[Early detection of cognitive impairment in relapsing-remitting multiple sclerosis: functional-anatomical correlations and longitudinal follow-up]. / Troubles cognitifs et sclérose en plaques rémittente: intérêt de leur détection précoce: corrélations anatomo-fonctionnelles et suivi longitudinal.

INTRODUCTION: Cognitive impairment is frequent in relapsing remitting Multiple Sclerosis and is often diagnosed after disruption of occupational and social relations. METHODS: We studied at baseline a homogeneous population of 32 RRMS patients, diagnosed for less than 5 years, with spontaneous memory complaints, and 20 controls. Sixteen patients were followed for 2 years, combining physical examination, neuropsychological tests, and brain MRI. Neuropsychological tests used evaluated memory capacities, attentional capacities, executive functions, language, and visuo-constructive praxis. Lesion load on brain MRI was measured with semi-automatic segmentation procedures and manual control. RESULTS: Eighty percent of patients presented cognitive impairment, and this proportion was higher than that found in the literature. These disorders were more marked for verbal episodic memory, attention, and executive functions. Patients with brain MRI that initially fulfilled the Barkhof criteria and those with callous lesions had more memory disorders. No link between global T1 and T2 lesion loads and neuropsychological scores was found. A statistical link between posterior fossa lesions and attentional disorders was shown. In the longitudinal follow-up, patients had better performances in memory and attentional domains, and a lower number of cognitive domains with dysfunction for each patient. This improvement on neuropsychological tests, whereas EDSS levels were stable, underlined a possible test-retest effect. CONCLUSION: During the initial phase of the disease, most of the relapsing remitting patients present a mild cognitive impairment. Early detection, therapeutic propositions, and recognition of disorders are necessary.

The apathy inventory: assessment of apathy and awareness in Alzheimer's disease, Parkinson's disease and mild cognitive impairment.

OBJECTIVE: This study was designed to establish the validity and reliability of the apathy inventory (IA), a rating scale for global assessment of apathy and separate assessment of emotional blunting, lack of initiative, and lack of interest. METHOD: Information for the IA can be obtained from the patient or from a caregiver. We evaluated 115 subjects using the IA, consisting of 19 healthy elderly subjects, 24 patients with Mild Cognitive Impairment (MCI), 12 subjects with Parkinson's disease (PD) and 60 subjects with Alzheimer's disease (AD). RESULTS: Internal consistency, item reliability, and between-rater reliability were high. A test-retest reliability study demonstrated that caregiver responses to IA questions were stable over short intervals. A concurrent validity study showed that the IA assesses apathy as effectively as the Neuro Psychiatric Inventory apathy domain. In the caregiver-based evaluation, AD subjects had significantly higher scores than controls, both for global apathy score and for the lack of interest dimension. When the AD patients were subdivided according to diagnostic criteria for apathy, apathetic patients had significantly higher scores than non apathetic patients. With the patient-based evaluations, no differences were found among the AD, MCI and control groups. The scores in the patient-based evaluations were only higher for the PD group versus the control subjects. The results also indicated that AD patients had poor awareness of their emotional blunting and lack of initiative. CONCLUSIONS: The IA is a reliable method for assessing in demented and non-demented elderly subjects several dimensions of the apathetic syndrome, and also the subject's awareness of these symptoms.

Fasting, postprandial, and post-methionine-load homocysteinaemia and methylenetetrahydrofolate reductase polymorphism in vascular disease.

