Axial rotation and pain are associated with facet joint osteoarthritis in adolescent idiopathic scoliosis.

OBJECTIVE: Facet joints are crucial for spinal stability but develop premature osteoarthritis in patients with adolescent idiopathic scoliosis (AIS). Here, we evaluated the association between facet joint cartilage and subchondral bone homeostasis, perceived back pain and 3-dimensional spinal deformity to better understand the role of facet joint degeneration in AIS progression and pain. METHOD: The osteoarthritic state of cartilage and bone of AIS facet joint surgical samples were characterized using histological OARSI scoring, visual morphological grading and µCT analysis, respectively. Back pain was self-reported using a numerical rating scale and expressed relative to the location on the patient's back. The scoliotic curves from our patient cohort were digitally reconstructed using biplanar radiographs and the eOS system (EOS imaging). The deformity was then reduced to three intervertebral angles (coronal, sagittal and axial) for each pair of bilateral facet joints. Statistical associations between the intervertebral angles, osteoarthritis parameters and pain intensity were performed using the Spearman method and Friedman test. RESULTS: Facet joint cartilage degeneration was associated with decreased subchondral bone volume and quality. Most importantly, asymmetrical, and overall degeneration of facet joints was strongly correlated to intervertebral axial rotation. Additionally, kyphotic intervertebral segments in the sagittal plane were good predictors of increased facet joint degeneration and back pain. CONCLUSION: Facet joint degeneration is associated with axial deformity, kyphotic intervertebral angle and back pain intensity in AIS. These results suggest that facet joints are important features to consider for rotational instability in AIS spines and related disease progression and perceived back pain.

Determining g_{A}/g_{V} with High-Resolution Spectral Measurements Using a LiInSe_{2} Bolometer.

Neutrinoless double beta decay (0νßß) processes sample a wide range of intermediate forbidden nuclear transitions, which may be impacted by quenching of the axial vector coupling constant (g_{A}/g_{V}), the uncertainty of which plays a pivotal role in determining the sensitivity reach of 0νßß experiments. In this Letter, we present measurements performed on a high-resolution LiInSe_{2} bolometer in a "source=detector" configuration to measure the spectral shape of the fourfold forbidden ß decay of ^{115}In. The value of g_{A}/g_{V} is determined by comparing the spectral shape of theoretical predictions to the experimental ß spectrum taking into account various simulated background components as well as a variety of detector effects. We find evidence of quenching of g_{A}/g_{V} at >5σ with a model-dependent quenching factor of 0.655±0.002 as compared to the free-nucleon value for the interacting shell model. We also measured the ^{115}In half-life to be [5.18±0.06(stat)_{-0.015}^{+0.005}(sys)]×10^{14} yr within the interacting shell model framework. This Letter demonstrates the power of the bolometeric technique to perform precision nuclear physics single-ß decay measurements, which along with improved nuclear modeling can help reduce the uncertainties in the calculation of several decay nuclear matrix elements including those used in 0νßß sensitivity calculations.

Psychosocial and psychophysical assessment in paediatric patients and young adults with chronic back pain: A cluster analysis.

