A Crossed Pure Agraphia by Graphemic Buffer Impairment following Right Orbito-Frontal Glioma Resection.

Pure agraphias are caused by graphemic buffer damage. The graphemic buffer stores graphemic representations that handle the transition from spelling lexicon to writing or oral spellings. The authors report a case of a crossed pure agraphia, following the post-surgical removal of a right frontal low-grade glioma in a right-handed French patient. He presented a pure agraphia displaying the features of a graphemic buffer impairment. Our patient only made spelling errors, whereas repetition and other oral language abilities remained perfect. We found a greater number of errors for longer stimuli, increased errors for the medially located graphemes, and agraphia for both words and non-words and error types, essentially consisting of omissions, substitutions, and letter transpositions. We also observed no significant effect of word frequency on spelling errors, but word length affected the rate of errors. The particularity of this case was linked to right frontal subcortical injuries in a right-handed subject. To our knowledge, it is the first report of a crossed pure agraphia caused by graphemic buffer impairment. Further studies are needed in order to analyse the role of subcortical structures, particularly the caudate nucleus in the graphemic buffer during writing tasks, as well as the participation of the non-dominant hemisphere in writing language.

Exploring Self-Consciousness From Self- and Other-Image Recognition in the Mirror: Concepts and Evaluation.

A historical review of the concepts of self-consciousness is presented, highlighting the important role of the body (particularly, body perception but also body action), and the social other in the construction of self-consciousness. More precisely, body perception, especially intermodal sensory perception including kinesthetic perception, is involved in the construction of a sense of self allowing self-other differentiation. Furthermore, the social other, through very early social and emotional interactions, provides meaning to the infant's perception and contributes to the development of his/her symbolization capacities. This is a necessary condition for body image representation and awareness of a permanent self in a time-space continuum (invariant over time and space). Self-image recognition impairments in the mirror are also discussed regarding a comprehensive developmental theory of self-consciousness. Then, a neuropsychological and neurophysiological approach to self-consciousness reviews the role of complex brain activation/integration pathways and the mirror neuron system in self-consciousness. Finally, this article offers new perspectives on self-consciousness evaluation using a double mirror paradigm to study self- and other- image and body recognition.

Examining the Inter Hemispheric Transfer Time Test: A new computerized cognitive test to incorporate into therapeutic strategy for patients with brain metastases? A pilot study.

OBJECTIVE: To evaluate the computerized Inter Hemispheric Transfer Time Test (IHTTT), a cognitive test designed for the detection of information processing speed impairment in patients undergoing stereotactic radiation therapy for brain metastases. METHODS: Inclusion criteria: age ≥18 years, brain metastases treated by stereotactic radiotherapy (SRT) with dose schedule: 33 Gy in 3 fractions, solid tumour, ≥70 Karnofsky Performance Status, Mini-Mental State Evaluation (MMSE) ≥ 24, no history of stroke brain injury. Twenty-nine patients were recruited from June 2014 to April 2015. All recruited patients were administered Frontal Assessment Battery at Bedside (FAB), IHTTT and QLQ-C30 quality of life questionnaire before SRT, at one-month, six-month and one-year follow-up. The primary endpoint was Interhemispheric Transfer Index (IHTI). Secondary endpoints included Interhemispheric Transfer Time (IHTT), MMSE, FAB, and quality of life. RESULTS: A significant evolution of cognitive function over time was assessed by the IHTTT: IHTT = 720 ±â€¯27 ms at baseline, 728 ±â€¯20 at one month, 736 ±â€¯36 at 6 months, 799 ±â€¯111 at one-year follow-up (p = 0.0010); IHTI = 13.1 ±â€¯31.4, 11.5 ±â€¯24.3, 50.6 ±â€¯57.9, 91.0 ±â€¯59.4 (p < 0.0001). There was also a significant evolution over time for MMSE (p = 0.014) but neither for FAB score nor the quality of life scores. IHTI was strongly related to progression-free survival (p = 0.0091). CONCLUSION: Our results suggest that IHTTT is able to detect the evolution of cognitive function over time. IHTTT could be an interesting sensitive cognitive test to include in evaluation of patients with brain metastases irradiated by SRT.

Self-other recognition impairments in individuals with schizophrenia: a new experimental paradigm using a double mirror.

