Reproducibility, interrater agreement, and age-related changes of fractional anisotropy measures at 3T in healthy subjects: effect of the applied b-value.

BACKGROUND AND PURPOSE: There is no reproducibility study of fractional anisotropy (FA) measurements at 3T using regions of interest (ROIs). Our purpose was to establish the extent and statistical significance of the interrater variability, the variability observed with 2 different b-values, and in 2 separate scanning sessions. MATERIALS AND METHODS: Twelve healthy volunteers underwent MR imaging twice. MR imaging was performed on a 3T unit, and FA maps were analyzed independently by 2 observers using ROIs positioned in the corpus callosum, internal capsules, corticospinal tracts, and right thalamus. Changes in FA values (x10(3)) measured with 2 b-values (700 and 1000 s/mm(2)), age-related differences, interobserver agreement, and measurement reproducibility were assessed. RESULTS: In the right internal capsule genu (FA = 702/728; b = 1000/700 s/mm(2)) and the left anterior limb of the internal capsule (AIC; FA = 617/745; b = 1000/700 s/mm(2)), the FA values were significantly different between the 2 b-values (P = .02 and .05, respectively). Significant age-related differences in FA were observed in the genu of the corpus callosum and in the left AIC. Interrater measurements showed fair-to-moderate agreement for most anatomic structures. The lowest significant change for a single subject regarding any FA values between the 2 sessions was in the corpus callosum (4%), whereas the highest one was in the corticospinal tracts (27%). The Bland-Altman plot analysis showed that the 1000-s/mm(2) b-value gave satisfactorily reproducible measurements equally good or better than the 700-s/mm(2) b-value. CONCLUSION: The reproducibility of FA estimates using ROIs was satisfactory. Measurements with a b-value at 1000 s/mm(2) showed superior reproducibility in most anatomic locations.

Traumatic injuries: imaging of head injuries.

Due to the forces of acceleration, linear translation, as well as rotational and angular acceleration, the brain undergoes deformation and distortion depending on the site of impact of traumatizing force direction, severity of the traumatizing force, and tissue resistance of the brain. Linear translation of accereration in a closed-head injury can run along the shorter diameter of the skull in latero-lateral direction causing mostly extra-axial lesions (subdural hematoma,epidural hematoma, subarachnoidal hemorrhage) or quite pronounced coup and countercoup contusions. Contusions are considerably less frequently present in medial or paramedial centroaxial blows (fronto-occipital or occipito-frontal). The centroaxial blows produce a different pattern of lesions mostly in the deep structures, causing in some cases a special category of the brain injury, the diffuse axonal injury (DAI). The brain stem can also be damaged, but it is damaged more often in patients who have suffered centroaxial traumatic force direction. Computed tomography and MRI are the most common techniques in patients who have suffered brain injury. Computed tomography is currently the first imaging technique to be used after head injury, in those settings where CT is available. Using CT, scalp, bone, extra-axial hematomas, and parenchymal injury can be demonstrated. Computed tomography is rapid and easily performed also in monitored patients. It is the most relevant imaging procedure for surgical lesions. Computed tomography is a suitable method to follow the dynamics of lesion development giving an insight into the corresponding pathological development of the brain injury. Magnetic resonance imaging is more sensitive for all posttraumatic lesions except skull fractures and subarachnoidal hemorrhage, but scanning time is longer, and the problem with the monitoring of patients outside the MRI field is present. If CT does not demonstrate pathology as can adequately be explained to account for clinical state, MRI is warranted. Follow-up is best done with MRI as it is more sensitive to parenchymal changes. In routine MR protocol gradient-recalled-echo sequences should be included at any other time after a traumatic event since they are very sensitive in detection of hemosiderin as well as former hematoma without hemosiderin. The MR signal intensity varies depending on sequences and time scanning after trauma.

[Importance of the CRH (corticotropin releasing hormone) test in the differential diagnosis of Cushing's syndrome]. / Vrijednost CRH-testa u diferencijalnoj dijagnozi Cushingova sindroma.