BACKGROUND: Identifying subgroups with different clinical profiles may inform tailored management and improve outcomes. The objective of this study was to identify psychosocial and psychophysical profiles of children and adolescents with chronic back pain. METHODS: One hundred and ninety-eight patients with chronic back pain were recruited for the study. Pain assessment was mainly conducted in the form of an interview and with the use of validated pain-related questionnaires assessing their psychosocial factors and disability. All patients underwent mechanical and thermal quantitative sensory tests assessing detection and pain thresholds, and conditioned pain modulation efficacy. RESULTS: Hierarchal clustering partitioned our patients into three clusters accounting for 34.73% of the total variation of the data. The adaptive cluster represented 45.5% of the patients and was characterized to display high thermal and pressure pain thresholds. The high somatic symptoms cluster, representing 19.2% of patients, was characterized to use more sensory, affective, evaluative and temporal descriptors of pain, more likely to report their pain as neuropathic of nature, report a more functional disability, report symptoms of anxiety and depression and report poor sleep quality. The pain-sensitive cluster, representing 35.4% of the cohort, displayed deep tissue sensitivity and thermal hyperalgesia. CONCLUSIONS: This study identified clinical profiles of children and adolescents experiencing chronic back pain based on specific psychophysical and psychosocial characteristics highlighting that chronic pain treatment should address underlying nociceptive and non-nociceptive mechanisms. SIGNIFICANCE: To our current knowledge, this study is the first to conduct cluster analysis with youth experiencing chronic back pain and displays clinical profiles based on specific physical and psychosocial characteristics. This study highlights that in a clinical context, chronic pain assessment should include multiple elements contributing to pain which can be assessed in a clinical context and addressed when pathoanatomical symptoms are unidentifiable.

Craniocervical abnormalities in osteogenesis imperfecta type V.

Craniocervical abnormalities in osteogenesis imperfecta (OI) such as basilar invagination or cervical kyphosis can cause severe neurological morbidity. These abnormalities may be more frequent in OI type V compared with other OI subtypes of similar disease severity, underlining the importance of screening in this group. INTRODUCTION: Craniocervical abnormalities in osteogenesis imperfecta (OI) can cause severe neurological morbidity. Although radiological cranial base abnormalities in OI have been well described in the literature, there are limited data on these abnormalities in OI type V and their association with clinical sequelae. METHODS: A retrospective case series on patients with craniocervical abnormalities in OI type V at our institution. RESULTS: Craniocervical abnormalities were present in 7 of 37 patients with OI type V (19%). For 5 patients (age at last follow-up: 5 to 26 years; 2 females), sufficient information was available for inclusion in the case series. All had genetically confirmed OI type V. Age range at diagnosis of the craniocervical abnormality was 1 day to 18 years. Basilar invagination was present in 3 patients; 2 had cervical kyphosis. Dysplasia of upper cervical vertebrae or base of skull was seen in 3 patients. The severity of the craniocervical abnormality did not clearly correlate with the severity of the OI phenotype. Three patients required surgical intervention (ages 7, 11, and 26 years) due to compression of the spinal cord or brainstem. Craniocervical abnormalities were detected incidentally or on screening in 3 patients, and only 2 had significant positive findings on neurological examination. CONCLUSION: A variety of craniocervical abnormalities are seen in OI type V including dysplasia of the cervical vertebrae. These cases highlight the importance of screening patients with OI type V with lateral skull and cervical spine x-rays throughout childhood and after skeletal maturity.

Treating brain diseases using systemic parenterally-administered protein therapeutics: Dysfunction of the brain barriers and potential strategies.

The parenteral administration of protein therapeutics is increasingly gaining importance for the treatment of human diseases. However, the presence of practically impermeable blood-brain barriers greatly restricts access of such pharmaceutics to the brain. Treating brain disorders with proteins thus remains a great challenge, and the slow clinical translation of these therapeutics may be largely ascribed to the lack of appropriate brain delivery system. Exploring new approaches to deliver proteins to the brain by circumventing physiological barriers is thus of great interest. Moreover, parallel advances in the molecular neurosciences are important for better characterizing blood-brain interfaces, particularly under different pathological conditions (e.g., stroke, multiple sclerosis, Parkinson's disease, and Alzheimer's disease). This review presents the current state of knowledge of the structure and the function of the main physiological barriers of the brain, the mechanisms of transport across these interfaces, as well as alterations to these concomitant with brain disorders. Further, the different strategies to promote protein delivery into the brain are presented, including the use of molecular Trojan horses, the formulation of nanosystems conjugated/loaded with proteins, protein-engineering technologies, the conjugation of proteins to polymers, and the modulation of intercellular junctions. Additionally, therapeutic approaches for brain diseases that do not involve targeting to the brain are presented (i.e., sink and scavenging mechanisms).