Clinical observations suggest early self-consciousness disturbances in schizophrenia. A double mirror combining the images of two individuals sitting on each side of the mirror was used to study self-other differentiation in 12 individuals with early onset schizophrenia (EOS) and 15 individuals with adult onset schizophrenia (AOS) compared to 27 typically developing controls (TDC) matched on age and sex. The effects of intermodal sensory perception (visual-tactile and visual-kinesthetic) on self-other recognition were also studied. The results showed that EOS and AOS individuals, independently of age and schizophrenia severity, were centered on their own image compared to TDC, with both significant earlier self-recognition and delayed other-recognition during the visual recognition task. In addition, there was no significant effect of intermodal sensory stimulation on self-other recognition in EOS and AOS patients, whereas self-centered functioning was significantly increased by visual-tactile stimulation and decreased by visual-kinesthetic stimulation in TDC. The findings suggest that self-other recognition impairments might be a possible endophenotypic trait of schizophrenia.

[Brain metastases: Focal treatment (surgery and radiation therapy) and cognitive consequences]. / Métastases cérébrales : rôle des traitements focaux (chirurgie et radiothérapie) et leur impact cognitif.

Brain metastases represent the first cause of malignant brain tumor. Without radiation therapy, prognosis was poor with fast neurological deterioration, and a median overall survival of one month. Nowadays, therapeutic options depend on brain metastases presentation, extra brain disease, performance status and estimated prognostic (DS GPA). Therefore, for oligometastatic brain patients with a better prognosis, this therapeutic modality is controversial. In fact, whole-brain radiation therapy improves neurological outcomes, but it can also induce late neuro-cognitive sequelae for long-term survivors of brain metastases. Thus, in this strategy for preserving good cognitive functions, stereotactic radiation therapy is a promising treatment. Delivering precisely targeted radiation in few high-doses in one to four brain metastases, allows to reduce radiation damage to normal tissues and it should allow to decrease radiation-induced cognitive decline. In this paper, we will discuss about therapeutic strategies (radiation therapy and surgery) with their neuro-cognitive consequences for brain metastases patients and future concerning preservation of cognitive functions.

Designing an operating theatre for awake procedures: A solution to improve multimodality information input.

OBJECTIVE: Many neurosurgical procedures are now performed with the patient aware in order to allow interactions between the patient and healthcare professionals. These procedures include awake brain surgery and spinal cord stimulation (SCS), lead placement for treatment of refractory chronic back and leg pain. Neurosurgical procedures under local anaesthesia require optimal intraoperative cooperation of the patient and all personnel involved in surgery. In addition to accommodating this extra source of intraoperative information all other necessary sources of data relevant to the procedure must be presented. The concept of an operating room dedicated to neurosurgical procedures performed aware and accommodating these concepts is presented, and some evidence for improvements in outcome presented, deriving from a series of patients implanted with spinal cord stimulators before and after the operating theatre was brought into service. RESULTS AND DISCUSSION: In addition to the description, two videos demonstrate the facility online. Beyond this qualitative evidence, quantitative improvement in patient outcome is evidenced by the series presented: 91.3% of patients operated in the awake anaesthesia-dedicated theatre obtained adequate low back pain coverage, versus 60.0% for patients operated before (p = 0.028). CONCLUSION: The concept of such an operating room is a step in improving the outcome by improving the presentation of all types of information to the operating room staff most notably in the example of aware procedures.

Genetic analysis of inherited leukodystrophies: genotype-phenotype correlations in the CSF1R gene.

