Radiosurgery for classical trigeminal neuralgia: impact of the shot size on clinical outcome.

BACKGROUND: This study compares the outcome of patients suffering from medically refractory classical trigeminal neuralgia (TN) after treatment with radiosurgery using two different shot sizes (5- and 6-mm). METHODS: All patients included in this open, prospective, non-controlled study were treated in a single institution for TN (95 cases in 93 patients) with LINear ACcelerators (LINAC) single-dose radiosurgery using a 5-mm shot (43 cases) or 6-mm shot (52 cases). The target was positioned on the intracisternal part of the trigeminal nerve. RESULTS: The mean Dmax (D0.035) to the brainstem was higher in the 6-mm group: 12.6 vs 21.3 Gy (p < 0.001). Pain relief was significantly better in the 6-mm group: at 12 and 24 months in the 6-mm group the rate of pain-free patients was 90.2 and 87.8%, respectively vs. 73.6 and 73.6% in the 5-mm group (p = 0.045). At 12 and 24 months post-radiosurgical hypoesthesia was more frequent in the 6-mm group: 47.0 and 58% vs.11.3 and 30.8% in the 5-mm group (p = 0.002). To investigate the effect of cone diameter and the dose to the brainstem on outcomes, patients were stratified into three groups: group 1 = 5-mm shot, (all Dmax < 25 Gy, 43 cases), group 2 = 6-mm shot, Dmax < 25 Gy (32 cases), group 3 = 6-mm shot Dmax > 25 Gy (20 cases). At 12 months the rates of hypoesthesia were 11.3, 33.5 and 76.0%, respectively in groups 1, 2 and 3 (p < 0.001) and the rates of recurrence of pain were 26.4, 16.5 and 5%, respectively, (p = 0.11). CONCLUSION: LINAC treatment with a 6-mm shot provided excellent control of pain, but increased the rate of trigeminal nerve dysfunction, especially when the maximum dose to the brainstem was higher than 25 Gy.

Identifying subcortical connectivity during brain tumor surgery: a multimodal study.

Bipolar direct electrical stimulation (DES) of an awake patient is the reference technique for identifying brain structures to achieve maximal safe tumor resection. Unfortunately, DES cannot be performed in all cases. Alternative surgical tools are, therefore, needed to aid identification of subcortical connectivity during brain tumor removal. In this pilot study, we sought to (i) evaluate the combined use of evoked potential (EP) and tractography for identification of white matter (WM) tracts under the functional control of DES, and (ii) provide clues to the electrophysiological effects of bipolar stimulation on neural pathways. We included 12 patients (mean age of 38.4 years) who had had a dMRI-based tractography and a functional brain mapping under awake craniotomy for brain tumor removal. Electrophysiological recordings of subcortical evoked potentials (SCEPs) were acquired during bipolar low frequency (2 Hz) stimulation of the WM functional sites identified during brain mapping. SCEPs were successfully triggered in 11 out of 12 patients. The median length of the stimulated fibers was 43.24 ± 19.55 mm, belonging to tracts of median lengths of 89.84 ± 24.65 mm. The electrophysiological (delay, amplitude, and speed of propagation) and structural (number and lengths of streamlines, and mean fractional anisotropy) measures were correlated. In our experimental conditions, SCEPs were essentially limited to a subpart of the bundles, suggesting a selectivity of action of the DES on the brain networks. Correlations between functional, structural, and electrophysiological measures portend the combined use of EPs and tractography as a potential intraoperative tool to achieve maximum safe resection in brain tumor surgery.

Towards linking diffusion MRI based macro- and microstructure measures with cortico-cortical transmission in brain tumor patients.

We aimed to link macro- and microstructure measures of brain white matter obtained from diffusion MRI with effective connectivity measures based on a propagation of cortico-cortical evoked potentials induced with intrasurgical direct electrical stimulation. For this, we compared streamline lengths and log-transformed ratios of streamlines computed from presurgical diffusion-weighted images, and the delays and amplitudes of N1 peaks recorded intrasurgically with electrocorticography electrodes in a pilot study of 9 brain tumor patients. Our results showed positive correlation between these two modalities in the vicinity of the stimulation sites (Pearson coefficient 0.54±0.13 for N1 delays, and 0.47±0.23 for N1 amplitudes), which could correspond to the neural propagation via U-fibers. In addition, we reached high sensitivities (0.78±0.07) and very high specificities (0.93±0.03) in a binary variant of our comparison. Finally, we used the structural connectivity measures to predict the effective connectivity using a multiple linear regression model, and showed a significant role of brain microstructure-related indices in this relation.