Hyperhomocysteinaemia is an independent risk factor for cardiovascular disease. The C677T mutation of the methylenetetrahydrofolate reductase (MTHFR) is a common genetic cause of increased homocysteine (HCY) levels. Post-methionine-load HCY concentrations allow identification of certain cases of hyperhomocysteinaemia not demonstrated by fasting levels. This study investigated the relationship between MTHFR polymorphism and (1) fasting HCY levels (77 patients); (2) post-methionine HCY levels (54 patients); and (3) postprandial HCY concentrations (36 patients) in cardiovascular disease. As expected, mean fasting HCY value was higher in the +/+ patients. Moreover, patients who were homozygous for the mutation exhibited significantly increased mean post-methionine-load HCY; in contrast, literature results are conflicting. Mean postprandial HCY, which is not known to be increased in controls, was also increased in the (+/+) patients, although the difference did not reach statistical significance, probably owing to the small size of the sample. MTFHR polymorphism is known to be aggravated by a drop in circulating folate. Additional risk factors may be more prevalent in patients with cardiovascular disease.

[Cerebral vascular complication of hyperhomocysteinemia. Controlling thromboembolic complications with folates]. / Accident vasculaire cérébral avec hyperhomocystéinémie. Arrêt des accidents thromboemboliques sous folates.

BACKGROUND: Young patients who experience cardiovascular events may have raised levels of homocysteine. There may be several causes for this hyperhomocysteinemia. CASE REPORT: Cerebrovascular disease occurred in a 40-year-old female smoker with hyperhomocysteinemia. This patient subsequently had several episodes of thromboembolism involving the brain and lower limb arteries. Prothrombin concentration was difficult to control with antivitamin K anticoagulants. Investigations to identify a genetic cause of hyperhomocysteinemia revealed that she was homozygous for the C677T mutation on the methylenetetrahydrofolate reductase gene. There was no G1691A mutation of the factor V gene, a risk factor for familial thrombosis. Supplementation with folic acid successfully halted episodes of thromboembolism (follow-up 2 years) and prothrombin levels stabilized under treatment. DISCUSSION: The C677T mutation, which is common in the general population (15.7%), cannot explain the effect of folate supplementation alone. Other mutations affecting homocysteine metabolism could have a potentializing effect on vascular events.

Total plasma homocysteine determination by liquid chromatography before and after methionine loading. Results in cerebrovascular disease.

Elevated homocysteine (HCY) levels in tissues and blood are associated with premature occlusive diseases. A number of techniques have been developed to assay HCY, including high-performance liquid chromatography (HPLC) with fluorimetric or electrochemical detection, and radioenzymatic methods. The present study evaluated the adaptation of a liquid chromatographic, ion-exchange technique with postcolumn derivatization using ninhydrin. Fasting and moreover post-methionine load total plasma HCY were assayed in 50 patients three months after a stroke and in 20 age-matched controls. Ion-exchange liquid chromatography was performed on an amino acid analyzer using a modified procedure to improve methionine and HCY separation. HCY values in the fasting state were moderately but significantly increased (P<0.05) in the patients compared to the controls: 10.5+/-3.4 versus 9.3+/-2.3 micromol/l. The difference between the two groups was amplified in post-load HCY results, which were significantly increased (P<0.05) in the patients: 41.6+/-17.8 versus 29.2+/-5.5 micromol/l in controls. The relationship between cerebrovascular disease and impaired HCY metabolism has previously been emphasized by other investigators. Our findings suggest that certain inherited and/or acquired HCY disorders observed in the fasting state (14%) and especially in post-methionine load conditions (32%) may occur during acute disease, and that total plasma HCY can be determined by ion-exchange chromatography even after oral methionine loading.

[Transesophageal echocardiography in the etiological evaluation of ischemic cerebral vascular accidents. Value in young subjects]. / Echocardiographie transoesophagienne dans le bilan étiologique des accidents vasculaires cérébraux ischémiques. Intérêt chez les sujets jeunes.

