BACKGROUND:Pathologic signs in orbital phlebographies have been reported in various neurological diseases. PURPOSE:To study if pathologic signs in orbital phlebography may be markers of inflammation primarily affecting intracranial capillaries, which would cause intracranial hypertension. MATERIAL AND METHODS:Two groups with different intracranial cerebrospinal fluid pressures (Pcsf) were compared as to inflammatory markers in serum and pathologic signs in orbital phlebographies. Nine consecutive patients with idiopathic intracranial hypertension (IIH) with bilateral papilledema and eight consecutive patients with chronic tension-type headache (CTTH) were investigated prospectively with fibrinogen, orosomucoid, haptoglobin in serum, and invasive orbital phlebograms. The angiograms were evaluated by two skilled neuroradiologists, independent of each other and without knowledge of the diagnoses or aim of the study, as to the following pathologic signs: (i) narrowing of superior ophthalmic veins; (ii) caliber changes of intraorbital veins; (iii) collaterals of intraorbital veins; (iv) flow to cavernous sinus; and (v) asymmetric drainage of cavernous sinus. RESULTS:Mean body mass index was >30 kg/m(2) in both groups. Pcsf was >200 < 250 mm H2O in 50% of the CTTH and >350 mm H2O in all IIH patients. No difference in inflammatory markers in blood was found. The phlebographies of the IIH patients had more pathologic signs and were considered pathologic significantly more often than the ones of the CTTH patients (P < 0.001). CONCLUSION:The difference as to phlebographic pathologic signs between the IIH and the CTTH patients with different Pcsf supports the hypothesis that such phlebographic signs are markers of inflammation primarily affecting intracranial capillaries, which would disturb cerebrospinal fluid regulation causing 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.

Objective This study aims to question the generally accepted cerebrospinal fluid (CSF) bulk flow theory suggesting that the CSF is exclusively absorbed by the arachnoid villi and that the cause of hydrocephalus is a CSF absorption deficit. In addition, this study aims to briefly describe the new hydrodynamic concept of hydrocephalus and the rationale for endoscopic third ventriculostomy (ETV) in communicating hydrocephalus.Critique The bulk flow theory has proven incapable of explaining the pivotal mechanisms behind communicating hydrocephalus. Thus, the theory is unable to explain why the ventricles enlarge, why the CSF pressure remains normal and why some patients improve after ETV.Hydrodynamic concept of hydrocephalus Communicating hydrocephalus is caused by decreased intracranial compliance increasing the systolic pressure transmission into the brain parenchyma. The increased systolic pressure in the brain distends the brain towards the skull and simultaneously compresses the periventricular region of the brain against the ventricles. The final result is the predominant enlargement of the ventricles and narrowing of the subarachnoid space. The ETV reduces the increased systolic pressure in the brain simply by venting ventricular CSF through the stoma. The patent aqueduct in communicating hydrocephalus is too narrow to vent the CSF sufficiently.

Syringomyelia is a condition that results in fluid-containing cavities within the parenchyma of the spinal cord as a consequence of altered cerebrospinal fluid dynamics. This review discusses the history and the classification of the disorder, the current theories of pathogenesis, and the advanced imaging modalities used in the diagnosis. The intramedullary pulse pressure theory (a new pathophysiologic concept of syringomyelia) also is presented. In addition, the current understanding of the painful nature of this condition is discussed and the current trends in medical and surgical management are reviewed.

