Space-occupying brain lesions, trauma-related tau astrogliopathy, and ARTAG: a report of two cases and a literature review.

Astrocytes with intracellular accumulations of misfolded phosphorylated tau protein have been observed in advanced-stage chronic traumatic encephalopathy (CTE) and in other neurodegenerative conditions. There is a growing awareness that astrocytic tau inclusions are also relatively common in the brains of persons over 70 years of age-affecting approximately one-third of autopsied individuals. The pathologic hallmarks of aging-related tau astrogliopathy (ARTAG) include phosphorylated tau protein within thorn-shaped astrocytes (TSA) in subpial, subependymal, perivascular, and white matter regions, whereas granular-fuzzy astrocytes are often seen in gray matter. CTE and ARTAG share molecular and histopathologic characteristics, suggesting that trauma-related mechanism(s) may predispose to the development of tau astrogliopathy. There are presently few experimental systems to study the pathobiology of astrocytic-tau aggregation, but human studies have made recent progress. For example, leucotomy (also referred to as lobotomy) is associated with a localized ARTAG-like neuropathology decades after the surgical brain injury, suggesting that chronic brain injury of any type may predispose to later life ARTAG. To examine this idea in a different context, we report clinical and pathologic features of two middle-aged men who came to autopsy with large (> 6 cm in greatest dimension) arachnoid cysts that had physically displaced and injured the subjects' left temporal lobes through chronic mechanical stress. Despite the similarity of the size and location of the arachnoid cysts, these individuals had dissimilar neurologic outcomes and neuropathologic findings. We review the evidence for ARTAG in response to brain injury, and discuss how the location and molecular properties of astroglial tau inclusions might alter the physiology of resident astrocytes. These cases and literature review point toward possible mechanism(s) of tau aggregation in astrocytes in response to chronic brain trauma.

Defective Gpsm2/Gαi3 signalling disrupts stereocilia development and growth cone actin dynamics in Chudley-McCullough syndrome.

Mutations in GPSM2 cause Chudley-McCullough syndrome (CMCS), an autosomal recessive neurological disorder characterized by early-onset sensorineural deafness and brain anomalies. Here, we show that mutation of the mouse orthologue of GPSM2 affects actin-rich stereocilia elongation in auditory and vestibular hair cells, causing deafness and balance defects. The G-protein subunit Gαi3, a well-documented partner of Gpsm2, participates in the elongation process, and its absence also causes hearing deficits. We show that Gpsm2 defines an ∼200 nm nanodomain at the tips of stereocilia and this localization requires the presence of Gαi3, myosin 15 and whirlin. Using single-molecule tracking, we report that loss of Gpsm2 leads to decreased outgrowth and a disruption of actin dynamics in neuronal growth cones. Our results elucidate the aetiology of CMCS and highlight a new molecular role for Gpsm2/Gαi3 in the regulation of actin dynamics in epithelial and neuronal tissues.

Long-term endocrine outcome of suprasellar arachnoid cysts.

OBJECTIVE Due to their distinct location, suprasellar arachnoid cysts are known to cause a wide variety of problems, such as hydrocephalus, endocrine symptoms, and visual abnormalities. The long-term outcome of these cysts has not been elucidated. To find out the long-term outcome of suprasellar arachnoid cysts, a retrospective review of the patients was performed. The neurological and endocrine symptoms were thoroughly reviewed. METHODS Forty-five patients with suprasellar arachnoid cysts, with an average follow-up duration of 9.7 years, were enrolled in the study. A comprehensive review was performed of the results of follow-up regarding not only neurological symptoms but also endocrine status. The outcomes of 8 patients who did not undergo operations and were asymptomatic or had symptoms unrelated to the cyst were included in the series. RESULTS Surgery was most effective for the symptoms related to hydrocephalus (improvement in 32 of 32), but endocrine symptoms persisted after surgery (4 of 4) and required further medical management. More surprisingly, a fairly large number of patients (14 of 40; 1 was excluded because no pre- or postoperative endocrine evaluation was available) who had not shown endocrine symptoms at the time of the initial diagnosis and treatment later developed endocrine abnormalities such as precocious puberty and growth hormone deficiency. The patients with endocrine symptoms detected during the follow-up included those in both the operated (n = 12 of 32) and nonoperated (n = 2 of 8) groups who had been stable during follow-up since the initial diagnosis. CONCLUSIONS This study implies that patients with suprasellar arachnoid cysts can develop late endocrine problems during follow-up, even if other symptoms related to the cyst have been successfully treated. Hence, patients with these cysts need long-term follow-up for not only neurological symptoms but also endocrine abnormalities.