In the group of 13 patients with Cushing's syndrome (CS) CRH test was performed by sampling the blood from peripheral vein and in eight patients also after inferior petrosal sinus catheterization (IPSC) to resolve the disease etiology. In the group of patients with Cushing's disease (CD, n = 11), which was proven by surgery and adenoma immunohistochemistry, 10/11 had in CRH test the significant increase of cortisol and ACTH in the peripheral blood. Among two patients with ectopic ACTH syndrome one had the significant increase of both hormones in CRH test. After IPSC the ratio of ACTH in the petrosal sinus and in the peripheral vein was significant in 4/8 patients before, and in 6/8 after CRH administration. The intersinus gradient was significant in 3/8 patients before, and in 4/8 after CRH test. According to our results we can conclude that the determination of ACTH in the blood from peripheral veins after CRH administration is a very sensitive method for differential diagnosis of CS, while the results after IPSC were less sensitive in our conditions than those described in the literature.

Evolution of clinical symptoms in a young woman with a recurrent gonadotroph adenoma causing ovarian hyperstimulation.

OBJECTIVE: To demonstrate the clinical course in a young female with gonadotroph adenoma causing ovarian stimulation. PATIENT AND METHODS: Our patient was a 23-year-old woman with a history of oligomenorrhea who had previously undergone bilateral ovarian wedge resection owing to the clinical appearance of polycystic ovaries. Two years later, she sought treatment for headache, galactorrhea, history of spotting and lower abdominal distension. FSH, LH, beta-LH, inhibin A and B, estradiol, prolactin (PRL), and beta-chorionic gonadotrophin (beta-CG) were measured, and the responses of FSH, LH and beta-LH to thyrotrophin-releasing hormone (TRH) were documented. Immunohistochemical analysis of the tumor tissue was performed after surgery. Five years after the trans-sphenoidal surgery, the patient again became oligomenorrheic. A large recurrent adenoma was diagnosed on CT one year later. Transvaginal ultrasound showed ovaries of normal size with multiple small cystic formations simulating a polycystic pattern, While the patient was awaiting surgery, a pituitary apoplexy occurred. Emergency decompressive surgery was performed and the patient fully recovered. RESULTS: Enlarged ovaries were found on ultrasound examination simulating a hyperstimulation-like pattern. At that time, elevated levels of FSH (13.4IU/l) and marginally elevated levels of beta-LH (1.43ng/ml) were found, whereas the level of LH (0.5IU/l) was subnormal. Plasma estradiol was markedly supranormal (6150pmol/l). Levels of inhibin A and B were elevated (326pg/ml and 588pg/ml respectively). The prolactin level (70ng/ml) was increased, whereas beta-chorionic gonadotrophin (beta-CG) was normal. Significantly increased FSH, LH, and beta-LH responses to TRH stimulation were documented. Pituitary macroadenoma was found on MRI scan and removed by trans-sphenoidal surgery. Immunohistochemical examination showed high positivity for beta-CG and LH, and slight positivity for FSH. Five years after the surgery, estradiol was elevated (1160pmol/l), whereas basal levels of LH (4.65IU/l) and FSH (3.98IU/l) were not suppressed. After the second operation, immunostaining of the adenoma tissue confirmed the previous findings. CONCLUSIONS: Measurement of gonadotrophins in our case did not prove to be a method for identifying a large recurrent gonadotroph pituitary adenoma. The sonographic ovarian imaging varied from a polycystic- to an ovarian hyperstimulation-like pattern during the evolution of the tumour.

Craniocerebral war missile injuries: clinical and radiological study.

In this study we reviewed the initial clinical and radiological management and early outcomes of 176 consecutive patients from the war in Croatia.

Clinical and morphological features of undifferentiated monomorphous GH/TSH-secreting pituitary adenoma.