Purpose: To detect skeletal muscle ischemia with first-pass gadolinium (Gd) kinetics after exercise.Materials and Methods: Eleven subjects with intermittent claudication performed a symptom-limited bilateral plantar flexion exercise in the magnet. Regional ROIs were placed bilaterally in the gastrocnemius and soleus muscles, and a signal intensity (SI) time-curve analysis was performed. Induced ischernia was validated prior to the MRI with the systolic ankle-arm blood pressure index (AAI) measured after a symptom-limited treadmill exercise.Results: Exercise induced ischemic pain in 16 of 22 legs with a significantly reduced AAI (0.31 +/- 0.15). The time to contrast arrival (TCA) was delayed in symptomatic ischemic legs vs. asymptomatic legs (16.3 +/- 6.9 seconds vs. 11.1 +/- 2.7 seconds, P < 0.05). The maximum SI during recovery was higher in the solcus muscle than in the gastrocnemius muscle in ischemic legs (1.55 +/- 0.1 vs. 1.44 +/- 0.1, P < 0.05). Symptomatic regions had a less steep upslope than asymptornatic regions (43 +/- 15 vs. 63 14, P < 0.001). with a graded upslope response to ischernia. However, a normal upslope was found in 10 of 29 ischemic regions. and some of the regions showed delayed contrast arrival, suggesting a pseudonormal upslope in ischemic regions.Conclusion: Exercise-induced ischernia was detected with the use of an SI time-curve analysis. However, disregarding the arterial input function and distribution volume of the tracer may lead to misinterpretation of some ischemic regions.

The pathophysiology of syringomyelia development is not fully understood. Current prevailing theories suggest that increased pulse pressure in the subarachnoid space forces cerebrospinal fluid (CSF) through the spinal cord into the syrinx. It is generally accepted that the syrinx consists of CSF. The here-proposed intramedullary pulse pressure theory instead suggests that syringomyelia is caused by increased pulse pressure in the spinal cord and that the syrinx consists of extracellular fluid. A new principle is introduced implying that the distending force in the production of syringomyelia is a relative increase in pulse pressure in the spinal cord compared to that in the nearby subarachnoid space. The formation of a syrinx then occurs by the accumulation of extracellular fluid in the distended cord. A previously unrecognized mechanism for syrinx formation, the Bernoulli theorem, is also described. The Bernoulli theorem or the Venturi effect states that the regional increase in fluid velocity in a narrowed flow channel decreases fluid pressure. In Chiari I malformations, the systolic CSF pulse pressure and downward motion of the cerebellar tonsils are significantly increased. This leads to increased spinal CSF velocities and, as a consequence of the Bernoulli theorem, decreased fluid pressure in narrow regions of the spinal CSF pathways. The resulting relatively low CSF pressure in the narrowed CSF pathway causes a suction effect on the spinal cord that distends the cord during each systole. Syringomyelia develops by the accumulation of extracellular fluid in the distended cord. In posttraumatic syringomyelia, the downwards directed systolic CSF pulse pressure is transmitted and reflected into the spinal cord below and above the traumatic subarachnoid blockage, respectively. The ensuing increase in intramedullary pulse pressure distends the spinal cord and causes syringomyelia on both sides of the blockage. The here-proposed concept has the potential to unravel the riddle of syringomyelia and affords explanations to previously unanswered clinical and theoretical problems with syringomyelia. It also explains why syringomyelia associated with Chiari I malformations may develop in any part of the spinal cord including the medullary conus. Syringomyelia thus preferentially develops where the systolic CSF flow causes a suction effect on the spinal cord, i.e., at or immediately caudal to physiological or pathological encroachments of the spinal subarachnoid space.

Postoperative myelography with water-soluble contrast media was performed in 36 children with a diagnosis of posterior cranial fossa tumour. The myelograms were normal in 15. In 5 an intramedullary tumour was present and 3 of these had in addition subarachnoid changes as evidence of tumour spread. The remaining 16 patient had subarachnoid changes of a different character, mainly located in the posterior thoracic region and similar to those seen after subarachnoid haemorrhage. It is suggested that they represent adhesions caused by blood from the operation. The blood is assumed to be distributed by the large cerebrospinal fluid pulsations to the cervical and thoracic regions. It is important to recognise and differentiate subarachnoid changes due to tumour and to postoperative adhesions to avoid unnecessary radiotherapy to the spinal cord.

