The Variable Appearance of Third Ventricular Colloid Cysts: Correlation with Histopathology and the Risk of Obstructive Ventriculomegaly.

BACKGROUND AND PURPOSE: While third ventricular colloid cysts may present as an incidental finding, they also harbor the potential to cause ventricular obstruction and sudden death. Herein we analyze the relationship between imaging appearance and the risk of obstructive ventriculomegaly. MATERIALS AND METHODS: This is a retrospective review of the MR imaging appearance of 64 patients with colloid cysts, 46 of whom also had a CT scan, obtained by a tertiary hospital imaging report data base search over a 10-year period. Cysts were categorized by appearance on T2-FLAIR and correlated with patient age, cyst size, and the risk of obstructive ventriculomegaly. Histopathologic correlation was available for 28 cases. RESULTS: The 64-patient cohort was 52% female, median age 50 years (range 10 to 99 years). Cysts hyperintense on T2-FLAIR (53.1%) were larger (P <.001), occurred in younger patients (P = .01), and had a higher risk of obstructive ventriculomegaly than homogeneously hypointense cysts (relative risk 6.18, 95% CI [2.04, 18.67]). Three patterns of T2 hyperintensity were identified: homogeneously hyperintense, hyperintense rim, and cysts with "dot sign." Although "dot sign" cysts were larger (P < .001), there was no significant difference in patient age or the risk of ventricular obstruction among T2 hyperintense cysts. Cyst wall histopathology did not vary with imaging appearance. CONCLUSIONS: Hyperintensity on T2-FLAIR, whether homogeneous, rim, or "dot sign," is associated with larger cyst size and younger patient age, and is an imaging risk factor for obstructive ventriculomegaly. The hyperintense rim does not represent a thickened cyst wall.

Cryopreserved human umbilical cord patch for in-utero spina bifida repair.

OBJECTIVE: To identify a patch system to repair surgically created spina bifida in a sheep model for its efficacy in healing the skin defect, protecting the underlying spinal cord and reducing the Chiari II malformation. METHODS: Spina bifida was created surgically in 16 fetuses from eight timed-pregnant sheep at gestational age of 75 days. Two fetuses did not survive the procedure. Repeat hysterotomy was performed at 95 days' gestation to cover the defect with either biocellulose film with underwater adhesive (BCF-adhesive) (n = 7) or human umbilical cord with suture (HUC-suture) (n = 7). Three fetuses without formation of the defect served as reference controls. The skin healing was examined by direct visualization after a planned Cesarean section at term, followed by histological analysis using hematoxylin and eosin and Masson's trichrome stains. Mid-sagittal sections of the fetal cranium and upper cervical spine were analyzed by a pediatric neuroradiologist who was blinded to the type of patch received. RESULTS: Three fetuses that received the BCF-adhesive and six fetuses that received the HUC-suture survived to term for final analysis. As a result of dislodgment of the BCF-adhesive, all spina bifida defects repaired using BCF-adhesive were not healed and showed exposed spinal cord with leakage of cerebrospinal fluid. In contrast, all spinal defects repaired by HUC-suture were healed with complete regrowth of epidermal, dermal and subdermal tissue components, with no exposed spinal cord. The maximal skin wound width was 21 ± 3.6 mm in the BCF-adhesive group but 3 ± 0.8 mm in the HUC-suture group (P < 0.001). The spinal cord area (P = 0.001) and the number of anterior horn cells (P = 0.03) was preserved to a greater degree in the HUC-suture group than in the BCF-adhesive group, whilst psammoma bodies, signifying neuronal degeneration, were only observed in the BCF-adhesive group. Anatomic changes, indicative of Chiari II malformation, were seen in all three fetuses of the BCF-adhesive group but in none of the HUC-suture group (P < 0.01). CONCLUSION: Cryopreserved umbilical cord graft is a promising regenerative patch for intrauterine repair of spina bifida.

Mitochondrial disorder, diabetes mellitus, and findings in three muscles, including the heart.

The authors describe the case of a 50-year-old man with chronic progressive external ophthalmoplegia (CPEO), diabetes mellitus (DM), and coronary artery disease. The patient had no cardiac conduction abnormalities. During coronary artery bypass surgery, his heart and two skeletal muscles were biopsied. All three muscles showed ragged red fibers. The heart muscle showed significant glycogen accumulation. Analysis of mitochondrial DNA (mtDNA) showed a 5019-base-pair deletion, with no duplications. There were morphologically abnormal mitochondria in all 3 muscles, with clinically apparent difference in preservation of function. The combination of diabetes mellitus and mtDNA deletion is fortuitous, as they can be causally linked. The cardiac pathology allows speculation about the possible adaptive processes that may occur in the heart in DM. There are few reported cases with CPEO and excess glycogen in the heart. Most show deposition of fat and poorer clinical outcomes as compared to those with glycogen deposition. This observation may lend support to the hypothesis that in the myocardium, adaptive responses are mediated via changes in glucose handling, whereas alterations in fat metabolism likely represent maladaptation.