A 41-year-old male presented with progressive visual defects, acromegaly and hyperthyroidism. After clinical evaluation a giant GH/TSH-secreting pituitary adenoma was diagnosed. Administration of the somatostatin analog octreotide at doses of 150 microg s.c. per day inhibited the secretion of both GH and TSH. A three-week treatment with octreotide prior to surgery led to slight visual improvement and CT scan showed some new necrotic areas within the tumor mass. Transcranial surgery was performed. By immunohistochemical analyses of the adenoma tissue GH, prolactin and beta-chorionic gonadotropin were detected; TSH was negative. Electron microscopy revealed an undifferentiated, monomorphous adenoma with morphological features of an acidophil stem cell adenoma such as the presence of misplaced exocytoses, fibrous bodies and mitochondrial gigantism. However, the tumor cells contained small secretory granules (up to 250 nm) accumulated along the cell membrane characteristic of thyrotrope cells. Furthermore, some adenoma cells were fusiform with long cytoplasmic processes resembling thyrotropes. Two months after the operation CT scan revealed a large residual tumor. Serum GH and TSH levels had increased again and the TSH level was even higher than before the treatment. The patient died suddenly, most probably of lethal arrhythmia. Specimens of the adenoma tissue obtained at autopsy confirmed the previous findings with the exception of positive immunostaining for TSH which was found in less than 1% of the adenoma cells. This undifferentiated, monomorphous GH/TSH-secreting pituitary adenoma represents an entity that is unusual both in its ultrastructural features and clinical manifestations suggesting a cytogenesis from an early, undifferentiated stem cell.

Megalencephalic leukoencephalopathy: a further case of a new neurodegenerative white matter disease.

The case is presented of a 4.5-year-old boy with cystic megalencephalic leukoencephalopathy who met the diagnostic criteria of a recently described neurodegenerative white matter disorder, i.e. leukoencephalopathy with swelling and a discrepantly mild clinical course (van der Knaap 1995). He demonstrated an extremely mild and slowly progressive clinical course with near normal psychomotor development, particularly of mental functions, which contrasted with somewhat disturbed gross and fine motor skills. Repeated CT and MRI scanning showed extensive hemispheral cerebral white matter changes and demonstrated predominant frontal involvement of the periventricular and subcortical white matter. MRI was more sensitive in the detection of preserved structures, i.e. occipital subcortical and central white matter, as well as in the visualisation of swelling and cystic lesions in the tip of the temporal lobes, which represent the hallmark of this entity. Thus, MRI is an essential diagnostic tool for this entity.

Cystic leukoencephalopathy in a megalencephalic child: clinical and magnetic resonance imaging/magnetic resonance spectroscopy findings.

A neurodegenerative disorder characterized by megalencephaly since early infancy and slowly progressive symptoms of cerebellar, pyramidal, and extrapyramidal dysfunction, pseudobulbar signs, and epilepsy was detected in an 8-year-old girl with severe neuromotor handicap but preservation of mental and sensory functions. Cranial computed tomography and magnetic resonance imaging revealed brain swelling as well as severe abnormalities of frontal, temporal, and parietal white matter, with an extended cystlike appearance isointense to cerebrospinal fluid. Localized proton magnetic resonance spectroscopy of affected cystic white matter showed a loss of all metabolites, in accordance with a complete disintegration of neuroaxonal and glial tissue. This case is likely a severe variant of a recently described megalencephalic leukoencephalopathy with swelling and discrepantly mild clinical course.

The course of the traumatising force in acceleration head injury: CT evidence.

Since brain damage in closed head injury of acceleration-deceleration type depends on the site of impact and on the course of the traumatising force, a reconstruction of these was attempted using CT. The study included 45 standard CT studies of adults with closed acceleration-deceleration head injuries. We selected 32 patients exclusively on the basis of CT findings of soft tissue contusion, skull fractures and cerebral contusions (coup and/or contrecoup, as well as other parenchymal lesions), while in the remaining 13 patients clinical findings were also used. On CT, the axial section of the skull was divided into 12 sections imitating the clock-face, to permit computerised graphic presentation of the direction of the traumatising force. Analysis of cerebral contusions on different CT studies in each case allowed location of "dominant coup" and "dominant contrecoup" lesions to be determined. The site of impact and the course of the traumatising force were reconstructed and graphically presented on the basis of these findings, supplemented with data on soft tissue contusions (present in 71% of cases), skull fractures (in 36%) and sometimes on other brain lesions. Comparison of the computerised graphic presentation of the site of impact and direction of the traumatic force and the location of lesions revealed a high correlation between them. In 80% of cases, the site of impact could be visualised only by CT. The acceleration force acted along the longer axis of the head (centroaxial or semioblique) in 87% and along the shorter axis in 13% of cases. Multiple lesions were found in 87% of cases. The lesions were most frequent in the frontal (51%) and temporal (26%) lobes. CT was very useful for reconstruction of the site of impact and of the course of the traumatising force in acceleration head injury. Data obtained by this procedure may have far-reaching prognostic and forensic implications.

