CGRP outflow into jugular blood and cerebrospinal fluid and permeance for CGRP of rat dura mater

Background Calcitonin gene-related peptide (CGRP) is released from activated meningeal afferent fibres in the cranial dura mater, which likely accompanies severe headache attacks. Increased CGRP levels have been observed in different extracellular fluid compartments during primary headaches such as migraine but it is not entirely clear how CGRP is drained from the meninges. Methods We have used an in vivo preparation of the rat to examine after which time and at which concentration CGRP applied onto the exposed parietal dura mater appears in the jugular venous blood and the cerebrospinal fluid (CSF) collected from the cisterna magna. Recordings of meningeal (dural) and cortical (pial) blood flow were used to monitor the vasodilatory effect of CGRP. In a new ex vivo preparation we examined how much of a defined CGRP concentration applied to the arachnoidal side penetrates the dura. CGRP concentrations were determined with an approved enzyme immunoassay. Results CGRP levels in the jugular plasma in vivo were slightly elevated compared to baseline values 5-20 min after dural application of CGRP (10 μM), in the CSF a significant three-fold increase was seen after 35 min. Meningeal but not cortical blood flow showed significant increases. The spontaneous CGRP release from the dura mater ex vivo was above the applied low concentration of 1 pM. CGRP at 1 nM did only partly penetrate the dura. Conclusions We conclude that only a small fraction of CGRP applied onto the dura mater reaches the jugular blood and, in a delayed manner, also the CSF. The dura mater may constitute a barrier for CGRP and limits diffusion into the CSF of the subarachnoidal space, where the CGRP concentration is too low to cause vasodilatation.

Controversies and Misconceptions Related to Cerebrospinal Fluid Circulation: A Review of the Literature from the Historical Pioneers’ Theories to Current Models

Models of cerebrospinal fluid (CSF) circulation have been mainly proposed in the last century: CSF goes from the ventricles to the subarachnoidal space (SAS), passing through the aqueduct and the foramen of Luschka and Magendie. Indeed, new models, involving the Virchow-Robin space (VRS) and the perivascular space (PVS), have been proposed. We critically reviewed the literature, in order to clarify the “classical” errors and to discuss the “new” models that are evolving currently. Conclusions of past experiments are often not justified, due to lack of reproducibility and methodological issues. On the other hand, investigation on the microanatomy of Virchow-Robin spaces (VRS) and several new experiments showed a potential pathway for a more complex CSF “circulation,” with chaotic and unpredictable flows. It seems reasonable to elaborate a new model of CSF physiology, including new findings and questioning old certainties. However, proved data are still missing and it is hazardous to come to final conclusions. More studies are needed.

Massive Cerebrospinal Fluid Leak of the Temporal Bone

Cerebrospinal fluid (CSF) leakage of the temporal bone region is defined as abnormal communications between the subarachnoidal space and the air-containing spaces of the temporal bone. CSF leak remains one of the most frequent complications after VS surgery. Radiotherapy is considered a predisposing factor for development of temporal bone CSF leak because it may impair dural repair mechanisms, thus causing inadequate dural sealing. The authors describe the case of a 47-year-old man with a massive effusion of CSF which extended from the posterior and lateral skull base to the first cervical vertebrae; this complication appeared after a partial enucleation of a vestibular schwannoma (VS) with subsequent radiation treatment and second operation with total VS resection.

Abstract TMP20: Extraischemic Hematomas Following Intravenous rt-PA For Acute Ischemic Stroke

