LARGE ANEURYSM OF BASILAR ARTERY TIP MIMICKING MIDBRAIN TUMOR AND CAUSING UNILATERAL OBSTRUCTIVE HYDROCEPHALUS: A CASE REPORT AND TECHNICAL NOTE.

Cerebral ventricular system is a sporadic location of intracranial aneurysms including those of basilar artery tip. Treatment of such aneurysms remains challenging regardless of endovascular or microsurgical techniques applied. Basilar tip aneurysm presenting as third ventricular mass is rarely associated with obstructive hydrocephalus, mimicking midbrain expansive process and urging precise diagnostics and prompt treatment. Hence, the management of such patients may be delicate, having an uncertain outcome. We report on a case of a patient with unilateral hydrocephalus caused by large basilar tip aneurysm mimicking a midbrain tumor. We also discuss different operative strategies influencing the outcome, including our own endovascular treatment technical modification. A 62-year-old female patient presented with slightly decreased cognition, minor gait disturbances and urinary incontinence. Computed brain tomography revealed a third ventricle mass with unilateral ventricular dilatation, indicating hypertensive obstructive hydrocephalus. Magnetic resonance and digital subtraction angiography identified the third ventricular mass as a large saccular basilar tip aneurysm. The patient was selected for endovascular treatment followed by cerebrospinal fluid derivation. After aneurysm endovascular occlusion and temporary external ventricular drainage, the symptoms diminished and ventricular dilatation decreased. On post-procedure day 10, the hydrocephalus was relieved and external drainage removed. The patient recovered fully and was discharged without neurological deficit. In conclusion, large basilar tip aneurysms associated with obstructive hydrocephalus are rare and best treated by a combination of endovascular obliteration and cerebrospinal fluid ventricular diversion. The possibility of such an aneurysm should always be considered on the differential diagnosis of cerebral ventricular growths.

Brain metastases from lung cancer show increased expression of DVL1, DVL3 and beta-catenin and down-regulation of E-cadherin.

The susceptibility of brain to secondary formation from lung cancer primaries is a well-known phenomenon. In contrast, the molecular basis for invasion and metastasis to the brain is largely unknown. In the present study, 31 brain metastases that originated from primary lung carcinomas were analyzed regarding over expression of Dishevelled-1 (DVL1), Dishevelled-3 (DVL3), E-cadherin (CDH1) and beta-catenin (CTNNB1). Protein expressions and localizations were analyzed by immunohistochemistry. Genetic alterations of E-cadherin were tested by polymerase chain reaction (PCR)/loss of heterozygosity (LOH). Heteroduplex was used to investigate mutations in beta-catenin. DVL1 and DVL3 showed over expression in brain metastasis in 87.1% and 90.3% of samples respectively. Nuclear staining was observed in 54.8% of cases for DVL1 and 53.3% for DVL3. The main effector of the Wnt signaling, beta-catenin, was up-regulated in 56%, and transferred to the nucleus in 36% of metastases. When DVL1 and DVL3 were up-regulated the number of cases with nuclear beta-catenin significantly increased (p=0.0001). Down-regulation of E-cadherin was observed in 80% of samples. Genetic analysis showed 36% of samples with LOH of the CDH1. In comparison to other lung cancer pathologies, the diagnoses adenocarcinoma and small cell lung cancer (SCLC) were significantly associated to CDH1 LOH (p=0.001). Microsatellite instability was detected in one metastasis from adenocarcinoma. Exon 3 of beta-catenin was not targeted. Altered expression of Dishevelled-1, Dishevelled-3, E-cadherin and beta-catenin were present in brain metastases which indicates that Wnt signaling is important and may contribute to better understanding of genetic profile conditioning lung cancer metastasis to the brain.

Isolated cerebellar intraparenchymal Rosai-Dorfman disease--case report and review of literature.

