Large molecules from the cerebrospinal fluid enter the optic nerve but not the retina of mice.

It has been proposed that cerebrospinal fluid (CSF) can enter and leave the retina and optic nerve along perivascular spaces surrounding the central retinal vessels as part of an aquaporin-4 (AQP4) dependent ocular 'glymphatic' system. Here, we injected fluorescent dextrans and antibodies into the CSF of mice at the cisterna magna and measured their distribution in the optic nerve and retina. We found that uptake of dextrans in the perivascular spaces and parenchyma of the optic nerve is highly sensitive to the cisternal injection rate, where high injection rates, in which dextran disperses fully in the sub-arachnoid space, led to uptake along the full length of the optic nerve. Accumulation of dextrans in the optic nerve did not differ significantly in wild-type and AQP4 knockout mice. Dextrans did not enter the retina, even when intracranial pressure was greatly increased over intraocular pressure. However, elevation of intraocular pressure reduced accumulation of fluorescent dextrans in the optic nerve head, and intravitreally injected dextrans left the retina via perivascular spaces surrounding the central retinal vessels. Human IgG distributed throughout the perivascular and parenchymal areas of the optic nerve to a similar extent as dextran following cisternal injection. However, uptake of a cisternally injected AQP4-IgG antibody, derived from a seropositive neuromyelitis optica spectrum disorder subject, was limited by AQP4 binding. We conclude that large molecules injected in the CSF can accumulate along the length of the optic nerve if they are fully dispersed in the optic nerve sub-arachnoid space but that they do not enter the retina.

Application of fluorescent dextrans to the brain surface under constant pressure reveals AQP4-independent solute uptake.

Extracellular solutes in the central nervous system are exchanged between the interstitial fluid, the perivascular compartment, and the cerebrospinal fluid (CSF). The "glymphatic" mechanism proposes that the astrocyte water channel aquaporin-4 (AQP4) is a major determinant of solute transport between the CSF and the interstitial space; however, this is controversial in part because of wide variance in experimental data on interstitial uptake of cisternally injected solutes. Here, we investigated the determinants of solute uptake in brain parenchyma following cisternal injection and reexamined the role of AQP4 using a novel constant-pressure method. In mice, increased cisternal injection rate, which modestly increased intracranial pressure, remarkably increased solute dispersion in the subarachnoid space and uptake in the cortical perivascular compartment. To investigate the role of AQP4 in the absence of confounding variations in pressure and CSF solute concentration over time and space, solutes were applied directly onto the brain surface after durotomy under constant external pressure. Pressure elevation increased solute penetration into the perivascular compartment but had little effect on parenchymal solute uptake. Solute penetration and uptake did not differ significantly between wild-type and AQP4 knockout mice. Our results offer an explanation for the variability in cisternal injection studies and indicate AQP4-independent solute transfer from the CSF to the interstitial space in mouse brain.

Neurosurgical and neuro-immunological management of IgG4-related hypertrophic sclerosing pachymeningitis. A literature survey and discussion of a unique index case.

BACKGROUND: Dural thickening is observed in lymphoma, dural carcinomatosis, meningioma, tuberculosis, and autoimmune diseases. We encountered a patient with dural thickening and complaints of neck and back pain, numbness and loss of strength in the hands. The patient also suffered from polychondritis and had previously received steroid and methotrexate treatment for this indication. The patients' serum was also positive for ANA, yet she did not have any other findings suggesting lupus. Our radiological and pathological analysis revealed IHSP (IgG4-related hypertrophic sclerosing pachymeningitis). In this review study, we provided a detailed literature survey to increase the awareness about IHSP in the neurosurgical community. METHODS: MRI (magnetic resonance imaging)-based radiological analyses revealed a posterior extramedullary spinal mass extending from C2 to T2-T3 level. The dural mass was surgically excised and a broad panel of immunohistochemical markers including S100, EMA, CD246/ALK-1, CD45, CD20, CD79a, CD138, CD68, CD1a and CD34 was studied. Immunoglobulin heavy chain/kappa chain gene rearrangement analysis was performed which ruled out a lymphoproliferative disorder. RESULTS: MRI and pathological findings suggested IHSP. As the disease relapsed with a new anterior extramedullary multilobulated lesion extending from C5 to T1 level, the patient is now closely monitored for further medical and surgical treatment. CONCLUSIONS: IHSP is a relatively novel entity of hypertrophic pachymeningitis and should be included in the differential diagnosis of dural thickening. The fibrosis accompanying IHSP may not respond to medical treatment, which includes steroids and immunosuppressive agents. Additionally, neurological deficits, seizures, spinal decompression, hydrocephalus, or brainstem compression necessitate early surgical intervention. A continued vigilance is also necessary as the disease may relapse long-term following surgical treatment.