Erratum to 'HMGB1/anti-HMGB1 antibodies define a molecular signature of early stages of HIV-Associated Neurocognitive Disorders (HAND)'.

[This corrects the article DOI: 10.1016/j.heliyon.2017.e00245.].

HMGB1/anti-HMGB1 antibodies define a molecular signature of early stages of HIV-Associated Neurocognitive Isorders (HAND).

BACKGROUND: HIV-associated neurocognitive disorders (HAND) persist in the post-HAART era, characterized by asymptomatic neurocognitive impairment (ANI) and mild neurocognitive disorders (MND). High mobility group box 1 (HMGB1) is a non-histone chromosomal protein widely expressed in the nucleus of all eukaryotic cells, including brain cells, which acts as a potent proinflammatory cytokine when actively secreted from immune cells. Recent reports suggested that HMGB1 acts on microglial cells to promote neuroinflammation. In this study, our aim was to determine whether HMGB1 is involved in HAND, but also to identify early new markers of neurological impairment in HIV-infected patients. METHODS: CSF and serum were collected from 103 HIV-1-infected patients enrolled in Neuradapt, a prospective study of the prevalence of HAND in HIV-1 infected patients at Nice University Hospital. Stored fluids were assessed for immunological, virological, and brain metabolite parameters. In addition to HIV RNA and DNA measurements, expression of T-cell surface markers of activation (CD38 and HLA-DR) was analyzed on whole blood. Concentration of 27 cytokines and chemokines was measured using multiplex bead assays on serum and CSF. Concentration of HMGB1 and anti-HMGB1 IgG autoantibodies were also measured on the same samples. Changes in cerebral metabolites N-acetyl aspartate (NAA), Choline (Cho) and creatinine (Cr) were assessed by magnetic resonance microscopy (MRS). RESULTS: Clinical, virological and immunological characteristics were comparable between HAND (n = 30) and no HAND (n = 73) patients, except the absolute numbers of CD8+ T cells, which were higher in patients with HAND. Among the 29 molecules tested, only 4 of them were significantly upregulated in the CSF from HAND patients as compared to healthy donors i.e. HMGB1, anti-HMGB1 IgG antibodies, IP-10 and MCP1. CSF HMGB1 levels were positively correlated with HIV-1 DNA in aviremic HAND patients, suggesting a positive impact of HMGB1 on HIV reservoirs. Moreover, in contrast to NAA/Cr and Cho/NAA ratios, circulating anti-HMGB1 IgG antibody levels could discriminate patients with no HAND from patients with no HAND and a single deficit (average ROC-AUC = 0.744, p = 0.03 for viremic patients), thus enabling the identification of a very early stage of neurocognitive impairment. CONCLUSION: We report that brain injury in chronically HIV-infected patients on stable HAART is strongly associated with persistent CNS inflammation, which is correlated with increased levels of HMGB1 and anti-HMGB1 IgG in the CSF. Moreover, we identified circulating anti-HMGB1 IgG as a very early biomarker of neurological impairment in patients without HAND. These results might have important implication for the identification of patients who are at high risk of developing neurological disorders.

A prospective study of patients with brain MRI showing incidental t2 hyperintensities addressed as multiple sclerosis: a lot of work to do before treating.