IMPORTANCE: The leukodystrophies comprise a clinically and genetically heterogeneous group of progressive hereditary neurological disorders mainly affecting the myelin in the central nervous system. Their onset is variable from childhood to adulthood and presentation can be with a variety of clinical features that include mainly for adult-onset cases cognitive decline, seizures, parkinsonism, muscle weakness, neuropathy, spastic paraplegia, personality/behavioral problems, and dystonia. Recently, Rademakers and colleagues identified mutations in the CSF1R gene as the cause of hereditary diffuse leukoencephalopathy with spheroids (HDLS), offering the possibility for an in-life diagnosis. The detection of mutations in this gene in cases diagnosed with different clinical entities further demonstrated the difficulties in the clinical diagnosis of HDLS. OBJECTIVE: To better understand the genetic role of mutations in this gene, we sequenced a large cohort of adult-onset leukodystrophy cases. DESIGN: Whole-exome sequencing and follow up-screening by Sanger sequencing. SETTING: Collaborative study between the Institute of Neurology, University College London and the Inserm, Paris, France. PARTICIPANTS: A total of 114 probands, mostly European patients, with a diagnosis of adult-onset leukodystrophy or atypical cases that could fit within a picture of leukodystrophy. These included 3 extended families within the spectrum of leukodystrophy phenotype. INTERVENTIONS: Whole-exome sequencing in a family and Sanger sequencing of CSF1R. MAIN OUTCOMES AND MEASURES: Mutations in CSF1R. RESULTS: We identified 12 probands with mutations in CSF1R. The clinical diagnoses given to these patients included dementia with spastic paraplegia, corticobasal degeneration syndrome, and stroke disorders. Our study shows that CSF1R mutations are responsible for a significant proportion of clinically and pathologically proven HDLS. CONCLUSIONS AND RELEVANCE: These results give an indication of the frequency of CSF1R mutations in a European leukodystrophy series and expand the phenotypic spectrum of disorders that should be screened for this gene.

Intraoperative monitoring of an aspect of executive functions: administration of the Stroop test in 9 adult patients during awake surgery for resection of frontal glioma.

BACKGROUND: Awake brain surgery allows extensive intraoperative monitoring of not only motor and sensory functions and language but also executive functions. OBJECTIVE: To administer the Stroop test intraoperatively to avoid dramatic side effects such as akinetic mutism and to monitor executive functions in an attempt to optimize the benefit/risk balance of surgery. METHODS: A series of 9 adult patients with frontal glioma were operated on for gross tumor resection under local anesthesia. All procedures involved the anterior cingulate cortex (ACC). RESULTS: Three types of response to the Stroop test were observed: 3 patients had a Stroop effect only for stimulation of the contralateral ACC; 3 patients had a Stroop effect for stimulation of the ipsilateral ACC; and 3 patients had no Stroop effect. Preoperative and postoperative neuropsychological and surgical results are presented and discussed. Stimulation sites eliciting a Stroop effect are compared with published image-based data, and insight provided by these surgical data regarding ACC function and plasticity is discussed. No operative complication related to intraoperative administration of the Stroop test was observed. CONCLUSION: Administration of the Stroop test during resection of gliomas involving the ACC in adult patients is an option for intraoperative monitoring of executive functions during awake surgery. Globally, these results suggest functional compensation, mediated by plasticity mechanisms, by contralateral homologous regions of the ACC in adult patients with frontal glioma.

[Cognitive-behavioral specialized units: predictive factors of readmissions within three months]. / Unité cognitivo-comportementale : facteurs prédictifs de réadmission à 3 mois.

BACKGROUND: Behavioral and psychological symptoms of dementia (BPSD) are frequent and belong to the natural evolution of the disease. Specialized cognitive-behavioral units (Unités cognitivo-comportementales) were created, in France (plan Alzheimer 2008-2012), to cope with this problem. Despite a stay in such a unit, some patients have to be rehospitalized. The main aim of the current study was to highlight the predictive factors of readmissions. METHOD: Descriptive, retrospective study of demented patients ≥75 years, hospitalized between January 2010 and April 2011. We compared patients that had to be rehospitalized within 3 months (group 1), with the patients that did not need to be rehospitalized or after 3 months of time (group 2). Patients characteristics included: basic daily living activities (French GIR score), MMSE score, neuropsychiatric inventory score, type of BPSD, length of stay and antipsychotropic drugs. RESULTS: Two hundred thirty-five patients were included including, 147 women (62.5%), with mean age of 82.74±7.13 years. SPCD was the main reason for hospitalization. Thirty patients (12.77%) belonged to group 1. The mean number of psychotropic treatments increased during the stay (p=0.02), particularly in group 2 (p=0.01). The NPI score decreased during the hospitalization in both groups. Linear regression analysis showed that behavioral type of symptoms (OR: 3.18; 95% CI 1.32-7.65) and association of antidepressant and antipsychotic drugs (OR: 4.77; 95% CI 1.35-16.83) were significantly predictive of an early readmission. The risk of readmission also significantly decreased as the length of stay increased. CONCLUSION: This work confirms the specificity and the need for such units. The results will help improving the outcome of demented patients with BPSD and treated with different antipsychotropic drugs.

