Olivier Klein

Immunohistochemical markers to distinguish between hemangioblastoma and metastatic clear-cell renal cell carcinoma in the brain: utility of aquaporin1 combined with cytokeratin AE1/AE3 immunostaining.

Distinguishing hemangioblastomas from metastatic clear-cell renal cell carcinomas (CCRCCs) in the brain is a diagnostic challenge owing to similar clinical and morphologic presentations. Inhibin-α and aquaporin1 were shown as positive markers of hemangioblastoma, but are not totally reliable distinguishing hemangioblastoma from metastatic CCRCC. This study shows that the diagnosis can be achieved using a combination of markers. To identify the panel of markers useful for this differential, 67 hemangioblastomas and 34 metastatic CCRCCs were analyzed using a panel of antibodies including aquaporin1, inhibin-α, D2-40, cytokeratin AE1/AE3, epithelial membrane antigen, and CD10. The study confirms the usefulness of aquaporin1 (97% sensitivity, 83% specificity) and inhibin-α (88% sensitivity, 79% specificity) as positive markers of hemangioblastoma and shows that aquaporin1 is a superior positive marker versus inhibin-α for the differential. Positivity of tumor cells with cytokeratin AE1/AE3 is the signature of a metastatic CCRCC (100% specificity, 88% sensitivity) and CD10 expression as well (100% specificity, 79% sensitivity). The combined use of aquaporin1 and AE1/AE3 yields a high degree of sensitivity and specificity to differentiate between hemangioblastoma and metastatic CCRCC. All tumors but one aquaporin1 positive and cytokeratin AE1/AE3 negative (65/66) correspond to hemangioblastomas (97% sensitivity, 97% specificity, 98.5% diagnostic positive predictive value). Tumors with the opposite profile, aquaporin1 negative, and cytokeratin AE1/AE3 positive, (25/25), correspond to metastatic CCRCC (74% sensitivity, 100% specificity, 100% diagnostic positive predictive value). In summary, aquaporin1 is the most sensitive positive marker of hemangioblastoma. Despite its moderate specificity, when used in combination with epithelial marker AE1/AE3, it allowed to reliably distinguish hemangioblastoma from metastatic CCRCC.

ANGIOLEIOMYOMA OF THE CAVERNOUS SINUS : CASE REPORT

OBJECTIVEAngioleiomyomas are soft tissue tumors with smooth muscle and vascular components. They are extremely rare in intracranial locations and only three cases have been reported in the literature, including one in the cavernous sinus. Furthermore, long-term follow-up after surgery for a tumor at this site has not been described. We report a new case of intracavernous angioleiomyoma with complete surgical removal and no recurrence after 6 years of clinical and radiological follow-up. CLINICAL PRESENTATIONA 50-year-old patient presented with vertical diplopia resulting from left trochlear nerve palsy. Magnetic resonance examination showed a left intracavernous tumor with hypersignal on T2-weighted images, hyposignal on T1-weighted images, and delayed homogeneous enhancement after gadolinium injection. INTERVENTIONSurgical treatment was completed by a left pterional approach. There was a clear plane separating the tumor from the vascular and nervous elements of the cavernous sinus. Complete tumor resection was achieved. Diplopia improved after surgery. Follow-up did not reveal any recurrence. CONCLUSIONAngioleiomyomas are rare benign tumors with an excellent prognosis after total removal that justifies surgical treatment as the first-line treatment.

Leptomeningeal enhancement and enlarged choroid plexus simulating the appearance of sturge-weber disease in a child with tuberous sclerosis

The associations of tuberous sclerosis (TS) with phakomatoses, like von Recklingshausen disease, have been reported in the literature (1). The coexistence of TS with Sturge–Weber syndrome (SWS) has been reported only rarely (2,3). We report a case of TS first seen on magnetic resonance imaging (MRI) with an extensive parietooccipital leptomeningeal enhancement, without gyriform calcifications. These features, classically described in SWS, have not been reported in association with TS. The patient, a 13-year-old girl, had a family history of TS (grandfather, mother, and two maternal aunts). The proband had hypomelanotic macules associated with a left frontal epidermal angiofibroma. Right-sided sensory motor seizures with secondary generalization were noted for the first time when she was 12 years old. She rapidly showed a mild right hemiparesis. Neurologic examination was otherwise normal, except for mild cognitive difficulties. Brain MRI and computed tomography (CT) scan revealed partially calcified left frontal cortical tubers and subependymal nodules and a right parietal white-matter migration line. With these, typical TS radiologic features were associated with a left parietooccipital leptomeningeal enhancement, with fluid-attenuated inversion recovery (FLAIR) hypersignal, highly evocative of pial angiomatosis, a homolateral enlarged choroid plexus and skull hypertrophy, and a mild left parenchymal atrophy (Fig. 1). Typical SWS gyriform calcifications were absent on CT scan. Abdominal, renal, and cardiac ultrasound examinations were normal. No trigeminal angiomatosis or port-wine stain was found. Ophthalmologic examination also was normal. Standard scalp EEG showed a left hemispheric focalization. SWS is a sporadic, congenital neurologic disorder often associated with epilepsy (4,5). Diagnosis is usually straightforward in the presence of cutaneous signs and typical neuroradiologic findings (6,7). When cutaneous signs are absent, the diagnosis can be made only if pial angiomatosis is demonstrated by imaging (5,6). Three cases of TS with superficial occipital gyriform calcifications, on CT examination, have been reported in the literature (8,9). In these cases, the radiologic features were those classically found in SWS, but at histopathologic examination, when available, the calcifications appeared to be located in extensive cortical tubers, which led

