Cerebral arterial stiffness is linked to white matter hyperintensities and perivascular spaces in older adults - A 4D flow MRI study.

White matter hyperintensities (WMH), perivascular spaces (PVS) and lacunes are common MRI features of small vessel disease (SVD). However, no shared underlying pathological mechanism has been identified. We investigated whether SVD burden, in terms of WMH, PVS and lacune status, was related to changes in the cerebral arterial wall by applying global cerebral pulse wave velocity (gcPWV) measurements, a newly described marker of cerebral vascular stiffness. In a population-based cohort of 190 individuals, 66-85 years old, SVD features were estimated from T1-weighted and FLAIR images while gcPWV was estimated from 4D flow MRI data. Additionally, the gcPWV's stability to variations in field-of-view was analyzed. The gcPWV was 10.82 (3.94) m/s and displayed a significant correlation to WMH and white matter PVS volume (r = 0.29, p < 0.001; r = 0.21, p = 0.004 respectively from nonparametric tests) that persisted after adjusting for age, blood pressure variables, body mass index, ApoB/A1 ratio, smoking as well as cerebral pulsatility index, a previously suggested early marker of SVD. The gcPWV displayed satisfactory stability to field-of-view variations. Our results suggest that SVD is accompanied by changes in the cerebral arterial wall that can be captured by considering the velocity of the pulse wave transmission through the cerebral arterial network.

Intrasellar Pressure is Related to Endocrine Disturbances in Patients with Pituitary Tumors.

OBJECTIVE: The aim of this study was to investigate the association between intraoperative intrasellar pressure (ISP) and pre- and postoperative endocrine disturbances with focus on hyperprolactinemia and hypopituitarism in patients with pituitary tumors. METHODS: The study is a consecutive, retrospective study with ISP collected prospectively. One hundred patients operated with transsphenoidal surgery due to a pituitary tumor, who had their ISP measured intraoperatively, were included. Data on patient endocrine status preoperatively and from 3-month postoperative follow-up were collected from medical records. RESULTS: The risk of preoperative hyperprolactinemia in patients with nonprolactinoma pituitary tumors increased with ISP (unit odds ratio 1.067, n = 70) (P = 0.041). Preoperative hyperprolactinemia was normalized at 3 months after surgery. Mean ISP was higher in patients with preoperative thyroid-stimulating hormone (TSH) deficiency (25.3 ± 9.2 mmHg, n = 37) than in patients with intact thyroid axis (21.6 ± 7.2 mmHg, n = 50) (P = 0.041). No significant difference in ISP was found between patients with and without adrenocorticotropic hormone(ACTH) deficiency. No association was found between ISP and postoperative hypopituitarism at 3 months after surgery. CONCLUSIONS: In patients with pituitary tumors, preoperative hypothyroidism and hyperprolactinemia may be associated with higher ISP. This is in line with the theory of pituitary stalk compression, suggested to be mediated by an elevated ISP. ISP does not predict the risk of postoperative hypopituitarism 3 months after surgical treatment.

Intrasellar pressure in patients with pituitary adenoma - relation to tumour size and growth pattern.

BACKGROUND: Only a few earlier publications on intrasellar pressure (ISP) have not been able to fully clarify any association between ISP and pituitary adenoma size and growth pattern. The aim of the study was to determine if intrasellar pressure (ISP) is elevated in patients with pituitary adenoma, and if the pressure is associated with tumour size and growth pattern. METHODS: The study included 100 patients operated for suspected pituitary adenoma, who have had their ISP measured intraoperatively. All adenomas were classified on the basis of Knosp and SIPAP, from which further classification of invasiveness was performed. MRT examinations were used to calculate the tumour volume and diameter in three axes. RESULTS: After exclusions, 93 cases were analysed. The mean ISP was 23.0 ± 8.4 mmHg. There were positive correlations between ISP and tumour volume and tumour diameters along all three axes. Coronal tumour diameter showed the strongest correlation with ISP elevation in a multivariate effect test. Adenomas classified as parasellar invasive (Knosp grade 3-4) showed higher mean ISP than adenomas considered as non-invasive (Knosp 0-2). CONCLUSIONS: ISP is affected by tumour anatomy and correlates positively with tumour volume. Tumour width, i.e. diameter in the coronal plane, appears to be the measure that most strongly affects the ISP. This is confirmed by the association between ISP elevation and parasellar growth.

Refeeding syndrome: multimodal monitoring and clinical manifestation of an internal severe neurotrauma.