Ectopic cerebellar tissue of the posterior cranial fossa: diffusion tensor tractography and MR spectroscopy findings.

PURPOSE: Well-differentiated ectopic cerebellar tissue is extremely rare, with only 12 cases in the literature. Here, we describe a unique case of radiologically proven ectopic cerebellar tissue, using diffusion tensor tractography (DTT) and MR spectroscopy (MRS) findings, in a 6-day-old newborn. CASE: A 6-day-old newborn who had previously a fetal MRI referred to our department with the suspicion of an arachnoid cyst of the posterior fossa. Including the central nervous system, all of his physical examination tests were normal. Postnatal transcranial ultrasound (US) imaging and brain MRI also revealed a large posterior fossa cyst and a solid mass nearby the cerebellar tissue. The tissue showed a small connection and isointense signal with the cerebellum. Upon DTT, both the cerebellum and nearby solid tissue represented the same FA values. Tractographic studies showed a connection with fibers extending along the left cerebellar hemisphere from this tissue. The single voxel MRS of this solid tissue also revealed high choline (Cho) and a smaller N-acetylaspartate (NAA) concentration similar to that of the normal newborn cerebellum. CONCLUSION: Ectopic cerebellar tissue can be characterized by advanced neuroimaging tools, like DTT and MRS, which provide information about brain metabolite concentrations and the microstructural integrity. In this way, unnecessary surgery can be avoided in order to obtain a histopathological diagnosis.

Detection of the communicating hole(s) of spinal extradural arachnoid cysts using time-spatial labeling inversion pulse magnetic resonance imaging.

STUDY DESIGN: Report of 2 cases. OBJECTIVE: To report the usefulness of time-spatial labeling inversion pulse magnetic resonance imaging (T-SLIP MRI) for detection of the communicating hole(s) of spinal extradural arachnoid cysts (SEACs). SUMMARY OF BACKGROUND DATA: SEACs normally communicate with the subarachnoid space via small communicating hole(s) in the dura. It is necessary to identify the accurate locations of these communicating hole(s) before attempting to close them through limited laminotomy/laminectomy. Myelocomputed tomography or conventional MRI may fail to detect the locations of the hole(s) because they comprise small dural defects. METHODS: Case 1: A 33-year-old female presented with an SEAC at the T11­L2 vertebral level. Case 2: An 82-year-old female presented with an SEAC at T12­L4 vertebral level. RESULTS: Case 1: T-SLIP MR image of the left parasagittal plane (not the midsagittal or right parasagittal plane) revealed cerebrospinal fluid flow from the subarachnoid space into the cyst at L1. After limited laminotomy at T12­L1 and partial cyst resection, we identified 2 contiguous dural holes immediately medial to the left L1 pedicle; this corroborated the preoperative T-SLIP MRI findings. The holes were sutured. Postoperative conventional MR image confirmed significant cyst shrinkage. Case 2: T-SLIP MR image revealed a curved line at the L1 pedicle in the right parasagittal plane. After L1 laminectomy and partial cyst resection, a dural hole was identified L1 pedicle, which was in agreement with the preoperative T-SLIP MRI findings. After surgery, the lower extremity pain disappeared. Postoperative conventional MR image revealed significant cyst shrinkage. CONCLUSION: T-SLIP MRI is useful for detection of the communicating hole(s) of SEACs. LEVEL OF EVIDENCE: N/A.

Increased NKCC1 expression in arachnoid cysts supports secretory basis for cyst formation.