B cell aplasia and hypogammaglobulinemia associated with levetiracetam.

Levetiracetam (LEV) is a second-generation antiepileptic drug approved for the treatment of several types of epilepsy. We report a 45-year-old female who developed hypogammaglobulinemia and B cell aplasia during LEV treatment. The Naranjo probability score for an adverse drug reaction was 6. After LEV discontinuation, the number of B cells gradually increased and reached normal levels within two months. This case suggests that monitoring of immunoglobulin levels and lymphocyte subsets analysis is important in patients treated with LEV, especially in cases of prolonged infections. SIMILAR CASES PUBLISHED: 1.

Fluorodeoxyglucose positron emission tomography/computed tomography findings in a patient with cerebellar mutism after operation in posterior fossa.

Cerebellar mutism is a transient period of speechlessness that evolves after posterior fossa surgery in children. Although direct cerebellar and brain stem injury and supratentorial dysfunction have been implicated in the mediation of mutism, the pathophysiological mechanisms involved in the evolution of this kind of mutism remain unclear. Magnetic resonance imaging revealed dentatothalamocortical tract injuries and single photon emission computed tomography showed cerebellar and cerebral hypoperfusion in patients with cerebellar mutism. However, findings with 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in this group of patients have not been documented previously. In this clinical case, we report a patient who experienced cerebellar mutism after undergoing a posterior fossa surgery. Right cerebellar and left frontal lobe hypometabolism was shown using FDG PET/CT. The FDG metabolism of both the cerebellum and the frontal lobe returned to normal levels after the resolution of the mutism symptoms.

The time course changes in expression of aquaporin 4 and aquaporin 1 following global cerebral ischemic edema in rat.

BACKGROUND: The aim of this global cerebral ischemia study was to study the changes in expression levels of aquaporin 4 (AQP4) and AQP1 over time. METHODS: Sprague-Dawley type male rats were divided into six groups. Sham group and ischemia/reperfusion were performed on five other groups using the four-vessel occlusion model. Reperfusion was done 30 min after the occlusion, and each group was tested at 1, 6, 12, 24, and 48 h for brain wet-dry weight ratio and AQP4 and AQP1 expression levels using immunohistochemistry. To prove ischemia development exists in both hippocampal neurons and epithelia of choroid plexus, hematoxylin, and eosin and  neuronal marker (NeuN) immune-staining have been applied to the sham experimental group at 48 h. AQP4 expression levels are also measured with western blotting. RESULTS: After ischemia/reperfusion it is observed that the decrease in brain water content between 12 and 24 h was statistically significant (P < 0.01). In parallel and based on immunohistochemical staining, AQP4 expression levels did not exhibit any statistically significant change. AQP4 levels did not show any statistically significant change in western blotting. AQP1 expression in choroid plexus epithelial cells decreased at the 12 and 24 h but increased in 48 h (P < 0.05). CONCLUSIONS: Lack of change in AQP4 expression levels is thought as its dual role in formation and elimination of ischemic brain edema. Decrease in AQP1 expression levels in 24 h can be explained with necrosis in choroid plexus after ischemia and the increase in 48 h mark can be related to recovery in choroid plexus.

Intracranial giant tuberculoma mimicking brain tumor: a case report.

