Contribution of the neuropsychological assessment in concussion.

INTRODUCTION: The neuropsychological assessment is a cornerstone in the care management of concussion or mild traumatic injury. OBJECTIVE: To present the different stages of an exhaustive neuropsychological assessment exploring cognitive and behavioral domains. METHOD: Description of the value of the main tests available for behavioral and cognitive assessment. The choice of tests is based on the clinical experience and expertise of the authors. RESULTS: Questionnaires are mainly used to explore the behavioral sequelae (depression, anxiety or fatigue) and the impact of these potential difficulties in daily life. Four cognitive abilities could be impaired by concussion: attention, memory, visuospatial functions and executive functions. These abilities could be explored with "paper and pencil" tests or with computerized test batteries. While cognitive sequelae in the context of a moderate or a severe traumatic brain injury are consolidated, in the context of concussion, neuropsychological sequelae tend to resolve in a short time. As a consequence, several neuropsychological assessments could be conducting in a short period involving some methodological considerations. Moreover, as concussion could be reported in a Whiplash injury from a car crash with forensic consequences, it is crucial to propose tests to be sure that the weak performance obtained into the neuropsychological assessment is not explained by poor effort and/or malingering. DISCUSSION/CONCLUSION: This article revises these aspects of a neuropsychological assessment in the specific context of concussion.

The natural history of prehypertension. A 20-year follow-up.

OBJECTIVE: According to the JNC7 report, prehypertension category includes subjects with systolic blood pressure between 120 and 139 mmHg and/or diastolic blood pressure between 80 and 89 mmHg that would be at risk for developing hypertension and its untoward sequelae as myocardial infarction and cerebrovascular disease. Moreover, ambulatory blood pressure monitoring made it possible to detect subjects with masked hypertension, who are at risk of greater target organ damage than those with normal ambulatory or home blood pressure. The aim of this study was to evaluate the risk of cardiac, cerebral and vascular events in a group of prehypertensive subjects, with and without masked hypertension. PATIENTS AND METHODS: We studied 204 consecutive asymptomatic prehypertensive subjects without history and signs of cardiovascular disease or diabetes. All the subjects underwent clinical evaluation, electrocardiogram, routine laboratory tests and ambulatory blood pressure monitoring. They were followed-up for a maximum of 237 months or until a cardiovascular event occurred. RESULTS: Twenty-seven cardiovascular events (13.2%) occurred, including 4 abdominal aortic aneurysms. Age (p<0.0001), total cholesterol (p=0.004), smoking (p=0.03) and clinically overt hypertension development (p=0.011) were related to cardiovascular events. Prognosis was not related to masked hypertension. CONCLUSIONS: The results of this study suggest that, in subjects with prehypertension, followed for 20 years, traditional cardiovascular risk factors and development of clinically overt hypertension could be more relevant than ambulatory hypertension in the prediction of an adverse outcome.

Effects of losartan on left ventricular mass: a three-year follow-up in elderly hypertensives with myocardial hypertrophy despite successful conventional antihypertensive treatment.

OBJECTIVE: Reversal of left ventricular hypertrophy (LVH) in hypertensive patients appears to be a desirable goal to the reduction cardiac risk. The Renin-Angiotensin System (RAS) seems to play a major role in the establishment and maintenance of LVH through the activated systemic RAS and the Intracardiac Angiotensin System (IAS). We focused on the effects of a three-year treatment with losartan supplement in hypertensive patients with LVH not responding to eight years of an effective previous antihypertensive pharmacological treatment. PATIENTS AND METHODS: Two groups of 28 sex-, age- and therapy-matched subjects with essential hypertension and LVH were taken into consideration. The two groups were in effective pharmacological treatment (BP < 140/90) for eight years previous to their enrollment. Patients of Group A were treated for three years with a losartan (100 mg/die) on-top treatment, whereas patients of Group B continued the follow-up of the previous conventional therapy. Both groups were submitted to an echocardiographic follow-up. RESULTS: Group A, showed a significant reduction of the mean LVH since the first step at six months with a further significant trend during the whole period (variance analysis: p < 0.001). Group B showed a non-significant trend toward LVH reduction during the three-year follow-up. No significant further reduction of systolic or diastolic blood pressure values was observed in both groups. CONCLUSIONS: The effects of losartan in hypertensive and hypertrophic patients are in agreement with the results of LIFE Trial. However, the reduction of left ventricular hypertrophy in our patients seems to be related to changes inducted by losartan on the IAS, since no further hemodynamic effects were observed. Losartan induced both a significant reduction of LVH and an improvement of LV diastolic function with a subsequent expected beneficial shift on the prognosis.

