Noninvasive Estimation of Pulsatile and Static Intracranial Pressure by Optical Coherence Tomography.

Purpose: To explore the ability of optical coherence tomography (OCT) to noninvasively estimate pulsatile and static intracranial pressure (ICP). Methods: An OCT examination was performed in patients who underwent continuous overnight monitoring of the pulsatile and static ICP for diagnostic purpose. We included two patient groups, patients with idiopathic intracranial hypertension (IIH; n = 20) and patients with no verified cerebrospinal fluid disturbances (reference; n = 12). Several OCT parameters were acquired using spectral-domain OCT (RS-3000 Advance; NIDEK, Singapore). The ICP measurements were obtained using a parenchymal sensor (Codman ICP MicroSensor; Johnson & Johnson, Raynham, MA, USA). The pulsatile ICP was determined as the mean ICP wave amplitude (MWA), and the static ICP was determined as the mean ICP. Results: The peripapillary Bruch's membrane angle (pBA) and the optic nerve head height (ONHH) differed between the IIH and reference groups and correlated with both MWA and mean ICP. Both OCT parameters predicted elevated MWA. Area under the curve and cutoffs were 0.82 (95% confidence interval [CI], 0.66-0.98) and -0.65° (sensitivity/specificity; 0.75/0.92) for pBA and 0.84 (95% CI, 0.70-0.99) and 405 µm (0.88/0.67) for ONHH. Adjusting for age and body mass index resulted in nonsignificant predictive values for mean ICP, whereas the predictive value for MWA remained significant. Conclusions: This study provides evidence that the OCT parameters pBA and ONHH noninvasively can predict elevated pulsatile ICP, represented by the MWA. Translational Relevance: OCT shows promise as a method for noninvasive estimation of ICP.

In Vivo Evidence for Impaired Glymphatic Function in the Visual Pathway of Patients With Normal Pressure Hydrocephalus.

Purpose: Impaired ability to remove toxic metabolites from central nervous system may be an important link between cerebral and ophthalmic degenerative diseases. The aim of the present study was to compare the glymphatic function in the visual pathway in patients with idiopathic normal pressure hydrocephalus (iNPH), a neurodegenerative dementia subtype, with a reference group. Methods: We compared 31 subjects with Definite iNPH (i.e., shunt-responsive) with 13 references in a prospective and observational study. After intrathecal injection of the magnetic contrast agent gadobutrol (Gadovist, 0.5 mL, 1.0 mmol/mL, Bayer Pharma AG), serving as a tracer, consecutive magnetic resonance imaging (MRI) scans were obtained (next 24-48 hours). The normalized MRI T1 signal recorded in the cerebrospinal fluid (CSF) and along the visual pathway served as a semi-quantitative measure of tracer enrichment. Gadobutrol does not penetrate the blood-brain barrier and is thus confined to the extravascular space. Overnight measurements of pulsatile intracranial pressure were used as a surrogate marker for the intracranial compliance. Results: The tracer enriched the prechiasmatic cistern similarly in both groups, but clearance was delayed in the iNPH group. Moreover, both delayed enrichment and clearance of the tracer were observed in the visual pathway in the iNPH subjects. The enrichment in the visual pathway and the CSF correlated. Individuals with elevated pulsatile intracranial pressure showed reduced enrichment within the visual pathway. Conclusions: There was delayed enrichment and clearance of a tracer in the visual pathway of iNPH patients, which suggests impaired glymphatic function in the visual pathway in this disease.

The Human Visual Pathway Communicates Directly With the Subarachnoid Space.

Purpose: Explore in vivo whether there is direct communication between the cerebrospinal fluid (CSF) and extravascular compartment of human visual pathway structures. Methods: A prospective and observational study included 10 subjects who underwent intrathecal gadolinium-enhanced magnetic resonance imaging (MRI) for suspected CSF circulation disorder, but with a negative result and with no known ophthalmic diseases. After precontrast T1-weighted MRI, 0.5 mL of gadobutrol (Gadovist, 1.0 mmol/mL) was injected intrathecally. Gadobutrol distributes in the extravascular space, and served as a CSF tracer. Consecutive MRI scans were obtained throughout 24 to 48 hours. To assess gadobutrol contrast enrichment, regions of interest (ROIs) were placed at multiple locations along the visual pathway, from the primary visual cortex to the eye's vitreous body. CSF tracer dependent T1 signal was measured in each ROI. A linear mixed-model was used for statistical analyses. Results: CSF tracer enrichment was found within the optic nerve, optic chiasm, optic tract, and primary visual cortex (P < 0.001). Peak tracer enrichment in the visual pathway generally occurred after 24 hours and was preceded by peak enhancement in the prechiasmatic cistern after 4 to 6 hours. Conclusions: The results indicate direct communication between CSF of subarachnoid space and the extravascular space of the human visual pathway. Extravascular entry of the CSF tracer is a prerequisite for a glymphatic system, the present findings may suggest its presence. The existence of a glymphatic system in the human visual pathway could bring novel perspectives on the pathophysiology and treatment of ophthalmic diseases.

Usefulness of the endoscope in microvascular decompression for trigeminal neuralgia and MRI-based prediction of the need for endoscopy.