Tuberculomas are small tumor-like lumps that can be seen, usually in large numbers, in central nervous system involvement of tuberculosis. Giant tuberculomas that are big enough to cause symptoms of compression are also encountered, though rarely. When they are really large, tuberculomas may result in increased intracranial compression, neurologic deficits, or epileptic attacks. Giant tuberculomas may be confused with brain tumors on cranial magnetic resonance imaging. Cranial magnetic resonance imaging and histopathology examinations are used for diagnosis. Although magnetic resonance imaging is useful for diagnosing tuberculoma, histopathology examination is the gold standard for a final diagnosis. This paper presents a case involving a 66-year-old patient who complained of headache, imbalance and dizziness, and underwent an operation in the neurosurgery clinic with a pre-diagnosis of brain tumor, and was then diagnosed with intracranial giant tuberculoma.

Resolution of papilledema after endoscopic third ventriculostomy versus cerebrospinal fluid shunting in hydrocephalus: a comparative study.

OBJECT: In this study the authors compare the efficacy of endoscopic third ventriculostomy (ETV) versus CSF shunting for resolution of papilledema in hydrocephalus. METHODS: This comparative case series study recruited 12 patients (24 eyes) with hydrocephalus who underwent either an ETV (Group 1, 6 patients [12 eyes]) or CSF shunt treatment (Group 2, 6 patients [12 eyes]). A complete ophthalmological examination including retinal nerve fiber layer (RNFL) evaluation by optical coherence tomography was provided for all patients before surgery and in the 1st week, 1st month, and 3rd month postoperatively. The 2 groups were compared for quantitative changes in RNFL thickness and, thereby, resolution of papilledema. Statistical evaluation was performed using the Mann-Whitney U-test with the aid of SPSS version 16.0. RESULTS: The mean preoperative RNFL thickness was 259.7 ± 35.8 µm in Group 1 and 244.5 ± 53.4 µm in Group 2 (p = 0.798). The mean decrease in RNFL thickness was 101.3 ± 38.8 µm, 141.2 ± 34.6 µm, and 162.0 ± 35.9 µm in Group 1 versus 97.0 ± 44.6 µm, 143 ± 45.6 µm, and 130.0 ± 59.8 µm in Group 2 for the postoperative 1st week, 1st month, and 3rd month, respectively. There was no significant difference between the two groups with respect to decrease in RNFL thickness during the 1st week, 1st month, and 3rd month (p = 0.563, p = 0.753, and p = 0.528, respectively). CONCLUSIONS: This is the first study to quantitatively evaluate papilledema in assessing the success of ETV and CSF shunting. The authors' results indicated that ETV is as effective as CSF shunting with respect to decreasing intracranial pressure and resolution of papilledema.

Accuracy of fluoroscopically-assisted pedicle screw placement: analysis of 1,218 screws in 198 patients.

