Superficial Brain Research Articles

Abstract 2363: Are White Matter Lesions Associated with Deep or Superficial Brain Atrophy or both?

Introduction White matter lesions (WMLs) are associated with cognitive decline, dementia and increased risk of stroke. Cerebral atrophy is also associated with future cognitive impairment and dementia. Both WMLs and atrophy are commonly found on MRI scans of elderly people, but whether they are related, and the strength of any relationship remains unclear. Hypotheses We hypothesised that 1) WMLs are associated with brain atrophy, 2) are more associated with deep (white matter) than superficial (cortical) atrophy, and 3) the association is similar for volumetric and visually rated WMLs. Methods We performed structural brain MRI on subjects from the Lothian Birth Cohort 1936 ( www.lothianbirthcohort.ed.ac.uk ) and measured intracranial (ICV), brain tissue (BTV), CSF ventricular, superficial subarachnoid space (SSS), grey matter (GM), normal appearing white matter (NAWM) and WML volumes using validated software (MCMxxxVI, http://sourceforge.net/projects/bric1936/ ). We also measured CSF + venous sinuses (V) + dural (D) volume (CSF+V+D) combined to further assess ICV changes due to brain atrophy and rated WMLs using the Fazekas scale. We used Spearman partial correlation to test associations between WMLs and brain atrophy, controlled for gender and ICV and performed general linear modelling (GLM). Results Amongst 672 subjects, mean age 73±1year, greater WML volume correlated: with reduced BTV (r=-0.10, P=0.01) and NAWM (r= -0.15, P<0.01), increased ventricular volume (r= 0.11, P<0.01) and CSF+V+D (r=0.11, P=0.01) but not with SSS (r=0.03, P=0.39), GM (r=-0.07, P=0.09) or CSF (r=0.06, P=0.13). A 1mm 3 increase in WML volume was associated with 0.43mm 3 decrease in BTV. We found similar associations for Fazekas WML scores. Gender and original brain size (i.e. ICV) explained 77.6% and 23.8% of the variance in BTV and ventricular volume, respectively, but WMLs explained <1% of either (GLM). Conclusions WMLs, assessed using both measured volumes and visual rating scales, are associated with brain atrophy mostly through deep white matter loss. Studies of brain atrophy in ageing or dementia should assess venous sinuses, dura and CSF, not just CSF, as sinuses and dura expand to occupy space left by brain atrophy. Further work to determine causes of age-related brain atrophy is required as WMLs only explain a small proportion of it.

CNS Penetration of Intrathecal-Lumbar Idursulfase in the Monkey, Dog and Mouse: Implications for Neurological Outcomes of Lysosomal Storage Disorder

A major challenge for the treatment of many central nervous system (CNS) disorders is the lack of convenient and effective methods for delivering biological agents to the brain. Mucopolysaccharidosis II (Hunter syndrome) is a rare inherited lysosomal storage disorder resulting from a deficiency of iduronate-2-sulfatase (I2S). I2S is a large, highly glycosylated enzyme. Intravenous administration is not likely to be an effective therapy for disease-related neurological outcomes that require enzyme access to the brain cells, in particular neurons and oligodendrocytes. We demonstrate that intracerebroventricular and lumbar intrathecal administration of recombinant I2S in dogs and nonhuman primates resulted in widespread enzyme distribution in the brain parenchyma, including remarkable deposition in the lysosomes of both neurons and oligodendrocytes. Lumbar intrathecal administration also resulted in enzyme delivery to the spinal cord, whereas little enzyme was detected there after intraventricular administration. Mucopolysaccharidosis II model is available in mice. Lumbar administration of recombinant I2S to enzyme deficient animals reduced the storage of glycosaminoglycans in both superficial and deep brain tissues, with concurrent morphological improvements. The observed patterns of enzyme transport from cerebrospinal fluid to the CNS tissues and the resultant biological activity (a) warrant further investigation of intrathecal delivery of I2S via lumbar catheter as an experimental treatment for the neurological symptoms of Hunter syndrome and (b) may have broader implications for CNS treatment with biopharmaceuticals.