Thermoreversible hyaluronan-hydrogel and autologous nucleus pulposus cell delivery regenerates human intervertebral discs in an ex vivo, physiological organ culture model.

Numerous studies show promise for cell-based tissue engineering strategies aiming to repair painful intervertebral disc (IVD) degeneration. However, clinical translation to human IVD repair is slow. In the present study, the regenerative potential of an autologous nucleus pulposus (NP)-cell-seeded thermoresponsive hyaluronic acid hydrogel in human lumbar IVDs was assessed under physiological conditions. First, agarose-encased in vitro constructs were developed, showing greater than 90 % NP cell viability and high proteoglycan deposition within HA-pNIPAM hydrogels following 3 weeks of dynamic loading. Second, a bovine-induced IVD degeneration model was used to optimise and validate T1ρ magnetic resonance imaging (MRI) for detection of changes in proteoglycan content in isolated intact IVDs. Finally, isolated intact human lumbar IVDs were pre-scanned using the established MRI sequence. Then, IVDs were injected with HA-pNIPAM hydrogel alone or autologous NP-cell-seeded. Next, the treated IVDs were cultured under cyclic dynamic loading for 5 weeks. Post-treatment T1ρ values were significantly higher as compared to pre-treatment scans within the same IVD and region of interest. Histological evaluation of treated human IVDs showed that the implanted hydrogel alone accumulated proteoglycans, while those that contained NP cells also displayed neo-matrix-surrounded cells within the gel. The study indicated a clinical potential for repairing early degenerative human IVDs using autologous cells/hydrogel suspensions. This unique IVD culture set-up, combined with the long-term physiological culture of intact human IVDs, allowed for a more clinically relevant evaluation of human tissue repair and regeneration, which otherwise could not be replicated using the available in vitro and in vivo models.

Spinal infections in children: a multicentre retrospective study.

Aims: This multicentre, retrospective study aimed to improve our knowledge of primary pyogenic spinal infections in children by analyzing a large consecutive case series. Patients and Methods: The medical records of children with such an infection, treated at four tertiary institutions between 2004 and 2014, were analyzed retrospectively. Epidemiological, clinical, paraclinical, radiological, and microbiological data were evaluated. There were 103 children, of whom 79 (76.7%) were aged between six months and four years. Results: We confirmed a significant male predominance in the incidence of primary pyogenic spinal infections in children (65%). The lumbar spine was the most commonly affected region, and 27 infections (26.2%) occurred at L4/5. The white blood cell count was normal in 61 children (59%), and the CRP level was normal in 43 (42%). Blood cultures were performed in 95 children, and were positive in eight (8%). A total of 20 children underwent culture of biopsy or aspiration material, which was positive in eight (40%). Methicillin-sensitive Staphylococcus aureus (MSSA) and Kingella ( K.) kingae were the most frequently isolated pathogens. Conclusion: MSSA remains the most frequently isolated pathogen in children with primary pyogenic infection of the spine, but K. kingae should be considered as an important pathogen in children aged between six months and four years. Therefore, an empirical protocol for antibiotic treatment should be used, with consideration being made for the triphasic age distribution and specific bacteriological aetiology. In the near future, the results of polymerase chain reaction assay on throat swabs may allow the indirect identification of K. kingae spondylodiscitis in young children and thus aid early treatment. However, these preliminary results require validation by other prospective multicentre studies. Cite this article: Bone Joint J 2018;100-B:542-8.

The revised Tokuhashi score; analysis of parameters and assessment of its accuracy in determining survival in patients afflicted with spinal metastasis.