Refeeding syndrome (RFS) is a rare, potentially life-threatening, condition seen in malnourished patients starting refeeding. RFS may provoke seizures and acute encephalopathy and can be considered an internal severe neurotrauma in need of specific treatment. The objective was to describe course of disease, treatment and, for the first time, multimodal monitoring output in a comatose patient suffering RFS. After gastric-banding and severe weight loss, the patient initiated self-starving and was transferred to our intensive care unit (ICU) following rapid refeeding. At arrival, seizures, decrease in consciousness (GCS 7) and suspected acute encephalitis was presented. Serum albumin was 8 g/l. Intracranial pressure (ICP), invasive blood pressure and electrocardiography (ECG) were monitored. Pressure reactivity (PRx) and compliance (RAP) were calculated. The patient developed congestive heart failure, anuria and general oedema despite maximal neuro- and general ICU treatment. Global cerebral oedema and hypoperfusion areas with established ischemia were seen. ECG revealed massive cardiac arrhythmia and disturbed autonomic regulation. PRx indicated intact autoregulation (-0.06 ± 0.18, mean ± SD) and relatively normal compliance (RAP = 0.23 ± 0.13). After 15 days the clinical state was improved, and the patient returned to the primary hospital. RFS was associated with serious deviations in homeostasis, high ICP levels, ECG abnormalities, kidney and lung affections. It is of utmost importance to recognize this rare syndrome and to treat appropriately. Despite the severe clinical state, cerebral autoregulation and compensatory reserve were generally normal, questioning the applicability of indirect measurements such as PRx and RAP during neuro-intensive care treatment of RFS patients with cerebral engagement.

Risk factors for developing subdural hematoma: a registry-based study in 1457 patients with shunted idiopathic normal pressure hydrocephalus.

OBJECTIVE: Subdural hematomas and hygromas (SDHs) are common complications in idiopathic normal pressure hydrocephalus (iNPH) patients with shunts. In this registry-based study, patients with shunted iNPH were screened nationwide to identify perioperative variables that may increase the risk of SDH. METHODS: The Swedish Hydrocephalus Quality Registry was reviewed for iNPH patients who had undergone shunt surgery in Sweden in 2004-2014. Potential risk factors for SDH were recorded preoperatively and 3 months after surgery. Drug prescriptions were identified from a national pharmacy database. Patients who developed SDHs were compared with those without SDHs. RESULTS: The study population consisted of 1457 patients, 152 (10.4%) of whom developed an SDH. Men developed an SDH more often than women (OR 2.084, 95% CI 1.421-3.058, p < 0.001). Patients on platelet aggregation inhibitors developed an SDH more often than those who were not (OR 1.733, 95% CI 1.236-2.431, p = 0.001). At surgery, shunt opening pressures had been set 5.9 mm H2O lower in the SDH group than in the no-SDH group (109.6 ± 24.1 vs 115.5 ± 25.4 mm H2O, respectively, p = 0.009). Antisiphoning devices (ASDs) were used in 892 patients but did not prevent SDH. Mean opening pressures at surgery and the follow-up were lower with shunts with an ASD, without causing more SDHs. No other differences were seen between the groups. CONCLUSIONS: iNPH patients in this study were diagnosed and operated on in routine practice; thus, the results represent everyday care. Male sex, antiplatelet medication, and a lower opening pressure at surgery were risk factors for SDH. Physical status and comorbidity were not. ASD did not prevent SDH, but a shunt with an ASD allowed a lower opening pressure without causing more SDHs.

Subdural hematomas in 1846 patients with shunted idiopathic normal pressure hydrocephalus: treatment and long-term survival.

OBJECTIVE Subdural hematoma (SDH) is the most common serious adverse event in patients with shunts. Adjustable shunts are used with increasing frequency and make it possible to noninvasively treat postoperative SDH. The objective of this study was to describe the prevalence and treatment preferences of SDHs, based on fixed or adjustable shunt valves, in a national cohort of patients with shunted idiopathic normal pressure hydrocephalus (iNPH), as well as to evaluate the effect of SDH and treatment on long-term survival. METHODS Patients with iNPH who received a CSF shunt in Sweden from 2004 to 2015 were included in a prospective quality registry (n = 1846) and followed regarding SDH, its treatment, and mortality. The treatment of SDH was categorized into surgery, opening pressure adjustments, or no treatment. RESULTS During the study period, the proportion of adjustable shunts increased from 75% to 95%. Ten percent (n = 184) of the patients developed an SDH. In 103 patients, treatment was solely opening pressure adjustment. Surgical treatment was used in 66 cases (36%), and 15 (8%) received no treatment. In patients with fixed shunt valves, 90% (n = 17) of SDHs were treated surgically compared with 30% (n = 49) in patients with adjustable shunts (p < 0.001). There was no difference in long-term patient survival between the SDH and non-SDH groups or between different treatments. CONCLUSIONS SDH remains a common complication after shunt surgery, but adjustable shunts reduced the need for surgical interventions. SDH and treatment did not significantly affect survival in this patient group, thus the noninvasive treatment offered by adjustable shunts considerably reduces the level of severity for this common adverse event.

