[Effects of the association of sulbutiamine with an acetylcholinesterase inhibitor in early stage and moderate Alzheimer disease]. / Effets de l'association de la Sulbutiamine à un inhibiteur de l'acétylcholinestérase dans les formes légères à modérées de la maladie d'Alzheimer.

The efficacy of the inhibitors of acetylcholinesterase in Alzheimer's Disease (AD) is moderated and some patients do not respond to these treatments. Sulbutiamine potentializes cholinergic and glutamatergic transmissions, mainly in hippocampus and prefrontal cortex. This multicentric, randomized and double-blind trial evaluates the effects of the association of sulbutiamine to an anticholinesterasic drug in cognitive functions in patients with AD at an early stage (episodic memory, working memory, executive functions, attention). Patients had first donepezil (D) or sulbutiamine (S) during three months. During this period, only attention improved in both groups. During the three following months, a placebo (P) in patients D and donepezil in patients S were added. Compared to entry results, episodic memory decreased in group D + P but improved in group S + D. At the same time the improvement of attention persisted in both groups. Daylife activities only improved in group S + D. In conclusion sulbutiamine can be an adjuvant to treatment in early stage and moderate AD by anticholinesterasic drugs.

[Effects of sulbutiamine (Arcalion 200) on psycho-behavioral inhibition in major depressive episodes]. / Etude des effets de la sulbutiamine (Arcalion 200) sur l'inhibition psychocomportementale des épisodes dépressifs majeurs.

UNLABELLED: Psycho-behavioural inhibition is characteristic of major depressive disorder and frequently recedes after the other depressive symptoms. This may induce an important psychosocial impairment which could be a risk factor for relapse. METHODS: The aim of this eight weeks, multicentric, randomized, double blind, placebo controlled trial was to assess the efficacy and safety of sulbutiamine (Arcalion) [600 mg p.d.] on the symptoms of psycho-behavioural inhibition of inpatients with DSM III-R defined Major Depressive Episode (MDE) treated by adjusted doses of clomipramine [75 to 150 mg pd]. Moderate doses of hypnotics and anxiolytics without potential activity on the mood were authorized during the trial. The MDE was assessed with the MADRS, HAM-A and CGI scales. Patients who did not respond adequately to the antidepressant treatment were prematurely withdrawn from the trial. The three Sheehan Disability Scales (SDS), the Norris Visual Analogue Scale (VAS) and the Depressive Psychomotor Retardation Scale (ERD) were used to monitor psycho-behavioural inhibition. RESULTS: The mean intake scores were, as expected, fairly high: MADRS (32), HAMA-A (23), CGI (5) and ERD (27). The SDS and EVA scores showed that the patients felt severely handicapped in their social, professional and family life functioning as well as in their emotional, affective, cognitive and behavioural performances. At four weeks the MADRS, HAM-A and CGI scores indicated that the global improvement of the MDE was comparable in both treatment groups. However, the scores at the EVA and SDS scales showed that the patients treated with sulbutiamine were significantly less incapacitated than the placebo group in all of the various facets (affective, cognitive, emotional, behavioural) of psycho-behavioural inhibition. Furthermore, the safety data shows that both treatment groups were comparable and in particular that sulbutiamine had not induced any inappropriate behaviour, including suicide attempts, or mania. CONCLUSIONS: Sulbutiamine has no antidepressive effect but it can hasten the resorption of psycho-behavioural inhibition occurring during major depressive disorder and thereby facilitate the rehabilitation of patients in their social, professional and family life functioning.

Pain and its treatments.

Among many relevant topics concerning pain and its treatments, the following will be considered: (1) definition of pain; (2) physiopathology; (3) methodology for clinical trials in pain research (4) use of drugs and surgical management of pain, and (5) future directions. The definition of pain as an unpleasant subjective, sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage, does not apply to living people incapable of self-report. Thus, nonverbal behavioral information is often needed and used for pain assessment. Major landmarks concerning physiopathology were: the liberation of substance P and other neuropeptides both at the spinal and peripheral endings, the anatomical and functional analysis of the nociceptive pathways, the characterization of endomorphins ligands and receptors. The difference between 'windup' and central sensitization were emphasized. Models of neuropathic pain have advanced our understanding of its specific pathophysiology. Sensoridiscriminative aspects of pain involve lateral thalamic nuclei and corresponding somesthetic cortices, whereas medial thalamic nuclei encode nociceptive stimuli during attention-directed tasks. Their cortical connections, namely anterior cingular cortex and insular cortex, support the postulate of a role in the affective-motivational dimensions of pain. An impressive increase in the number and quality of randomised clinical trials has been observed since 1950. The use of analgesics, opioids, antidepressants and other drugs is addressed, as well as new aspects concerning surgery or new drugs.

Pharmacology of neuropathic pain.

The development of new animal models now allows the pharmacological study of the neuropathic pain. Our results concern mainly antidepressants and opiates; although the results are incomplete, they show that the different components of the pain syndrome depend on various mechanisms and require adapted treatments and that the treatment must begin as soon as possible, before plastic processes sustain a vicious circle of pain. In the future, pharmacological studies will permit better specification of indications for drugs already used, as well as the associations that improve their efficacy; studies will also encourage development of new treatments more adapted to the physiopathology of the pain syndrome.

[Serotonin agonists and antagonists in migraine]. / Agonistes et antagonistes de la sérotonine et migraine.