FDTD analysis of a noninvasive hyperthermia system for brain tumors

BackgroundHyperthermia is considered one of the new therapeutic modalities for cancer treatment and is based on the difference in thermal sensitivity between healthy tissues and tumors. During hyperthermia treatment, the temperature of the tumor is raised to 40–45°C for a definite period resulting in the destruction of cancer cells. This paper investigates design, modeling and simulation of a new non-invasive hyperthermia applicator system capable of effectively heating deep seated as well as superficial brain tumors using inexpensive, simple, and easy to fabricate components without harming surrounding healthy brain tissues.MethodsThe proposed hyperthermia applicator system is composed of an air filled partial half ellipsoidal chamber, a patch antenna, and a head model with an embedded tumor at an arbitrary location. The irradiating antenna is placed at one of the foci of the hyperthermia chamber while the center of the brain tumor is placed at the other focus. The finite difference time domain (FDTD) method is used to compute both the SAR patterns and the temperature distribution in three different head models due to two different patch antennas at a frequency of 915 MHz.ResultsThe obtained results suggest that by using the proposed noninvasive hyperthermia system it is feasible to achieve sufficient and focused energy deposition and temperature rise to therapeutic values in deep seated as well as superficial brain tumors without harming surrounding healthy tissue.ConclusionsThe proposed noninvasive hyperthermia system proved suitable for raising the temperature in tumors embedded in the brain to therapeutic values by carefully selecting the systems components. The operator of the system only needs to place the center of the brain tumor at a pre-specified location and excite the antenna at a single frequency of 915 MHz. Our study may provide a basis for a clinical applicator prototype capable of heating brain tumors.

MAN WITH POSTERIOR FOSSA TUMORS 15 YEARS APART

A 48-year-old man with a history of hypertension, peripheral vascular disease and a 50-pack-year history of smoking presented with new onset vertigo, tinnitus, diplopia and ataxia in January 1978. CT scan showed a radiolucent defect in the left cerebellar hemisphere with a possible mural nodule. In ensuing months, he experienced worsening symptoms with a corresponding increase in lesion size on re-imaging. Months later, a left posterior fossa craniotomy was performed and revealed a single cystic lesion containing copious amounts of straw-colored fluid and a single mural nodule in the inferior portion of the cyst. Following resection, he was followed clinically until 1985 at which time follow-up was discontinued. He did well until January 1993 when he presented with progressively worsening episodic headaches and retro-orbital pressure. Subsequent MRIs of the brain and spine (February 1993, March 1993) showed multiple lesions along the neuraxis involving the superficial brain parenchyma, leptomeninges, and dura. Despite therapy, his condition progressively declined until he succumbed. A brain-only autopsy revealed numerous small tumor nodules involving the base of the brain over both frontal and temporal lobes, midbrain, pons, right optic nerve, pituitary fossa, and the base of the skull. Pathologic evaluation revealed metastatic hemangioblastoma. Metastatic hemangioblastoma is a rare entity, with only a few reported cases in the literature to date.

Distribution and Severity of Hypoxic-Ischemic Lesions on Brain MRI Following Therapeutic Cooling: Selective Head Versus Whole Body Cooling

Because whole body cooling (WBC) cools different regions of the brain uniformly, whereas selective head cooling (SHC) cools the superficial brain (cortex) more than the deeper brain (basal ganglia & thalamus, or BGT), we hypothesized that severity of hypoxic-ischemic (HI) lesions following cooling would differ between cooling modalities.