[Principle of the useful field of view and normative data]. / Principes de réalisation du champ visuel attentionnel et élaboration de normes.

PURPOSE: The useful field of view is a test which takes into account the influence of patient attention during the evaluation of the visual field. This study aims to generate normative data for an adaptation of the useful field of view (UFOV) test. These normative data are essential to judge, in a clinical setting, whether patients' performance is normal or not across demographically similar peers, in order to advise whether or not to resume driving after a brain injury (traumatic brain injury, stroke or cerebral tumour). PATIENTS AND METHODS: This study examined demographic influences on an UFOV adaptation in a sample of 52 control participants (17 males and 35 females, aged 19 to 69) with no prior ophthalmologic or neurologic history. This adaptation used three visual attention tasks. In a simple task (ST), the participant had to detect, as fast as (s)he could, a single target in a visual display; in a double task (DT,) (s)he had to detect both a central and a lateral target in a double task with visual distractions present on the screen. The number of missed targets and the time needed to detect them are measured. RESULTS: Time to detect target was found to differ by gender and by age. Men and young people (from 19 to 29 years) are faster at detecting central and lateral targets. However, no demographic influence was observed on the number of missed targets. CONCLUSIONS: A normative table for this French UFOV adaptation is provided. This will allow clinicians to compare patient performance with similar peers and may help in identifying persons who would benefit from training on a driving simulator or having a road test with a driving-school.

Neuropsychological assessment and cerebral vascular disease: the new standards.

Vascular cognitive impairment (VCI) includes vascular dementia (VaD), vascular mild cognitive impairment (VaMCI) and mixed dementia. In clinical practice, VCI concerns patients referred for clinical stroke or cognitive complaint. To improve the characterization of VCI and to refine its diagnostic criteria, an international group has elaborated a new standardized evaluation battery of clinical, cognitive, behavioral and neuroradiological data which now constitutes the reference battery. The adaption of the battery for French-speaking subjects is reported as well as preliminary results of the on-going validation study of the GRECOG-VASC group [Clinical Trial NCT01339195]. The diagnostic accuracy of various screening tests is reviewed and showed an overall sub-optimal sensitivity (<0.8). Thus, the general recommendation is to perform systematically a comprehensive assessment in stroke patients at risk of VCI. Furthermore,the use of a structured interview has been shown to increase the detection of dementia. In addition to the well known NINDS-AIREN criteria of VaD, criteria of VCI have been recently proposed which are based on the demonstration of a cognitive disorder by neuropsychological testing and either history of clinical stroke or presence of vascular lesion by neuroimaging suggestive of a link between cognitive impairment and vascular disease. A memory deficit is no longer required for the diagnosis of VaD as it is based on the cognitive decline concerning two or more domains that affect activities of daily living. Both VaMCI and VaD are classified as probable or possible. These new criteria have yet to be validated. Considerable uncertainties remain regarding the determinant of VCI, and especially the lesion amount inducing VCI and VaD. The interaction between lesion amount and its location is currently re-examined using recent techniques for the analysis of MRI data. The high frequency of associated Alzheimer pathology is now assessable in vivo using amyloid imaging. The first studies showed that about a third of patients with VaD due to small vessel disease or with poststroke dementia have amyloid PET imaging suggestive of AD. These new techniques will examine the interaction between vascular lesions and promotion of amyloid deposition. Although results of these on-going studies will be available in few years, these data indicate that efforts should be done in clinical practice to reduce underdiagnosis of VCI; VCI should be examined using a specific protocol which will be fully normalized soon for French-speaking patients; the sub-optimal sensitivity of screening tests prompts to use a structured interview to grade Rankin scale and to perform systematically a comprehensive assessment in stroke patients at risk of VCI; poststroke dementia occurring after 3 months poststroke may be preventable by treatment of modifiable vascular risk factors and secondary prevention of stroke recurrence according to recent recommendations.