Postural stability in patients with chronic subdural hematoma.

BACKGROUND: Gait disturbances and falls are common in patients with chronic subdural hematoma (cSDH). Postural stability is mainly visually assessed and has not been described using an objective and quantitative measurement tool. The objective of this prospective study was to evaluate postural stability in cSDH patients by measuring trunk sway during stance and gait compared to healthy elderly (HE). It was also to evaluate the relationships among postural stability and age, hematoma size, brain midline shift and hematoma location. METHODS: Using a gyroscopic method, trunk sway was measured in 22 cSDH patients preoperatively, 5 postoperatively and 58 HE during seven standing and walking tasks. Trunk sway amplitude and velocity in the anterior-posterior and medial-lateral directions were assessed. RESULTS: Postural stability was reduced in the cSDH group compared to HE for all standing tasks. During gait, the sway angle was increased while velocity was decreased in the cSDH group. Only 18 % of the patients could perform all tasks without losing their balance. Postoperatively, postural stability was normalized in the medial-lateral direction during standing. There were no correlations among age, hematoma size, brain midline shift or location of the hematoma and trunk sway. CONCLUSIONS: The majority of cSDH patients had reduced postural stability that was partly reversed soon after surgery. It was not correlated to hematoma characteristics, indicating that an increased risk to fall is present regardless of hematoma size and midline shift. This must be accounted for when handling these patients and measures taken to prevent further fall accidents during hospital stays.

The complications and the position of the Codman MicroSensor™ ICP device: an analysis of 549 patients and 650 Sensors.

BACKGROUND: Complications of and insertion depth of the Codman MicroSensor ICP monitoring device (CMS) is not well studied. OBJECTIVE: To study complications and the insertion depth of the CMS in a clinical setting. METHODS: We identified all patients who had their intracranial pressure (ICP) monitored using a CMS device between 2002 and 2010. The medical records and post implantation computed tomography (CT) scans were analyzed for occurrence of infection, hemorrhage and insertion depth. RESULTS: In all, 549 patients were monitored using 650 CMS. Mean monitoring time was 7.0 ± 4.9 days. The mean implantation depth was 21.3 ± 11.1 mm (0-88 mm). In 27 of the patients, a haematoma was identified; 26 of these were less than 1 ml, and one was 8 ml. No clinically significant bleeding was found. There was no statistically significant increase in the number of hemorrhages in presumed coagulopathic patients. The infection rate was 0.6 % and the calculated infection rate per 1,000 catheter days was 0.8. CONCLUSION: The risk for hemorrhagic and infectious complications when using the CMS for ICP monitoring is low. The depth of insertion varies considerably and should be taken into account if patients are treated with head elevation, since the pressure is measured at the tip of the sensor. To meet the need for ICP monitoring, an intraparenchymal ICP monitoring device should be preferred to the use of an external ventricular drainage (EVD).

Pulsatility in CSF dynamics: pathophysiology of idiopathic normal pressure hydrocephalus.

BACKGROUND: It is suggested that disturbed CSF dynamics are involved in the pathophysiology of idiopathic normal pressure hydrocephalus (INPH). The pulsatility curve describes the relationship between intracranial pressure (ICP) and the amplitude of cardiac related ICP pulsations. The position of baseline ICP on the curve provides information about the physiological state of the CSF dynamic system. The objective of the study was to investigate if shunt surgery modifies the pulsatility curve and the baseline position on the curve, and how this relates to gait improvement in INPH. METHODS: 51 INPH patients were investigated with lumbar CSF dynamic investigations preoperatively and 5 months after shunt surgery. During the investigation, ICP was measured at baseline, and then a CSF sample was removed, resulting in pressure reduction. After this, ICP was regulated with an automated infusion protocol, with a maximum increase of 24 mm Hg above baseline. The pulsatility curve was thus determined in a wide range of ICP values. Gait improvement was defined as a gait speed increase ≥0.1 m/s. RESULTS: The pulsatility curve was unaltered by shunting. Baseline ICP and amplitude were reduced (-3.0±2.9 mm Hg; -1.1±1.5 mm Hg; p<0.05, n=51). Amplitude reduction was larger for gait improvers (-1.2±1.6 mm Hg, n=42) than non-improvers (-0.2±0.5 mm Hg, n=9) (p<0.05) although mean ICP reduction did not differ. CONCLUSIONS: The pulsatility curve was not modified by shunt surgery, while the baseline position was shifted along the curve. Observed differences between gait improvers and non-improvers support cardiac related ICP pulsations as a component of INPH pathophysiology.