Treatment of canine fucosidosis by intracisternal enzyme infusion

The blood brain barrier is the major obstacle to treating lysosomal storage disorders of the central nervous system such as canine fucosidosis. This barrier was overcome by three, monthly injections of recombinant canine α- l-fucosidase enzyme were given intracisternally. In dogs treated from 8 weeks of age enzyme reached all areas of central nervous system as well as the cervical lymph node, bone marrow and liver. Brainstem and spinal cord samples from regions adjacent to the injection site had highest enzyme levels (39–73% of normal). Substantial enzyme activity (8.5–20% of normal controls) was found in the superficial brain compared to deeper regions (2.6–5.5% of normal). Treatment significantly reduced the fucosyl-linked oligosaccharide accumulation in most areas of CNS, liver and lymph node. In the surface and deep areas of lumbar spinal cord, oligosaccharide accumulation was corrected (79–80% reduction) to near normal levels ( p < 0.05). In the spinal meninges (thoracic and lumbar) enzyme activity (35–39% of normal control) and substrate reduction (58–63% affected vehicle treated samples) reached levels similar to those seen in phenotypically normal carriers ( p < 0.05).The procedure was safe and well-tolerated, treated (average 16%) dogs gained more weight ( p < 0.05) and there was no antibody formation or inflammatory reaction in plasma and CSF following treatments. The capacity of early ERT to modify progression of biochemical storage in fucosidosis is promising as this disease is currently only amenable to treatment by bone marrow transplantation which entails unacceptably high risks for many patients.

Enhanced Functional Brain Imaging by Using Adaptive Filtering and a Depth Compensation Algorithm in Diffuse Optical Tomography

Reflectance diffuse optical tomography (rDOT) of brain function is limited by its high sensitivity to the superficial tissues (i.e., the scalp and skull) and by its severe decrease in measurement sensitivity with increased depth. Significant interference in rDOT results from spontaneous fluctuations that are embedded in both the superficial tissues and brain, such as arterial pulsation and vasomotion. In this study, first we investigate coherence and phase shift of the spontaneous fluctuations in the resting state, within the superficial tissues and at various depths of the brain, respectively. We demonstrate that the spontaneous fluctuations originating from arterial pulsations ( ∼ 1 Hz) are spatially global and temporally coherent, while the fluctuations originating from vasomotion ( ∼ 0.1 Hz) tend to have less coherence with increased depth. Second, adaptive cancellation of spontaneous fluctuations with a frequency-specific strategy is utilized and validated in both resting and activation (evoked by a finger-tapping task) states. Third, improved depth localization of motor activation in reconstructed rDOT images is achieved by combining adaptive cancellation with a depth compensation algorithm that we recently reported.

Use of 3D visualisation of medical images for planning and intraoperative localisation of superficial brain tumours: our experience

Background. In the present article, we assessed the role, adequacy and application accuracy of intraoperative visual guidance based on the computer 3D visualisation of preoperative medical images in the surgery of superficial brain tumours.Materials and methods. For 30 consecutive patients with convexity meningioma or cortical/subcortical brain tumour, we used 3D visualisation of post-contrast fast spoiled gradient recalled (FSPGR) MR images to plan optimal positions for the trepanation opening and/or corticotomy site. At the beginning of the surgery, planned positions were transferred to the scalp and the cortical surface of the patient by visually matching the 3D surfaces with the operative field. The feasibility of visual matching was assessed by counting the number of cases in which this was possible. On the exposed cortical surface, we measured the mismatch between the centre of the actual trepanation opening and the planned corticotomy site, where possible.Results. During computer-assisted 3D planning, the centre of the trepanation opening, initially defined on the basis of 2D diagnostic images, was redefined in all our cases by an average repositioning distance of 19.7 mm ± 7.6 mm. During surgery, the transfer of the planned centre of the trepanation opening and the corticotomy site was possible in all (30/30) and in 70% (19/27) of the cases, respectively. Where assessable, the mismatch between the centre of the actual trepanation opening and the planned corticotomy site was less than 1 cm in 70% of cases (12/17) and more than 2 cm in 6% (1/17) of cases.Conclusions. Intraoperative visual guidance based on 3D visualisation proved to be adequate and accurate for locating superficial brain tumours in cases where transfer of planned surgical targets to the surgical field was possible. Decision about its use should be based on preoperative computer-assisted 3D planning, in which the feasibility of visual matching during surgery can and must be assessed.