BACKGROUND: Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy) rarely affects intracranial structures without involvement of other sites. We herein review the tumour characteristics, differential diagnosis and treatment policy of this rare disease. METHOD: We conducted a PUBMED search using a combination of words 'Rosai-Dorfman disease', 'Central nervous system', and identified 42 cases of such a disease infecting exclusively central nervous system. Out of those cases only one case was reported to be purely intracerebellar making our case the second one in the literature. Clinical features, differential diagnosis, treatment details and follow-up were discussed. We also described the case of 41-year-old man presented with vertiginous symptoms and mild cerebellar ataxia who was diagnosed with a solitary lesion localised deep in the right cerebellar hemisphere. Immunohistological findings revealed Rosai-Dorfman disease. FINDINGS: The most common locations of the tumour were frontal and parietal region, but CNS lesions have commonly involved the skull base with a leptomeningeal component too. The median age at presentation was in the third decade, ranging from 3 to 78 years. There is a slight male predominance. The follow-up ranged from 1 month to 11 years. Recurrence was not observed in the cases where total surgical excision was performed. CONCLUSION: Though Rosai-Dorfman disease is a rarity, one should take it into a consideration when treating solitary intracerebellar lesion. Thorough preoperative evaluation is mandatory and biopsy should be done whenever feasible. Surgical treatment of this type of tumour is not always necessary, however, it is essential for postulating the right diagnosis. When total tumour removal is achieved, the outcome is generally better, with minimal risk of recurrence and with no need for further additional therapy.

Accidental finding of an anomalous spinal nerve root during lumbar-disc surgery: a case report and a review of literature.

Anomalies of lumbosacral nerve roots, even though are rare, have been well documented so far in the medical literature. The early diagnosis of these anomalies may be difficult and it is crucial to develop specific methods for depicting them. Preoperative diagnosis of anomalous lumbosacral spinal nerve roots using the magnetic resonance imaging is essential to facilitate thorough surgical planning in order to avoid unnecessary complications for the patient during surgery. The operative management of these anomalies depends on the patient's neurological problems and while asymptomatic and accidentally diagnosed cases do not require treatment, patients who suffer low back or sciatic pain need surgical intervention in order to decompress nerve roots. We report a 45-years old woman presented with severe low back pain associated with left lumboischialgia. Intraoperative finding of an aberrant L5/S1 nerve root, optimal surgical therapy and different classifications are discussed together with a review of literature.

Thoracic intramedullary sarcoidosis mimicking an intramedullary tumor.

Sarcoidosis is a chronic, systemic granulomatous reticulosis of unknown origin, characterized by formation of hard tubercles and noncaseatinggranulomas. Since other infectious diseases such as berylliosis, mycobacterium and fungal infections may present with a noncaseating granulomas, histological diagnosis of sarcoidosis is made using the elimination method. Central nervous system manifestations of sarcoidosis may be present in 5-10% of the cases involving cranial nerves, leptomeninges and third ventricle respectively. Any part of the central nervous system can be affected. Involvement of spinal cord in sarcoidosis is extremely rare and presents with only 0.3-0.4% in patients with systemic sarcoidosis. Intramedullary sarcoidosis is a rare first manifestation of the disease and it can mimic an intramedullary tumor, which is often manifested with symptoms that initiate from spinal cord compression, resulting in paraparesis, sensory disorders and sphincter dysfunction. We present a case of intramedullary sarcoidosis that mimics a tumor of the thoracic spinal cord. Clinical features, neuroradiological, pathohistological findings, laboratory analysis and surgical treatment of such a rare entity are being discussed.

Genetic alterations of E-cadherin and beta-catenin in germinoma and teratoma: report of two central nervous system cases.