Influence of age, gender and severity of tremor on outcome after thalamic and subthalamic DBS for essential tremor.

Deep brain stimulation (DBS) is an established treatment for essential tremor (ET). The nucleus ventralis intermedius thalami (Vim) is the target of choice, but promising results have been presented regarding DBS in the posterior subthalamic area (PSA). The aim of this study was to evaluate the possible influence of gender, age and severity of disease on the outcome of these procedures. Sixty eight patients (34 Vim, 34 PSA) with ET were included in this non-randomised study. Evaluation using the Essential Tremor Rating Scale (ETRS) was performed before, and one year after surgery concerning PSA DBS, and at a mean of 28 ± 24 months concerning Vim DBS. Items 5/6 and 11-14 (hand tremor and hand function) were selected for analysis of tremor outcome. The efficacy of DBS on essential tremor was not related to age or gender. Nor was it associated with the severity of tremor when the percentual reduction of tremor on stimulation was taken into account. However, patients with a more severe tremor at baseline had a higher degree of residual tremor on stimulation. Tremor in the treated hand and hand function were improved with 70% in the Vim group and 89% in the PSA group.

Testicular enlargement in a patient with a FSH-secreting pituitary adenoma.

Clinically non-functional pituitary adenomas are often derived from gonadotropin producing cells. However, gonadotropinomas causing elevated serum levels of follicle-stimulating hormone (FSH) and clinical signs of FSH hypersecretion are very rarely described. Our patient, a 56-year-old man, was referred to our clinic with signs of hypogonadism. Magnetic resonance imaging (MRI) and biochemical examinations showed a large pituitary adenoma and excessive levels of serum FSH. Clinical examination and ultrasound measurement revealed bilaterally enlarged testes. After pituitary surgery, serum FSH levels normalized and there was a decrease in testicular volume. This case suggests that supraphysiological levels of FSH from a gonadotropinoma can cause a clinically observable effect, i.e. testicular enlargement. This is in line with experimental studies showing biological effect of FSH from pituitary adenomas and previous occasional reports of ovarian hyperstimulation and testicular enlargement in patients with FSH-secreting gonadotropinomas.

Cerebrospinal fluid pulse pressure method: a possible substitute for the examination of B waves.

OBJECT: The appearance of numerous B waves during intracranial pressure (ICP) registration in patients with idiopathic adult hydrocephalus syndrome (IAHS) is considered to predict good outcome after shunt surgery. The aim of this study was to describe which physical parameters of the cerebrospinal fluid (CSF) system B-waves reflect and to find a method that could replace long-term B-wave analysis. METHODS: Ten patients with IAHS were subjected to long-term registration of ICP and a lumbar constant-pressure infusion test. The B-wave presence, CSF outflow resistance (R(out)), and relative pulse pressure coefficient (RPPC) were assessed using computerized analysis. The RPPC was introduced as a parameter reflecting the joint effect of elastance and pulsatory volume changes on ICP and was determined by relating ICP pulse amplitudes to mean ICP. CONCLUSIONS: The B-wave presence on ICP registration correlates strongly with RPPC (r = 0.91, p < 0.001, 10 patients) but not with CSF R(out). This correlation indicates that B waves-like RPPC-primarily reflect the ability of the CSF system to reallocate and store liquid rather than absorb it. The RPPC-assessing lumbar short-term CSF pulse pressure method could replace the intracranial long-term B-wave analysis.

Nitric oxide inhibition by L-NAME but not 7-NI induces a transient increase in cortical cerebral blood flow and affects the cerebrovasodilation induced by TRH.

The tripeptide thyrotropin releasing hormone (TRH) has multiple interesting and complex physiological effects. One of these is the cerebrovasodilating effect, which has been described under several different conditions. The final mechanism for this effect is unknown. In the present study, we found an initial atropine-resistant cerebral vasodilation (24%) elicited by the NOS inhibitor L-NAME in the rat. D-NAME and 7-NI did not produce this effect. TRH (300 microg kg(-1), i.v.) induced an increase in cerebral blood flow by 62%. L-NAME reduced this effect significantly. The cerebrovasodilating mechanism of TRH, at least in part, is endothelial NO dependent as the neuronal 7-NI NOS inhibitor does not affect the TRH response.