Mitochondrial disorder, diabetes mellitus, and findings in three muscles, including the heart.

The authors describe the case of a 50-year-old man with chronic progressive external ophthalmoplegia (CPEO), diabetes mellitus (DM), and coronary artery disease. The patient had no cardiac conduction abnormalities. During coronary artery bypass surgery, his heart and two skeletal muscles were biopsied. All three muscles showed ragged red fibers. The heart muscle showed significant glycogen accumulation. Analysis of mitochondrial DNA (mtDNA) showed a 5019-base-pair deletion, with no duplications. There were morphologically abnormal mitochondria in all 3 muscles, with clinically apparent difference in preservation of function. The combination of diabetes mellitus and mtDNA deletion is fortuitous, as they can be causally linked. The cardiac pathology allows speculation about the possible adaptive processes that may occur in the heart in DM. There are few reported cases with CPEO and excess glycogen in the heart. Most show deposition of fat and poorer clinical outcomes as compared to those with glycogen deposition. This observation may lend support to the hypothesis that in the myocardium, adaptive responses are mediated via changes in glucose handling, whereas alterations in fat metabolism likely represent maladaptation.

Fatal Epstein-Barr virus meningitis: an autopsy report.

A 3-year-old Asian female presented with fever for 1 week and neck swelling for 1 day. Serology revealed a recent Epstein-Barr virus (EBV) infection. Late on the evening of admission, she developed confusion and would not follow commands. A CT scan showed diffuse cerebral edema and a cerebral flow scan demonstrated no blood flow to the brain. She was declared brain dead and expired on the following day. At autopsy, the brain weighted 1175 grams and grossly showed significant edema. Microscopically, the entire neuraxis revealed extensive leptomeningeal infiltrate of mainly CD8+ T lymphocytes, the majority of which expressed activated markers, HLA-DR and/or CD45RO, and monocytes/macrophages with intermixed numerous apoptotic/karyorrhectic nuclear fragments. These nuclear fragments were considered to be due to apoptosis of the expanded population of CD8+ T lymphocytes. Focal venulitis was noted. EBV-encoded small nuclear RNA in situ hybridization revealed positivity in the occasional lymphocytes. Interestingly, most intraparenchymal as well as leptomeningeal vascular endothelium showed HLA-DR immunoreactivity. This finding has been reported primarily in the acute inflammatory/demyelinating conditions, not in the viral meningitis/meningoencephalitis, and was thought to be related to cytokines due to widespread inflammation in our case. Massive edema secondary to severe EBV-meningitis can be fatal.

Reduced nerve growth factor in Rett syndrome postmortem brain tissue.

To determine whether reduced nerve growth factor (NGF) and/or its high affinity receptor, trkA, play a role in the pathophysiology of Rett syndrome (RS), we used immunohistochemistry in paraffin-embedded human autopsy brain tissue, to quantify NGF and trkA levels within the frontal cortex of 9 RS females and 10 female controls of similar age. The results showed a significant reduction of NGF expression in RS patients (p < 0.001). Specifically, all RS brains exhibited NGF levels at or below the minimum level observed in controls. In 3 RS brains there was no NGF detected. TrkA expression was also reduced in the RS group (p = 0.035). Interestingly, the expression of NGF in the RS group was significantly related to the presence of cortical astrogliosis (r = 0.91) as indicated by immunostaining for glial fibrillary acidic protein (GFAP). This suggests that while the signals for NGF production during injury remain intact, the critical developmental signals required for early NGF production are impaired.

Intracanalicular meningioma.

Intracanalicular meningiomas are extremely rare and difficult to differentiate from intracanalicular vestibular schwannomas. We report an unusual case of a posterior fossa meningioma in the proximal internal auditory canal that was originally diagnosed as a vestibular schwannoma due to its appearance on magnetic resonance imaging. However, closer inspection of the preoperative neuroimages revealed features inconsistent with vestibular schwannoma that suggested the possibility of other less common lesions.

Cytogenetic analysis of 120 primary pediatric brain tumors and literature review.