OBJECTIVES: We conducted this study to evaluate the role of transoesophageal echocardiography in the aetiologic diagnosis of ischaemic cerebral vascular events in young subjects. METHODS: Over a 16-month period, 70 consecutive patients under 55 (mean age 49 years; range 32-55; 34 females, 36 males) underwent transoesophageal echocardiography as part of a complete work-up after a recent (< 1 month) cerebral event considered to be ischaemic in nature. Exclusion criteria were age over 55, vascular stenosis or ulcerated plaque, embologenic heart disease and valve prosthesis. 24-h Holter recordings were also obtained in all patients. RESULTS: The cerebral event was temporary in 11 subjects and permanent in the other 59. The ischaemic nature of the event was confirmed in all patients with computed tomography or magnetic resonance imagery. All patients were in sinus rhythm at examination and supraventricular paroxysmal arrhythmia was observed in 7 during the Holter recordings. The transoesophageal echocardiography was normal in 37 patients (52%) and pathologic in 33 (48%). The source of the embolus was identified in 4 cases (6%) and the probable cause of the cerebral event was found in 29 (42%). Among the abnormal structures observed were permeable oval foramens, inter-atrial septum aneurysms and plaques on the ascending aorta. CONCLUSIONS: In our selected population of patients under 55 years of age, transoesophageal echocardiography detected the certain or probable source of the ischaemic cerebral event in 48% of the cases, a diagnostic yield better than most other methods. Nevertheless, there is no known therapeutic response to several of the potential sources of embolus observed.

[Infarction of the caudate nucleus or anterior striato-capsular infarction?]. / Infarctus du noyau caudé ou infarctus striato-capsulaires antérieurs?

Eight patients with caudate nucleus infarcts are reported. The main clinical findings were often transient facio-brachial weakness (6 patients), depression (4 patients), subcortical aphasia with decreased spontaneous verbal activity (2 patients), and aboulia (2 patients). The ischemic lesions of caudate nucleus often extend into the adjacent anterior limb of the internal capsule and the anterior putamen owing to vascularization pattern. The specific clinical picture of this entity also includes lesions of nearby white matter tracts. Risk factors, etiology of infarcts, clinical findings and prognosis were similar to those reported in striato-capsular infarcts. We suggest replacing the term caudate infarct by anterior striato-capsular infarct.

[Orbital apex syndrome disclosing naso-oculo-cerebral zygomycosis]. / Syndrome de l'apex orbitaire révélateur d'une zygomycose naso-oculo-cérébrale.

In a 70-year-old male patient with untreated diabetes a febrile orbital apex syndrome of rapid onset revealed a rhino-orbito-cerebral zygomycosis. Biopsies of the ethmoidal mucosa showed numerous colonies of the Rhizopus genus. Despite medical treatment (amphotericin B) and surgery (ethmoidectomy), the patient died within one week. Rhino-cerebral zygomycosis is a rare disease which occurs in diabetic and immunocompromised patients.

[Cholesterol emboli with neurologic manifestation in the spinal cord]. / Embolies cholestéroliques à expression neurologique médullaire.

A 71-year old man presented with a progressive chronic paraparesis combined with inflammatory biological features including hypereosinophilia and an aneurysm of the abdominal aorta. Disseminated cholesterol embolization of arterioles was evidenced by the identification of cholesterol crystals in biopsies of the quadriceps muscle and of an iliac lymph node. Despite the lack of post mortem study of the spinal cord, the presentation was highly suggestive of cholesterol emboli in the spinal arteries. Only ten documented cases have been reported.

[A case of myopathy with carnitine deficiency]. / Un cas de myopathie avec déficit en carnitine.