CT analysis of missile head injury.

Between August 1991 and December 1992, CT was performed on 154 patients who had suffered missile head injury during the war in the Republic of Croatia. In 54% CT was performed 1-24 h after injury, and in 27% follow-up CT was also obtained. The wounds were penetrating, tangential or perforating (45%, 34% and 21%, respectively). Haemorrhage was the most frequent lesion in the brain (84%). Follow-up CT evolution of haemorrhage, oedema, cerebritis, abscess, secondary vascular lesions, necrosis, encephalomalacia and hydrocephalus. The most dynamic changes occurred 7-14 days after injury. In 14% of cases, deep cerebral lesions were found in the corpus callosum, septum pellucidum periventricular region and pons, although bone and shell fragments were in a different part of the brain parenchyma. Such lesions were found in penetrating injuries only. CT proved very useful for assessing the extent and type of lesions. Although different mechanisms of brain damage in missile head injury are known, here they are, to the best of our knowledge, shown for the first time by CT.

Patterns of lesions of corpus callosum in inner cerebral trauma visualized by computed tomography.

Computed tomographic analysis of lesions of the corpus callosum in 13 patients with "inner cerebral trauma" showed significant congruence of linear translation of acceleration and the topographic distribution of such lesions. This congruence permits computed tomography to be used to reconstruct the course of linear translation and the site of the main blow, which can be important for forensic use. The findings of even a small lesion in the corpus callosum indicates the need for further investigation of other structures which are usually involved in inner cerebral trauma, such as the hippocampus and brain stem.

Hypoxic-ischemic brain damage in term neonates--the relation of neurodevelopmental handicap to cranial ultrasound findings.

This study presents ultrasound findings and neurodevelopmental follow-up in ten infants born at term suffering most severe grade of hypoxic-ischemic encephalopathy. Early ultrasound findings showed in nine of these ten neonates signs of cerebral edema accompanied in two children by intraventricular haemorrhage. Late ultrasound findings in all infants examined demonstrated severe cerebral atrophy, predominantly affecting the cortico-subcortical area. In three children multiple subcortical cysts were also present, corresponding to ultrasound findings of subcortical leukomalacia. Cranial computerized tomography was performed in six of the ten children, showing more precisely the predominant site of cortical atrophy, whereas in children with ultrasound findings of subcortical leukomalacia extensive low density areas in the subcortical white matter were present. All children had neurodevelopmental follow-up for between two and seven years. Six of the ten children have multiple disabilities suffering from spastic quadriparesis, epilepsy, mental retardation and/or visual disability. Among these six were all three children with subcortical leukomalacia. All the children demonstrated poor head growth and became markedly microcephalic. We consider ultrasonography to be very useful in the diagnosis of hypoxic-ischemic brain damage in term neonates as well in predicting the neurodevelopmental outcome in asphyxiated term infants.

CT detection of minimal brain lesions in closed cerebral trauma.