BACKGROUND: Microvascular decompression (MVD) is a documented effective treatment of trigeminal neuralgia (TN). Lately, reports on endoscopy-assisted microvascular decompression (eaMVD) with better outcome and less risk have emerged. This study was undertaken to verify under which circumstances the endoscope proved essential in identifying the neurovascular conflict (NVC) during eaMVD for TN, and to assess the possibility to predict the need for the endoscope on preoperative magnetic resonance imaging (MRI). METHODS: Retrospective analysis of 97 patients with TN undergoing eaMVD at the Oslo University Hospital - Rikshospitalet, 1999-2009. To assess the NVC and anatomical variations, surgical reports were evaluated. MRI was available in 66 patients. The MRIs were evaluated by a blinded neuroradiologist. RESULTS: In 27 of the 97 patients (27.8 %), the endoscope was a significant aid in identifying the NVC, due to a bony ridge obscuring the view of the fifth nerve, a very distal vascular compression, or a combination of both. The preoperative MRI over-diagnosed the presence of a bony ridge. However, the MRI-based fraction of microscopically visible trigeminal nerve (FVN) in the cerebellopontine angle cistern proved diagnostic (ROC curve, AUC 0.89, p = <0.001) with an optimal cut-off value of 0.35. Hence, if less than 35 % of the trigeminal nerve is visible on preoperative MRI, the endoscope will be needed to identify the NVC. CONCLUSIONS: The endoscope is a valuable tool during MVD for TN, especially under anatomical circumstances such as a bony ridge hiding the direct microscopic view of the NVC. These anatomical circumstances can be predicted with good accuracy on preoperative MRI.

Hypertension in patients with cranial nerve vascular compression syndromes and comparison with a population-based cohort.

OBJECT: Although essential arterial hypertension (AH) represents a major health issue, its underlying causes remain unknown. An intriguing hypothesis is that AH in some cases may be caused by vascular compression of the rostral ventrolateral medulla (RVLM). Because hemifacial spasms (HFSs) are caused by vascular compression of the seventh cranial nerve in close proximity to the RVLM, one would, if this hypothesis is correct, expect to find a positive association between the occurrence of AH and chronic HFSs. Such a positive association would not be expected in patients with trigeminal neuralgia (TN), since TN is caused by vascular compression of the fifth cranial nerve, which is not close to the RVLM. METHODS: In view of this background, the authors conducted a retrospective population-based study to investigate how the occurrence of AH in patients with either HFSs or TN compares with the prevalence of AH in the general population, when adjusted for sex and age. The general population was represented by participants of the Nord-Trøndelag Health Study 3 (HUNT3). RESULTS: The prevalence of AH in the authors' patients with HFSs was significantly higher than in a sex- and age-adjusted sample from the general population; this was not true for the patients with TN. CONCLUSIONS: The authors suggest that the data provide supporting evidence to the theory that compression of the RVLM may be one cause of AH.

Local and systemic pro-inflammatory and anti-inflammatory cytokine patterns in patients with chronic subdural hematoma: a prospective study.

OBJECTIVE AND DESIGN: Innate immune pro- and anti-inflammatory responses in patients with chronic subdural hematoma (CSDH) were investigated by measuring and comparing the systemic and subdural fluid levels of cytokines. MATERIALS AND METHOD: Cytokine values were analyzed in samples obtained during surgery of 56 adult patients who were operated on for unilateral CSDHs using a Multiplex antibody bead kit. RESULTS: There were significantly higher levels of the pro-inflammatory IL-2R (p = 0.004), IL-5 (p < 0.001), IL-6 (p < 0.001), and IL-7 (p < 0.001), and anti-inflammatory mediators IL-10 (p < 0.001) and IL-13 (p = 0.002) in CSDH fluid compared with systemic levels. The pro-inflammatory TNF-alpha (p < 0.001), IL-1beta (p < 0.001), IL-2 (p = 0.007) and IL-4 (p < 0.001) were significantly lower in hematoma fluid compared with systemic levels. The ratios between pro- versus anti-inflammatory cytokines were statistically significant higher in CSDH (7.8) compared with systemic levels (1.3). CONCLUSIONS: The innate immune responses occur both locally at the site of CSDH, as well as systematically in patients with CSDH. The local hyper-inflammatory and low anti-inflammatory responses exist simultaneously. The findings suggest poorly coordinated innate immune responses at the site of CSDH that may lead to propagating of local inflammatory process and basically contribute to formation and progression of CSDH.

Chemokines as markers of local inflammation and angiogenesis in patients with chronic subdural hematoma: a prospective study.

OBJECTIVE: The goal of this study was to investigate the chemokines CCL2, CXCL8, CXCL9 and CXCL10 as markers of the inflammatory responses in chronic subdural hematoma (CSDH). METHODS: Samples of peripheral venous blood and CSDH fluid (obtained during surgery) in 76 adult patients were prospectively analyzed. Chemokine values were assessed by a Multiplex antibody bead kit. RESULTS: We found significantly higher levels of chemokines CCL2, CXCL8, CXCL9 and CXCL10 in hematoma fluid compared with serum. CONCLUSIONS: Chemokines are elevated in the hematoma cavity of patients with CSDH. It is likely that these signaling modulators play an important role in promoting local inflammation. Furthermore, biological activity of CCL2 and CXCL8 may promote neovascularization within the outer CSDH membrane, and a compensatory angiostatic activity of CXCL9 and CXCL10 may contribute to repairing this disorder. This phenomenon was restricted to the hematoma site, and the systemic chemokine levels might not reflect local immune responses.