BACKGROUND CONTEXT: We retrospectively analyzed a total of 1,218 pedicle screws for accuracy, with postoperative computed tomography (CT), in 198 patients who were operated on between March 2004 and September 2012. PURPOSE: To determine the incidence of screw misplacement in patients who received a transpedicular screw fixation, with intraoperative fluoroscopy in the lateral and lateral with anteroposterior (AP) positions. The results are compared between the two groups. STUDY DESIGN: Retrospective comparative study of accuracy of pedicle screw placement in thoracic and lumbar spine. PATIENT SAMPLE: The sample consists of 198 consecutive patients who underwent transpedicular screw fixation. OUTCOME MEASURES: Accuracy of screw placement was evaluated by postoperative CT scan. Misplacement was defined in cases where more than 25% of the screw size was residing outside the pedicle. METHODS: The indications for hardware placement, radiologic studies, patient demographics, and reoperation rates were recorded. Five hundred twenty-eight screws (Group A, n=81) were inserted into the vertebral body with the assistance of lateral fluoroscopy only, whereas 690 screws (Group B, n=117) were inserted with the assistance of lateral fluoroscopy, and the final positions of the screws were checked with AP fluoroscopy. RESULTS: A total of 1,218 screws were analyzed, with 962 screws placed at the lumbosacral region and 256 screws at the thoracic region. According to the postoperative CT scan, 27 screws (2.2%) were identified as breaching the pedicle. Nineteen of them (3.6%) were in Group A, whereas 8 (1.16%) were in Group B. The rate of pedicle breaches was significantly different between Group A and B (p=.0052). In Group A, the lateral violation of the pedicle was seen in 10 screws (1.9%), whereas medial violation was seen in 9 screws (1.7%). In Group B, the lateral violation of the pedicle was seen in six screws (0.87%), whereas medial violation was seen in two screws (0.29%). The medial and lateral penetration of screws were significantly different between Groups A and B (p<.05). A pedicle breach occurred in 21 patients, and 15 of them underwent a revision surgery to correct the misplaced screw. Of these patients, 11 (13.6%) were in Group A, and 4 (3.4%) were in Group B (p=.0335). CONCLUSIONS: In this study, we evaluated and clarified the diagnostic value of intraoperative fluoroscopy in both the lateral and AP imaging that have not yet been evaluated in any comparative study. We concluded that the intraoperative use of fluoroscopy, especially in the AP position, significantly decreases the risk of screw misplacement and the results are comparable with other advanced techniques.

Neuroprotective effect of aquaporin-4 deficiency in a mouse model of severe global cerebral ischemia produced by transient 4-vessel occlusion.

Astrocyte water channel aquaporin-4 (AQP4) facilitates water movement across the blood-brain barrier and into injured astrocytes. We previously showed reduced cytotoxic brain edema with improved neurological outcome in AQP4 knockout mice in water intoxication, infection and cerebral ischemia. Here, we established a 4-vessel transient occlusion model to test the hypothesis that AQP4 deficiency in mice could improve neurological outcome following severe global cerebral ischemia as occurs in cardiac arrest/resuscitation. Mice were subjected to 10-min transient bilateral carotid artery occlusion at 24h after bilateral vertebral artery cauterization. Cerebral blood flow was reduced during occlusion by >94% in both AQP4(+/+) and AQP4(-/-) mice. The primary outcome, neurological score, was remarkably better at 3 and 5 days after occlusion in AQP4(-/-) than in AQP4(+/+) mice, and survival was significantly improved as well. Brain water content was increased by 2.8±0.4% in occluded AQP4(+/+) mice, significantly greater than that of 0.3±0.6% in AQP4(-/-) mice. Histological examination and immunofluorescence of hippocampal sections at 5 days showed significantly greater neuronal loss in the CA1 region of hippocampus in AQP4(+/+) than AQP4(-/-) mice. The neuroprotection in mice conferred by AQP4 deletion following severe global cerebral ischemia provides proof-of-concept for therapeutic AQP4 inhibition to improve neurological outcome in cardiac arrest.

Greatly improved survival and neuroprotection in aquaporin-4-knockout mice following global cerebral ischemia.

Aquaporin-4 (AQP4), the principal water channel in astrocytes, is involved in brain water movement, inflammation, and neuroexcitation. In this study, there was strong neuroprotection in mice lacking AQP4 in a model of global cerebral ischemia produced by transient, bilateral carotid artery occlusion (BCAO). Survival and neurological outcome were greatly improved in the AQP4(-/-) vs. AQP4(+/+) mice after occlusion, with large and robust differences in both outbred (CD1) and inbred (C57bl/6) mouse strains without or with mechanical ventilation. Improved survival was also seen in mice lacking the scaffold protein α-syntrophin, which manifest reduced astrocyte water permeability secondary to defective AQP4 plasma membrane targeting. Intracranial pressure elevation and brain water accumulation were much reduced in the AQP4(-/-) vs. AQP4(+/+) mice after carotid artery occlusion, as were blood-brain barrier (BBB) disruption and neuronal loss. Brain slices from AQP4(-/-) mice showed significantly reduced cell swelling and cytotoxicity in response to oxygen-glucose deprivation, compared with slices from AQP4(+/+) mice. Our findings suggest that the neuroprotective effect of AQP4 deletion in global cerebral ischemia involves reduced astrocyte swelling and brain water accumulation, resulting in reduced BBB disruption, inflammation, and neuron death. AQP4 water transport inhibition may improve survival and neurological outcome after cardiac arrest and in other conditions associated with global cerebral ischemia.