Multi-point accelerometric detection and principal component analysis of heart sounds.

Heart sounds are a fundamental physiological variable that provide a unique insight into cardiac semiotics. However a deterministic and unambiguous association between noises in cardiac dynamics is far from being accomplished yet due to many and different overlapping events which contribute to the acoustic emission. The current computer-based capacities in terms of signal detection and processing allow one to move from the standard cardiac auscultation, even in its improved forms like electronic stethoscopes or hi-tech phonocardiography, to the extraction of information on the cardiac activity previously unexplored. In this report, we present a new equipment for the detection of heart sounds, based on a set of accelerometric sensors placed in contact with the chest skin on the precordial area, and are able to measure simultaneously the vibration induced on the chest surface by the heart's mechanical activity. By utilizing advanced algorithms for the data treatment, such as wavelet decomposition and principal component analysis, we are able to condense the spatially extended acoustic information and to provide a synthetical representation of the heart activity. We applied our approach to 30 adults, mixed per gender, age and healthiness, and correlated our results with standard echocardiographic examinations. We obtained a 93% concordance rate with echocardiography between healthy and unhealthy hearts, including minor abnormalities such as mitral valve prolapse.

Genome-wide shRNA screen reveals increased mitochondrial dependence upon mTORC2 addiction.

Release from growth factor dependence and acquisition of signalling pathway addiction are critical steps in oncogenesis. To identify genes required on mammalian target of rapamycin (mTOR) addiction, we performed a genome-wide short hairpin RNA screen on a v-H-ras-transformed Pten-deficient cell line that displayed two alternative growth modes, interleukin (IL)-3-independent/mTOR-addicted proliferation (transformed growth mode) and IL-3-dependent/mTOR-non-addicted proliferation (normal growth mode). We screened for genes required only in the absence of IL-3 and thus specifically for the transformed growth mode. The top 800 hits from this conditional lethal screen were analyzed in silico and 235 hits were subsequently rescreened in two additional Pten-deficient cell lines to generate a core set of 47 genes. Hits included genes encoding mTOR and the mTOR complex 2 (mTORC2) component rictor and several genes encoding mitochondrial functions including components of the respiratory chain, adenosine triphosphate synthase, the mitochondrial ribosome and mitochondrial fission factor. Small interfering RNA knockdown against a sizeable fraction of these genes triggered apoptosis in human cancer cell lines but not in normal fibroblasts. We conclude that mTORC2-addicted cells require mitochondrial functions that may be novel drug targets in human cancer.

Viral-load and B-lymphocyte monitoring of EBV reactivation after allogeneic hemopoietic SCT in children.