Bilateral femoral neuropathy after massive toxic ingestion in a suicide attempt.

INTRODUCTION: Bilateral femoral nerve injury can occur after various surgical and nonsurgical processes, but has rarely been reported. CASE REPORT: We describe a case of bilateral femoral neuropathy after a suicide attempt in a 41-year-old woman. We suggest a stretch mechanism to explain this observation. We also discuss the other causes of bilateral nerve palsy, usually secondary to a compressive injury, with a review of the medical literature. CONCLUSIONS: The patient reported is the first in the literature to have suffered from bilateral femoral nerve palsy after a suicide attempt. Half of the reported cases are secondary to a surgical process (particularly abdominopelvic surgery). If a compressive origin is most frequent, a stretch mechanism may at times explain a bilateral femoral neuropathy.

A novel approach to clinical-radiological correlations: Anatomo-Clinical Overlapping Maps (AnaCOM): method and validation.

We present a new clinical-radiological correlation method (AnaCOM) that aims at establishing structure-function relationships. We validated AnaCOM by assessing the location of lesions that are associated with altered performances in a well-studied task: the verbal fluency task. We retrospectively reviewed 64 brain-damaged patients who had focal lesions in a variety of cortical sites due to stroke, hemorrhage or tumor surgery. All patients were tested for verbal fluency at the time of the MRI examination. MRI volumes were normalized using a mask covering brain lesions and artifacts. The brain lesions were then segmented using the normalized MRI. In each patient, a verbal fluency score was assigned to each voxel in the segmented area. Subsequently, segmentations were superimposed and voxels were gathered in clusters defined by the overlap of the patients' lesion. For each cluster, the scores were statistically compared to those obtained by controls for the same task. This process allowed the construction of cluster-by-cluster statistical maps of anatomo-clinical correlations. As expected, the statistical map indicated that two regions were significantly associated with a deficit in the fluency task: one located in Broca's area and the other in the preSMA. AnaCOM does not require a priori selection of the location of lesions or task scores. The method complements the functional imaging techniques, as it tells which regions are necessary for a given function and it explores cortical regions as well as the white matter.

Functions of the left superior frontal gyrus in humans: a lesion study.

The superior frontal gyrus (SFG) is thought to contribute to higher cognitive functions and particularly to working memory (WM), although the nature of its involvement remains a matter of debate. To resolve this issue, methodological tools such as lesion studies are needed to complement the functional imaging approach. We have conducted the first lesion study to investigate the role of the SFG in WM and address the following questions: do lesions of the SFG impair WM and, if so, what is the nature of the WM impairment? To answer these questions, we compared the performance of eight patients with a left prefrontal lesion restricted to the SFG with that of a group of 11 healthy control subjects and two groups of patients with focal brain lesions [prefrontal lesions sparing the SFG (n = 5) and right parietal lesions (n = 4)] in a series of WM tasks. The WM tasks (derived from the classical n-back paradigm) allowed us to study the impact of the SFG lesions on domain (verbal, spatial, face) and complexity (1-, 2- and 3-back) processing within WM. As expected, patients with a left SFG lesion exhibited a WM deficit when compared with all control groups, and the impairment increased with the complexity of the tasks. This complexity effect was significantly more marked for the spatial domain. Voxel-to-voxel mapping of each subject's performance showed that the lateral and posterior portion of the SFG (mostly Brodmann area 8, rostral to the frontal eye field) was the subregion that contributed the most to the WM impairment. These data led us to conclude that (i) the lateral and posterior portion of the left SFG is a key component of the neural network of WM; (ii) the participation of this region in WM is triggered by the highest level of executive processing; (iii) the left SFG is also involved in spatially oriented processing. Our findings support a hybrid model of the anatomical and functional organization of the lateral SFG for WM, according to which this region is involved in higher levels of WM processing (monitoring and manipulation) but remains oriented towards spatial cognition, although the domain specificity is not exclusive and is overridden by an increase in executive demand, regardless of the domain being processed. From a clinical perspective, this study provides new information on the impact of left SFG lesions on cognition that will be of use to neurologists and neurosurgeons.