Does the insula contribute to emotion-related distortion of time? A neuropsychological approach.

The literature points to a large distributed brain network involved in the estimation of time. Among these regions, the role of the insular cortex is still poorly understood. At the confluence of emotional, interoceptive, and environmental signals, this brain structure has been proposed to underlie awareness of the passage of time and emotion related time dilation. Yet, this assumption has not been tested so far. This study aimed at exploring how a lesion of the insula affects subjective duration, either in an emotional context or in a non-emotional context. Twenty-one patients with a stroke affecting the insula, either left or right, were studied for their perception of sub and supra second durations. A verbal estimation task and a temporal bisection task were used with either pure tones or neutral and emotional sounds lasting between 300 and 1500 ms and presented monaurally. Results revealed that patients with a right insular lesion, showed less temporal sensitivity than both control participants and patients with a left insular lesion. Unexpectedly, emotional effects were similar in patients and control participants. Altogether, these results suggest a specific role of the right insula in the discrimination of durations, but not in emotion related temporal distortion. In addition, an ear × emotion interaction in control participants suggests that temporal processing of positive and negative sounds may be lateralized in the brain.

CSF IgA NMDAR antibodies are potential biomarkers for teratomas in anti-NMDAR encephalitis.

OBJECTIVE: To evaluate the presence of immunoglobulin A (IgA) subtype of anti-NMDA receptor (NMDAR) antibodies (IgA-NMDAR-Abs) in the CSF of patients with immunoglobulin G (IgG)-NMDAR-Ab encephalitis and to describe the potential association with a specific clinical pattern. METHODS: The retrospective analysis for the presence of IgA-NMDAR-Abs in 94 CSF samples from patients with anti-NMDAR encephalitis diagnosed between October 2007 and February 2014 was conducted at the French Reference Centre on Paraneoplastic Neurological Syndrome. This observational study compared 39 patients with both IgA- and IgG-NMDAR-Abs to 55 patients with only IgG-NMDAR-Abs. RESULTS: In the retrospective cohort, 41% of the patients with NMDAR-Ab encephalitis had both CSF IgG- and IgA-NMDAR-Abs. Approximately half of the IgA-NMDAR-Ab-positive patients (18/38, 49%) definitively possessed associated tumors, primarily ovarian teratomas (17/18, 94%), compared with only 5% (3/55) of the patients in the IgA-NMDAR-Ab-negative group (p < 0.001). In the adult female population at risk for ovarian teratoma, the detection of CSF IgA-NMDAR-Ab positivity showed 85% sensitivity, 70% specificity, a 57% positive predictive value, and a 90% negative predictive value for the diagnosis of ovarian teratoma. No other specific clinical features or clinical outcome were associated with CSF IgA-NMDAR-Ab positivity. CONCLUSION: These results suggest that in patients with IgG-NMDAR-Ab encephalitis, CSF IgA-NMDAR-Abs could be used as a biological marker for the presence of an ovarian teratoma.

Treatment and outcome of children and adolescents with N-methyl-D-aspartate receptor encephalitis.

The objective of this study is to describe the treatment and outcome of children and adolescents with N-methyl-D-aspartate receptor (NMDA-R) encephalitis. A retrospective study of children and adolescents with NMDA-R encephalitis was performed by the French Paraneoplastic Neurological Syndrome Reference Center between January 1, 2007 and December 31, 2012. The modified Rankin scale (mRS) was used to assess outcome. Thirty-six children and adolescents with NMDA-R encephalitis were studied. All of the patients received first-line immunotherapy (corticosteroids, intravenous immunoglobulins or plasma exchange), and 81% received second-line immunotherapy (rituximab or cyclophosphamide). Median time between first-line and second-line treatment was 26 days. During the first 24 months, 30 of 36 patients (83%) achieved a good outcome (mRS ≤ 2) and 20 of 36 patients (56%) achieved complete recovery (mRS = 0). Median time to good outcome and to complete recovery was 6 and 24 months, respectively. Three patients (8%) relapsed, one patient died. In multivariate analysis, age >12 years was a predictor of good outcome and initial mRS ≤ 3 was a predictor of complete recovery. Despite a higher rate of patients who received second-line immunotherapy, the outcome of the patients in the present series was very similar to the outcome reported in previous series. The present study highlights the need for clinical trials to determine the optimal treatment of NMDA-R encephalitis.

