Subject(s)
Autoantibodies/blood , Glutamate Decarboxylase/immunology , Opsoclonus-Myoclonus Syndrome/blood , Anorexia/blood , Anorexia/diagnosis , Anorexia/etiology , Dizziness/blood , Dizziness/diagnosis , Dizziness/etiology , Humans , Male , Middle Aged , Nausea/blood , Nausea/diagnosis , Nausea/etiology , Opsoclonus-Myoclonus Syndrome/diagnosis , Opsoclonus-Myoclonus Syndrome/immunologyABSTRACT
INTRODUCTION: Cognitive impairment is now well-known in multiple sclerosis (MS). However, few rehabilitation interventions are proposed or really efficient. OBJECTIVES: To present a review of cognitive rehabilitation intervention research conducted in people with multiple sclerosis (MS), regarding different findings about episodic memory, working memory, attention and executive function disorders in MS. DATA SOURCES: A search of Medline (yield 20 papers) and of PsychInfo (yield 1 article), using combinations of the following terms: cognitive rehabilitation, multiple sclerosis, cognitive therapy, neuropsychological rehabilitation, in the title or in the abstract, from 1960 to March 2010, excluding animal studies. RESULTS: Episodic memory rehabilitation studies appear to be promising. Programs on working memory, attention and executive functions are in the very early phases. CONCLUSIONS: Results are encouraging and allow specific recommendations for future research about: (1) inclusion criteria, often not defined, (2) a specific baseline adapted to the program of rehabilitation, (3) a control measure regarding program efficiency and (4) a role for the psychologist (presence and advice during the program).
Subject(s)
Cognition Disorders/psychology , Cognition Disorders/rehabilitation , Multiple Sclerosis/psychology , Multiple Sclerosis/rehabilitation , Attention/physiology , Cognition Disorders/etiology , Cognitive Behavioral Therapy , Executive Function/physiology , Humans , Memory/physiology , Memory Disorders/etiology , Memory Disorders/therapy , Multiple Sclerosis/complications , Recovery of FunctionABSTRACT
INTRODUCTION: Cerebral venous thrombosis (CVT) is uncommon with a variable clinical presentation and an unpredictable outcome. Heparin is used for first-line treatment in association with symptomatic and etiologic management. Despite adequate anticoagulation, the condition may deteriorate in some patients warranting the use of local thrombolysis (LT) known for good efficacy and safety. But there are few cases and trials upon which to base guidelines for the use of LT. METHODS: A retrospective review of the medical and radiological records of patients with CVT was managed in the Caen hospital over a six-year period. We compared clinical factors of poor prognosis and radiological findings according to treatment delivered. RESULTS: Thirty-six patients are treated for CVT. LT was performed in eight of them; dose-adjusted intravenous heparin was the only treatment in the 28 others. Good outcome was achieved in two thirds of the patients with functional sinus patency in all cases. Based on an analysis of the radiological data of the 36 patients, we propose a summary of radiological risk factors associated with a worsening condition despite adequate anticoagulation. DISCUSSION/CONCLUSION: Based on our experience and a review of the literature which includes 98 previous cases, LT appears to be a relative effective end safe procedure even in the presence of a hemorrhagic infarct. The treatment by LT should be considered in patients who present clinical criteria of gravity and radiological risk factors associated with failure of heparin treatment. The usefulness of LT remains to be determined in a randomized trial comparing heparin alone and heparin associated with LT.
