUSIONS: Variations in brain structures detectible in infants predicted subtle impairments in inhibition and emotional control. However, in this population-based study, we could not demonstrate that early structural brain variations precede symptoms of ADHD.

Transcranial sonography reveals cerebellar, nigral, and forebrain abnormalities in Friedreich's ataxia.

BACKGROUND: Friedreich's ataxia (FA) is essentially characterized by degeneration of the dorsal root ganglia, the dorsal nuclei of Clarke, and the long spinal fiber tracts, yet there is accumulating evidence that neurodegeneration extends beyond these predilection sites. Transcranial sonography (TCS) has evolved as a valuable complementary neuroimaging tool in the assessment of neurodegenerative diseases due to its capacity to well depict structural changes and the accumulation of heavy metals. Its use for assessing cerebellar neurodegeneration, however, has not yet been investigated.Here we investigated whether TCS allows to assess particular features of cerebellar as well as midbrain and forebrain abnormalities in FA. METHODS: Comprehensive TCS imaging of 34 FA patients and 34 age-matched healthy controls. RESULTS: Hyperechogenicity of the dentate nucleus was very frequent in FA patients (85%) and could even be observed in patients with short disease duration, suggesting that dentate alterations are a common and probably early feature of FA. Substantia nigra was significantly hypoechogenic, possibly indicating regional changes in subcellular brain iron regulation. FA patients showed significantly enlarged 4th, 3rd, and lateral ventricles, thus corroborating earlier MRI and postmortem findings of substantial cerebellar and forebrain atrophy in FA. CONCLUSIONS: TCS provides a quick-to-apply and inexpensive in vivo assessment of both cerebellar and noncerebellar abnormalities in FA, in particular highlighting dentate hyperechogenicity as a core feature. It might serve as a promising tool for imaging aspects of cerebellar neurodegeneration also in other neurodegenerative disorders.

Sonographic discrimination of corticobasal degeneration vs progressive supranuclear palsy.

OBJECTIVE: To study the use of brain parenchyma sonography (BPS) in discriminating between patients with corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP). METHODS: Thirteen patients with PSP and eight with CBD were studied with BPS according to a standardized protocol. RESULTS: Seven (88%) of the eight CBD patients showed marked hyperechogenicity of the substantia nigra (SN) but none of eleven PSP patients (Mann-Whitney U test, p < 0.001). This finding indicated CBD with a positive predictive value of 100%. Marked dilatation of the third ventricle (width > 10 mm) was found in 10 (83%) of 12 PSP patients, but in none of the CBD patients (p < 0.005). BPS measurements of ventricle widths closely matched MRI measurements (Pearson correlation, r = 0.90, p < 0.001). The presence of at least one of the BPS findings 1) marked SN hyperechogenicity and 2) third-ventricle width < 10 mm indicated CBD with a sensitivity of 100%, a specificity of 83%, and a positive predictive value of 80%. Other BPS findings such as echogenicity of lentiform and caudate nuclei and widths of the frontal horns did not discriminate between CBD and PSP. One PSP patient could not be assessed because of insufficient acoustic temporal bone windows. CONCLUSIONS: Substantia nigra hyperechogenicity, reported earlier as characteristic brain parenchyma sonography finding in idiopathic Parkinson disease, is also typical for corticobasal degeneration.

Transcranial sonography of the brain parenchyma: comparison of B-mode imaging and tissue harmonic imaging.