The genetic basis as well as mechanisms of development of germ cell tumors of the CNS are still unexplained. In the present article changes of Ecadherin (CDH1) and beta-catenin (CTNNB1) genes in two CNS germ cell tumors are reported. Both gene products are components of adherens junctions, but are also involved in the Wnt signaling pathway. A case of germinoma of the central nervous system and a case of spinal channel teratoma were tested for loss of heterozygosity (LOH) of E-cadherin gene by PCR amplification of tetranucleotide polymorphism (D16S752). Changes of beta-catenin were tested by heteroduplex method. Both germ cell tumors analyzed demonstrated LOH of the CDH1 gene. Analysis of exon 3 of the CTNNB1 gene showed additional band in the germinoma, suggesting that this sample harbors mutation in the beta-catenin gene. Immunostaining showed that LOHs in our samples were accompanied with the absence of E-cadherin protein. We also investigated E-cadherin expression in four other germinomas, of which three were negative and one was mildly positive. Our findings may contribute to better understanding of the genetic profile of germ cell tumors.

Genetic changes of CDH1, APC, and CTNNB1 found in human brain tumors.

This paper focuses on changes in E-cadherin (CDH1), adenomatous polyposis coli (APC), and beta-catenin (CTNNB1) in 50 tumors of the central nervous system. All gene products are components of adherens junctions, but are also involved in wnt signaling. The results of our analysis showed LOH of CDH1 gene in 31% of meningiomas examined (significant correlation; p=0.002). LOH was noted in a single case of germinoma, while other tumor types did not demonstrate any change in CDH1. Fourteen samples (29.2%) with changes in APC gene were observed. The changes were seen in 33.3% of glioblastomas and in 27% of meningiomas; LOH occurred in five informative astocytomas (20%) and in six informative neurinomas (17%). One oligoastrocytoma showed LOH at exon 11, and one medulloblastoma had allelic imbalance at both exons. Five samples (10%) showed heteroduplexes in exon 3 of beta-catenin. Potential mutations were confined to two meningiomas, one astrocytoma, one glioblastoma, and one germinoma. Our results suggest that genetic changes in wnt components are involved in brain tumor genesis. Changes in E-cadherin are involved in meningiomas, while changes in APC gene occur in different tumor types, with glioblastomas showing the highest percentage.

General recommendations for the management of aneurysmal subarachnoid hemorrhage.

Subarachnoid hemorrhage is a neurologic emergency and a detrimental cerebrovascular event with a high rate of death and complications. Recommendations have been developed and based on literature search, evaluation of the results of large international clinical trials, collective experience of the authors, and endorsed by the Croatian Society of Neurovascular Disorders, Croatian Society of Neurology including Section for Neurocritical Care, Croatian Neurosurgical Society, Croatian Society for Difficult Airway Management and Croatian Medical Association. The aim of these guidelines is to provide current and comprehensive recommendations and to assist physicians in making appropriate decisions in the management of subarachnoid hemorrhage. Evidence based information on the epidemiology, risk factors and prognosis, as well as recommendations on diagnostic work up, monitoring and management are provided, with regard to treatment possibilities in Croatia.

Recommendations for the management of medical complications in patients following aneurysmal subarachnoid hemorrhage.

These are evidence based guidelines for the management of medical complications in patients following aneurysmal subarachnoid hemorrhage, developed and endorsed by the Croatian Society of Neurovascular Disorders, Croatian Society of Neurology including Section for Neurocritical Care, Croatian Neurosurgical Society, Croatian Society for Difficult Airway Management and Croatian Medical Association. They consist of recommendations for best monitoring, medical treatment and interventions based on the literature, evaluation of the results of large international clinical trials, and collective experience of the authors.

Tumor-like multiple sclerosis.

Multiple sclerosis is a chronic demyelinating disease of the central nervous system. Tumor-like manifestation of multiple sclerosis is one of the rare clinical variants and it is frequently misdiagnosed. This is a report on a 45-year-old man who presented with right-sided hemiparesis. Initial computed tomography and magnetic resonance imaging studies of the brain revealed a large hyperintense signal lesion in the left hemisphere surrounding the cerebral edema. Low grade glioma was among the likely differential diagnoses. The patient underwent surgery. Brain biopsy showed demyelination. Lumbar puncture was performed and cerebrospinal fluid was positive for intrathecal synthesis of immunoglobulins. Other findings were compatible with the unusual form of multiple sclerosis. This case report illustrates a demyelinating process mimicking tumor lesions of the brain and it is of high importance to consider the diagnosis of multiple sclerosis on differential diagnosis of a tumor-like lesion of the central nervous system.