Subject(s)
Heparin/therapeutic use , Intracranial Thrombosis/drug therapy , Thrombolytic Therapy/methods , Venous Thrombosis/drug therapy , Adult , Anticoagulants/therapeutic use , Disease Progression , Female , Humans , Intracranial Thrombosis/diagnostic imaging , Male , Middle Aged , Radiography , Retrospective Studies , Safety , Venous Thrombosis/diagnostic imagingSubject(s)
Brain/blood supply , Stroke/etiology , Telangiectasia, Hereditary Hemorrhagic/complications , Brain/pathology , Cerebrovascular Circulation/physiology , Diffusion Magnetic Resonance Imaging , Echocardiography, Transesophageal , Embolization, Therapeutic , Humans , Male , Stroke/diagnosis , Stroke/therapy , Telangiectasia, Hereditary Hemorrhagic/diagnosis , Young AdultABSTRACT
INTRODUCTION: Cerebral metastases occur in 15 to 20% of cancers and their incidence is increasing. The majority occur at an advanced stage of the disease, but metastasis may be the inaugural sign of cancer. The aim of treatments, which are often palliative, is to preserve the neurological status of the patient with the best quality of life. STATE OF ART: Corticosteroids are widely used for symptomatic palliation, requiring close monitoring and regular dose adaptation. Antiepileptic drugs should be given only for patients who have had a seizure. In case of multiple cerebral metastases occurring at an advanced stage of the disease, whole brain radiation is the most effective therapy for rapid symptom control. However, radiotherapy moderately improves overall survival, which often depends on the progression of disseminated systemic disease. On the contrary, surgery is indicated in case of a solitary metastasis, particularly when the patient is young (less than 65 years), with good general status (Karnofsky greater than 70), and when the systemic disease is under control. Radiosurgery offers an attractive alternative for these patients with good prognostic factors and a small number of cerebral metastases (< or = 4). PERSPECTIVES: Chemotherapy, considered in the past as not effective, is taking on a more important place in patients with multiple nonthreatening metastases from chemosensitive cancers (breast, testes...). Radiosurgery and whole brain radiotherapy are complementary techniques. Their respective role in the management of multiple metastases (< 4) remains to be further investigated. CONCLUSIONS: Therapeutic options are increasingly effective to improve the functional prognosis of patients with cerebral metastases. Ideally, a multidisciplinary assessment offers the best choice of therapeutic modalities.
Subject(s)
Brain Neoplasms/diagnosis , Brain Neoplasms/drug therapy , Brain Neoplasms/secondary , Neoplasm Metastasis/drug therapy , Brain Neoplasms/epidemiology , Brain Neoplasms/physiopathology , Combined Modality Therapy , Humans , Neoplasm Metastasis/physiopathologyABSTRACT
Taking in charge cognitive disorders is a new concept in the global care of MS patients. Cognitive disorders are observed in the all forms of the disease, sometimes early on in the evolution. These disorders can be evaluated in details even detected despite any complain in the patient. Because of the lack of clear demonstration that disease-modifying treatments could act on cognition, new specific therapeutic issues have emerged during last years. This article first discusses relationships between disease-modifying treatments and cognition for the different forms of the disease, then analyse the effects of symptomatic drug therapy especially the use of anticholinesterasics. In the last part of the article new issues about antagonists of excitatory amino-acids and individual or group cognitive training are discussed. Recent functional imaging data concerning cerebral adaptation and their modifications by drug or non-drug procedures in MS patients suggest interesting therapeutic development in a next future.
Subject(s)
Cognition Disorders/drug therapy , Cognition Disorders/etiology , Multiple Sclerosis/complications , Adrenal Cortex Hormones/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Cholinesterase Inhibitors/therapeutic use , Cognition Disorders/psychology , Humans , Immunologic Factors/therapeutic use , Immunosuppressive Agents/therapeutic use , Multiple Sclerosis/psychologyABSTRACT
INTRODUCTION: Alteration of episodic memory is one of the main cognitive deficits observed in MS patients. PATIENTS AND METHODS: We studied episodic memory in a group of 71 MS patients (37 RR, 34 SP) with the California Verbal Learning test (CVLT). Direct scores and calculated indices from CVLT performances were analyzed in comparison with controls. RESULTS: We observed a deficit of episodic memory in 69 p.cent of patients. This deficit was related to an alteration of encoding and retrieval processes. Despite SP-MS patients performances were constantly lower than those of RR-MS patients no significant difference was observed between the two groups. Significant correlation between the disease duration and CVLT performances were observed for the whole group but not for RR- or SP-MS groups separately, indicating that duration is more important than the phase of the disease in the worsening of memory deficit.