Spontaneous Intracranial Hypotension: Characteristics of the Serious Form in a Series of 24 Patients

BACKGROUNDnRecommended treatments for spontaneous intracranial hypotension (SIH) range from bed rest only to neurosurgery. However, the serious form of SIH is poorly defined. A better description of patient characteristics and their outcome may help define therapeutic options.nnnMETHODSnWe reviewed 24 cases of patients with SIH and separated them into 2 groups according to whether or not they presented with signs of severity at admission: disturbance of consciousness, subdural hematomas (SDHs), and cerebral venous thrombosis.nnnRESULTSnNine patients (37%) were classified as having a serious form of SIH: six (25%) presented SDHs; three (12%) disturbance of consciousness; and one (4%) cerebral venous thrombosis. Bed rest and epidural blood patches (EBPs) were sufficient to treat all patients in the nonserious form group and 4 patients in the serious form group. Two patients (8%) had to undergo cerebrospinal fluid leak repair, and 3 others (12%) evacuation of SDHs. Outcome was good in both groups, with only one (4%) death due to extensive SDHs. Times to diagnosis in the serious form group (63 vs. 35 days, P = 0.052) and to recovery (9 months vs. 5 months, P = 0.088) tended to be higher without reaching difference.nnnCONCLUSIONSnThe presence of SDHs, disturbance of consciousness, and a trend toward a longer time to diagnosis and recovery seem to define the serious form of SIH. These patients may require exploration and surgical repair of cerebrospinal fluid leak, only after failure of conservative measures--bed rest and time--and EBP, with good outcome.

Gene expression profile of blood cells for the prediction of delayed cerebral ischemia after intracranial aneurysm rupture: a pilot study in humans.

Background: Delayed cerebral ischemia (DCI) is a potentially devastating complication after intracranial aneurysm rupture and its mechanisms remain poorly elucidated. Early identification of the patients prone to developing DCI after rupture may represent a major breakthrough in its prevention and treatment. The single gene approach of DCI has demonstrated interest in humans. We hypothesized that whole genome expression profile of blood cells may be useful for better comprehension and prediction of aneurysmal DCI. Methods: Over a 35-month period, 218 patients with aneurysm rupture were included in this study. DCI was defined as the occurrence of a new delayed neurological deficit occurring within 2 weeks after aneurysm rupture with evidence of ischemia either on perfusion-diffusion MRI, CT angiography or CT perfusion imaging, or with cerebral angiography. DCI patients were matched against controls based on 4 out of 5 criteria (age, sex, Fisher grade, aneurysm location and smoking status). Genome-wide expression analysis of blood cells obtained at admission was performed by microarrays. Transcriptomic analysis was performed using long oligonucleotide microarrays representing 25,000 genes. Quantitative PCR: 1 µg of total RNA extracted was reverse-transcribed, and the resulting cDNA was diluted 10-fold before performing quantitative PCR. Microarray data were first analyzed by ‘Significance Analysis of Microarrays software which includes the Benjamini correction for multiple testing. In a second step, microarray data fold change was compared using a two-tailed, paired t test. Analysis of receiver-operating characteristic (ROC) curves and the area under the ROC curves were used for prediction analysis. Logistic regression models were used to investigate the additive value of multiple biomarkers. Results: A total of 16 patients demonstrated DCI. Significance Analysis of Microarrays software failed to retrieve significant genes, most probably because of the heterogeneity of the patients included in the microarray experiments and the small size of the DCI population sample. Standard two-tailed paired t test and C-statistic revealed significant associations between gene expression and the occurrence of DCI: in particular, the expression of neuroregulin 1 was 1.6-fold upregulated in patients with DCI (p = 0.01) and predicted DCI with an area under the ROC curve of 0.96. Logistic regression analyses revealed a significant association between neuroregulin 1 and DCI (odds ratio 1.46, 95% confidence interval 1.02-2.09, p = 0.02). Conclusions: This pilot study suggests that blood cells may be a reservoir of prognostic biomarkers of DCI in patients with intracranial aneurysm rupture. Despite an evident lack of power, this study elicited neuroregulin 1, a vasoreactivity-, inflammation- and angiogenesis-related gene, as a possible candidate predictor of DCI. Larger cohort studies are needed but genome-wide microarray-based studies are promising research tools for the understanding of DCI after intracranial aneurysm rupture.