INTRODUCTION: With the development of magnetic resonance imaging (MRI) and publications about radiologically isolated syndrome (RIS), a lot of patients are referred to multiple sclerosis (MS) tertiary centers to confirm diagnosis of RIS or MS when brain T2 abnormalities are identified, whatever their characteristics. We evaluate prospectively the occurrence of RIS or MS and sensitivity, specificity and predictive value of McDonald criteria in diagnosis for patients presenting with incidental brain MRI T2 lesions. METHODS: The authors ran standardized procedures on 220 consecutive patients addressed by general practitioners or neurologists to confirm RIS or MS diagnosis on brain MRI and give a therapeutic advice. All patients underwent neurological tests, extensive blood screening, cerebrospinal fluid (CSF) examination, visual evoked potential (VEP) and follow-up MRI after 3, 6, 12 and 24 months to consider dissemination in time and space. RESULTS: Patient characteristics were: 165 women and 55 men, mean age: 42.7 years old (23-59). The major symptom motivating MRI was headaches (39%), sensitive atypical manifestations or pain (12%), mood disorders (10%), transient visual symptoms (9%), fatigue (8%), hormonal screening (6%), vertigo (6%), cranial trauma (5%), and dummy run for clinical study (5%). After a structured analysis of T2 lesions, the suspected diagnosis was: inflammatory disease 45%, vascular 33%, non-pathological 19%, genetic 2%, and metabolic 1%. Extensive screening confirmed the proposed diagnosis in 97% of cases. Among all the 220 proposed RIS patients, only 35.4% fulfilled the 2010 McDonald criteria, and 8% can be categorized as RIS. Dissemination in time criteria was present for 82.7% of MS patients and 36% of RIS patients but none of the vascular or non-pathological T2 abnormalities. CONCLUSION: Even if RIS was initially suspected on MRI, only a third of the patients had an inflammatory disease. Most of the patients had either non-specific T2 lesions or a non-inflammatory disease. Others were initially well categorized but had experienced clinical symptoms that could possibly be considered as a first clinical event. Overdiagnosis of MS can lead to propose an inappropriate disease-modifying therapy.

[Papillary meningioma: a very rare and aggressive variant of meningioma]. / Méningiome papillaire: une forme rarissime et agressive de méningiome.

Papillary meningioma (MP) is a rare and aggressive variant of meningioma, occurring preferentially in young subjects. Histopathological features of papillary meningiomas are characterized by papillary or perivascular pseudorosette patterns. We report the case of a right frontal MP in a 16-year-old boy. Differential diagnosis included other primitive or secondary intracranial papillary neoplasms. MP diagnosis should not be missed due to its aggressive behavior with brain invasion, local recurrence and metastases.

Abnormalities of cerebral arteries are frequent in patients with late-onset Pompe disease.

Cerebral aneurysms and arteropathies causing severe cerebrovascular events have been reported as rare complications in patients with late-onset Pompe disease. We investigated the frequency of cerebrovascular anomalies in six patients with late-onset Pompe disease followed at our institution. Clinical data collection and magnetic resonance angiography were performed as part of routine annual examinations. Four out of six patients had brain vascular anomalies including dolichoectasia of the basilar artery and ectasia of internal carotids. These patients also complained of gastrointestinal symptoms (chronic constipation and gastrointestinal reflux). Two patients had clinical signs related to the arteriopathy, including partial paralysis of the third cranial nerve and transient ischemic attacks. At 1 year follow-up, enzyme replacement therapy did not modify the size of cerebral vessels, but patients reported a marked improvement of intestinal symptoms. In conclusion, neurologists should be aware that intracranial artery abnormalities are not infrequent in patients with late-onset Pompe disease, and they should be specifically investigated in the presence of unexplained CNS symptoms.

CyberKnife stereotactic radiotherapy for spinal tumors: value of computed tomographic myelography in spinal cord delineation.

OBJECTIVE: For para- and intraspinal tumors, precise spinal cord delineation is critical for CyberKnife (Accuray, Inc., Sunnyvale, CA) stereotactic radiotherapy. We evaluated whether computed tomographic (CT) myelography is superior to magnetic resonance imaging (MRI) for accurate spinal cord delineation. Treatment parameters and short-term outcome and toxicity are also presented. METHODS: The planning CT scan, the gadolinium-enhanced, T1-weighted, 3-dimensional (3D) fast imaging employing steady-state acquisition MRI scan, and the CT myelogram were fused before volume-of-interest delineation. The planning target volume margin was less than 1 mm using the Xsight Spine tracking system (Accuray). We present data from 11 heavily pretreated patients who underwent CyberKnife stereotactic radiosurgery between November 2006 and January 2008. RESULTS: Spatial resolution was 0.46 and 0.93 mm/pixel for CT myelography and 3D-fast imaging employing steady-state acquisition MRI, respectively. The contrast between cerebrospinal fluid and spinal cord was excellent with CT myelography. A transient postmyelography headache occurred in 1 patient. The mean gross tumor volume was 51.1 mL. The mean prescribed dose was 34 Gy in 4 fractions (range, 2-7 fractions) with 147 beams (range, 79-232 beams) to the 75% reference isodose line (range, 68-80%), covering 95% (range, 86-99%) of the gross tumor volume with a mean conformity index of 1.4 (range, 1.1-1.8). No short-term toxicity on the spinal cord was noted at 1- to 6-months of follow-up. CONCLUSION: CT myelography was more accurate for spinal cord delineation than 3D-fast imaging employing steady-state acquisition MRI (used for its myelographic effect), particularly in the presence of ferromagnetic artifacts in heavily pretreated patients or in patients with severe spinal compression. Because other MRI sequences (T2 and gadolinium-enhanced T1) provide excellent tumor characterization, we suggest trimodality imaging for spinal tumor treatment to yield submillimetric delineation accuracy. Combined with CyberKnife technology, CT myelography can improve the feasibility of dose escalation or reirradiation of spinal tumors in selected patients, thereby increasing local control while avoiding myelopathy. Further follow-up and prospective studies are warranted.