CSF neopterin level as a diagnostic marker in primary central nervous system lymphoma.

BACKGROUND: The diagnosis of primary central nervous system lymphoma (PCNSL) can be challenging. PCNSL lesions are frequently located deep within the brain, and performing a cerebral biopsy is not always feasible. The aim of this study was to investigate the diagnostic value of CSF neopterin, a marker of neuroinflammation, in immunocompetent patients with suspected PCNSL. METHODS: We retrospectively reviewed the characteristics of 124 patients with brain tumor (n = 82) or an inflammatory CNS disorder (n = 42) in whom CSF neopterin levels were assessed. Twenty-eight patients had PCNSL, 54 patients had another type of brain tumor (glioma n = 36, metastasis n = 13, other n = 5), and 13 patients had a pseudotumoral inflammatory brain lesion. RESULTS: CSF neopterin levels were significantly higher in the patients with PCNSL than in those with other brain tumors (41.8 vs 5.1 nmol/L, P < .001), those with pseudotumoral inflammatory brain lesions (41.8 vs 4.3 nmol/L, P < .001), and those with nontumefactive inflammatory CNS disorders (41.8 vs 3.8 nmol/L, P < .001). In the 95 patients with space-occupying brain lesions, at a cutoff of 10 nmol/L, the sensitivity of this approach was 96% and the specificity was 93% for the diagnosis of PCNSL. The positive and negative predictive values were 84% and 98%, respectively. CONCLUSION: Assessing CSF neopterin levels in patients with a suspected brain tumor might be helpful for the positive and differential diagnosis of PCNSL. A prospective study is warranted to confirm these results.

Embolic and Hemodynamic Transcranial Doppler Characteristics in Patients with Acute Ischemic Stroke due to Carotid Occlusive Disease: Contribution to the Different Infarct Patterns on MRI.

BACKGROUND AND PURPOSE: Whether hemodynamic and/or embolic transcranial Doppler (TCD) features of internal carotid artery (ICA) stenosis contribute to the classification of stroke patterns on MRI. PATIENTS AND METHODS: Consecutive patients presenting symptomatic ≥50% ICA stenosis were included. Microembolic signals (MES) detection and measurement of cerebral vasoreactivity (VR) were performed by TCD. Only acute MRI lesions, territorial (TT) and/or borderzone (BZ) were considered. RESULTS: A total of 72 ICA stenoses, 27 (38%) moderate (50-69%), and 45 (62%) high grade (70-99%) were included. MRI lesions showed 32 (44%) pure TT, 20 (28%) pure BZ, and 20 (28%) mixed TT and BZ. Impaired VR was found more frequently among patients with higher degrees of stenoses (P < .001) whereas MES were similarly encountered in both groups (P = NS). Impaired VR was more common in the BZ (10/20, 50%) than in the TT group (9/32, 28%, P < .1) while MES were present in 47% (15/32) of patients with TT and in 30% (6/20, P < .1) of those with BZ lesions, in particular in cortical BZ infarcts (P < .02). CONCLUSION: Our findings suggest that TCD characteristics of the ICA stenosis contribute to better define stroke patterns on MRI in about one-third of the patients presenting with pure TT or BZ lesions.

18FDG-PET-CT: an imaging biomarker of high-risk carotid plaques. Correlation to symptoms and microembolic signals.

