A spinal thecal sac constriction model supports the theory that induced pressure gradients in the cord cause edema and cyst formation.

OBJECTIVE: Spinal cord cysts are a devastating condition that occur secondary to obstructions of the spinal canal, which may be caused by congenital malformations, trauma, spinal canal stenosis, tumors, meningitis, or arachnoiditis. A hypothesis that could explain how spinal cord cysts form in these situations has been presented recently. Therefore, a novel spinal thecal sac constriction model was implemented to test various aspects of this hypothesis. METHODS: Thecal sac constriction was achieved by subjecting rats to an extradural silk ligature at the T8 spinal cord level. Rats with complete spinal cord transection served as a second model for comparison. The animals underwent high-resolution magnetic resonance imaging and histological analysis. RESULTS: Thecal sac constriction caused edema cranial and caudal to the ligation within 3 weeks, and cysts developed after 8 to 13 weeks. In contrast, cysts in rats with spinal cord transection were located predominantly in the cranial spinal cord. Histological sections of spinal cords confirmed the magnetic resonance imaging results. CONCLUSION: Magnetic resonance imaging provided the specific advantage of enabling characterization of events as they occurred repeatedly over time in the spinal cords of individual living animals. The spinal thecal sac constriction model proved useful for investigation of features of the cerebrospinal fluid pulse pressure theory. Edema and cyst distributions were in accordance with this theory. We conclude that induced intramedullary pressure gradients originating from the cerebrospinal fluid pulse pressure may underlie cyst formation in the vicinity of spinal canal obstructions and that cysts are preceded by edema.

Increased levels of proinflammatory cytokines and nitric oxide metabolites in neuropsychiatric lupus erythematosus.

OBJECTIVE: To investigate systemic and intrathecal production of proinflammatory cytokines in relation to cerebrospinal fluid (CSF) nitric oxide (NO) release in patients with neuropsychiatric lupus erythematosus (NPLE). METHODS: Thirty patients with NPLE rated as mild, moderate, or severe were studied and CSF was obtained from 21 of these. Cytokine mRNA expressing cells were detected by in situ hybridisation. Soluble cytokines were assessed by enzyme linked immunosorbent assay (ELISA). Nitrite and nitrate were determined by capillary electrophoresis. RESULTS: Patients with NPLE had high numbers of lymphocytes expressing mRNA for tumour necrosis factor alpha (TNFalpha), interferon gamma, and interleukin 10 in blood. The number of peripheral blood TNFalpha mRNA positive cells correlated strongly with the level of NO metabolites in the CSF (r(2)=0.69). Both the number of peripheral blood mononuclear cells expressing mRNA for TNFalpha as well as the CSF level of NO metabolites correlated with NPLE disease severity. CONCLUSION: These data suggest that increased peripheral production of proinflammatory cytokines such as TNFalpha may contribute both to an increased production of NO in the central nervous system and to generation of clinical NPLE. The data also support the possibility that measurements of NO metabolites in CSF may be of value in the diagnosis of neurological symptoms related to SLE.

Reliability and reproducibility of brain tissue volumetry from segmented MR scans.

Reliable measurement of different tissue volumes in the living brain is of great importance for human brain research. In this article, we report on the inter- and intraoperator reliability and scan-rescan reproducibility of segmented intracranial tissue volumes from MR images using the image analysis software suite BRAINS. The absolute data of tissue volume measurements are also presented. The reliability and consistency of the measurements of the segmented volumes were excellent. The segmentation is robust and rapid and the volume measurements are plausible and suitable for quantitative studies in clinical brain research.

Magnetic resonance imaging and echocardiography in assessment of ventricular function in atrially corrected transposition of the great arteries.