Clinical and biological criteria of myopathies associated with carnitine deficiency allow to distinguish a muscular and a systemic form of the condition. In this report, the results of clinical, pathological and electrophysiological data obtained from a patient with carnitine deficiency-linked myopathy are described. The patient was a 23-year-old girl who was previously known to suffer from muscle weakness when suddenly acidosis associated with a severe drop in plasma carnitine appeared. In addition there were hypermetabolic symptoms similar to those described in Luft's syndrome. Biopsy from the quadriceps femoris muscle before treatment revealed that all type I fibers were either hypotrophic or atrophic. They showed lipid overloading manifested by triglyceride droplets adjacent to the mitochondrial membrane. Furthermore, the level of soluble muscle carnitine was 83 p. 100 less than in controls and membrane linked muscle carnitine was also 73.5 p. 100 less than in controls. The patient rapidly recovered after the initiation of daily treatment with 4.40 g carnitine chlorhydrate associated with 50 g Lipogram 20. Nine months later, lipid overloading completely disappeared and the level of plasma carnitine returned to near normal whereas the level of both soluble and linked carnitine remained very low. To provide more information on the origin of the myopathy (myogenic, neurogenic or humoral) we carried out an electrophysiological investigation of cultured skeletal muscle cells from the patient and from biopsies of patients not known to be suffering from myopathy. The electrophysiological data showed that the patient myotubes were less polarized than myotubes from control patients. Furthermore, the amplitude of the action potential was smaller than the amplitude of the action potential measured in control cells. Daily addition of 50 microM carnitine chlorhydrate to the cultured myotubes induced a recovery of the action potential amplitude. Taken together these results indicate that the carnitine deficiency reported here was probably of systemic origin in addition to a myogenic component. Muscle deficiency could be either linked to an alteration in the carnitine pathway or to overconsumption of carnitine by muscle. This latter point is discussed.

[Acute chorea and disseminated lupus erythematosus (author's transl)]. / Chorée aiguë et lupus érythémateux disséminé.

A case of acute chorea in a young woman with disseminated lupus erythematosus is described and 27 similar cases reported in the literature are reviewed. As in other neurological complications of the disease, signs of diffuse, labile angeitis (dysoric nodules) were present as well as antilymphocyte antibodies characteristics of these forms. Acute chorea is however a rare finding when compared with other types of complications. It keeps its clinical picture resembling that of Sydenham's chorea, and with which is can be compared also as regard the immunological syndromes frequently observed in acute rheumatic fever, and that which occasionally occurs during disseminated lupus erythematosus.

[Bidimensional electrophoresis in the study of cerebrospinal fluid protein (author's transl)]. / Apports de l'immuno-électrophorèse bidimensionnelle dans l'étude des protéines du liquide céphalo-rachidien

The authors report 650 bidimensional electrophoreses of the cerebrospinal fluid (CSF). All examinations were carried out after prior concentration of CSF protein. The technic used is that described by Rebeyrotte in 1970. Four types of tracing were noted: -- Two tracings were unusual by the presence of a large peak in the alpha-2 region. -- One tracing was of the hypergamma type. -- One tracing was comparable to serum by the richness of the precipitations. A change in the first migration permitted us to obtain electrophoretic separations from 100 microlitres of pure CSF. The bidimensional immunoelectrophoresis tracings are comparable to those described previously.

[2-dimensional immunoelectrophoresis of CSF proteins]. / Immuno-électrophorèse bidimensionnelle des protéines du L.C.R.

Two-dimensional electrophoresis isolates the various proteins in the CSF in peaks ; this a method which gives very reliable results ; the height of the peaks has a certain quantitative value, similar to that obtained with electro-immunodiffusion. The peaks visible in the CSF can be increased separately -- mainly the "alpha 2", "alpha 2 beta", the IgA and IgG peaks -- in another type of recording, the height and number of the peaks may be increased, indicating the presence in the CSF of normally absent protein originating in the serum. An increase in the "alpha 2" or "alpha 2 beta" peaks is not specific, but it is always indicative that the development of a neurological process is under way ; the increase of IgG and IgA retains its character of great specificity in evolutive inflammatory conditions. Multiple peaks indicate the passage of serum proteins into the CSF in oedematous and destructive processes, in expansive or compressive processes and in polyradiculoneuritis. This method with its well-codified technique, which may be carried out on an unconcentrated CSF without risk of denaturing the proteins, may be carried out routinely in clinical practice with human anti-serum immune serum or with more specific serum, anti CSF for example, which seems to give quite reliable results.