The effect of microvascular decompression in patients with multiple sclerosis and trigeminal neuralgia.

BACKGROUND: Trigeminal neuralgia (TN) in patients with multiple sclerosis (MS) is thought to be caused by demyelinating plaques within the nerve root entry zone, the trigeminal nucleus, or the trigeminal tracts. OBJECTIVE: To review our experience of microvascular decompression (MVD) in patients with MS and symptomatic TN. METHODS: All first-time MVDs for symptomatic trigeminal neuralgia in patients with MS performed by the senior author during an 8-year period (1999-2007) in this department were reviewed. The preoperative pain components were differentiated as being 100% episodic pain, > 50% episodic pain, or > 50% constant pain. At follow-up, pain relief was assessed with a standard mail questionnaire; those still having residual pain were further examined in the outpatient clinic or interviewed by phone. RESULTS: Of the 19 MS patients, 15 were available for follow-up. The median observation period was 55 months (range, 17-99 months). At follow-up, 7 of 15 patients (47%) were completely free of their episodic pain, and an additional 4 (27%) had significant relief of episodic pain (ie, worst pain marked as 0 to 3 cm on a 10-cm visual analog scale). Among the subgroup of 8 patients with a constant pain component, all were free of their constant pain, and 4 (50%) were free of their episodic pain. CONCLUSION: In our 8-year experience of doing MVD in MS patients with TN, we found complete and significant relief of episodic TN in a large proportion of patients. Even those with a constant pain component before MVD were completely relieved of their constant pain. Thus, in patients with TN (with or without a constant pain component), the presence of MS should not prevent patients from being offered MVD.

Effect of microvascular decompression in trigeminal neuralgia patients with or without constant pain.

OBJECTIVE: To study the effect of microvascular decompression (MVD) in trigeminal neuralgia (TN) patients with or without constant pain. METHODS: The study includes all first-time MVDs for facial pain performed by the senior author (PKE) during the 6-year period from 1999 to 2005 in the Department of Neurosurgery at the National Hospital. At the time of follow-up, pain relief was assessed using a standard mail questionnaire; those patients still having residual pain were further examined in the outpatient clinic or interviewed by phone. RESULTS: The total study population includes 135 patients who underwent initial MVDs (67% of MVDs for TN without constant pain and 33% of MVDs for TN with constant pain). At the time of follow-up, the response rate was 95%, which provided us with 128 patients. The median observation period was 38 months (range, 12-87 mo). For episodic pain, MVD caused complete (i.e., 100%) pain relief in 78% of TN patients without constant pain and in 77% of TN patients with constant pain before MVD, and a significant pain relief (i.e., worst pain marked as 0-3 cm on a 10-cm visual analog scale) in 85 and 81%, respectively. For constant pain, MVD caused complete pain relief in 70% of the TN patients with constant pain before MVD, and significant pain relief in 77%. CONCLUSION: In TN patients with constant pain before MVD, significant relief of episodic and constant pain was observed in 81 and 77%, respectively. Hence, the presence of constant pain should not prevent TN patients from being offered MVD.

[Treatment of intracranial aneurysms]. / Behandling av intrakraniale aneurismer.

BACKGROUND: The department of neurosurgery at the University Hospital of North Norway has treated intracranial aneurysms since 1986. This study was conducted in order to evaluate outcomes after the introduction of endovascular therapy in 2000. MATERIAL AND METHODS: We included all patients treated for intracranial aneurysms during the years 1999 through 2002 in a retrospective, cross-sectional study. Data were collected from patient files. RESULTS: We treated 113 aneurysms in 104 patients in 108 procedures. 81 (78 %) patients were treated after a subarachnoid haemorrhage, while 23 (22 %) underwent treatment of an unruptured aneurysm. 75 (66 %) aneurysms were operated with craniotomy and clipping of the aneurysm neck, 38 (34 %) were treated with coiling. The choice of modality was dependent on the location and shape of the lesion. Complications related to the treatment were more common after surgical treatment than after coiling (41 versus 16 %, p=0.009), but the method of treatment did not influence long-term outcome evaluated according to the Glasgow Outcome Scale (GOS). All patients who underwent treatment for an unruptured aneurysm achieved a good outcome (GOS score 4 or 5), while patients treated after subarachnoid haemorrhage experienced significantly (p = 0.003) less favourable outcomes. Regression analysis revealed poor clinical condition (high Hunt & Hess grades) after the haemorrhage as the only independent predictor of outcome. INTERPRETATION: The university hospital has treated an increasing proportion of patients with intracranial aneurysms with endovascular coiling after introduction of this method in 2000. The outcomes presented in this study equal those published from international multicentre trials.