RNA Sequencing Analysis of Intracranial Aneurysm Walls Reveals Involvement of Lysosomes and Immunoglobulins in Rupture.

BACKGROUND AND PURPOSE: Analyzing genes involved in development and rupture of intracranial aneurysms can enhance knowledge about the pathogenesis of aneurysms, and identify new treatment strategies. We compared gene expression between ruptured and unruptured aneurysms and control intracranial arteries. METHODS: We determined expression levels with RNA sequencing. Applying a multivariate negative binomial model, we identified genes that were differentially expressed between 44 aneurysms and 16 control arteries, and between 22 ruptured and 21 unruptured aneurysms. The differential expression of 8 relevant and highly significant genes was validated using digital polymerase chain reaction. Pathway analysis was used to identify enriched pathways. We also analyzed genes with an extreme pattern of differential expression: only expressed in 1 condition without any expression in the other. RESULTS: We found 229 differentially expressed genes in aneurysms versus controls and 1489 in ruptured versus unruptured aneurysms. The differential expression of all 8 genes selected for digital polymerase chain reaction validation was confirmed. Extracellular matrix pathways were enriched in aneurysms versus controls, whereas pathways involved in immune response and the lysosome pathway were enriched in ruptured versus unruptured aneurysms. Immunoglobulin genes were expressed in aneurysms, but showed no expression in controls. CONCLUSIONS: For rupture of intracranial aneurysms, we identified the lysosome pathway as a new pathway and found further evidence for the role of the immune response. Our results also point toward a role for immunoglobulins in the pathogenesis of aneurysms. Immune-modifying drugs are, therefore, interesting candidate treatment strategies in the prevention of aneurysm development and rupture.

Factors influencing blood loss and allogeneic blood transfusion practice in craniosynostosis surgery.

OBJECTIVE/AIMS: To identify factors influencing perioperative blood loss and transfusion practice in craniosynostotic corrections. BACKGROUND: Craniosynostotic corrections are associated with large amounts of blood loss and high transfusion rates. METHODS: A retrospective analysis was performed of all pediatric craniosynostotic corrections during the period from January 2003 to October 2009. The primary endpoint was the receipt of an allogeneic blood transfusion (ABT) during or after surgery. Pre-, intra-, and postoperative data were acquired using the electronic hospital registration systems and patients' charts. RESULTS: Forty-four patients were operated using open surgical techniques. The mean estimated blood loss during surgery was 55 ml·kg(-1). In 42 patients, red blood cells were administered during or after surgery with a mean of 38 ml·kg(-1). In 23 patients, fresh frozen plasma was administered with a mean of 28 ml·kg(-1). A median of two different donors per recipient was found. Longer duration of surgery and lower bodyweight were associated with significantly more blood loss and red blood cell transfusions. Higher perioperative blood loss and surgery at an early age were correlated with a longer duration of admission. CONCLUSIONS: In this study, craniosynostotic corrections were associated with large amounts of blood loss and high ABT rates. The amount of ABT could possibly be reduced by appointing a dedicated team of physicians, by using new less-invasive surgical techniques, and by adjusting anesthetic techniques.

Noninvasive detection of the distinction between progressive and compensated hydrocephalus in infants: is it possible?

OBJECT: Clinical signs and symptoms of hydrocephalus can be clear and specific, but also subtle, nonspecific, or even absent. It may be difficult to decide whether shunt placement is indicated, especially in infants. Therefore, there is a need for the development of better noninvasive detection methods to distinguish between compensated and (slowly) progressive hydrocephalus. Early interference can reverse the cerebral damage, whereas the detection of a nonpathological state in infants with compensated hydrocephalus avoids the complications of unnecessary shunt procedures. Using MR imaging, the authors investigated cerebral blood flow (CBF) and apparent diffusion coefficients (ADCs) measured in infants with clinically compensated hydrocephalus. METHODS: The diagnosis of compensated hydrocephalus was made on the basis of clinical criteria, consisting of no signs or symptoms of increased intracranial pressure (ICP), measurement of a normal ICP, and standard MR imaging showing enlarged ventricles. Flow measurements through both internal carotid arteries and the basilar artery were considered to represent the total CBF. In addition, ADC values were assessed in 5 different regions of interest in the brain parenchyma using diffusion weighted imaging. Brain volumetric measurement was performed to express CBF in ml/100 cm(3) brain/min, thus compensating for physiological CBF growth over time. Mean arterial blood pressure was manually measured to exclude this factor as a cause of a possible change in CBF. Intracranial pressure measurement was performed noninvasively using the Rotterdam Teletransducer. RESULTS: Eighteen infants with clinically compensated hydrocephalus were included. The mean CBF was 53.5 ml/100 cm(3) of brain/min. The individual CBF values were graphically compared with age-related normal CBF values and fell in the normal range. Mean ADC value was 890.0 x10(-6) mm(2)/sec. Apparent diffusion coefficient values per region of interest were graphically compared with normal ADC values per region of interest and fell within the normal range. CONCLUSIONS: In infants with hydrocephalus, normal CBF and low ADC values, as measured using MR imaging, are associated with compensated hydrocephalus and may support a conservative approach with respect to the decision on whether to place a shunt.

New transcranial Doppler index in infants with hydrocephalus: transsystolic time in clinical practice.