Transcranial color-coded Duplex sonography (TCCS) has been used for the identification of cerebrovascular disorders. Recently, its value in the diagnosis of disorders of the brain parenchyma has been proposed. The object of this study was to determine systematically the echo pattern of the brain parenchyma and to compare conventional B-mode imaging with tissue harmonic imaging (THI). Transcranial sonography (TCS) was performed in 54 healthy individuals through the temporal bone window using conventional B-mode imaging and THI by two experienced investigators. Identification rates for several brain structures were assessed, and the quality of depiction of each method was graded semiquantitatively. In addition, several parts of the ventricular system and the basal cerebral cisterns were measured. Four subjects did not have an adequate bone window for transcranial examination. In the remaining people, the bone window was assessed to be adequate (59%) or excellent (33%). In the majority (> 80%), TCS allowed an unequivocal identification of various brain structures. Inter-rater variability of the assessments of tissue echogenicity and measurements of the ventricular width were found to be low for several structures (e.g., brainstem, thalamus, or 3rd ventricle). The echo pattern of brain tissue in THI is identical to that described for B-mode imaging. Using THI, contours of brain structures were typically visualized more clearly and the reproducibility of measurements was more consistent. In our experience, insonation of the contralateral lobes was limited when depths were higher than 12 cm using THI. In conclusion, TCS allowed the sonographic examination of the brain parenchyma in the majority of our subjects. THI substantially improves the identification of parenchymal structures when the depth is below 12 cm.

Cerebral magnetic resonance imaging and ultrasonography findings after neonatal hypoglycemia.

OBJECTIVE: The aim of this study was to investigate sequential neuroradiologic changes in the brains of infants after transient neonatal hypoglycemia. We used magnetic resonance imaging (MRI) and ultrasonography (US) head scans. METHODS: Eighteen symptomatic full-term infants whose serum glucose concentrations were

Cranial ultrasound abnormalities identified at birth: their relationship to perinatal risk and neurobehavioral outcome.

OBJECTIVES: Minor cranial ultrasound abnormalities, such as mild ventricular enlargement, choroid plexus cysts, and subependymal cysts, have been identified in 3% to 5% of the newborn population. Although clinicians generally consider these abnormalities to be insignificant for the outcome of the newborn, few convincing data have been published to support this optimism. The objectives of this study were to identify potential risk factors associated with the identification of cranial ultrasound abnormalities at birth and to determine if the abnormalities were related to neurobehavioral sequelae in the newborn. METHODS: Three hundred eight women were enrolled in this prospective, longitudinal maternal-infant health and development study either at the time they entered the public health care system for prenatal care or at delivery if they had no prenatal care. Each woman participated in an in-depth psychosocial interview at the end of each trimester of pregnancy. Retrospective chart review by experienced medical personnel was used to compile data for the Hobel perinatal risk score for each study participant after delivery. Offspring underwent cranial ultrasound evaluation, the Amiel-Tison Neurologic Assessment, and the Brazelton Neonatal Behavioral Assessment Scale within 96 hours of birth by experienced examiners blinded to any maternal-infant history. RESULTS: Of the 308 women originally enrolled in the study, 301 delivered living infants. Of these, 266 infants (88%) underwent a cranial ultrasound evaluation and are the subject of this article. For the purposes of the current study, infants were divided into those with normal (n = 239) and those with abnormal (n = 27) ultrasound results. Abnormal ultrasound results included the following lesions: subependymal cyst (n = 13); mild ventricular enlargement (n = 6); choroid plexus cysts (n = 3); a combination of cysts and increased ventricular size (n = 2); a 7-mm midline cyst in the superior posterior portion of the third ventricle (n = 1); subependymal hemorrhage and ventricular enlargement (n = 1); and increased ventricular size, subependymal hemorrhage and cysts, and two small, right thalamic calcifications (n = 1). There were no significant differences between those with an abnormal ultrasound and those with a normal ultrasound for birth weight, length, gestational age, rate of prematurity, frequency of nulliparity, or frequency of small for gestational age infants. However, infants with an abnormal ultrasound had a significantly smaller mean head circumference than those with a normal ultrasound (34.5 +/- 1.9 cm vs 33.7 +/- 1.9 cm). The infants with an abnormal ultrasound had a higher median prenatal (50 vs 45), neonatal (14 vs 8), and total (94 vs 77) Hobel risk score but not a higher labor-delivery score. There were no significant differences when these groups were compared on additional risk factors not included in the Hobel scoring system such as race and socioeconomic status. In addition, mothers who used a greater number of drugs during the first trimester of pregnancy were more likely to have an infant with an abnormal ultrasound at birth such that the probability of having an abnormal ultrasound rose to 22% by the time the pregnant women were using four drugs. Neurologic examinations revealed no differences between the infants with normal and abnormal ultrasounds. There were also no group differences for five of the seven Brazelton cluster scores, the excitable or depressed clusters, or eight of the nine qualifier scores. However, infants with abnormal ultrasounds performed significantly better on the habituation (7.3 +/- 0.8 vs 6.6 +/- 1.5) and autonomic regulation (6.5 +/- 0.8 vs 6.0 +/- 1.0) clusters but more poorly on the cost of attention qualifier score (4.9 +/- 1.2 vs 5.5 +/- 1.2) on the Brazelton Neonatal Behavioral Assessment Scale. CONCLUSION: Infants with an abnormal cranial ultrasound at birth had higher perinatal risk scores. (ABSTRACT TRUNCATED)