PURPOSE: To determine the significance of each parameter of the revised Tokuhashi score and identify which is associated with survival. BACKGROUND: Spinal metastases are common and can be a challenging medical issue. Treatment options depend on patients' prognosis. Many scoring systems in the literature help estimate prognosis, such as the Tokuhashi, revised Tokuhashi, and Tomita scoring systems. METHODS: A retrospective review of all patients from 2003 to 2012 treated for spinal metastases in one center was conducted. Imaging, pathology, and charts were reviewed to determine the modified Tokuhashi scores. Scores were then compared to the actual documented survival. Univariate and multiple regression analyses were used to assess the importance of each individual parameter and survival time. Linear regression was used to determine the relationship between the Tokuhashi score and weighted Tokuhashi score with survival time. RESULTS: A total of 126 patients were reviewed. All parameters in the revised Tokuhashi score were significantly associated with survival time except for primary site using univariate analysis. Only the number of spinal metastases and metastasis to major organs showed statistical significance when multiple variable analysis was used. CONCLUSION: A number of spinal metastases and metastasis to major organs were the most important predictors of actual survival. Modification to the score based on population characteristics would help better identify patients with spinal metastases that can benefit from surgery.

Comparative analysis in continuous expansion of bovine and human primary nucleus pulposus cells for tissue repair applications.

Autologous NP cell implantation is a potential therapeutic avenue for intervertebral disc (IVD) degeneration. However, monolayer expansion of cells isolated from surgical samples may negatively impact matrix production by way of dedifferentiation. Previously, we have used a continuous expansion culture system to successfully preserve a chondrocyte phenotype. In this work, we hypothesised that continuous expansion culture could also preserve nucleus pulposus (NP) phenotype. We confirmed that serial passaging drove NP dedifferentiation by significantly decreasing collagen type II, aggrecan and chondroadherin (CHAD) gene expression, compared to freshly isolated cells. Proliferation, gene expression profile and matrix production in both culture conditions were compared using primary bovine NP cells. Both standard culture and continuous culture produced clinically relevant cell populations. However, continuous culture cells maintained significantly higher collagen type II, aggrecan and CHAD transcript expression levels. Also, continuous expansion cells generated greater amounts of proteoglycan, collagen type II and aggrecan protein deposition in pellet cultures. To our surprise, continuous expansion of human intervertebral disc cells - isolated from acute herniation tissue - produced less collagen type II, aggrecan and CHAD genes and proteins, compared to standard culture. Also, continuous culture of cells isolated from young non-degenerate tissue did not preserve gene and protein expression, compared to standard culture. These data indicated that primary bovine and human NP cells responded differently to continuous culture, where the positive effects observed for bovine cells did not translate to human cells. Therefore, caution must be exercised when choosing animal models and cell sources for pre-clinical studies.

Brain repair and reprogramming: the route to clinical translation.

The adult brain has a very limited capacity for generation of new neurons, and neurogenesis only takes place in restricted regions. Some evidence for neurogenesis after injury has been reported, but few, if any, neurons are replaced after brain injury or degeneration, and the permanent loss of neurons leads to long-term disability and loss of brain function. For decades, researchers have been developing cell transplantation using exogenous cell sources for brain repair, and this method has now been shown to successfully restore lost function in experimental and clinical trials. Here, we review the development of cell-replacement strategies for brain repair in Parkinson's disease using the example of human foetal brain cells being successfully translated from preclinical findings to clinical trials. These trials demonstrate that cell-replacement therapy is a viable option for patients with Parkinson's disease, but more importantly also show how the limited availability of foetal cells calls for development of novel cell sources and methods for generating new neurons for brain repair. We focus on new stem cell sources that are on the threshold of clinical application for brain repair and discuss emerging cellular reprogramming technologies. Reviewing the current status of direct neural conversion, both in vitro and in vivo, where somatic cells are directly reprogrammed into functional neurons without passing through a stem cell intermediate, we conclude that both methods result in the successful replacement of new neurons that mature and integrate into the host brain. Thus, this new field shows great promise for future brain repair, although much work is still needed in preclinical animal models before it can be seriously considered for clinical applications.

GSK-3ß-induced Tau pathology drives hippocampal neuronal cell death in Huntington's disease: involvement of astrocyte-neuron interactions.