OBJECTIVE: Patients with atrial correction of transposition of the great arteries (TGA) may develop right ventricular (RV) failure with time. A reliable non-invasive method for assessment of ventricular function is therefore needed. To evaluate the accuracy of echocardiography in assessment of ventricular volumes and function in these patients we compared echocardiography with magnetic resonance imaging (MRI) in 10 patients late after the Mustard and Senning procedures. DESIGN: Prospective echocardiography and MRI examinations were performed on the same day. Two different echocardiography technicians examined all patients. All echocardiography and MRI examinations were performed at the university hospital outpatient clinic and MRI department respectively. Ten patients, age 14.0+/-2.9 years, who had been operated on with atrial correction of TGA at 8 (2-60) months of age (median and range) were examined. Echocardiography RV and left ventricular (LV) end-systolic volumes (ESVs), end-diastolic volumes (EDVs), stroke volumes (SVs) and ejection fractions (EFs) were calculated, using the modified Simpson method, and compared with the same measurements obtained from MRI. RESULTS: For RV function there was good agreement between echocardiography- and MRI-derived measurements. Both echocardiography and MRI revealed reduced RV function with EFs of 42.6+/-9.1% and 46.4+/-7.2% respectively. For RV volumes there were no significant differences between echocardiography and MRI. LV function was significantly overestimated by echocardiography (EF with echocardiography = 72.7+/-4.4% vs. MRI = 50.5+/-7.6%) while all LV volumes were greatly underestimated. Echocardiography measurements of volumes in repeated examinations by different technicians showed large variations, 13-50%, for different variables in individual patients. CONCLUSION: Echocardiography can provide clinically important information concerning RV function in follow-up of patients late after atrial correction of TGA. It has limited value in assessment of LV function in these patients. Volume measurements by echocardiography are, however, highly user-dependent and interobserver variation is high. MRI may accordingly serve as an important reference method in individual patients.

MR spectroscopy shows reduced frontal lobe concentrations of N-acetyl aspartate in patients with juvenile myoclonic epilepsy.

PURPOSE: Neuropsychological studies suggest frontal lobe dysfunctions in patients with juvenile myoclonic epilepsy (JME). In this study we investigated whether an underlying mechanism could be a regional neuronal damage not visible with structural magnetic resonance (MR), but detectable with magnetic resonance spectroscopy (MRS). METHODS: The study included 15 patients with JME and 10 matched healthy controls. Quantitative single voxel MRS was conducted at 1.5 Tesla by using a STEAM sequence (TR/TE/TM = 6,000/30/13.7 ms). The voxels were placed over the right cerebellum, right thalamus, and the prefrontal and occipital cortex. The quantitation included fitting of transmitter gain, and correction for partial volume of cerebrovascular fluid. LC-Model was used for estimation of the absolute concentrations of total N-acetyl aspartate (NAA), cholines, total creatine, and myoinositol. RESULTS: Patients with JME had significantly reduced prefrontal concentrations of NAA in relation to controls (9.1 +/- 1.0 vs. 10.2 +/- 0.8 mM; p = 0.031 after Bonferroni correction). The other regions showed normal NAA values, as did the other metabolites. CONCLUSIONS: The observed reduction in NAA levels suggests a prefrontal neuronal lesion in patients with JME.

Changes in cross-sectional area in human exercising and non-exercising skeletal muscles.

This research was performed to study how the cross-sectional area (CSA) changes in the skeletal muscles of exercising (E-leg) and contralateral non-exercising (N-leg) legs and to evaluate to what extent changes in CSA mirror changes in blood flow or extravascular water displacement. Seven healthy volunteers performed plantar flexion exercise at three different exercise intensities for 10 min each. Six plantar flexions followed by a 2-s rest in between allowed repeated measurement of the blood flow to the lower limbs by duplex ultrasonography in the popliteal artery and CSA by magnetic resonance imaging. The CSA was measured using manual planimetry at rest and after 3 and 9 min of the exercise periods. The CSA increased in the E-leg by 4.5% and decreased in the N-leg by -2.4%, from rest to highest exercise intensity. Post-exercise imaging of the E-leg showed a bi-phasic recovery of CSA with a rapid phase followed by a slower phase while the blood flow very rapidly returned almost to basal. The time course of the post-exercise decrease indicated that about 50% of the increase in CSA at the highest exercise intensity might have been a result of extravascular water displacement and 50% of an increase in the vasculature volume related to the flow increase. The CSA reduction in N-leg seems to have been related to vasoconstriction, probably mainly of the capacitance vessels since blood flow was not reduced.