A High CSF Signal on FLAIR: It is Not Always Blood

We describe a patient with progressive neurologic deficit due to middle cerebral branch occlusion. Temporary partial balloon occlusion of the abdominal aorta led to an increased signal in the subarachnoid space on fluid-attenuated inversion recovery images with no evidence of subarachnoid hemorrhage. After spontaneous recanalization, the increased signal of the subarachnoid space returned to normal. We assume that signal changes in the subarachnoid space were due to a temporary increase in blood volume in the superficial brain vessels.

Opening of the Blood-Brain Barrier by Low-Frequency (28-kHz) Ultrasound: A Novel Pinhole-Assisted Mechanical Scanning Device

Disruption of the blood-brain barrier (BBB) may be transiently achieved via high-frequency focused spherical ultrasound in the presence of microbubbles. In this experimental animal study, we sought to determine whether focal reversible opening of the BBB may be achieved using low-frequency ( i.e., 20–30 kHz) planar ultrasonic waves. In the presence of microbubbles, we were able to obtain BBB opening using non-focused ultrasound irradiation with a frequency as low as 28 kHz. We also achieved a tight regulation of the ultrasound patterns by using a mechanical scanning device equipped with a pinhole. Histologic examination of the brains supported the feasibility of our system. The areas of BBB disruption obtained with this method were large enough to cover a typical circumscribed cerebral tumor mass. The inherent advantages of our BBB opening method include an improved portability, the possibility to obtain fairly wide areas of BBB opening and a low incidence of hemorrhagic complications. In addition, our system has the potential to reduce the need for image guidance for treating superficial brain lesions. (E-mail: haoliliu@mail.cgu.edu.tw).

Deep Brain Hyperthermia While Rewarming from Hypothermic Circulatory Arrest

Neurologic injury is a feared and serious long-term complication of cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA). Postoperative hyperthermia was found to enhance postischemic neurologic injury. The use of core temperature as the reference point through CPB assumes parallel changes in brain temperature. We tested the hypothesis that regional and deep brain temperature (DBT) differ during cooling, DHCA, and rewarming. Neonatal piglets (n = 9) were subject to CPB and cooled to rectal temperature (RT) of 18 degrees C, 30 minutes of DHCA were initiated, and subsequently the piglets were rewarmed to RT of 36.5 degrees C and weaned from CPB. Temperature probes were inserted into the DBT targeting the caudate and thalamic nuclei, their position confirmed by pathology. Superficial brain temperature was measured by a temperature probe inserted extradurally. RT, nasopharyngeal (NPT), and tympanic (TT) temperatures were recorded. During cooling the deep brain cooled faster and to lower temperatures compared to RT and TT; NPT reflected DBT accurately. During rewarming DBT was significantly higher than RT and TT. By the end of rewarming the difference between the deep brain and the RT reached statistical significance (30 minutes: 35.1 +/- 0.7 vs. 32.3 +/- 0.7 p < 0.05, respectively, 40 minutes: 37.5 +/- 0.3 vs. 34.7 +/- 0.8 p < 0.05, respectively). Deep brain hyperthermia routinely occurs during the last stages of rewarming following DHCA. DBT is accurately reflected by NPT and is directly correlated with inflow temperature. Therefore, during rewarming inflow temperatures should not exceed 36 degrees C and NPT should be closely monitored.