Glycogen synthase kinase-3ß (GSK-3ß) has emerged as a critical factor in several pathways involved in hippocampal neuronal maintenance and function. In Huntington's disease (HD), there are early hippocampal deficits both in patients and transgenic mouse models, which prompted us to investigate whether disease-specific changes in GSK-3ß expression may underlie these abnormalities. Thirty-three postmortem hippocampal samples from HD patients (neuropathological grades 2-4) and age- and sex-matched normal control cases were analyzed using real-time quantitative reverse transcription PCRs (qPCRs) and immunohistochemistry. In vitro and in vivo studies looking at hippocampal pathology and GSK-3ß were also undertaken in transgenic R6/2 and wild-type mice. We identified a disease and stage-dependent upregulation of GSK-3ß mRNA and protein levels in the HD hippocampus, with the active isoform pGSK-3ß-Tyr(216) being strongly expressed in dentate gyrus (DG) neurons and astrocytes at a time when phosphorylation of Tau at the AT8 epitope was also present in these same neurons. This upregulation of pGSK-3ß-Tyr(216) was also found in the R6/2 hippocampus in vivo and linked to the increased vulnerability of primary hippocampal neurons in vitro. In addition, the increased expression of GSK-3ß in the astrocytes of R6/2 mice appeared to be the main driver of Tau phosphorylation and caspase3 activation-induced neuronal death, at least in part via an exacerbated production of major proinflammatory mediators. This stage-dependent overactivation of GSK-3ß in HD-affected hippocampal neurons and astrocytes therefore points to GSK-3ß as being a critical factor in the pathological development of this condition. As such, therapeutic targeting of this pathway may help ameliorate neuronal dysfunction in HD.

Dynamic loading, matrix maintenance and cell injection therapy of human intervertebral discs cultured in a bioreactor.

Low back pain originating from intervertebral disc (IVD) degeneration affects the quality of life for millions of people, and it is a major contributor to global healthcare costs. Long-term culture of intact IVDs is necessary to develop ex vivo models of human IVD degeneration and repair, where the relationship between mechanobiology, disc matrix composition and metabolism can be better understood. A bioreactor was developed that facilitates culture of intact human IVDs in a controlled, dynamically loaded environment. Tissue integrity and cell viability was evaluated under 3 different loading conditions: low 0.1-0.3, medium 0.1-0.3 and high 0.1-1.2 MPa. Cell viability was maintained > 80 % throughout the disc at low and medium loads, whereas it dropped to approximately 70 % (NP) and 50 % (AF) under high loads. Although cell viability was affected at high loads, there was no evidence of sGAG loss, changes in newly synthesised collagen type II or chondroadherin fragmentation. Sulphated GAG content remained at a stable level of approximately 50 µg sGAG/mg tissue in all loading protocols. To evaluate the feasibility of tissue repair strategies with cell supplementation, human NP cells were transplanted into discs within a thermoreversible hyaluronan hydrogel. The discs were loaded under medium loads, and the injected cells remained largely localised to the NP region. This study demonstrates the feasibility of culturing human IVDs for 14 days under cyclic dynamic loading conditions. The system allows the determination a safe range-of-loading and presents a platform to evaluate cell therapies and help to elucidate the effect of load following cell-based therapies.

Fusionless surgery in early-onset scoliosis.

BACKGROUND: Surgical treatment of early-onset scoliosis has greatly developed in recent years. Early-onset scoliosis covers a variety of etiologies (idiopathic, neurologic, dystrophic, malformative, etc.) with onset before the age of 5 years. Progression and severity threaten respiratory development and may result in respiratory failure in adulthood. Many surgical techniques have been developed in recent years, aiming to protect spinal and thoracic development. MATERIAL AND METHODS: Present techniques are based on one of two main principles. The first consists in posterior distraction of the spine in its concavity (single growing rod, or vertical expandable prosthetic titanium rib [VEPTR]), or on either side (dual rod); this requires iterative surgery, for lengthening, unless motorized using energy provided by a magnetic system. The second option is to use spinal growth force to lengthen the assembly; these techniques (Luque Trolley, Shilla), using a sliding assembly, are known as growth guidance. RESULTS: These techniques are effective in controlling early scoliotic deformity, and to some extent restore spinal growth. However, they show a high rate of complications: infection, rod breakage, spinal fixation pull out and, above all, progressive spinal stiffness, reducing long-term efficacy. Respiratory gain is harder to assess, as thoracic expansion does not systematically improve respiratory function, particularly due to impaired compliance of the thoracic cage.