EBV-associated post transplant lymphoproliferative disease (EBV-PTLD) is a life-threatening complication that may occur after hemopoietic SCT. We prospectively screened 80 children on a weekly basis using nested quantitative PCR to evaluate EBV genome copies. EBV viral load <1000 copies per 10(5) PBMC was observed in 63% of transplants, whereas it was between 1000 and 9999 copies per 10(5) PBMC in 13%, and between 10 000 and 19 999 in 10%, with no significant increase in percentage of CD20+ lymphocytes. Viral load reached > or = 20 000 copies per 10(5) PBMC in 14% of patients, and rituximab was administered to 75% of them. None of the patients except one developed a lymphoproliferative disease. Our study found that only 13% of unrelated donor HSCT recipients had a very high risk of EBV-PTLD defined as > or = 20 000 geq per 10(5) PBMC associated with an increase in CD20+ lymphocyte. We suggest that rituximab could be administered in the presence of very high levels of EBV-DNA viral load or in the presence of mid levels of EBV-DNA viral load associated with an increase in the percentage of CD20+ lymphocytes. Through this approach, we significantly reduced the number of patients treated with rituximab, and consequently the acute and chronic adverse events related to this treatment.

Cognitive function and 99mTc-ECD brain SPECT are significantly correlated in patients with primary Sjogren syndrome: a case-control study.

OBJECTIVES: To assess subclinical central nervous system (CNS) involvement in primary Sjögren syndrome (pSS), by comparing standard brain MRI, in-depth neuropsychological testing and (99m)Tc-ECD brain single-photon emission computed tomography (SPECT) of patients with pSS with matched controls. METHODS: 10 women (<55 years old), with pSS defined using European-American criteria, presence of anti-SSA and/or anti-SSB antibodies and no history of neurological involvement were prospectively investigated, and compared with 10 age- and sex-matched controls. All subjects underwent, within 1 month, brain MRI, neuropsychological testing, including overall evaluation and focal cognitive function assessment, and (99m)Tc-ECD brain SPECT. RESULTS: (99m)Tc-ECD brain SPECT abnormalities were significantly more common in patients with pSS (10/10) than controls (2/10; p<0.05). Cognitive dysfunctions, mainly expressed as executive and visuospatial disorders, were also significantly more common in patients with pSS (8/10) than controls (0/10; p<0.01). Notably, between-group comparisons enabled a significant correlation to be established between neuropsychological assessment and (99m)Tc-ECD brain SPECT abnormalities in patients with pSS (r(s) = 0.49, p<0.01). MRI abnormalities in patients and controls did not differ significantly. CONCLUSIONS: Neuropsychological testing and (99m)Tc-ECD brain SPECT seem to be the most sensitive tools to detect subclinical CNS dysfunction in pSS. The strong correlation between cortical hypoperfusion in (99m)Tc-ECD brain SPECT and cognitive dysfunction suggests an organic aetiology of CNS dysfunction in pSS. These data should be confirmed in a larger study.

[Validation of a brief screening scale evaluating praxic abilities for use in memory clinics. Evaluation in 419 controls, 127 mild cognitive impairment and 320 demented patients]. / Validation d'une batterie brève d'évaluation des praxies gestuelles pour consultation Mémoire. Evaluation chez 419 témoins, 127 patients atteints de troubles cognitifs légers et 320 patients atteints d'une démence.

INTRODUCTION: The aim of this study was to build a brief clinical scale evaluating praxic abilities of the upper limbs for use in memory clinics and to produce norms. PATIENTS AND METHODS: The scale includes three subtests: symbolic gestures (five gestures), pantomimes (five gestures) and imitation of meaningless gestures (eight gestures). Data were collected in a sample of 419 normal subjects. Sensitivity and specificity were established from their comparison to data collected from 320 demented patients. A group of 127 patients with mild cognitive impairment was also studied. RESULTS: Cut-off scores were proposed based on the fifth percentile observed in three classes of age and three levels of education. The specificity was high. Sensitivity was higher for imitation of meaningless gestures than for pantomimes and the least for symbolic gestures. The group of patients with mild cognitive impairment was half-way between demented patients and normal subjects. CONCLUSION: The proposed scale meets its initial aims of brevity and high specificity. It can easily be used in memory clinics and identifies apraxia in dementia patients. It therefore usefully contributes to clinical diagnosis.

Rare viral infections in children receiving hemopoietic stem cell transplant.