Obstruction of the spinal canal and tethering of the spinal cord are the predominant causes for development of syringohydromyelia in humans. Spinal canal obstructions may be caused by Chiari I malformations, posttraumatic spinal stenosis, intraor extra-medullary tumors, meningitis and arachnoiditis. The cyst formation starts just above or just below the obstruction. It is generally accepted that cyst formation has a mechanical cause related to cerebrospinal fluid (CSF) dynamics. However, there has been considerably controversy as to the distending force responsible for the formation of the cyst, as well as to the nature of any communication between the subarachnoid space and the cyst. The general accepted view is that the cyst is filled with CSF from the subarachnoid space. A common opinion is that a communication from the subarachnoid space via the central canal to the cyst is needed for cyst formation. However, cysts develop in the cord or in the central canal although the surrounding parts of the central canal are obliterated.

Brain tissue movements were studied in axial, sagittal and coronal planes in 15 healthy volunteers, using a gated spin echo MRI sequence. All movements had characteristics different from those of perfusion and diffusion. The highest velocities occurred during systole in the basal ganglia (maximum 1.0 mm/s) and brain stem (maximum 1.5 mm/s). The movements were directed caudally, medially and posteriorly in the basal ganglia, and caudally-anteriorly in the pons. Caudad and anterior motion increased towards the foramen magnum and towards the midline. The resultant movement occurred in a funnel-shaped fashion as if the brain were pulled by the spinal cord. This may be explained by venting of brain and cerebrospinal fluid (CSF) through the tentorial notch and foramen magnum. The intracranial volume is assumed to be always constant by the Monro-Kellie doctrine. The intracranial dynamics can be viewed as an interplay between the spatial requirements of four main components: arterial blood, capillary blood (brain volume), venous blood and CSF. These components could be characterized, and the expansion of the arteries and the brain differentiated, by applying the Monro-Kellie doctrine to every moment of the cardiac cycle. The arterial expansion causes a re-moulding of the brain that enables its piston-like action. The arterial expansion creates the prerequisites for the expansion of the brain by venting CSF to the spinal canal. The expansion of the brain is, in turn, responsible for compression of the ventricular system and hence for the intraventricular flow of CSF.

According to Starling's hypothesis, the osmotic pressure of plasma proteins in the capillary is the principal force for fluid absorption. The leakage of plasma proteins from capillaries to tissue during 24 h accounts for the total amount of plasma proteins in the vascular system. The same amount must therefore be reabsorbed by the lymphatic system, which is considered to be the sole absorber of proteins from tissue. However, it is a well-established routine in all kinds of organ transplantation to not restore the lymphatic system of the transplant. Experience has shown that this reconstruction is unnecessary, which consequently implies that the lymphatics are not of crucial importance for the survival of the organ. Inevitably, we must therefore question the vital role that the lymphatic system has been attributed in maintaining homeostasis as the sole absorber of proteins. Instead, it is proposed that the major part of plasma proteins in tissue is actively absorbed by the capillaries.

While spinal cord injury leads to permanent neurological deficits, experimental data now suggest that a combination of different neuroprotective and reparative measures may eventually help us to decrease the final degree of handicap suffered. Here we review the expression of neurotrophic factors and their receptors in the spinal cord and their regulations in response to different forms of injury. While the spinal cord is less prone than the brain to upregulate these proteins, GDNF and NGF are upregulated in the meninges following weight-drop injury. GFR-alpha1, BDNF, p75 and truncated trkB are also upregulated. Vascular endothelial growth factor (VEGF) is shown to offer neuroprotection if delivered immediately after impact injury. Olfactory ensheathing glial cells express a limited number of neurotrophic molecules, but are able to improve the final outcome of a weight-drop injury following transplantation to the spinal cord. Transplantation of cells containing neurotrophic factors, such as those found in developing dental pulp, offers additional neuroprotective alternatives. Cyst formation is an important clinical problem which can be modeled in rats to further our understanding of factors that cause their development. To monitor sensory deficits and sensory recovery, we have developed fMRI techniques and find that full recovery of hindlimb walking as determined by the BBB scale can occur in the absence of sensory-evoked fMRI signals in the brain. Preliminary data suggest that the implantation of biodegradable tubes containing olfactory ensheathing cells may be beneficial in partial spinal cord injury. Finally, bone marrow stromal cells, proliferated in vitro, survive grafting to the spinal cord and differentiate.