Perfusion SPECT findings in a suspected case of Rasmussen encephalitis.

We report the case of a 35-year-old who was referred for brain perfusion single photon emission computed tomography (SPECT) for pharmacoresistant epilepsy. Her medical history included brain surgery for an inflammatory lesion of unknown origin at age 23 before partial epilepsy occurred. The seizures became refractory to standard antiepileptic drugs and she developed epileptic negative myoclonus of the right upper limb, nocturnal motor seizures, and progressive intellectual impairment. Neurological symptoms slowly worsened with mild aphasia and right visual neglect. Inter-ictal brain SPECT showed decreased cerebral blood flow on the left hemisphere corresponding on magnetic resonance imaging (MRI) with moderate left hemiatrophy, a left frontal defect in accordance with the history of surgery, and a crossed cerebellar diaschisis. Clinical and imaging data were in favor of a late-onset form of Rasmussen encephalitis. Rasmussen syndrome is a rare unilateral devastating disease with childhood onset that can also occur in adulthood, characterized by intractable epileptic seizures associated with progressive neurological deterioration and unilateral progressive atrophy. Brain perfusion SPECT can speed up the diagnosis when exhibiting a strictly unilateral hemispheric hypoperfusion in such a clinical context. It can also guide brain biopsy in cases of inconclusive MRI.

[Ependymal variant of dysembryoplastic neuro-epithelial tumor]. / Tumeur neuro-épithéliale dysembryoplasique à différenciation épendymaire.

Dysembryoplastic neuro-epithelial tumors (DNET) are glioneuronal tumors with a common astrocytic or oligodendroglial differentiation. We report a case of DNET with an ependymal differentiation. A 13 years-old girl had refractory focal seizures for 3 years. Successive MRI showed a stable cortical lesion of the right temporal lobe with DNET characteristics. The lesion was resected. Histological examination revealed a pure ependymal differentiation characterized by perivascular pseudorosettes containing EMA immunoreactive cells. Mib1 positive cells were absent. In spite of histologic features of ependymoma, this tumor showed clinical, radiological and behaviour characteristics of DNET. We are not aware of any other case of DNET with ependymal differentiation in the literature. Our observation suggests that the glial component of DNET may show an ependymal differentiation.

[An unusual and misleading form of pilocytic astrocytoma]. / Une forme rare et trompeuse d'astrocytome pilocytique.

Pilocytic astrocytoma is histologically characterized by a biphasic pattern. We report a myxoid form of frontocallosal pilocytic astrocytoma in a 13-year-old girl. MRI showed a relatively well-defined tumor with necrosis and ring-like zone of contrast enhancement. Histological examination showed a monophasic tumor composed of piloid cells on a myxoid background corresponding to a pilomyxoid astrocytoma. This unusual form of pilocytic astrocytoma can be mistaken for a high grade infiltrating glioma. Pilomyxoid astrocytoma is more aggressive than classic pilocytic astrocytoma and has to be distinguished from it.

Atlas-based automatic segmentation of MR images: validation study on the brainstem in radiotherapy context.