Management of intramedullary cystic pilocytic astrocytoma with rhenium-186 intracavitary irradiation: case report.

OBJECTIVEWe report a case of cystic spinal cord pilocytic astrocytoma treated with surgical resection and 2 intracavitary injections of 186rhenium. CLINICAL PRESENTATIONA 22-year-old man presented with low-back pain, saddle dysesthesia, and sphincter and sexual dysfunction. Spinal cord magnetic resonance showed a large, cystic, intramedullary tumor extending from T9 to T12. TREATMENTTwo surgical approaches and 1 computed tomography (CT)-scan guided tapping allowed shrinkage of the cystic component but each time the cyst enlarged and neurological symptoms worsened. Pathological examination allowed the diagnosis of pilocytic astrocytoma. The patient underwent 2 intracystic CT-scan guided injections of 186rhenium that achieved good control of cystic component. CONCLUSIONInterstitial intracavitary 186rhenium brachytherapy of recurrent spinal cord cystic astrocytomas achieved excellent stabilization of the cyst with minor side-effects and dramatic improvement of neurological deficits.

Modern robot-assisted radiosurgery of cerebral angiomas—own experiences, system comparisons, and comprehensive literature overview

Cerebral arteriovenous malformations (AVMs) are rare vascular lesions potentially responsible for substantial neurological morbidity and mortality. Over the past four decades, radiosurgery has become a valid therapeutic option for many patients with small intracranial AVMs, but reports describing the use of robotic stereotactic radiosurgery (SRS) are rare. The purposes of this study are to describe the efficacy and toxicity of robotic SRS for AVMs and to review the literature. The reports of 48 consecutive patients treated with SRS were reviewed. A total dose of 18xa0Gy in a single fraction was prescribed to the 70% isodose line. Efficacy (i.e., total obliteration of the AVM) and toxicity were analyzed. Literature search was performed on Embase and PubMed for the terms “Radiosurgery and AVMs”, “Cyberknife and AVMs” and “Radiation therapy and AVMs.” The median follow-up was 41xa0months. The median AVM volume was 2.62xa0cm3. The incidence of obliteration was 59% at 3xa0years. Regarding toxicity, 92% of patients remained symptom-free, 66% developed radiogenic edema on MRI, and none developed radionecrosis. Forty-one patients (85%) had embolization prior to SRS. Our study was incorporated in an exhaustive review of 25 trials categorized by SRS technique. In this review, the median follow-up was 60xa0months. The median nidus volume was 2xa0cm3. The median overall obliteration rate for SRS was 68% (range 36 to 92). The median embolization rate prior to SRS was 31% (range 8.23 to 90). Compared to other studies, tolerability was excellent and the obliteration rate was acceptable but probably affected by the high embolization rate prior to radiosurgery. Our study suggests that a higher dose is feasible. A larger cohort with a longer follow-up period will be needed to confirm the safety and effectiveness, and subsequently validate different prognosis and predictive scores with this treatment modality to maximize the benefits of this technology for selected patients in the long term.

Intraparenchymal central nervous system Ewing’s sarcoma. A case treated according to the modified Euro-EWING protocol

Ewings sarcoma (ES) is the second most common malignant bone tumor in children and young adults. ES may also occur as a primary soft tissue neoplasm without involvement of the bone and is then referred to as extraosseous ES (EES). The paediatric central nervous system extraosseous Ewings sarcoma (CNS-EES) is an extremely rare entity since less than 20 cases have been reported in literature. Moreover, only less than 10 cases correspond to brain parenchyma primary tumors. These cases have been often misdiagnosed with other varieties of primary brain tumors, particularly those which were called PNET (Primitive Neuro-Ectodermal Tumor). We present a case of true intraparenchymal CNS-EES and a comparison of epidemiology, behaviour, treatment, and prognosis of CNS-EES and intracranial PNET cases.