From the group of patients with clinically manifested closed head injuries, patients with minimal traumatic lesions in the brain parenchyma, were separated and in addition radiographically analyzed. There were 22 patients in the group. On plain CT scans they had foci 5 to 10 mm large caused by trauma. CT is suitable investigation technique for detecting minimal traumatic brain lesions. Besides, CT is suitable for the follow up of the lesion evolution dynamics, which comprises not only changes in the lesions density but also the possibility of registering primarily reversible but macroscopically (invisible) lesions into (visible) reversible lesions on the control scans. The finding of only one or two minimal lesions in critical locations in the "inner cerebral trauma" always indicated the existence of possible lesions in other locations within the known pattern of the ICT. Minimal traumatic lesions of the brain frequently occur in ICT or in all cases where the acceleration of traumatizing forces has anteroposterior or postero-anterior course of direction. Their recognition by neuroimaging methods is of great importance due to the central localization of the foci, which otherwise cannot be detected by other methods.

Diagnostic possibilities of closed head injuries of acceleration type using computed tomography.

A group of 42 patients with closed head injuries of acceleration type is reported. All of them were treated at various departments of the General Hospital in Maribor. The aim of investigation was to find out the diagnostic possibilities of head and brain damages in closed head injuries of acceleration type by the method of computed tomography (CT) and making comparison with the clinical picture of each individual patient. The patients were not investigated at random but were grouped in accordance with the direction of traumatic force action. The CT analyses were performed according to characteristic patterns of traumatic brain disease. The circumstances of head injury were reliable guidelines for devoting more attention to some brain areas. The density of each lesion was examined, too. The investigation has shown that lesions of "inner cerebral trauma" pattern (ICT-Grcevic 1965) are visible on CT at least as often as coup-contrecoup lesions or even more. Only in cases with latero-lateral direction of traumatizing force (control group) coup-contrecoup lesions were found more frequently. Deep cerebral lesions of the latero-lateral type of acceleration head trauma were never or seldom encountered.

Dumbbell meningioma of the cervico-clavicular region.

The authors are reporting on a case of a 55-year-old man with an epidural meningioma in the region from the C VII. to the Th I. segment. The tumor encircled this region, and to the front and right involved the channels through which pass the C VI, C VII. and C VIII. roots. Subdurally, no tumoral mass was found. Another part of this tumor, of the same histological architecture as the epidural cervicospinal part was found in the supraclavicular region to the right, closely connected to the arteries and nerves of this region. The authors discuss the possibility of the tumoral occurrence at this site, primarily taking into account the origin of this tumor from the cells of the outer surface of the arachnoidea, i.e. cap cells which can invade the dura, with later separation from the main arachnoidal layer. The other possibility of such dumbbell meningioma occurring at the outgoing openings of the neural paths from the spinal channel should be looked for in the remnants of the arachnoidal cells in the region of the outgoing openings. In the paper are also discussed and correlated clinico-pathological, CT and angiographic findings.

Correlative tissue pathology of intracranial neurinomas with computed tomography scans.

On computed tomography (CT) layers through the tumor the quality of picture depends upon the tumoral tissue structure, i.e., upon its histological appearance. In the formation of this histological appearance to a greater or lesser extent a series of various elements are involved, which are responsible for the density on CT scan, e.g., blood vessels, fatty tissue, calcium, connective tissue, collagen, etc. For some tumors the most important characteristic is specific organization of tissues in the volume, which can be clearly seen on high-quality CT scan. Possible limitations are due to technical capabilities of a CT apparatus. In our study we have obtained the most valuable results by analyzing the quality of picture of neurinomas on the so-called native CT scans, and by evaluating the way in which the picture of the tumoral tissue changed by opacification after an intravenous injection of contrast medium. Our study included 23 intracranial neurinomas. Twenty of them were neurinomas of the statoacoustic nerve, 1 of the orbit, 1 of the Gasser's gaglion and 1 was in the parasagittal region. For each particular tumor on histological specimens Antoni A and Antoni B types of tissue were semiquantitatively identified. In our study we have chosen only those cases for which we had a plenty of tumoral tissue suitable for semiserial analysis. The results of the histological analysis were compared with the results of the CT assessment of the tumoral tissue. Larger necrotic areas and cystic formations within tumoral tissue, which we could not analyze on our histological specimens, were excluded from the evaluation of CT scans of these tumors. Our results indicate a positive correlation between the histological appearance of neurinomas and their CT scans. This correlation between the histological properties of the tumoral tissue and the CT scan was almost 100% in those cases in which one histological type of neurinomas significantly prevailed. The prevalence of one type of neurinoma tissue was found in 74% of cases. In almost 61% of neurinomas in the histological appearance Antoni A type of tissue prevailed, what was clearly seen on CT in the form of hyperdense areas of the tumor. Antoni B type of tissue was histologically found in about 13% of neurinomas. These tumors had a marked hypodense picture of the tumoral tissue. The rest of neurinomas had mixed types of tissue. In this group of tumors we could not use the CT findings as an indicator in preoperative analysis of histopathological tissue characteristics.