PURPOSE: Brain tumor radiotherapy requires the volume measurements and the localization of several individual brain structures. Any tool that can assist the physician to perform the delineation would then be of great help. Among segmentation methods, those that are atlas-based are appealing because they are able to segment several structures simultaneously, while preserving the anatomy topology. This study aims to evaluate such a method in a clinical context. METHODS AND MATERIALS: The brain atlas is made of two three-dimensional (3D) volumes: the first is an artificial 3D magnetic resonance imaging (MRI); the second consists of the segmented structures in this artificial MRI. The elastic registration of the artificial 3D MRI against a patient 3D MRI dataset yields an elastic transformation that can be applied to the labeled image. The elastic transformation is obtained by minimizing the sum of the square differences of the image intensities and derived from the optical flow principle. This automatic delineation (AD) enables the mapping of the segmented structures onto the patient MRI. Parameters of the AD have been optimized on a set of 20 patients. Results are obtained on a series of 6 patients' MRI. A comprehensive validation of the AD has been conducted on performance of atlas-based segmentation in a clinical context with volume, position, sensitivity, and specificity that are compared by a panel of seven experimented physicians for the brain tumor treatments. RESULTS: Expert interobserver volume variability ranged from 16.70 cm(3) to 41.26 cm(3). For patients, the ratio of minimal to maximal volume ranged from 48% to 70%. Median volume varied from 19.47 cm(3) to 27.66 cm(3) and volume of the brainstem calculated by AD varied from 17.75 cm(3) to 24.54 cm(3). Medians of experts ranged, respectively, for sensitivity and specificity, from 0.75 to 0.98 and from 0.85 to 0.99. Median of AD were, respectively, 0.77 and 0.97. Mean of experts ranged, respectively, from 0.78 to 0.97 and from 0.86 to 0.99. Mean of AD were, respectively, 0.76 and 0.97. CONCLUSIONS: Results demonstrate that the method is repeatable, provides a good trade-off between accuracy and robustness, and leads to reproducible segmentation and labeling. These results can be improved by enriching the atlas with the rough information of tumor or by using different laws of deformation for the different structures. Qualitative results also suggest that this method can be used for automatic segmentation of other organs such as neck, thorax, abdomen, pelvis, and limbs.

Effect of subthalamic nucleus stimulation on obsessive-compulsive disorder in a patient with Parkinson disease. Case report.

The authors report on a patient with Parkinson disease (PD) and severe obsessive-compulsive disorder (OCD), in whom bilateral stimulation of the subthalamic nucleus (STN) was used to treat both PD and OCD symptoms. This 49-year-old man had displayed symptoms of PD for 13 years. Progressively, his motor disability became severe despite optimal medical treatment. In parallel, he suffered severe OCD for 16 years, with obsessions of accumulation and compulsions of gathering and rubbing that lasted more than 8 hours per day. Bilateral high-frequency STN stimulation was performed to treat motor disability. After surgery (at 1-year follow up), motor and OCD symptoms were dramatically improved. The pre- and postoperative Yale-Brown Obsessive-Compulsive Scale scores were 32 and 1, respectively. No additional antiparkinsonian drugs were administered. This case and other recent reports indicate that OCD symptoms can be improved by deep brain stimulation, a finding that opens new perspectives in the surgical treatment of severe and medically intractable OCD.

[Standards, Options and Recommendations 2002 for the management of adult patients with intracranial gliomas (summary report)]. / Standards, options et recommandations 2002 pour la prise en charge des patients atteints de gliomes intracrâniens de l'adulte (rapport abrégé).

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, which started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French Regional Cancer Centers, and specialists from French public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. OBJECTIVE: To define clinical practice guidelines for the management of adult patients with intracranial glioma in collaboration with the Association of French-speaking Neuro-oncologists (Anocef) and the French society of neurosurgeons (SNCLF). These recommendations cover diagnosis, classification, treatment and follow-up of patients with these tumors. METHOD: The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts who define the CPGs according to the definitions of the Standards, Options and Recommendations project. Once the guidelines has been defined, the document is submitted for review by independent reviewers. RESULTS: This article is a summary version of the full document presenting the clinical practice guidelines with algorithms. The main recommendations concern the place of the surgery, radiotherapy, chemiotherapy, imagery and concomitant medical treatments in the specific treatment strategy of grade III and IV glioma, grade II glioma, gliomatosis cerebri, pilocytic astrocytoma, subependymoma, xanthoastrocytoma, intracranial ependymoma and brain stem glioma.