Skeletal muscle perfusion during exercise using Gd-DTPA bolus detection.

The study was performed to evaluate if skeletal muscle perfusion can be determined during exercise using an IV bolus injection of Gd-DTPA. A fast spoiled gradient echo sequence (T1 weighted) was used with intermittent imaging during one-legged plantar flexion at different workloads. Between repetitive flexions, a 2-sec rest allowed magnetic resonance imaging (MRI) of the lower legs and measurements of the blood flow in the popliteal artery by ultrasonography for subsequent calculation of muscle perfusion. Maximal signal intensity, upslope and downslope of the bolus, mean transit time, and integrated curve area were measured within regions of interest bilaterally. The skeletal muscle perfusion estimated by ultrasonography increased in the exercising leg from 4 ml x 100 g(-1) x min(-1) at rest to 38 ml at low, 86 ml at medium, and 110 ml x 100 g(-1) x min(-1) at high workload. The SImax increased from 1.38 +/- 0.12 to 1.58 +/- 0.15 and the negative slope of the peak nonsignificantly from - 2.38 +/- 1.75 to - 12.05 +/- 9. 71. All obtained MRI parameters could visually separate the muscles into exercising, nonexercising, and presumably low active muscles. It is concluded that the signal intensity curve using a fast spoiled gradient echo sequence did not overall quantitatively mirror the perfusion, evaluated as the blood flow measured by ultrasonography. However, the signal intensity seemed to follow the blood flow velocity within a limited range of 15-60 cm x sec(-1), corresponding to 35-90 ml x 100 g(-1) x min(-1). Nonetheless, it might be useful when studying ischemia or endothelial dysfunction in skeletal muscles during exercise.

Global cerebral blood flow during infusion of adenosine in humans: assessment by magnetic resonance imaging and positron emission tomography.

Adenosine, an endogenous vasodilator, induces a cerebral vasodilation at hypotensive infusion rates in anaesthetized humans. At lower doses (< 100 micrograms kg-1 min-1), adenosine has shown to have an analgesic effect. This study was undertaken to investigate whether a low dose, causing tolerable symptoms of peripheral vasodilation affects the global cerebral blood flow (CBF). In nine healthy volunteers CBF measurements were made using axial magnetic resonance (MR) phase images of the internal carotid and vertebral arteries at the level of C2-3. Quantitative assessment of CBF was also obtained with positron emission tomography (PET) technique, using intravenous bolus [15O]butanol as tracer in four of the subject at another occasion. During normoventilation (5.4 +/- 0.2 kPa, mean +/- s.e.m.), the cerebral blood flow measured by magnetic resonance imaging technique, as the sum of the flows in both carotid and vertebral arteries, was 863 +/- 66 mL min-1, equivalent to about 64 +/- 5 mL 100 g-1 min-1. The cerebral blood flow measured by positron emission tomography technique, was 59 +/- 4 mL 100 g-1 min-1. All subjects had a normal CO2 reactivity. When adenosine was infused (84 +/- 7 micrograms kg-1 min-1.) the cerebral blood flow, measured by magnetic resonance imaging was 60 +/- 5 mL 100 g-1 min-1. The end tidal CO2 level was slightly lower (0.2 +/- 0.1 kPa) during adenosine infusion than during normoventilation. In the subgroup there was no difference in cerebral blood flow as measured by magnetic resonance imaging or positron emission tomography. In conclusion, adenosine infusion at tolerable doses in healthy volunteers does not affect global cerebral blood flow in unanaesthetized humans.