Subject(s)
Memory/physiology , Multiple Sclerosis/psychology , Psychological Tests , Speech , Adult , Humans , Learning/physiology , Memory, Short-Term/physiology , Middle Aged , Reference ValuesSubject(s)
Botulinum Toxins, Type A/therapeutic use , Dyskinesias/drug therapy , Ear , Neuromuscular Agents/therapeutic use , Depression/drug therapy , Electromyography , Female , Humans , Middle Aged , Muscle Contraction , Paroxetine/therapeutic use , Selective Serotonin Reuptake Inhibitors/therapeutic useABSTRACT
Familial idiopathic basal ganglia calcification (FIBGC) is a rare condition and its pathophysiology has not so far been elucidated. We report the results of a clinical study in two patients of a family affected with FIBGC. Brain imaging with 18-FDG-PET was performed in one. Psychiatric and cognitive troubles were the main clinical symptoms. Basal ganglia calcifications were associated with white matter lesions. The PET study performed in one patient revealed a striatal and a posterior cingulate hypometabolism. Posterior cingulate gyrus is involved in episodic memory processing, and could be involved in episodic memory deficit observed in this patient. These results suggest that a cortical dysfunction could be associated to the disease. The underlying mechanism, that could be a neuronal loss, a cortical deafferentation or an alteration of synaptic transmission, remains to be elucidated.
Subject(s)
Brain Diseases/genetics , Calcinosis/genetics , Dentate Gyrus/pathology , Globus Pallidus/pathology , Neostriatum/pathology , Adult , Aged , Brain Chemistry , Brain Diseases/diagnostic imaging , Brain Diseases/metabolism , Calcinosis/diagnostic imaging , Calcinosis/metabolism , Dentate Gyrus/diagnostic imaging , Family , Female , Fluorodeoxyglucose F18 , Globus Pallidus/diagnostic imaging , Humans , Male , Middle Aged , Neostriatum/diagnostic imaging , Pedigree , Tomography, Emission-Computed , Tomography, Emission-Computed, Single-Photon , Tomography, X-Ray ComputedABSTRACT
In contrast to childhood brainstem gliomas, adult brainstem gliomas are rare and poorly understood. The charts of 48 adults suffering from brainstem glioma were reviewed in order to determine prognostic factors, evaluate the effect of treatment and propose a classification of these tumours. Mean age at onset was 34 years (range 16-70 years). The main presenting symptoms were gait disturbance (61%), headache (44%), weakness of the limbs (42%) and diplopia (40%). Four patterns were identified on MRI, representing non-enhancing, diffusely infiltrative tumours (50%), contrast-enhancing localized masses (31%), isolated tectal tumours (8%) and other patterns (11%). Treatment consisted of partial resection (8%), radiotherapy (94%) and chemotherapy (56%). Overall median survival was 5.4 years. On univariate analysis, the following favourable prognostic factors were identified (P< 0.01): age of onset <40 years, duration of symptoms before diagnosis >3 months, Karnofski performance status >70, low-grade histology, absence of contrast enhancement and 'necrosis' on MRI. On multivariate analysis, the duration of symptoms, the appearance of 'necrosis' on MRI and the histological grade of the tumour remained significant and independent prognostic factors (P< 0.05). Eighty-five percent of the tumours could be classified into one of the following three groups on the basis of clinical, radiological and histological features. (i) Diffuse intrinsic low-grade gliomas (46%) usually occurred in young adults with a long clinical history before diagnosis and a diffusely enlarged brainstem on MRI that did not show contrast enhancement. These patients were improved by radiotherapy in 62% of cases and had a long survival time (median 7.3 years). Anaplastic transformation (appearance of contrast enhancement, 27%) and relentless growth without other changes (23%) were the main causes of death. (ii) Malignant gliomas (31%) occurred in elderly patients with a short clinical history. Contrast enhancement and necrosis were the rule on MRI. These tumours were highly resistant to treatment and the patients had a median survival time of 11.2 months. (iii) Focal tectal gliomas (8%) occurred in young patients and were often revealed by isolated hydrocephalus. The course was indolent and the projected median survival period exceeded 10 years. In conclusion, adult brainstem gliomas are different from the childhood forms and resemble supratentorial gliomas in adults. Low-grade tumours have a clinicoradiological pattern that is so characteristic that the need for a potentially harmful biopsy is debatable. The optimum timing of treatment for supratentorial low-grade tumours remains unclear. In high-grade gliomas, the prognosis remains extremely poor despite aggressive treatment with radiotherapy and chemotherapy.