Focal and bidirectional modulation of lower limb motor cortex using anodal transcranial direct current stimulation

Because we are interested in non-invasive transcranial brain stimulation as an adjuvant to post-stroke walking therapy, we applied direct current stimulation (tDCS) preferentially to either the left or right lower limb motor cortex (M1) in two separate sessions and assessed the resulting modulation in both cortices. We hypothesized that tDCS applied preferentially to one lower limb M1 of healthy subjects would induce between-hemisphere opposite sign modulation. Transcranial magnetic stimulation (TMS) with the coil offset 2 cm either side of vertex was used to assess the percent change in rectified motor evoked potential (MEP) area recorded bilaterally from vastus lateralis (VL) and tibialis anterior (TA) of 10 subjects during weak tonic contraction. ANOVA revealed an up-regulation of the target cortex and a down-regulation of the non-target cortex (p = 0.001) and no effects of hemisphere (left, right) or muscle (TA, VL). Significant modulation was evident in 78% of VL and TA muscles (all p < 0.05). Excitability increased in 60%, but decreased in 18%. For 43% when excitability increased, a simultaneous decrease in excitability was evident in homologous muscle responses providing support for our hypothesis. The results indicate a modest effectiveness and focality of anodal tDCS when applied to lower limb M1, suggesting in a human model that the strength and depth of polarizing cortical currents induced by tDCS likely depend on inter-individual differences in the electrical properties of superficial brain structures.

Whole-Cell Recording and Voltage-Sensitive Dye Imaging In Vivo: Figure 1.

INTRODUCTIONThis protocol describes an in vivo technique for combining whole-cell (WC) recordings of membrane potentials of individual neurons with voltage-sensitive dye (VSD) imaging of the ensemble neocortical network dynamics. If careful experimental measurements and controls are performed, VSD imaging can be used to define the ensemble spatiotemporal subthreshold membrane potential dynamics within which the membrane potential changes of individual neurons are embedded. Data from these individual neurons can be recorded simultaneously with the ensemble dynamics using the WC technique. This approach has been tested on rodent barrel cortex, but it is likely to be applicable, with minor modifications, to other superficial brain areas (including other neocortical areas, cerebellum, and olfactory bulb) and other species (such as cat or monkey).

Using simultaneous repetitive Transcranial Magnetic Stimulation/functional Near Infrared Spectroscopy (rTMS/fNIRS) to measure brain activation and connectivity

IntroductionSimultaneously acquiring functional Near Infrared Spectroscopy (fNIRS) during Transcranial Magnetic Stimulation (rTMS) offers the possibility of directly investigating superficial cortical brain activation and connectivity. In addition, the effects of rTMS in distinct brain regions without quantifiable behavioral changes can be objectively measured. MethodsHealthy, nonmedicated participants age 18–50 years were recruited from the local community. After written informed consent was obtained, the participants were screened to ensure that they met inclusion criteria. They underwent two visits of simultaneous rTMS/fNIRS separated by 2 to 3 days. In each visit, the motor cortex and subsequently the prefrontal cortex (5 cm anterior to the motor cortex) were stimulated (1 Hz, max 120% MT, 10 s on with 80 s off, for 15 trains) while simultaneous fNIRS data were acquired from the ipsilateral and contralateral brain regions. ResultsTwelve healthy volunteers were enrolled with one excluded prior to stimulation. The 11 participants studied (9 male) had a mean age of 31.8 (s.d. 10.2, range 20–49) years. There was no significant difference in fNIRS between Visit 1 and Visit 2. Stimulation of both the motor and prefrontal cortices resulted in a significant decrease in oxygenated hemoglobin (HbO2) concentration in both the ipsilateral and contralateral cortices. The ipsilateral and contralateral changes showed high temporal consistency. DiscussionSimultaneous rTMS/fNIRS provides a reliable measure of regional cortical brain activation and connectivity that could be very useful in studying brain disorders as well as cortical changes induced by rTMS.