Dysplastic granulo-molecular hypertrophy of the cerebellar cortex (L'hermitte-Duclos disease): report of three cases.

In this paper three cases with peculiar disease of the cerebellar cortex are presented. The disease is well known as L'hermitte-Duclos disease (LDD), but nowadays it is also called "dysplastic granulo-molecular hypertrophy of the cerebellar cortex" according to the modern theories of its etiology. Curious changes of the cerebellum in LDD are probably the result of a combination of delayed migration of Purkinje cells which occurs during the intrauterine period of cerebellar development, and of reactive hypertrophy of granular cells. Presented cases of L'hermitte-Duclos disease are, according to the literature, more or less typical by their clinical appearance and by their histological findings. Our electromicroscopical data support the findings of those authors who found only axodendritic sinapses on the hypertrophied ganglion cells, according to the idea that those cells are originally granular cells of the cerebellar cortex. CT scan of all our patients revealed parallel, worm-like, hyperdense formations in a hypodense process of the cerebellum. The same picture existed in some other described patients, but attention was paid to it. We consider this picture on the computed tomography to be characteristic, if not even patognomonic for the L'hermitte-Duclos disease, which gives us an entirely new scientific contribution in the process of the diagnosis of this peculiar disease.

Cranial ultrasonography in the evaluation of macrocrania in infancy.

Cranial ultrasonography was used in the initial evaluation of 40 infants with macrocrania. Three of the infants had normal findings. The other 37 had evidence of various types of abnormality: intraventricular obstructive hydrocephalus, external hydrocephalus, arrested hydrocephalus with atrophy, or mild ventriculomegaly. All the infants were given neurological and developmental examinations at the time of presentation and were followed up for one year. Sonograms and head-circumference and intracranial pressure measurements were done at intervals, according to the initial ultrasound findings and the clinical status of the children. Neurodevelopmental outcome was related to the type of abnormality. The majority of children with external hydrocephalus were neurodevelopmentally normal at follow-up. In contrast, those with obstructive or arrested hydrocephalus had unfavourable outcomes, which may be related to the significant perinatal insult causing the hydrocephalus. CT confirmation was available for 16 of the infants.

[Computerized tomography and ultrasound in the early diagnosis of brain damage]. / Kompjutorizirana tomografija I ultrazvuk u dijagnostici ranog ostecenja mozga.

Eighty-one neonates were evaluated clinically by ultrasound and/or CT with the aim of assessing diagnostic possibilities of both methods in the cases of pathomorphologic findings linked with perinatal risk factors and subsequent neurologic deficits. In perinatal at-risk infants (N = 11), premature infants (N = 6) and term infants (N = 5) ultrasound is a reliable diagnostic method in the detection and follow-up of intraventricular hemorrhage and perivascular leukomalacia in preterm infants, while for the diagnosis of hypoxic-ischemic lesions, especially focal cortico-subcortical changes in term infants, besides ultrasound it is necessary to perform CT. In perinatal infants (N = 50) with neurologic deficits at the age of 2-5 years, on CT scanning, atrophic changes were found in 50% of cases, while in 10% vascular lesions were observed, and a combination of atrophic and vascular lesions was found in 28% of the cases examined. In the group of infants (N = 20) with neurologic deficits (II and III trimenon) without risk factors, on CT scanning the pathomorphologic finding was identified as a vascular or atrophic lesion. In the authors' opinion, CT is the only objective method in the detection of the precise localization and evaluation of lesions in children with neurologic deficits after their first year of life.