Brain perfusion abnormalities in Rett syndrome: a qualitative and quantitative SPET study with 99Tc(m)-ECD.

Rett syndrome is a progressive neurological paediatric disorder associated with severe mental deficiency, which affects only girls. The aim of this study was to determine if brain blood flow abnormalities detected with 99Tc(m)-ethyl-cysteinate-dimer (99Tc[m]-ECD) single photon emission tomography (SPET) can explain the clinical manifestation and progression of the disease. Qualitative and quantitative global and regional brain blood flow was evaluated in 12 girls with Rett syndrome and compared with an aged-matched reference group of children. In comparison with the reference group, SPET revealed a considerable global reduction in cerebral perfusion in the groups of girls with Rett syndrome. A large statistical difference was noted, which was more evident when comparing the control group with girls with stage IV Rett syndrome than girls with stage III Rett syndrome. The reduction in cerebral perfusion reflects functional disturbance in the brain of children with Rett syndrome. These data confirm that 99Tc(m)-ECD brain SPET is sensitive in detecting hypoperfused areas in girls with Rett syndrome that may be associated with brain atrophy, even when magnetic resonance imaging appears normal.

Third ventricle: size and appearance in normal fetuses through gestation.

PURPOSE: To define the size and appearance of the normal fetal third ventricle. MATERIALS AND METHODS: The third ventricle was prospectively assessed in 441 consecutive normal second- and third-trimester fetuses. The fetuses were divided into six gestational age ranges. Data regarding the size and configuration of the third ventricle were analyzed for each group. RESULTS: The third ventricle was seen in 435 of 440 (98.9%) fetuses. It appeared as a single echogenic line between the thalami in 171 (38.9%) fetuses, as parallel echogenic lines outlining a fluid-filled lumen in 243 (55.2%) fetuses, and as divergent lines delineating a V-shaped fluid-filled structure in 21 (4.8%) fetuses. The single-line configuration was most common early in the second trimester. Later in pregnancy, the ventricle walls could be discerned as separate parallel or divergent lines outlining a fluid-filled lumen. The average width of the ventricle was relatively constant at approximately 1 mm from 12 to 28 weeks. After this time, it enlarged, reaching a maximum 1.9 mm. CONCLUSION: The third ventricle can be imaged in most second- and third-trimester fetuses. Its size and configuration evolve through the second and third trimesters. This evolution must be considered in the evaluation of normality. At any gestational age, a third ventricle greater than 3.5 mm in width should be viewed with concern for abnormality.

High incidence of cranial ultrasound abnormalities in full-term infants with congenital heart disease.