Cystamine/cysteamine rescues the dopaminergic system and shows neurorestorative properties in an animal model of Parkinson's disease.

The neuroprotective properties of cystamine identified in pre-clinical studies have fast-tracked this compound to clinical trials in Huntington's disease, showing tolerability and benefits on motor symptoms. We tested whether cystamine could have such properties in a Parkinson's disease murine model and now provide evidence that it can not only prevent the neurodegenerative process but also can reverse motor impairments created by a 6-hydroxydopamine lesion 3 weeks post-surgery. Importantly, we report that cystamine has neurorestorative properties 5 weeks post-lesion as seen on the number of nigral dopaminergic neurons which is comparable with treatments of cysteamine, the reduced form of cystamine used in the clinic, as well as rasagiline, increasingly prescribed in early parkinsonism. All three compounds induced neurite arborization of the remaining dopaminergic cells which was further confirmed in ex vivo dopaminergic explants derived from Pitx3-GFP mice. The disease-modifying effects displayed by cystamine/cysteamine would encourage clinical testing.

Acute mechanical injury of the human intervertebral disc: link to degeneration and pain.

Excessive mechanical loading or acute trauma to intervertebral discs (IVDs) is thought to contribute to degeneration and pain. However, the exact mechanisms by which mechanical injury initiates and promotes degeneration remain unclear. This study investigates biochemical changes and extracellular matrix disruption in whole-organ human IVD cultures following acute mechanical injury. Isolated healthy human IVDs were rapidly compressed by 5% (non-injured) or 30% (injured) of disc height. 30% strain consistently cracked cartilage endplates, confirming disc trauma. Three days post-loading, conditioned media were assessed for proteoglycan content and released cytokines. Tissue extracts were assessed for proteoglycan content and for aggrecan integrity. Conditioned media were applied to PC12 cells to evaluate if factors inducing neurite growth were released. Compared to controls, IVD injury caused significant cell death. Injury also caused significantly reduced tissue proteoglycan content with a reciprocal increase of proteoglycan content in culture media. Increased aggrecan fragmentation was observed in injured tissue due to increased matrix metalloproteinase and aggrecanase activity. Injured-IVD conditioned media contained significantly elevated interleukin (IL)-5, IL-6, IL-7, IL-8, MCP-2, GROα, and MIG, and ELISA analysis showed significantly increased nerve growth factor levels compared to non-injured media. Injured-disc media caused significant neurite sprouting in PC12 cells compared to non-injured media. Acute mechanical injury of human IVDs ex vivo initiates release of factors and enzyme activity associated with degeneration and back pain. This work provides direct evidence linking acute trauma, inflammatory factors, neo-innervation and potential degeneration and discogenic pain in vivo.

MyD88 deficiency results in both cognitive and motor impairments in mice.

The myeloid differentiation primary response gene 88 (MyD88) product is the most common adaptor protein implicated in Toll-like and interleukin receptor (TIR) domain signaling and thus plays an important role in the innate immune system. Despite the fact that the MyD88-dependent pathway has emerged as an important player in cell death processes described in several animal models of neurodegenerative disorders, the contribution of this pathway to specific behavioral phenotypes has been largely ignored. To understand the full implication of this pathway, we tested MyD88(-/-) mice for both motor and cognitive functions in normal conditions. MyD88(-/-) mice displayed impaired spatial and working memory as detected by the Barnes maze, the water T-maze and the passive avoidance tests. Furthermore, MyD88(-/-) mice demonstrated hypolocomotion in the open-field and wheel activity systems, as well as impairments in motor coordination and balance using the pole test and the rotarod. Our findings shed light on behavioral alterations that are associated with the deletion of the MyD88 protein in physiological conditions. These behavioral effects should be taken into consideration when assessing the role of the MyD88-dependent pathway in various infectious and non-infectious conditions.