Symptomatic pneumorrhachis.

Pneumorrhachis (PR) is the presence of air within the spinal canal, whether localized in the epidural or in the subarachnoid space. Evidence of intraspinal air, especially in the subarachnoid space, had been thought to be merely a radiological artifact of serious underlying pathology until it was proven that PRs can be related to neurologic symptoms ranging from radicular pain to serious neurologic deficits. The etiologies, pathomechanisms, and natural courses show differences from case to case, with the result that no consistent treatment strategies exist in the literature. Although the conservative treatment modalities seem to be more appropriate in nonsymptomatic cases, treatment strategies in symptomatic cases remain the subject of discussion. In this study, we present two symptomatic cases of PR arising from different causes and review the literature, focusing especially on the symptomatic cases and strategies for treating them.

Lung adenocarcinoma metastasis to frontal sinus mimicking Pott's puffy tumor.

Metastasis of the lung adenocarcinoma to the paranasal sinuses is a rare clinical entity. We present a 75-year-old male patient who presented with swelling of the forehead and left upper eyelid with proptosis in left eye due to metastasis from lung adenocarcinoma. It appears as a puffy swelling of the forehead like a Pott's puffy tumor. Pott's puffy tumor is a subperiostal abscess of the frontal bone associated with osteomyelitis and usually occurs as a complication of sinusitis or trauma.

Obstructive hydrocephalus caused by giant basilar artery aneurysm.

Giant basilar artery aneurysms are rarely associated with hydrocephalus. When it occurs the treatment usually addresses the hydrocephalus rather than the aneurysm itself, especially if it is already thrombosed. The treatment options include ventriculoperitoneal shunting and endoscopic third ventriculostomy, which may be related to high complication rates. However, reducing the intracranial hypertension may produce aneurysmal growth. We report a patient with obstructive hydrocephalus due to thrombosed giant basilar artery aneurysm. The patient initially presented with symptoms of increased intracranial pressure, and was managed by ventriculoperitoneal shunting with significant symptomatic improvement. Fifteen days after operation, the patient died due to a cerebrovascular event. We report a case that deteriorated because of cerebral infarction due to aneurysmal growth after ventriculoperitoneal shunting. We also discuss the treatment options in such cases.

Thyrotropin secreting pituitary adenoma accompanying a silent somatotropinoma.

Thyroid stimulating hormone (TSH) secreting pituitary adenomas are rare tumors manifested as hyperthyroidism with goiter in the presence of elevated TSH. We present a case with pituitary adenoma secreting both TSH and growth hormone (GH) with the prominent clinical findings of hyperthyroidism but without clinical findings of acromegaly. Pituitary magnetic resonance imaging revealed a macroadenoma. Transsphenoidal surgery was performed twice. The immunohistochemical staining showed that tumor cells were strongly reactive to GH and relatively mildly reactive to TSH. Control pituitary imaging revealed a residual macroadenoma, and long acting octreotide treatment was administered. After two years of the treatment, tumor size remained the same while thyroid function tests and insulin-like growth factor 1 (IGF-I) values returned to normal ranges. In conclusion, we always recommend hormonal examinations for all patients who have pituitary adenoma without signs and symptoms of acromegaly.

Thoracic and lumbar intraforaminal ligaments.