The objective of this retrospective study was to determine the incidence and types of cranial ultrasound abnormalities in full-term infants with congenital heart disease (CHD). We reviewed the cranial ultrasound scans of 49 full-term infants with CHD and compared them to 42 healthy full-term control infants. The relationship of each abnormality with the type of CHD, the presence of cyanosis, and cardiac catheterization and cardiac surgery were examined. We found that infants with CHD had a higher incidence of cranial ultrasound abnormalities than control infants (59% versus 14%; p < 0.001). Cerebral atrophy and linear echodensities in the basal ganglia and thalamus were the most common sonographic findings in infants with CHD, particularly in those with coarctation of the aorta or ventricular septal defect. Intraventricular hemorrhage occurred more often in infants with acryanotic CHD than in those with cyanotic CHD. Cardiac catheterization and cardiac surgery had no significant effects on cranial ultrasound findings. We conclude that cranial ultrasound abnormalities are very frequent in full-term infants with CHD. These findings emphasize the importance of cranial ultrasonography and long-term neurodevelopmental follow-up of infants with CHD.

Intracranial lesions in the fullterm infant with hypoxic ischaemic encephalopathy: ultrasound and autopsy correlation.

To test the hypothesis that cranial ultrasound correlated with post-mortem findings in neonates with hypoxic ischaemic encephalopathy (HIE), the brains of 20 infants who died after at least two real time ultrasound scans were examined. The ultrasound abnormalities detected in the periventricular/subcortical white matter, cortex or thalami were compared with the macroscopic and histological appearances. Comparing the last ultrasound scan which was performed no longer than 12 hours before the infant died, with histological data, the sensitivity and specificity for lesions in the thalamus was 100% and 83.3% respectively; for cortical lesions 76.9 and 100% respectively and for lesions in the periventricular white matter 80% and 75% respectively. The value of cranial ultrasound for detecting intracranial abnormalities in infants with HIE was considerably better than reported previously. This could mainly be attributed to the use of a 10 MHz transducer which was of critical importance to identify lesions in the superficial cortical layer.

Neurosonographic findings in full-term infants born to maternal cocaine abusers: visualization of subependymal and periventricular cysts.

Neuroanatomical abnormalities have been linked to maternal cocaine abuse since Chasnoff et al's report of cerebral infarction in a single full-term offspring of a cocaine-abusing mother. Neurosonography was performed on 18 full-term offspring of cocaine-abusing mothers and 19 age-matched controls to look for possible abnormalities. There were no cases of infarction or intraparenchymal or intraventricular hemorrhage. There were, however, 6 patients with abnormalities among the cocaine-abusing group: 5 patients with unilateral or bilateral germinal matrix cysts and 3 patients with subtle cystic or predominantly cystic areas in watershed zones consistent with periventricular leukomalacia.

[Intraventricular brain pressure in newborn infants with asphyxia and the means for its correction]. / Vnutrizheludochhkovoe davlenie mozga u novorozhdennykh s asfiksiei i sposoby ego korrektsii.

The paper deals with the information noninvasive tool of echoencephalographic determination of cerebral intraventricular pressure in the newborns. With this mode, spinal fluid pressures were measured in 80 patients with prior degrees II and III asphyxia and in 25 healthy children in the early neonatal period. To enhance the efficiency of treating the fluid-hypertensive syndrome in the newborns with hypoxically afflicted central nervous system, an atraumatic method of reflex therapy, including superficial acupuncture, metallic plate acupuncture and application has been developed and proposed if chemotherapeutical loads are restricted. Recommendations to choose acupuncture points are given and the advantages of the method are analyzed.

Cerebral metabolism and atrophy in Huntington's disease determined by 18FDG and computed tomographic scan.

Patterns of local cerebral glucose utilization were measured with positron emission, computed tomography using the 18F-fluorodeoxyglucose method in 13 patients with Huntington's disease (HD), 15 subjects at risk for HD, and 40 normal control subjects. These data were compared with computed tomographic measures of cerebral atrophy, with age, and with duration and severity of symptoms. The results indicate that in HD there is a characteristic decrease in glucose utilization in the caudate and putamen and that this local hypometabolism appears early and precedes bulk tissue loss. In contrast to patients with senile dementia, in these HD patients glucose utilization typically was normal throughout the rest of the brain, regardless of the severity of symptoms and despite apparent shrinkage of brain tissue. Our results suggest the possibility that the caudate may be hypometabolic in some asymptomatic subjects who are potential carriers of the autosomal dominant gene for HD.