Background and purpose: Extraischemic hematoma (EIH) is defined as hemorrhage that appears in regions of the brain without visible ischemic damage. The frequency, clinical features, disease-related factors, and prognosis of patients with EIH after IV recombinant tissue-type plasminogen activator (rt-PA) are not well known. We aimed to elucidate EIH and associated factors after IV rt-PA for acute ischemic stroke. Methods: We studied consecutive stroke patients who received IV rt-PA from 2005 through 2011. EIH was defined as any extra-ischemic hemorrhages identified on the follow-up CT within the initial 36 h after rt-PA. Results: Of the total 266 patients (177 men, 73±13 years old) studied, EIH was identified in 11 (4%, 5 men, 77±7 yo, 1 multiple EIH); 8 patients in the parenchyma (5 subcortex, 1 thalamus, 1 corona radiate, 1 cerebellum), 2 in the intraventricule, 1 in the subdural space, and 1 in the subarachnoidal space. As compared with 47 patients with hemorrhagic transformation (HT) from the index infarct (30 men, 73±10 yo) and 208 with “no hemorrhage” (NH, 142 men, 73±14 yo), Fazekas grade of periventricular hyperintensity (PVH) was higher [median 2 in EIH, 1 in HT, 1 in NH; P<0.001), DWI-ASPECTS was lower [7, 7.5, 9; P<0.001), and reduced eGFR (<60 ml/min/1.73 m2) was more common in patients with EIH (82%, 32%, 38%; P=0.007). On multivariate analysis, higher grade of PVH (OR 5.06, 95%CI 1.92-16.09 per 1 point; P<0.001) and reduced eGFR (OR 6.94, 95%CI 1.40-54.69; P=0.02) were associated with EIH. Percentages of the mRS 5-6 at 3 months were 46% in EIH, 36% in HT, and 16% in NH (P=0.001). EIH was an independent predictor of the mRS 5-6 (OR 4.90, 95%CI 1.11-22.35; P=0.036), along with older age, lower DWI-ASPECTS, higher NIHSS score, and prior antithrombotic use. Of 132 patients undergoing T2*-WI before or within several days after thrombolysis, microbleeds were more common in patients with EIH (86%) than the others (19% in HT, 24% in NH, P<0.001). Conclusions: EIH developed in 4% of the stroke patients after IV rt-PA. Severe PVH and renal dysfunction were associated with the occurrence of EIH. Severe PVH might indicate prevalent existence of microbleeds. EIH was predictive of unfavorable outcome following IV rt-PA.

sICAM-1 intrathecal synthesis and release during the acute phase in children suffering from Coxsackie A9 and S. pneumoniae meningoencephalitis

The intercellular adhesion molecule is a transmembrane glycoprotein belonging to the immunoglobulin superfamily. Serum and cerebrospinal fluid (CSF) soluble intercellular adhesion molecule 1 (sICAM-1) from normal control children as well as from children with Guillain-Barré syndrome (GBS), with Coxsackie A9 virus meningoencephalitis and with Streptococcus pneumoniae meningoencephalitis were studied. sICAM-1 was quantified using an immunoenzimatic assay and albumin using the immunodiffusion technique in both biological fluids. Increased sICAM-1 values in CSF in patients with GBS correspond to an increase of the albumin CSF/serum quotient. In contrast, in inflammatory diseases like S. pneumoniae and Coxsackie A9 virus meningoencephalitis an increased brain-derived fraction was observed. In particular cases these values are 60-65% and 70-75% respectively. The results indicate an additional synthesis of sICAM-1 in subarachnoidal space during central nervous system (CNS) inflammatory process. An important role of sICAM-1 in the transmigration of different cell types into CSF during CNS inflammation in children with S. pneumoniae and Coxsackie A9 meningoencephalitis may be suggested.

Microsurgical Anatomic Features of the Olfactory Nerve: Relevance to Olfaction Preservation in the Pterional Approach

OBJECTIVE: The pterional approach represents the standard approach for most lesions of the anterior and middle cranial fossa. It requires some degree of frontal lobe retraction, which may result in temporary or permanent damage of olfaction because of nerve avulsion or mechanical compression. The purpose of this study, based on microanatomic dissection of human cadaveric specimens, was to review the microsurgical anatomic features of the nerve and suggest operative nuances that may contribute to reducing the rate of postoperative olfactory dysfunction. METHODS: Twenty olfactory nerves and tracts were examined in 10 human cadaveric heads obtained from three fresh and seven formalin-fixed adult cadavers. A standard pterional craniotomy was performed. The olfactory nerve was dissected from its arachnoidal envelopes and then mobilized for an average length of 30 mm (range, 25–35 mm). RESULTS: The possible retraction of the frontal lobe was 10 to 15 mm. More retraction invariably resulted in nerve disruption. CONCLUSION: The standard sylvian and basal cistern opening may be insufficient to guarantee preservation of olfactory function. Early identification and arachnoidal dissection of the nerve may reduce the rate of olfaction compromise. The opening of the subarachnoidal space should be performed in a proximal-to-distal manner to allow early visualization of the olfactory bulb and its dissection. The arachnoidal dissection should be performed with sharp instruments, avoiding any traction on the posterior portion of the olfactory tract. Any direct retractor compression should also be avoided to spare the microvasculature lying on the dorsal surface of the nerve.