Arachnoid cysts (AC) are filled with liquid very similar to cerebrospinal fluid (CSF). The mechanisms of fluid accumulation have remained unknown; previous studies have however indicated both fluid secretion and a one-way valve as a mechanism. If the filling was caused by fluid secretion, mechanisms similar to those underlying CSF production would be anticipated. We have investigated the expression levels of all genes known to be involved in mammalian CSF production in surgically removed AC. Based on mRNA microarray analysis of AC and normal arachnoid tissue, we extracted the RNA expression profiles of all genes known to code for proteins involved in CSF production. A selection of genes was further investigated with quantitative real-time polymerase chain reaction (qRT-PCR). For selected CSF production proteins, electron microscopic immunogold techniques (EM) and Western blots were performed. Seven genes were expressed in both cysts and controls. The gene encoding the Na(+)-K(+)-2Cl(-) cotransporter NKCC1 was significantly up-regulated in AC. Gene expression data were supported by Western blot. EM demonstrated NKCC1 expressed at the plasma membranes of the cyst-lining cells. This result points at secretion as the main mechanism of cyst filling, and NKCC1 as the key candidate of fluid transport. Based on these findings, we hypothesize that selective NKCC1 inhibitors could be used in preventing expansion of temporal AC.

Immunohistochemical expression of aromatase and estrogen, androgen and progesterone receptors in normal and neoplastic human meningeal cells.

Evidence suggests that sex hormones may play a role in the tumorigenesis of meningiomas, and studies have demonstrated the expression of hormone receptors in these tumors. Aromatase expression has been detected in several normal tissues, including neurons in the CNS, and tumor tissues. We aim to assess the expression of aromatase (ARO) and of progesterone receptor (PR), estrogen receptor (ER) and androgen receptor (AR) in both normal and neoplastic meningeal cells. A cross-sectional study was conducted with 126 patients diagnosed with meningioma (97 women and 29 men; mean age, 53.6 years) submitted to neurosurgery at Hospital São José, Complexo Hospitalar Santa Casa de Porto Alegre, southern Brazil. Control sections of normal meningeal cells, 19 patients, were obtained by evaluating the arachnoid tissue present in the arachnoid cyst resected material. Immunohistochemistry was applied to assess ARO, PR, ER and AR. Aromatase expression was detected in 100% of the control patients and in 0% of the patients with meningioma. ER was present in 24.6% of the meningiomas and in 0% of the controls, AR in 18.3% of the meningiomas and in 0% of the controls, and PR in 60.3% of the meningiomas and in 47.4% of the controls. A positive association was observed between the presence of AR and ER (OR 3.7; P = 0.01) in meningiomas. There were no significant differences in the presence of hormone receptors between meningioma histological subtypes. PR expression in women with meningioma was significantly higher than that found in men (OR 2.3; P = 0.08). Behavior pattern differences observed between aromatase expression, present in normal tissues and absent in meningiomas, and estrogen and androgen hormone receptors, absent in normal tissues and present in meningiomas, suggest that there is heterogeneity in modulation by sex steroids in the development of these tumors.

Increased excitatory amino acid levels in brain cysts of epileptic patients.

We studied two epileptic patients with arachnoid brain cysts by proton magnetic resonance spectroscopy (1H MRS). In addition, histochemical analyses of surgical specimens, cerebrospinal fluid, and cystic fluid were performed in one of the patients. In both patients, greatly increased levels of excitatory amino acids (EAAs) glutamate and aspartate were present in the cystic fluid, while there was only a moderate increase of glutamate in the epileptogenic brain tissue adjacent to the cyst in one of the patients. In non epileptic brain regions, no elevations of the EAAs were present. Since EAAs are involved in induction and maintenance of epileptogenesis, their extremely high concentrations in the cystic fluid may explain seizures in some patients with such brain cysts. Our findings may have therapeutical consequences for patients with drug resistant epilepsy, in whom elevated concentrations of EAAs in the cysts can be verified. Surgery with the aim to create a communication between the cyst and the subarachnoidal space may prevent an accumulation of the EAAs and thus result in a relief of seizures.

Progesterone receptors in arachnoid cysts. An immunocytochemical study in 2 cases.

We report 2 cases of arachnoid cysts, one with a retrocerebellar and the other with a left temporal localization, in which immunohistochemical studies had been conducted. The results of the immunohistochemistry on the presence of carcino-embryonic antigen (CEA) and glial fibrillary acidic protein (GFAP), and of the scanning- and transmission electron microscopy revealed the cyst lining to be identical to subdural neurothelium. Progesterone receptors were found in the nuclei of cells lining the cyst, which also suggests the similarity of the cyst lining to arachnoid granulations and meningiomas as derivatives of subdural neurothelium, which also possess progesterone receptors.