Treatment of metastatic spinal cord compression: cepo review and clinical recommendations.

BACKGROUND: Metastatic spinal cord compression (mscc) is an oncologic emergency that, unless diagnosed early and treated appropriately, can lead to permanent neurologic impairment. After an analysis of relevant studies evaluating the effectiveness of various treatment modalities, the Comité de l'évolution des pratiques en oncologie (cepo) made recommendations on mscc management. METHOD: A review of the scientific literature published up to February 2011 considered only phase ii and iii trials that included assessment of neurologic function. A total of 26 studies were identified. RECOMMENDATIONS: Considering the evidence available to date, cepo recommends that cancer patients with mscc be treated by a specialized multidisciplinary team.dexamethasone 16 mg daily be administered to symptomatic patients as soon as mscc is diagnosed or suspected.high-loading-dose corticosteroids be avoided.histopathologic diagnosis and scores from scales evaluating prognosis and spinal instability be considered before treatment.corticosteroids and chemotherapy with radiotherapy be offered to patients with spinal cord compression caused by myeloma, lymphoma, or germ cell tumour without sign of spinal instability or compression by bone fragment.short-course radiotherapy be administered to patients with spinal cord compression and short life expectancy.long-course radiotherapy be administered to patients with inoperable spinal cord compression and good life expectancy.decompressive surgery followed by long-course radiotherapy be offered to appropriate symptomatic mscc patients (including spinal instability, displacement of vertebral fragment); andpatients considered for surgery have a life expectancy of at least 3-6 months.

Parkinson's Disease in a Dish: What Patient Specific-Reprogrammed Somatic Cells Can Tell Us about Parkinson's Disease, If Anything?

Technologies allowing for the derivation of patient-specific neurons from somatic cells are emerging as powerful in vitro tools to investigate the intrinsic cellular pathological behaviours of the diseases that affect these patients. While the use of patient-derived neurons to model Parkinson's disease (PD) has only just begun, these approaches have allowed us to begin investigating disease pathogenesis in a unique way. In this paper, we discuss the advances made in the field of cellular reprogramming to model PD and discuss the pros and cons associated with the use of such cells.

Impact of the cognitive status on the memory complaints in MS patients.

OBJECTIVE: Despite the evidence of cognitive deficits in Multiple Sclerosis (MS) patients, evaluation of their cognitive integrity is often limited to the use of clinical interviews and questionnaires. However, the consensus in the literature is that these patients under- or overestimate their deficits and repercussions. The objective of this study was to clarify why some patients overestimate while others underestimate their memory deficits. METHOD: Fifty-four participants (30 MS, 24 controls) completed the Prospective and Retrospective Memory Questionnaire (PRMQ) and were tested on a battery of neuropsychological tests. Based on the test results, MS patients were categorized as having either mild or moderate/severe cognitive deficits. RESULTS: The moderate/severe MS group differed from the two other groups on the Rey Auditory Verbal Learning Test (RAVLT) but did not differ from the control group on the PRMQ. Conversely, the mild MS group did not differ from the control group on the RAVLT but did report significantly more problems than this group on the PRMQ. There was no difference between the two clinical groups on the Depression Index (Beck) but there was a significant correlation (r=.409) between the depression scores and the overestimation of prospective memory problems (PRMQ). CONCLUSION: The results explain the contradiction in the literature. It is the mild group who overestimates, maybe because they are overly concerned by their deficits, whereas the cognitive impairments of the moderate/severe group lead them to underestimate and may make their self-assessment unreliable. Formal testing or information from a significant other would be advisable.