A new view on the CSF-circulation with the potential for pharmacological treatment of childhood hydrocephalus.

A new model of the cerebrospinal fluid (CSF) circulation is proposed, implying that the main absorption of CSF occurs through the brain capillaries. This model is based on recent observations of CSF dynamics using radionuclide cisternography and cardiac gated magnetic resonance imaging. Magnetic resonance imaging of communicating hydrocephalus has demonstrated a highly significant decrease of CSF flow through the foramen magnum, which is explained by decreased expansion of the intracranial arteries. This invariable finding in combination with the new view of the CSF-circulation makes a hemodynamic pathogenesis of hydrocephalus very probable. Communicating hydrocephalus may be caused by any process that restricts the arterial pulsations and is therefore termed restricted arterial pulsation hydrocephalus. In obstructive hydrocephalus, the ventricular dilatation leads to a compression of the cortical veins and consequently is termed venous congestion hydrocephalus. Based on these considerations, a new concept of pharmacological treatment of hydrocephalus is proposed by using a selective venous constrictor.

Further studies on a male monozygotic triplet with schizophrenia: cytogenetical and neurobiological assessments in the patients and their parents.

We previously described a Swedish set of male schizophrenic monozygotic triplets. In this study the patients as well as their parents were further characterized. By high-resolution chromosomal analysis an extra band at chromosome 15p was found in all the triplets and the father. Microdissection, degenerate oligonucleotide-primed PCR (DOP-PCR) amplification and reverse painting indicates that the extra band probably contains only repetitive DNA sequences with no known effect on the phenotype. Magnetic resonance imaging (MRI) showed similar borderline ventricular enlargement and widened subarachnoid spaces over frontoparietal and basal regions as well as around the pituitary gland (empty sella) in all the triplets. The father also had widened subarachnoid spaces over the frontal and basal regions. The mother had an empty sella indicating widened subarachnoid spaces. All the boys also had a right-sided conductive hearing defect, probably due to malformation and fixation of the ossicular chain. The parents did not present any otological abnormalities. Neuropsychological assessment demonstrated similar marked reductions of attentional, mnestic, and executive functions in all the triplets, but the mother showed a normal pattern. Possible joint etiological mechanisms for the psychological and somatic abnormalities recorded in the triplets are discussed.

Theoretical and experimental evaluation of phase-dispersion effects caused by brain motion in diffusion and perfusion MR imaging.

We investigated intravoxel phase dispersion caused by pulsatile brain motion in diffusion spin-echo pulse sequences. Mathematical models were used to describe the spatial and temporal velocity distributions of human brain motion. The spatial distribution of brain-tissue velocity introduces a phase spread over one voxel, leading to signal loss. This signal loss was estimated theoretically, and effects on observed diffusion coefficient and perfused capillary fraction were assessed. When parameters from a diffusion pulse sequence without motion compensation were used, and ECG triggering with inappropriate delay times was assumed, the maximal signal loss caused by brain-motion-induced phase dispersion was predicted to be 21%. This corresponds to a 95% overestimation of the diffusion coefficient, and the perfusion-fraction error was small. Corresponding calculations for motion-compensated pulse sequences predicted a 1% to 1.5% signal loss due to undesired phase dispersion, whereas experimental results indicated a signal loss related to brain motion of 4%.

A proposed model of cerebrospinal fluid circulation: observations with radionuclide cisternography.