Theoretical evaluations of therapeutic systemic and local cerebral hypothermia

PurposeTo simulate cerebral temperature behaviour with hypothermia treatment applying different cooling devices and to find the optimal brain temperature monitoring. MethodsModels based on hourly temperature values recorded in patients with severe aneurysmal subarachnoid hemorrhage, taking MRI data, thermal conductive properties, metabolism and blood flow into account were applied to different scenarios of hypothermia. ResultsSystemic hypothermia by endovascular cooling leads to an uniform temperature decrease within the brain tissue. Cooling with head caps lead to 33°C only in the superficial brain while the deep brain remains higher than 36°C. Cooling with neckbands lead to 35.8°C for dry and 32.8°C for wet skin in the deep brain. ConclusionsWith head caps temperatures below 36°C cannot be reached in the deep brain tissue, whereas neckbands, covering the carotid triangles, may lead to hypothermic temperatures in the deep brain tissue. Temperature sensors have to be applied at least 2cm below the cortical surface to give values representative for deep brain tissue.

Management of a large superficial brain abscess with repeated aspirations.

Management of brain abscesses is still an issue of debate. Large superficial abscesses should be totally extirpated through a craniotomy. We present a case of a 66-year old man with a brain pyogenic abscess, without neurological symptoms and signs, without positive cultures, larger than 4cm in size, located superficially who was treated successfully by two repeated aspirations without intracavitary application of antibiotics. We conclude that it is effective to treat a large superficial in capsular stage brain abscess with repeated elective aspirations, since the clinical picture of the patient is mild.

Investigation of diffuse correlation spectroscopy in multi-layered media including the human head

In this work, diffuse correlation spectroscopy (DCS) is explored in multi-layered geometries. A quantitative comparison of an homogeneous versus a two-layered model efficiencies to recover flow changes is presented. By simulating a realistic human head with MRI anatomical data, we show that the two-layered model allows distinction between changes in superficial layers and brain. We also show that the two-layered model provides a better estimate of the flow change than the homogeneous one. Experimental measurements with a two-layered dynamical phantom confirm the ability of the two-layered analytical model to distinguish flow increase in each layer.

Human Sectional Anatomy – Atlas of body sections, CT and MRI images

With evolving technology we are now easily able to produce images of the human body from virtually any plane or perspective. Accordingly, the need for resources to help translate three-dimensional anatomical knowledge into two dimensions (and vice versa) has arisen. This book has a wide intended audience – radiologists, radiographers, anatomists, medical students and those taking postgraduate qualifications in radiology, surgery and medicine. Primarily, I see this book on the shelf of a radiologist but it will appeal and be valuable to anyone who uses sectional imaging as a part of their practice. This resource would assist preparation for postgraduate examinations, particularly in the fields of radiology and surgery, and would be a useful teaching aid in the undergraduate classroom. The hardback edition is quite a large, heavy text that will withstand the rigours of constant reference by the CT or MRI machine or the hands of eager students. The main feature of this atlas is the presentation of high quality coloured photographs from embalmed cadavers. They are labelled with superimposed numbers and despite the comprehensiveness of the labelling remain exceptionally clear. Corresponding imaging is predominantly axial CT or MRI with didactic equivalent line drawings to reduce distortion of the image. For each cadaveric section the reader is presented with relevant notes pertaining to the image. These include features such as explanation of pathology within the image or of anatomical variation. The book is logically organized from head to toe making location of specific slices quick and easy without the index. It opens with a brief account of the history of cross-sectional anatomy, a description of how the cadaveric slices were obtained and an introduction to the imaging modalities used. For the benefit of medical students and those not accustomed to looking at sectional anatomy or images there are introductory ‘helpful hints’ offering a structured approach to identifying structures in this way. This atlas devotes 100 pages to the head and neck at 1-cm serial axial slices through the head and 1.5-cm slices through the neck. Also included within this section are images of superficial brain dissections, coronal sections and specific dissections with imaging of the petrous temporal bone. Following on are 2-cm serial slices through the thorax, abdomen and pelvis with extra slices included to show important anatomical differences between the male and female body. The upper and lower limbs are represented at selected levels in axial, coronal and sagittal sections. Interspersed through the book are some beautiful 3D volume rendered CT images, displaying the capabilities of modern imaging techniques and adding a touch of radiological decadence to this new edition. There are few aspects of this book that will be likely to disappoint, other than that it is out of the price range for most students to buy their own copy. For students and trainees, the pocket edition of this atlas would likely suffice. My one criticism would be that I would have liked to have seen larger radiological images, probably by sacrificing the relatively large size of the orientation markers (although these markers do help keep the book accessible to the student or novice reader). In conclusion, this is an authoritative reference text and the quality of presentation goes a long way to justifying the price. It is a beautifully aesthetic atlas and a pleasure to study from; it will be a valuable addition to the bookshelf of anyone involved in radiological diagnosis.