Viral infections are a rare complication in autologous hemopoietic stem cell transplant (HSCT) recipients but represent a frequent cause of disease after allogeneic HSCT. In the last years, there has been an increase in the number of viral diseases observed in these patients. This fact may be at least partially due to an improvement in diagnostic facilities, but the increasing number of transplant procedures and the more severe immunosuppression may also have played an important role.

Invasive mycoses in children receiving hemopoietic SCT.

Invasive mycoses represent a rare but severe complication following hemopoietic SCT (HSCT) in children. Their incidence is related to the type of donor, being higher after allogeneic transplant, especially from alternative donors. Moreover, the incidence of invasive mycoses varies in the different post transplant phases. Neutropenia, lymphopenia, GvHD, high-dose steroids or other immunosuppressive drugs represent well-known risk factors. The clinical features of invasive mycoses after HSCT in children are similar to those observed in adults, and the diagnostic tools, including Aspergillus galactomannan antigen detection, are feasible also in pediatrics. Mortality due to invasive mycoses after HSCT in children is high.

Bacteremias in children receiving hemopoietic SCT.

The incidence of bacteremia following hemopoietic SCT (HSCT) changes over time from the procedure. The first 30 days have the highest incidence, both in autologous and allogeneic HSCT recipients. In the following periods, bacteremia is a frequent complication in allogeneic HSCT, especially from alternative donors. Gram-positive cocci represent the most frequent cause of single-agent bacteremia. Knowledge of epidemiology (incidence and etiology) of bacteremias following HSCT is pivotal for planning management strategies (prevention, diagnosis and therapy) that must be distinct in the different post-transplant period.

Nitric oxide and peroxynitrite platelet levels in women with small-for-gestational-age fetuses.

OBJECTIVE: The placenta produces reactive oxygen species (ROS) including nitric oxide (NO) and peroxynitrite (ONOO(-)) that have pronounced effects on placental function. Excessive ROS production may occur in pathological pregnancies, such as those complicated by small-for-gestational-age (SGA) fetuses. DESIGN: The aim of the present work was to study NO and ONOO(-) levels in platelets of pregnant women with SGA fetuses compared with a control group. SETTING AND POPULATION: The study was performed on 30 pregnant women with SGA fetuses (SGA group) and on 30 healthy pregnant women (appropriate-for-gestational-age [AGA] group) matched for maternal and gestational age. All women included in this study were in the third trimester of pregnancy. METHODS: Platelets were isolated by differential centrifugation. NO metabolites, after enzymatic conversion followed by the Griess reaction, were measured as nitrite by spectrophotometric detection. Peroxynitrite (ONOO(-)) levels were evaluated using the fluorescence probe 2,7-dichlorofluorescein diacetate (DCFDA). MAIN OUTCOME MEASURES: The following determinations were made: platelet nitric oxide and peroxynitrite levels in the SGA group and controls; inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS) and nitrotyrosine (N-Tyr) expression in the same groups. RESULTS: Our results show that both platelet NO and ONOO(-) levels were significantly higher in the SGA group than in the controls. CONCLUSION: Increased platelets levels of nitric oxide and peroxynitrite might play a role in the pathophysiology of intrauterine growth restriction. Further investigations are in progress to clarify if these molecules are pathogenetic factors, an epiphenomenon or a pathophysiological marker.

Incidence of bacteremias and invasive mycoses in children undergoing allogeneic hematopoietic stem cell transplantation: a single center experience.