PURPOSE: To determine the mechanisms of the tracer distribution at radionuclide cisternography (RC). METHODS: Ten patients with venous vasculitis were studied with RC. Flow phantom studies were performed mimicking cerebrospinal fluid (CSF) circulation with and without a main outlet comparable to the pacchionian granulations. RESULTS: Nine of the 10 patients had normal findings on RC images, including a maximum uptake over the vertex at 24 hours. In all patients, a second maximum occurred in the lumbosacral area. The flow phantom studies showed no tracer accumulation at an open outlet corresponding to the pacchionian granulations. On the contrary, a maximum arose without such an outlet. A maximum always arose at the closed dead ends of the phantom, including the lumbosacral area. CONCLUSION: The commonly accepted flow model for CSF circulation needs to be revised. The pattern of the normal RC cannot be explained by a bulk flow transport of the tracer to an outlet at the pacchionian granulations but rather by a primary mixing caused by pulsatile flow with a secondary dilution by newly formed CSF from the ventricular system. We suggest that the main absorption of the CSF is through the central nervous system to the blood.

Is there a relationship between obesity and intracranial hypertension?

BACKGROUND: Intracranial hypertension and obesity have been reported in recent studies of patients with periorbital venous vasculitis. These findings indicate that obese patients should be investigated for signs of inflammation in serum and lumbar cerebrospinal fluid (CSF) pressure. PATIENTS AND METHODS: Twenty obese females, aged 27-68 years participated in the study of associated symptoms, signs of inflammation in serum, intracranial hypertension and magnetic resonance imaging of the brain (MR). Twenty randomly selected age- and sex-matched females were also investigated for associated symptoms and MR as controls. RESULTS: There were no statistically significant differences in associated symptoms and diseases except for infertility (P < 0.05) between the two groups. The values for orosomucoid, haptoglobin, IgG, IgM and tests for rheumatic and antinuclear factors were significantly increased in the obese group compared with normal values at the hospital. The lumbar CSF pressure was increased above 20 cm water in 79% and above 25 cm water in 42% in the obese patients. MR showed that the subarachnoidal space in the obese patients were significantly smaller than in the controls. CONCLUSIONS: Signs of inflammation in serum, intracranial hypertension and decreased subarachnoidal space were statistically significantly more common in patients with obesity, than in controls.

A set of male monozygotic triplets with schizophrenic psychoses: nature or nurture?

A set of schizophrenic male monozygotic triplets is described. At age 20 years, within 8 months the three men independently developed acute fulminant schizophrenic disorders (DSM-III-R) with auditory hallucinations, bizarre delusions, and thought disturbances. There were also great similarities between the triplets with regard to the chronic intermittent course of the disorder, impairment of social adjustment, and loss of working ability. The psychoses responded rapidly to conventional neuroleptic treatment. Neuropsychological assessment demonstrated similar marked reductions of attentional, mnestic, and executive functions. Magnetic resonance imaging (MRI) showed similar borderline ventricular enlargement and widened subarachnoid spaces over frontoparietal and basal regions as well as around the pituitary gland (empty sella). All the boys also had a right-sided hearing defect with a marked reduction of the ossicular bones on the right side. Possible clues as to etiological mechanisms were the lack of reported family history for the disorder and a possible influenza infection in the mother during the first trimester. It is suggested that a DNA aberration being present or occurring at conception initiated a precise time-programmed series of events that produced the very similar schizophrenic phenotypes. Such an aberration might have been induced by an external agent, occurred spontaneously, or been inherited by a recessive mechanism. It seems possible that the psychoses, the reductions of neuropsychological functions, the morphological MRI changes, and the right-sided ossicular reductions may all be related to such a DNA alteration.

MR imaging of cerebrospinal fluid dynamics in health and disease. On the vascular pathogenesis of communicating hydrocephalus and benign intracranial hypertension.

The CSF flows in the aqueduct and at the foramen magnum were examined in 5 patients with communicating hydrocephalus (HC) and in 10 with benign intracranial hypertension (BIH) as well as in 5 healthy volunteers. As compared to normal individuals, the aqueductal flow in HC was about 10 times larger and the cervical flow was half as large. In BIH the CSF flows were not different from those of normal volunteers. The decreased arterial expansion as reflected in the reduced cervical flow in HC may be due to pathologic changes in the arteries and paravascular spaces. The large aqueductal flow in HC reflects a large brain expansion, causing increased transcerebral mantle pressure gradient and ventricular dilatation. In BIH there is a normal brain expansion (aqueductal flow) and consequently no ventricular dilatation. It is argued that BIH be caused by an obstruction on the venous side, as opposed to the vascular alterations in HC, which are on the arterial side.