BACKGROUND AND PURPOSE: We investigated whether uptake of (18)fluoro-2-deoxy-d-glucose (18FDG) positron emission tomography-computed tomography (PET-CT) correlated to clinical symptoms and presence of microembolic signals (MES) detected by transcranial Doppler in patients with carotid stenosis. METHODS: 18FDG-PET-CT and MES detection was performed in consecutive patients with 50% to 99% symptomatic or asymptomatic carotid stenoses. Uptake index was defined by a target to background ratio (TBR) between maximum standardized uptake value of the carotid plaque and the mean standardized uptake value of the jugular veins. End points for analysis were presence of symptoms and presence of MES. RESULTS: We included 123 stenosis derived from 110 patients, 60 symptomatic and 63 asymptomatic. MES positive (+) lesions were found in 16%. TBR values were higher in symptomatic compared with asymptomatic (median 2.07 versus 1.78; P<0.0018) and in MES+ compared with MES- plaques (median 2.14 versus 1.86; P<0.008). TBR values were also higher in asymptomatic MES+ compared with MES- plaques (median 1.97 versus 1.76; P<0.03). The best TBR threshold value for symptomatic versus asymptomatic, for MES+ versus MES-, for symptomatic MES+ versus symptomatic or asymptomatic MES-, and for asymptomatic MES+ versus asymptomatic MES- plaques was 1.9. Sensitivity/specificity were, respectively, 56/77%, 73/63%, 79/64%, and 80/77%. We found a strong correlation between number of MES and TBR values (ρ 0.26; P=0.0043). CONCLUSIONS: 18FDG-PET-CT accurately detected high-risk carotid plaques. Also given its strong correlation to MES, 18FDG-PET-CT may be a useful tool in clinical practice.

Clinical specificities of adult male patients with NMDA receptor antibodies encephalitis.

OBJECTIVE: The aim of this study was to describe the clinical features and specificities of adult male patients with NMDA receptor antibodies (NMDAr-Abs) encephalitis. METHODS: Observational study of 13 adult male patients who were diagnosed with NMDAr-Abs encephalitis at the French Paraneoplastic Neurological Syndrome Reference Center. RESULTS: Adult male patients frequently presented initially with a seizure (8/13, 61.5%). Seizures were partial in 5/8 patients and were followed only a few days later (median 12 days; range 2-17 days) by psychiatric or cognitive symptoms. Conversely, adult female patients rarely presented with a seizure initially (8/58, 14%, p < 0.001), and most of their seizures were generalized and were rapidly followed (median 2 days; range 1-7 days) by behavioral and psychiatric features. Additionally, in male patients the disease was rarely associated with a tumor (1/13 or 8%, a perineal schwannoma); in contrast, 41% of female patients had an associated tumor (95% of which were ovarian teratomas; p = 0.02 male vs female association with tumor). The incidences of abnormalities in ancillary tests, treatment modalities, clinical evolution, and outcome were equal for both subgroups. CONCLUSION: Adult male patients who have partial seizures, normal MRI results, and no clear etiology should be tested for NMDAr-Abs to avoid any delays in treatment initiation. Adult female patients who had a seizure as the first symptom are infrequent when NMDAr-Abs encephalitis is diagnosed; additionally, their clinical pattern is different from male patients, with more generalized seizures and rapid development of behavioral and psychiatric symptoms. The differences in hormonal influence could contribute to this difference in clinical pattern.

Contrast-enhanced ultrasound imaging of carotid plaque neo-vascularization: accuracy of visual analysis.

The aim of our study was to evaluate whether neo-vascularization of the carotid plaque can be accurately assessed by visual analysis of contrast-enhanced ultrasound images and whether these findings correlate with intensity-over-time curve analysis (ITC) and histopathology. Patients with ≥50% symptomatic or ≥60% asymptomatic stenosis according to European Carotid Surgery Trial criteria were included. Four investigators evaluated contrast enhancement visually (three grades), with positive agreement when three or more investigators were unanimous. ITC analysis of contrast enhancement was performed in the plaque and in the lumen. Histopathology (microvessel density with CD34 + staining) was completed when endarterectomy was performed. Visual grading (33 patients, inter-observer agreement = 94%) correlated significantly with ITC analysis (p = 0.03). Histopathology (n = 19) revealed a larger CD34 + area in patients with grade 1/2 versus grade 0 (p = 0.03). Visual analysis of neo-vascularization by means of contrast-enhanced ultrasound imaging is accurate and reproducible, with significant correlations with ITC and histopathology.