Molecular alterations of E-cadherin and beta-catenin in brain metastases.

The molecular mechanisms and candidate genes involved in metastasis to the brain need elucidation. In the present study brain metastases were analyzed regarding changes of E-cadherin (CDH1) and beta-catenin (CTNNB1). Loss of heterozygosity (LOH) of the CDH1 gene was detected in 42.2% of samples. The highest frequency of LOHs was observed in metastases from primary sites of lung adenocarcinoma and small cell lung cancer. Metastases from breast and colon demonstrated changes in 55.6% and 50% of cases. Downregulation of E-cadherin protein was observed in 83% of samples. Only 21.1% of samples with E-cadherin LOH had beta-catenin located in the nucleus. Image analysis showed that the quantities of E-cadherin and beta-catenin were significantly positively correlated (P = 0.008). Changes of E-cadherin were frequent in brain metastases that we investigated. Lack of mutations of beta-catenin, the fact that it was not frequently found in the nucleus and the positive correlation between the two proteins may suggest that the break-up of adherens junctions, and not the activation of wnt signaling, is responsible for metastasis formation.

Meningiomas exhibit loss of heterozygosity of the APC gene.

The molecular mechanisms and candidate genes involved in development of meningiomas still need investigation and elucidation. In the present study 33 meningiomas were analyzed regarding genetic changes of tumor suppressor gene Adenomatous polyposis coli (APC), a component of the wnt signaling. Gene instability was tested by polymerase chain reaction/loss of heterozygosity (LOH) using Restriction Fragment Length Polymorphism (RFLP) method. RFLP was performed by two genetic markers, Rsa I in APC's exon 11 and Msp I in its exon 15. The results of our analysis showed altogether 15 samples with LOH of the APC gene out of 32 heterozygous patients (47%). Seven patients had LOHs at both exons, while four LOHs were exclusive for exon 11 and four for exon 15. The changes were distributed according to pathohistological grade as follows: 46% of meningothelial meningioma showed LOH; 33% of fibrous; 75% of mixed (transitional); 75% of angiomatous, and one LOH was found in a single case of psammomatous meningioma. None of the LOHs were found in atypical and anaplastic cases. Immunostaining showed that samples with LOHs were accompanied with the absence of APC protein expression or presence of mutant APC proteins (chi(2 )= 13.81, df = 2, P < 0.001). We also showed that nuclear localization of beta-catenin correlates to APC genetic changes (chi(2 )= 21.96, df = 2, P < 0.0001). The results of this investigation suggest that genetic changes of APC gene play a role in meningioma formation.

Traumatic leptomeningeal cyst in a 24-year-old man: case report.

OBJECTIVE AND IMPORTANCE: Traumatic leptomeningeal cysts represent a rare complication of a childhood cranial fracture, and occur in only 0.05 to 0.6% of all cranial fractures. In adults, clinical manifestations of a childhood trauma are very rare and usually appear in the form of nontender, nonpulsatile, subcutaneous mass, accompanied by a progressive neurological deficit and seizures, as shown in our case. CLINICAL PRESENTATION: We present the case of a 24-year-old man with seizures caused by a traumatic leptomeningeal cyst resulting from the head injury he suffered at the age of 9 months. INTERVENTION: Right-sided craniotomy was performed with consequent microsurgical removal of the leptomeningeal cyst. The dura was reconstructed in a watertight manner and a cranioplasty was performed with Palacos (Howmedica International, Limerick, Ireland). CONCLUSION: It is important to consider traumatic leptomeningeal cysts when treating adult patients with erosive bone lesions who have a history of head trauma.