Subject(s)
Brain Stem Neoplasms/classification , Brain Stem Neoplasms/mortality , Glioma/classification , Glioma/mortality , Adult , Age Factors , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Brain Stem/pathology , Brain Stem Neoplasms/pathology , Brain Stem Neoplasms/therapy , Disease Progression , Female , Glioma/pathology , Glioma/therapy , Humans , Hydrocephalus/etiology , Hydrocephalus/pathology , Magnetic Resonance Imaging , Male , Multivariate Analysis , Prognosis , Radiotherapy , Survival Rate , Tectum Mesencephali/pathologyABSTRACT
Diffuse invasion of the brain by tumor cells is a hallmark of human glioblastomas and a major cause for the poor prognosis of these tumors. This phenomenon is only partially reproduced by rodent models of gliomas that display a very high rate of proliferation and limited cell migration. We have analyzed the development of human glioblastoma cells (GL15) xenografted into the brain of immunosuppressed rats, in order to define the characteristics of tumor cell invasion. As identified by the specific immunolabeling of the tumor cells for the human HLA-ABC antigen, GL15 tumors reproduced the three types of intraparenchymal invasion observed in patients. First, a majority of multipolar tumor cells intermingled rapidly and profusely with host neural cells in the margin of the injection site. This progressively enlarging area was principally responsible for the tumor growth over time. Second, in the gray matter, columns of thin bipolar tumor cells aligned along capillary walls. Third, in the white matter, elongated bipolar isolated tumor cells were observed scattered between axonal fibers. The maximum migration distances along white matter fibers remained significantly higher than the maximum migration distances along blood vessels, up to two months after injection. Development of the tumor was associated with a significant increase of vascularization in the area of tumor spread. Xenografting of human GL15 glioblastoma cells into the immunosuppressed rat brain allowed to differentiate between the three classical types of invasion identified in the clinic, to quantify precisely the distances of migration, and to evaluate cell morphology for each of these routes. The present results support the existence of host/tumor cells interactions with specific characteristics for each type of invasion.
Subject(s)
Brain Neoplasms/pathology , Brain Tissue Transplantation , Brain/pathology , Glioblastoma/pathology , Neoplasm Invasiveness/pathology , Neoplastic Stem Cells/transplantation , Transplantation, Heterologous/pathology , Animals , Antigens, Neoplasm/analysis , Biomarkers , Brain Neoplasms/blood supply , Capillaries/pathology , Cell Movement , Cyclosporine/toxicity , Glioblastoma/blood supply , HLA Antigens/analysis , Humans , Immunocompromised Host , Immunosuppressive Agents/toxicity , Male , Middle Aged , Neoplasm Transplantation , Neoplastic Stem Cells/pathology , Neovascularization, Pathologic/pathology , Rats , Rats, Sprague-Dawley , Tumor Cells, Cultured/pathology , Tumor Cells, Cultured/transplantationABSTRACT
Twenty one MS patients suffering from a relapsing-remitting (four patients), a secondary progressive (12 patients) or a primary progressive form of the disease (five patients) were assessed using a cognitive battery specifically devoted to executive and memory processes. Results showed that, patients without significant depressive state evaluated by the MADR scale, exhibited significant impairments in executive processes, working, episodic and procedural memories whereas short term memory, language and global intellectual efficiency were normal. The preliminary data suggest an impairment of encoding, a process previously underestimated in this disease. In addition, the battery was easily administered to the patients and relevant for the cognitive assessment of MS.