Paraneoplastic neurological syndromes: general treatment overview.

OPINION STATEMENT: Major recent discoveries have bringing out a revised definition of paraneoplastic neurological syndromes (PNS), bringing out the concept of antibody-mediated neurological disorders, triggered or not by cancer. Classification of these diseases is not based anymore on the clinical pattern or an underlying tumor, but on the location of the targeted antigens. Indeed, evolution, response to treatment, and pathophysiology are radically different according to the associated antibodies. In some patients with newly described antibodies targeting cell-surface antigens, humoral immunity seems to play a direct role and a dramatic improvement is observed with immunomodulator treatments. In these patients, an associated tumor is less frequent. Conversely, patients with antibodies directed against intracellular targets are, in most cases, characterized by a high degree of irreversible neuronal death mediated by cytotoxic T-cells and do not improve after immunomodulator treatments. In these patients, an associated tumor is highly frequent and must be cured as soon as possible. A third group of patients can be identified with anti-GAD65 and anti-Amphiphysin antibodies. In patients with these antibodies, the efficiency of immunomodulator treatments is less clear as well as the type of immune response that could be a mix between humoral and cellular. In this last group, the antigen is intracellular, but patients may improve with immunomodulator treatments and associated tumors are rare. Thus, identification of associated antibodies should be prompt and the treatment guided according the identified antibody. Mainstream of treatment include the quest of a tumor and its cure. Immunotherapy must be promptly initiated, targeting humoral, or cellular immune response, or both, according to the associated antibodies. Furthermore, in some situations such as Lambert-Eaton Myasthenic Syndromes and Stiff-Person Syndromes, symptomatic drugs can be useful to control the symptoms.

Focal common carotid artery intramural hematoma.

BACKGROUND AND PURPOSE: Isolated focal common carotid artery dissection is a rare condition. CASE REPORT: A 43-year-old healthy woman suffered for the first time from a transient episode of word-finding difficulties, which was associated with her typical migraine headaches. A month prior to this event she had suffered from a minor whiplash injury. On routine work-up we found an isolated focal left common carotid mural hematoma and tiny acute left posterior watershed lesions on diffusion weighted images. CONCLUSION: Focal isolated common carotid artery dissection is a rare condition not to be overlooked. This case presents an incidental finding possibly of traumatic nature. In the presence of concomitant migraine its causal embolic relation to the transient word-finding difficulties must remain open.

Chemotherapy in low-grade gliomas.

PURPOSE OF REVIEW: This review summarizes the recent studies in adults' diffuse low-grade gliomas (LGGs) chemotherapy, including response assessment and potential predictive biomarkers of chemosensitivity. RECENT FINDINGS: Recent studies have confirmed that chemotherapy is an interesting treatment option in LGGs. About 25-50% of LGGs achieve radiological responses with temozolomide or a procarbazine-CCNU-vincristine (PCV) regimen. Clinical and quality-of-life improvements are commonly observed with more than half of the patients with epilepsy, demonstrating a significant reduction of seizure frequency. Dynamic volumetric studies have provided a better description of LGGs evolution after chemotherapy. They have shown that an ongoing volume decrease can be observed many months after chemotherapy discontinuation, particularly after PCV, raising the question of how and for how long should LGGs be treated. New response criteria have been defined by the Response Assessment in Neuro-Oncology group. In addition to 1p/19q codeletion and MGMT promoter methylation, IDH1 mutation might also be a potential predictive biomarker of chemosensitivity. SUMMARY: It has now been widely accepted that chemotherapy is an interesting treatment option in LGGs. However, several questions remain unanswered regarding its optimal use. Ongoing phase III studies will allow a better delineation of the role of chemotherapy in LGGs and will also help to better determine the potential predictive value of a 1p/19q codeletion, a MGMT promoter methylation and an IDH1 mutation.