Periorbital venous vasculitis, intracranial hypertension and empty sella.

Sixteen patients with chronic periorbital venous vasculitis without nerve involvement and 9 patients with active episodic cluster headache were studied as to cerebrospinal fluid (CSF) pressure. Eighty-one percent of the patients with chronic and 33% with episodic symptoms had pathologically increased CSF pressure. Magnetic resonance imaging of the brains in the chronic group showed empty sella in 60%, cerebral atrophy in 21% and white matter lesions with high signal intensity on T2 weighted sequences in 29%. Abnormal obesity was found in 31% of the patients with chronic periorbital venous vasculitis under 60 years of age. Venous vasculitis is suggested as a cause of intracranial hypertension, empty sella, and endocrinologic dysfunctions.

On the pulsatile nature of intracranial and spinal CSF-circulation demonstrated by MR imaging.

Cerebrospinal fluid (CSF) flow was studied in 24 healthy volunteers using gated MR phase imaging. The subarachnoid space (SAS) was divided into 5 compartments depending on the magnitude of the pulsatile CSF flows: a high velocity compartment in the area of the brain stem and spinal cord, 2 slow ones at the upper and lower extremes of the SAS, and finally 2 intermediate velocity compartments in between. The main pulsatile spinal flow channel had a meandering pattern. The extraventricular CSF-circulation can be explained by pulsatile CSF flow without the necessity of assuming existence of a net flow. A successive time offset during the cardiac cycle has been found in the fronto-occipital direction of the interplay between the arterial expansion, brain expansion, volume changes of the CSF spaces and of the veins. It is proposed to name this time offset the intracranial "volume wave" (VoW).

A theoretical study of amplitude modulation and time shifting in quantitative MR measurements of motion in brain tissue.

MR imaging pulse sequences can be made sensitive to motion by adding gradients with different strengths at different time intervals. In the well-known phase mapping method, such velocity encoding gradients are used to obtain phase information linear to the velocity of the studied object in the direction of the gradient. When very low velocities are studied, a long duration velocity-encoded gradient is required to obtain sufficient velocity sensitivity. In such cases, variation in the object velocity during the execution of the sequence may hamper the accuracy of the method. In this study, we have made a computer simulation of the performance of a phase mapping method sequence (TE = 46 msec) designed for quantitative studies of motion in brain tissue. Using a Gaussian-shaped velocity input function, the time shifting and the amplitude modulation properties of the sequence was studied for various values of the duration, defined as the full width of tenth of maximum (FWTM), of the input function. The time shift corresponded well to the center of the 180 degrees RF pulse, and the amplitude modulation was seen to decrease with increasing time duration of the velocity input function. Applied on in vivo data, where an approximately gaussian-shaped brain motion velocity pattern was assumed to have a duration of 150 msec, the amplitude modulation of the sequence was estimated to 2%.

Gamma knife surgery in acoustic tumours.

Presentation of the experiences with 254 acoustic neurinomas, treated at the Karolinska Gamma Knife Center from 1969 to 1991, with a minimum follow-up of 12 months. Early loss of contrast enhancement on CT or MRI was seen in 70%. Unilateral tumours showed size decrease in 55%, no change in 33%, and increase in 12%. NF 2 tumours had decrease in 33%, no change in 43%, and increase in 24%. Some degree of facial weakness was seen after 17% of treatments, but always with later improvement of function. The incidence of trigeminal neuropathy was 19%. Preservation of hearing was 77%. Gamma knife treatment is as efficient as microsurgery, but without risk of infection, bleeding or CSF leak. It requires no hospitalisation. The patient can go back to work after a few days. It therefore should be offered as an alternative to every acoustic neurinoma patient.