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.

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.

Purpose: To examine cerebrospinal fluid (CSF) dynamics and pressure gradients at obstructions of the spinal canal, and to introduce for consideration a new hypothesis for the origin and growth of spinal cord cysts/syringomyelia. This new hypothesis is based on the presence of increased intramedullary pressure; a medullary-arachnoid pressure dissociation; and filling of the cyst by extracellular fluid.Methods: Six patients with posttraumatic syringomyelia, seven patients with Chiari I malformations, and three patients with spinal block were examined with pulse-gated magnetic resonance imaging.Results: The patients with posttraumatic syringomyelia had increased systolic and diastolic CSF velocities at the posttraumatic stenosis, indicating an increased intramedullary pressure gradient at and distal to the stenosis. In patients with Chiari I malformations, systolic volume conduction through the foramen magnum was maintained. This may indicate an increased systolic pulse pressure in the spinal subarachnoid space (SAS).Conclusion: The new hypothesis explains the development of syringomyelia, regardless of its etiology, according to two general principles. First, spinal cord cysts are caused by and formed by mechanical distension of the cord. Second, the cysts are filled by extracellular fluid from the microcirculation of the cord, not by CSF. Increased extracellular fluid in the distended cord may precede cyst formation. Four mechanisms for the mechanical distension of the cord must be considered: 1) increased intramedullary pressure gradients occur at and just distal to obstructions of the spinal canal, and CSF pulse pressure is transmitted into and attenuated within the cord, causing centrifugally directed intramedullary pressure gradients, which distend the cord distal to the obstruction; 2) these centrifugally directed intramedullary pressure gradients are increased by tethering of the cord at the obstruction; 3) in Chiari I malformations, increased pulse pressure in the subarachnoid space may distend the cord by a "milking" action on the cord; and 4) if the cord is tethered, direct mechanical distension of the cord occurs by flexion of the spine.

Adenosine, an endogenous vasodilator, induces a cerebral vasodilation at hypotensive infusion rates in anaesthetized humans. At lower doses (< 100 μg 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 emmission tomography technique, was 59 ± 4 mL 100 g−1 min−1. All subjects had a normal CO2 reactivity. When adenosine was infused (84 ± 7 μg 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 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.

Purpose: To question the prevailing opinion that communicating hydrocephalus is due to a disturbance of the CSF circulation and to introduce for consideration a new model for the morphology and hemodynamic features of communicating hydrocephalus.Methods: Measurements of cerebrospinal fluid (CSF) pulsations at the foramen magnum by magnetic resonance imaging (MRI) consistently show a decreased arterial expansion in patients with communicating hydrocephalus.Conclusion: The new model successfully explains the ventricular dilatation, the compression of the subarachnoid space seen at the vertex, the relationship between CSF pulsations and cerebral blood flow in healthy individuals, the reduction in cerebral blood flow observed with hydrocephalus, and the improvement in cerebral blood flow after shunting. The model also explains why communicating hydrocephalus may be caused by any process that decreases the compliance of the arteries or of the subarachnoid space, and accordingly restricts the arterial pulsations. For this reason, it is suggested that communicating hydrocephalus be renamed restricted arterial pulsation (RAP) hydrocephalus to emphasize its pathogenesis. Hydrocephalus that is caused by obstruction of intraventricular CSF flow leading to ventricular distension, compression of the cortical veins by the dilated ventricles, and secondary venous congestion might similarly be renamed venous congestion hydrocephalus to emphasize the secondary pathophysiology that follows an intraventricular block.

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%.