Immune cell entry into the central nervous system: Involvement of adhesion molecules and chemokines

In multiple sclerosis and in its animal model experimental autoimmune encephalomyelitis (EAE), inflammatory cells migrate across the highly specialized endothelial blood–brain barrier (BBB) and gain access to the central nervous system (CNS). It is well established that leukocyte recruitment across this vascular bed is unique due to the predominant involvement of α4-integrins in mediating the initial contact to as well as firm adhesion with the endothelium. In contrast, the involvement of the selectins, L-selectin, E- and P-selectin and their respective carbohydrate ligands such as P-selectin glycoprotein (PSGL)-1 in this process has been controversially discussed. Intravital microscopic analysis of immune cell interaction with superficial brain vessels demonstrates a role for E- and P-selectin and their common ligand PSGL-1 in lymphocyte rolling. However, E- and P-selectin-deficient SJL- or C57Bl/6 mice or PSGL-1-deficient C57Bl/6 mice develop EAE indistinguishable from wild-type mice. Considering these apparently discrepant observations, it needs to be discussed whether the molecular mechanisms involved in leukocyte trafficking across superficial brain vessels are irrelevant for EAE pathogenesis or whether the therapeutic efficacy of targeting α4-integrins in EAE is truly dependent on the inhibition of leukocyte trafficking across the BBB.

Hyperthermia as an Early Sign of Intracranial Hemorrhage in Full-term Neonates

Intracranial hemorrhage (ICH) in full-term infants is uncommon and is a rare cause of neonatal fever. This study was conducted to estimate the incidences of ICH and fever in a hospital-based population, and to determine if the clinical features of neonatal ICH with and without hyperthermia differ. We selected 315 afebrile neonates who received cranial ultrasonography screening from 2003 to 2004 as the control group, and 153 neonates diagnosed with fever from 1998 to 2004 as the study group. During the same period, 28 full-term neonates with birth weights >2500g and ICH in the first week of life were enrolled retrospectively. They were divided into hyperthermia (n=11) and nonhyperthermia (n=17) groups. Three babies in the control group and 11 in the study group had ICH; the incidence of ICH in the hyperthermia group was significantly higher (3/315 vs. 11/153; p < 0.001). Compared with the nonhyperthermia group, the hyperthermia group had Less cyanosis (2/11 vs. 10/17; p = 0.04), Less lymphocyte predominance (33.7 vs. 80%; p = 0.032), higher neutrophil/lymphocyte ratio (1.9 vs. 0.3; p = 0.006), higher erythrocyte/leukocyte ratio (425 vs. 79.5; p = 0.05) in cerebrospinal fluid and an increased incidence of subarachnoid hemorrhage accompanied by intracerebral parenchymal hemorrhage (4/11 vs. 0/17; p = 0.016). The incidence of ICH was higher in febrile than in afebrile neonates. ICH presenting with hyperthermia might go unrecognized, because its other symptoms are subtle and a neutrophil predominance in the cerebrospinal fluid might result in a misdiagnosis of meningitis. ICH in the interior brain tended to manifest more commonly as hyperthermia than did ICH in the superficial brain. A cranial image examination should be considered in the evaluation of neonatal fever.