Raised intracranial pressure (ICP) in infants with hydrocephalus may cause (ir)reversible damage to the brain parenchyma but can be present without clinical signs and/or symptoms. Therefore, new, favorably noninvasive, detection methods are needed to distinguish between compensated hydrocephalus with normal intracranial pressure and slowly progressive hydrocephalus with increased intracranial pressure. Because early ischemic changes in the brain parenchyma are associated with increased intracranial pressure, transcranial Doppler (TCD) indices may be useful to detect increased intracranial pressure in infants with hydrocephalus. Twenty-four infants with hydrocephalus underwent noninvasive ICP measurement, magnetic resonance imaging and TCD before and after cerebrospinal fluid (CSF) diversion. The TCD indices were paired to the anterior fontanelle pressure findings and compared for correlation. After CSF diversion, ICP decreased significantly from 21.8 cm H(2)O to 7.7 cm H(2)O (p<0.005). The transsystolic time (TST) as measured with TCD increased significantly from 176 to 221 ms (p<0.005), whereas the pulsatility index (PI) decreased significantly from 1.3 to 1.0 (p<0.05). The resistance index (RI) decreased significantly from 0.73 to 0.63 (p<0.05). Mean bloodflow velocity through the middle cerebral artery increased significantly from 55.5 to 75.8 cm/s (p<0.005). TST has a strong correlation with the ICP (p<0.005). Measuring TST with TCD can be helpful in the decision-making process about whether to perform CSF diversion in infants with hydrocephalus. Because TST is related solely to the relative changes in the flow velocity caused by intracranial physical properties, it has a closer relation to ICP than the PI and the RI.

Myeloid sarcoma presenting as a recurrent, multifocal nerve root entrapment syndrome.

BACKGROUND: Myeloid sarcoma is an extramedullary manifestation of haematologic malignancy, most commonly acute myeloid leukemia (AML), which can cause neurological symptoms. CASE DESCRIPTION: A 45-year-old male with a history of AML presented with a lumbosacral nerve root entrapment syndrome followed by cauda equina compression, but without systemic signs of AML recurrence. MRI showed a mass compressing the spinal cord at level L5-S2. After surgically removing the tumour pathologic examination yielded a myeloid sarcoma. Combined chemotherapy and radiation therapy followed. Five months later the patient developed a thoracal (Th10-Th11) radiculopathy due to a relapse of the myeloid sarcoma, followed by C8-Th1-radiculopathy caused by leptomeningeal spread. CONCLUSION: This case forms the first description of recurrent, multifocal and progressive radiculopathy due to myeloid sarcoma. This diagnosis should be considered in patients with radiculopathy with previous haematological malignancy and/or signs or symptoms of such disease; the absence of systemic disease activity does not rule out myeloid sarcoma.

Nasal encephalocele in a child with Beckwith-Wiedemann syndrome.

Beckwith-Wiedemann syndrome (BWS) is a rare congenital syndrome characterized by gigantism, macroglossia, exophthalmos, postpartum hypoglycemia, and multiple midline defects such as omphalocele. The authors describe, to the best of their knowledge, the first case of a child in whom BWS was diagnosed and who was subsequently treated for a nasal encephalocele. Because the authors believe that this feature might not be an incidental finding in patients with BWS, intranasal masses in these patients should be carefully differentiated, as complications might be severe.

Postoperative hemicerebellar inflammation mimicking recurrent tumor after resection of a medulloblastoma. Case report.

The authors present the case of a 4-year-old boy in whom a medulloblastoma in the left cerebellar hemisphere was successfully resected with no signs of residual tumor on the postoperative magnetic resonance (MR) images. A second MR imaging study performed 1 month after surgery demonstrated an extensive, contrast-enhancing lesion in the left cerebellar hemisphere, which simulated massive recurrent tumor, and repeated surgery was considered. A third postoperative MR imaging study, performed for evaluation of the craniospinal axis 10 days after the second postoperative study, still showed some contrast enhancement in the left cerebellar hemisphere, but the lesion had almost disappeared. Postoperative hemicerebellar inflammation seemed to be the most likely explanation. This case illustrates that early postoperative inflammation can mimic recurrent tumor on MR images obtained after resection of a medulloblastoma and caution should be taken in interpreting such images. Clinical history, neurological examination, laboratory findings, and repeated MR imaging studies can be helpful in evaluating the patient accurately.

Navigated laser-assisted endoscopic fenestration of a suprasellar arachnoid cyst in a 2-year-old child with bobble-head doll syndrome. Case report.

The authors present the case of a 2-year-old boy with bobble-head doll syndrome (BHDS) associated with a large suprasellar arachnoid cyst and enlarged ventricles, who was successfully treated with neuronavigated laser-assisted endoscopic ventriculocystocisternostomy. The clinical history, surgical treatment, and clinical follow up of the patient are described. A navigated laser-assisted endoscopic ventriculocystocisternostomy of the suprasellar arachnoid cyst led to cessation of the head bobbing, and notable reduction of the cyst and ventricles was visible on the postoperative magnetic resonance images. Caused by a suprasellar arachnoid cyst, BHDS can be successfully treated with navigated laser-assisted endoscopic ventriculocystocisternostomy. The advantages of this procedure are minimal invasiveness and facilitated guidance of the neuronavigation system to the target area when normal anatomical landmarks are not visible.