Subject(s)
Cognition/physiology , Memory/physiology , Multiple Sclerosis/physiopathology , Multiple Sclerosis/psychology , Adult , Cognition Disorders/etiology , Humans , Intelligence , Neuropsychological TestsABSTRACT
Different surgical strategies have been suggested to treat PD patients. Cerebral grafting remains experimental and pallidotomy is not performed among the French neurosurgery departments. Therefore selection criteria for surgical interventional therapies will be only discussed for deep brain stimulation (DBS) even if these criteria are not really different between grafting, pallidotomy and DBS. Choice of selection criteria is very important in order to separate PD patients with a high probability of clinical benefit after surgery from those in whom the surgical procedure includes a high risk of morbidity. A selection procedure is proposed according to data of the literature and to the results of a questionnaire filled by 7 french expert centers involved in surgical therapies of PD. The selection procedure in a patient with a parkinsonian syndrome lasting for more 5 years has to include:
Subject(s)
Parkinson Disease/surgery , Humans , Patient SelectionSubject(s)
Anticonvulsants/adverse effects , Epilepsy, Complex Partial/drug therapy , Mental Disorders/chemically induced , Vigabatrin/adverse effects , Adolescent , Anticonvulsants/poisoning , Electroencephalography/drug effects , Female , Humans , Mental Disorders/physiopathology , Vigabatrin/poisoningABSTRACT
This study describes issues related to the safety and tolerability of fetal striatal neural allografts as assessed in five patients with Huntington's disease. Huntington's disease (HD) is characterized by motor, cognitive, and behavioral disturbances. The latter include psychological disturbances and, as a consequence, we took particular care to analyze behavioral changes, in addition to the usual "safety" follow-up. We conducted multidisciplinary follow-up at least 2 years before and 1 year after grafting. Psychological care extended to close relatives. The grafting procedure itself was altogether safe and uneventful, and there were no apparent clinical deleterious effects for 1 year. The immunosuppressive treatment, however, was complicated by various problems (irregular compliance, errors of handling, side effects). Direct psychological consequences of the transplantation procedure were rare and not worrisome, although mood alteration requiring treatment was observed in one patient. Indirectly, however, the procedure required patients and relatives to accept constraints that tended to complicate familial situations already marred by aggressivity and depression. All patients and close relatives expressed major expectations, in spite of our strong and repeated cautioning. It is clearly important to be aware of these particular conditions since they may eventually translate into psychological difficulties in coping with the long-term clinical outcome of the procedure, if not beneficial. Despite an overall good tolerance, therefore, this follow-up calls for caution regarding the involvement of HD patients in experimental surgical protocols.
Subject(s)
Brain Tissue Transplantation , Corpus Striatum/surgery , Fetal Tissue Transplantation , Huntington Disease/surgery , Adult , Cognition , Cyclosporine/adverse effects , Family , Female , Follow-Up Studies , Humans , Huntington Disease/pathology , Huntington Disease/psychology , Immunosuppressive Agents/adverse effects , Magnetic Resonance Imaging , Male , Middle Aged , Patient Satisfaction , Postoperative Care , Preoperative Care , Safety , Treatment OutcomeABSTRACT
We have measured the pharmacokinetics of three retinoids, all-trans retinoic acid, 13-cis retinoic acid, and fenretinide in rat blood and rat brain [especially white matter (WM) and gray matter (GM)] to help select retinoids for treating human malignant glioma. All-trans retinoic acid permeated well into the WM, giving peak concentration in WM of 25.7 microg/g, 6 to 7 times higher than the peak serum concentration. There was less 13-cis retinoic acid in WM: area under the curve (AUC)(0-->infinity) WM/AUC(0-->infinity) serum = 18.00 microg ml(-1) h/32.67 microg ml(-1) h. The ratio WM/GM was over 1 for these two compounds, but the half-lives were short in the serum and cerebral tissue (0.57-1.02 h). Fenretinide had different pharmacokinetics: the peak concentrations were in serum (1.7 microg/ml) and WM (1.2 microg/ml)-low, but the AUC(0-->infinity) was large (25.55 microg ml(-1) in serum and 57.53 microg ml(-1) in WM) due to its long elimination half-life (13.78 h in serum and 17.77 h in WM). These findings provide information that may be used to select a retinoid and establish therapeutic regimens that provide optimal efficacy with minimal toxicity.