We performed a retrospective single center study to define the epidemiology of bacteremias or invasive mycoses in pediatric allogeneic hematopoietic SCT (HSCT) from matched related donors (MRD) or alternative donors (AD). During 119 213 days of follow-up, 156 infections were observed: 130 bacteremias (27 in MRD-HSCT and 103 in AD-HSCT recipients) and 26 invasive mycoses (8 in MRD-HSCT and 18 in AD-HSCT recipients). Overall, the risk of bacteremia was fivefold that of invasive mycosis (P<0.001). AD-HSCT recipients had a higher percentage of infections (89 vs 27%; P<0.001), a higher rate/100 days of immunosuppression (infection rate (IR): 0.21 vs 0.06; P<0.001) and a higher proportion of repeated infections (44 vs 9%; P=0.001). In AD-HSCT, the relative risk of bacteremia was 2.87 in the pre-engraftment period, 5.84 in the early post-engraftment period and 6.46 in the late post-engraftment period (P<0.001) compared to MRD-HSCT. Only after 1 year did the epidemiology become similar. The epidemiology of invasive mycoses did not differ significantly between the two types of transplant.

[Memory symptom exaggeration in a patient with progressive multiple sclerosis outside any medico-legal context]. / Exagération de symptômes mnésiques hors contexte médicolégal chez un patient atteint de sclérose en plaques.

INTRODUCTION: Memory symptom exaggeration or malingering in the forensic neuropsychological evaluation of well-documented brain pathology is seldom described. For some, documented neuropathology and malingering are considered to be mutually exclusive. CASE REPORT: We report an original clinical observation of an amnesic factitious disorder in a patient with progressive multiple sclerosis. This patient, who was seen for a routine comprehensive neuropsychological evaluation, demonstrated a severe memory encoding deficit in a classical standard episodic memory test. This amnesic syndrome was not in agreement with the neurological condition where deficits in retrieval memory processes are essentially observed. Moreover, his performance at two symptom validity tests fell below the admitted cut-off scores. In fact, the patient obtained an accuracy score of 3 (cut-score<10) in the Rey's 15-Items Test, a well known malingered amnesia measure. His performance in the 21-Items Test French adaptation was well below the proposed cut-off score of 15/21 and inferior to the results obtained by an Alzheimer patients group (n=30). A clinical approach of memory symptom exaggeration is described. We discuss the diagnosis of this false disorder. CONCLUSION: This case report demonstrates unequivocally that memory symptom exaggeration or malingering can and does occur in patients seen without litigious contexts and who have a well-documented neurological pathology. Failure to address malingering may compromise neuropsychological clinical findings. Nevertheless, there is a lack of up-to-date standard French-language documentation in this topic.

Nebulized liposomal amphotericin B and combined systemic antifungal therapy for the treatment of severe pulmonary aspergillosis after allogeneic hematopoietic stem cell transplant for a fatal mitochondrial disorder.

Nebulized liposomal amphotericin B (20-15 mg twice daily by nebulizer) was combined with high dose intravenous liposomal amphotericin B (10 mg/kg/day) and high dose caspofungin (100 mg/m(2)) for the treatment of severe, recurrent pulmonary aspergillosis following allogeneic hematopoietic stem cell transplantation from alternative donor in a patient with mitochondrial disease (Pearson's syndrome). This combined treatment was administered for 8 days. Nebulized liposomal amphotericin B was well tolerated. Since severe transplant complications developed, nebulized administration was withdrawn and intravenous doses of liposomal amphotericin B and caspofungin were tapered to usual schedules. Pulmonary aspergillosis responded well to 45 days of combined intravenous antifungal therapies which were maintained for 2 years with secondary prophylaxis, because of persistent immunosuppressive treatment.

Nitazoxanide or CD3+/CD4+ lymphocytes for recovery from severe Cryptosporidium infection after allogeneic bone marrow transplant?

We describe a case of Cryptosporidium infection occurring in a child after allogeneic SCT for acute non-lymphoblastic leukemia. This patient presented an intestinal, biliar, and pancreatic Cryptosporidium disease associated with an intestinal aGvHD. The increase in CD3+/CD4+ cells secondary to the reduction of steroid therapy associated with the improvement of aGvHD and the use of antiparasitic treatments (especially nitazoxanide) improved the infection-related symptoms and led to a complete clearance of the Cryptosporidium.