OBJECT: The author conducted a study to investigate the anatomy of the intraforaminal ligaments of the thoracic and lumbar nerve roots and describe their anatomical relationships and functional properties. This anatomical study performed on the intervertebral foramina, intraforaminal ligaments, transforaminal ligaments, and nerve roots of the thoracic and lumbar spine was performed in human cadavers. METHODS: The foraminal anatomy was studied in 11 whole cadavers (5 females, 6 males) previously prepared with formaldehyde, whose ages at the time of death ranged from 16 to 71 years. The thoracic and lumbar spinal columns were separated from the cervical and sacral segments en bloc using an electric band saw. The paraspinal muscles and their attachments were removed by sharp and meticulous dissection, and the thoracic and lumbar intervertebral foramina were examined under a surgical microscope. The intervertebral foraminal ligaments and nerve roots were exposed. The foraminal contents were identified and studied in detail. The intraforaminal ligaments were stained using H & E to determine ligamentous fiber. RESULTS: Intraforaminal ligaments connect the periosteum and transforaminal ligaments to the nerve root sleeves and vessels within the fatty areolar tissue. Histologically, the ligamentous attachment of the nerve roots within the foramina consists of adipose and connective tissue. CONCLUSIONS: The nerve roots are surrounded by intraforaminal ligaments, which may act in conjunction with the dura and periosteum to protect the nerve roots mechanically.

Lateral orbitotomy approach to orbital tumors: report of 10 cases.

AIM: Lateral orbitotomy is a well-known approach for lesions of the lateral orbital cone. It is still appropriate for laterally situated tumors although contemporary cranial base approaches were defined and developed within the last decades. MATERIAL AND METHODS: Here we report 10 orbital lesions operated with lateral orbitotomy, nine of which were extraconal. Cholesterol granuloma, arachnoid cyst, pleomorphic adenoma, malign epithelial tumor, dermoid cyst, inflammatory granuloma and cavernoma were the pathologies encountered. RESULTS: The extent of lateral orbitotomy should depend on the size, consistency and nature of the lesion for easy removal and less bony resection. In this regard, contrast enhanced CT scans give useful information for operative strategy. The success of surgery can be improved and cosmetic problems can be minimized if meticulous care is taken during orbital rim resection. CONCLUSION: Although there is a wide range of histopathological diagnosis for orbital tumors, lateral orbitotomy is a safe approach, particularly if the lesions are extraconal.

Electrophysiological and clinical assessment of response to surgery in carpal tunnel.

The objective of this study was to assess the clinical and electrophysiological changes before and after surgery in 44 patients who underwent surgical intervention due to the diagnosis of carpal tunnel syndrome (CTS). Patients who were diagnosed with a slight, moderate, and severe idiopathic CTS were assessed clinically and by electrophysiological tests before (mean 2-4 weeks) and after surgery (at sixth month). Improvement in clinical parameters was achieved more significantly than electrophysiological recovery.

Macrocephaly and bitemporal arachnoid cysts not associated with glutaric aciduria type I in a child.

A 45-month-old child who had bitemporal arachnoid cysts and macrocephaly unrelated to glutaric aciduria type 1 (GA 1) was reported. The patient was admitted to the emergency unit after head trauma at 11 months of age. CT and MRI showed bitemporal arachnoid cysts (BACs). Acylcarnitine profile was normal in serum using tandem mass spectrometry. Urine and blood screening tests were within normal range for metabolic disorders. There were no unusual organic acids in urine and blood samples. No additional clinical findings of metabolic disorders such as GA 1 developed during follow-up. The majority of children affected with GA 1 have macrocephaly and BACs on CT or MRI. These signs should alert neurosurgeons to the possibility of GA 1. Neurosurgeons evaluating patients with head trauma or suspected non-accidental head injury should include GA 1 in the differential diagnosis of BACs associated with macrocephaly, and an evaluation should be performed.

Delayed chiasmal herniation after transsphenoidal removal of a pituitary adenoma - case report.

We report a 41-year-old woman who experienced visual deterioration after successful removal of a pituitary adenoma. Possible mechanisms of this visual deterioration and contribution of chiasmal herniation into the sella as well as defect in the diaphragma sellae are discussed with emphasis on the regulation of medical treatment for pituitary adenomas. We conclude that medical therapy after pituitary surgery should be carefully managed together with periodic visual examinations.