We report chromosome results from 108 pediatric central nervous system (CNS) tumors. From our data and those in the literature we found that (1) cerebellar and low-grade astrocytic tumors, including gangliogliomas, are most often karyotypically normal; (2) supratentorial tumors were more frequently high-grade tumors that demonstrated a complex karyotype. Chromosome abnormalities were similar to those described in adult astrocytic tumors, namely, +7, 9p abnormalities, and -10; (3) primitive neuroectodermal tumors (PNETs) were virtually always karyotypically abnormal with a high frequency of +7, -8, i(17q), and -22. PNETs with -22 may represent a subset of tumors; (4) typical choroid plexus papillomas showed a normal karyotype, atypical papillomas showed a hyperdiploid karyotype (with +7, +12, and +20), choroid plexus carcinomas showed a hyperhaploid karyotype; (5) a few ependymomas showed hyperdiploidy or hypertetraploidy; (6) germ cell tumors showed complicated karyotypes; (7) monosomy 22 or 22q abnormalities appear to be a recurring finding in the malignant rhabdoid tumors; and (8) meningiomas showed -22 or 22q abnormalities associated with a complex karyotype. In general, in pediatric CNS tumors the least differentiated neoplasms have the greatest number of cytogenetic abnormalities. However, our present morphologic criteria for tumor diagnosis do not always correlate with a consistent karyotype, and further study of pediatric brain tumor morphology, site, behavior, and karyotype is required.

p53 protein in pediatric malignant astrocytomas: a study of 21 patients.

Malignant astrocytomas are uncommon brain tumors in children and it is known that astrocytic tumors with similar degrees of histologic anaplasia often show different biologic behaviour. Their uncommon occurrence has resulted in relatively few studies of the molecular biology and genetics of pediatric malignant astrocytomas with somewhat conflicting results, in contrast with the many studies addressing astrocytomas in adults. p53 immunoreactivity has been used to screen tissues for the abnormal presence of the p53 protein and abnormal immunoreactivity has been demonstrated in one-half to two-thirds of adult astrocytomas. We studied the frequency of p53 immunoreactivity and gene alteration in 21 children with malignant astrocytomas (anaplastic astrocytoma and glioblastoma multiforme) and analysed the survival of patients with p53 immunoreactive versus non-reactive tumors. Of the cases examined, 8 were anaplastic astrocytoma (AA) and 13 were glioblastoma multiforme (GM). We found that the overall frequency of p53 immunoreactivity of 47% in this group of pediatric malignant astrocytomas is similar to that reported for adult astrocytomas. The median survival in both p53-positive and p53-negative groups of pediatric malignant astrocytomas was similar: however, the number of deaths in each group and the distribution of p53 scores is not statistically significant. Further studies to precisely identify p53 and other genetic mutations in pediatric gliomas are needed to understand their biology and the rationale for therapeutic options.

Quantitative MRI of spinal cord injury in a rat model.

Sequential in vivo MRI studies of experimental spinal cord injuries (SCI) were performed using a three-dimensional implementation of the FATE (Fast low-Angle spin echo sequence with short TE) sequence. MRI-observed pathology was quantified using a multispectral segmentation algorithm. Neurological analysis was performed on the same animals concurrently, in addition to end-point histology, for comparison with quantitative MRI results. These studies suggest that it is possible to use MRI to detect the onset of secondary injury in the spinal cord. The data also indicate that early detection of MRI-visible pathology may provide the necessary markers for predicting the long-term level of neurologic deficit.

Primary cerebral lymphoma: a study of 47 cases probed for Epstein-Barr virus genome.

AIMS: To determine the prevalence of Epstein-Barr virus genome in primary cerebral lymphomas occurring in the absence of immune suppression. METHODS: Forty eight consecutive patients with lymphomas restricted to the central nervous system were identified, all of whom had had neurosurgical biopsies performed at the National Hospitals for Neurology and Neurosurgery, London. Only five patients had some form of underlying immune deficiency; 43 were apparently normal. The tumours were studied with immunohistochemical markers and by in situ hybridisation, using a biotinylated probe to the internal repeat region of Epstein-Barr virus. RESULTS: All the lymphomas were B cell in origin. Tumours from the five immunosuppressed patients all showed hybridisation, as did two of the "spontaneous" tumours. CONCLUSIONS: This is the largest series of cerebral lymphomas so far probed for Epstein-Barr virus genome: as more are examined, it is suggested that a small proportion of the tumours from immunocompetent patients will also contain the virus.

Sinus histiocytosis with massive lymphadenopathy--isolated suprasellar involvement.

An unusual case of an isolated histioproliferative lesion arising from the suprasellar region is described. The presence of lymphophagocytosis suggested that this represented an extranodal intracranial form of sinus histiocytosis with massive lymphadenopathy.