Serotonin agonists (for the acute treatment of attacks) and antagonists (for prophylactic treatment) are the most widely used drugs to treat migraine. However, their effectiveness is not complete and their use is limited by side effects. The activity and presumptive mode of action of these drugs provide support for the role of serotonin in the pathophysiology of migraine and suggest that the trigeminal-vascular system is at the center of the attack; however, other factors and mechanisms may also be involved.

[Platelets and migraine]. / Plaquettes et migraine.

Platelet function studies in migraine patients have evidenced a number of anomalies (hyperreactivity and serotonin metabolism disorders) that have been suggested as causative factors in migraine attacks. However, a review of the literature shows that these disorders are inconsistent and are probably consequences rather than causes of the headache, although they may contribute to the pathophysiology of the attack. From a broader perspective, the demonstration of platelet dysfunction in migraine raises questions as to the source of these disorders (secondary to plasma factors or due to platelet anomalies) and their significance (do they have any link with transient ischemic attacks or central serotonin neurotransmission dysfunction?).

Dopaminergic insufficiency reflecting cerebral ageing: value of a dopaminergic agonist, piribedil.

Amongst the various disturbances of neurotransmission accompanying cerebral ageing, dopaminergic insufficiency is undoubtedly the most constant, the earliest and the most severe. It affects the three ascending dopaminergic systems and may explain many of the motor, emotional, affective and cognitive disorders associated with cerebral ageing. In particular, the psychobehavioural syndrome of cerebral ageing is marked by disorders affecting the capacities for abstraction, conceptualization, reasoning, elaboration of strategies and problem-solving and therefore analogous to those of frontal symptomatology. They probably reflect disafferentation of the frontal lobe, deprived of effective dopaminergic innervation. This hypothesis is supported by the beneficial effects of the dopaminergic agonist piribedil on symptoms of cerebral ageing, particularly on the psycho-behavioural changes.

[Pharmacological treatment of neuropathic pain]. / Traitement pharmacologique de la douleur neuropathique.

Neuropathic pain, i.e., pain resulting from functional changes in peripheral and central pathways subsequent to injury to the peripheral nervous system, offers a most difficult challenge to therapy. To date, only the antidepressants and the anticonvulsants have shown any effectiveness, albeit incomplete and inconsistent, and many questions remain unanswered: What are the exact indications for the antidepressants? What component of neuropathic pain do they relieve, and through which mechanisms? Which type of antidepressants should be prescribed? A first-generation tricyclic? Or a new compound with a selective action on serotonin reuptake? What are the effective dosage and duration of the treatment? What is it mechanism of action? What other antalgic effects do carbamazepine and baclofen possess apart from their action on trigeminal neuralgia? The opiates are generally considered to be without effect, but recent clinical and experimental findings seem to point otherwise. In the meantime, following a few simple rules will optimize the benefit of drug treatment in neuropathic pain: treatment tailored to individual cases; adequate dosage and duration of treatment. However, it is from the near future that breakthroughs are being expected, dues to the multiplication of animal models and more accurate analysis; new clinical evaluation tools which help in distinguishing the different mechanisms underlying the various aspects of pain; the development of new substances, such as capsaicin, local anesthetics, anti-inflammatory agents (NSAIDs for example); and better defined methodological conditions for therapeutic trials.

Alcohol and central neurotransmission.

The study of the relationships between alcohol consumption and central neurotransmission is difficult: they are different from one individual to another, from one neurotransmission system to another and from one cerebral area to another. Moreover, there is no fully satisfactory animal model of alcoholism and the human studies have to cope with a lot of methodological problems. In spite of these difficulties a bidirectional relationship between alcohol and central neurotransmission is well established. Neuronal dysfunctions are the neurobiological basis for the alcohol behaviour, and ethanol craving seems specifically related to hypofunction of the noradrenergic, GABAergic and serotoninergic systems, and maintained by a positive reinforcement mediated by the dopaminergic and opioid systems. Ethanol alters almost all membrane functions, but it behaves essentially like a barbiturate-type GABAergic agonist. In the short-term, it also stimulates central monoaminergic neurotransmissions. With chronic intoxication, membrane tolerance develops, which is the substratum for tolerance and dependence. Concurrently there are adaptative processes and a depletion of the capacities for synthesis of neurotransmitters, therefore a hypofunctioning of all neurotransmission systems. This hypofunctioning is an additive mechanism for tolerance and dependence, pushing the individual into drinking always more alcohol to palliate it; it is sharply revealed during withdrawal, particularly the GABAergic deficiency.

[Chronic hepatic encephalopathies. Acquired cerebral degeneration not due to Wilson's disease]. / Les encéphalopathies hépatiques permanentes. Dégénérescence cérébrale acquise non wilsonienne.

We report on 4 cases of perennial hepatic encephalopathy and review similar published cases. The neurological picture consists of a cerebellar syndrome, both static and kinetic, dysarthria, choreo-athetoid abnormal movements and mental deterioration. Symptoms are permanent and usually worsen progressively. Some patients may present with a myelopathy, either isolated or combined with an encephalopathy. Relevant anatomical alterations, either encephalic or spinal, may be observed similarly in several varieties of liver disease, but in every case the role of portocaval shunts, whether spontaneous or surgically performed, appears essential. Altered results of laboratory studies, such as EEG or ammonemia, are described. Histological changes include a peculiar sort of hyperplasia of the protoplasmic astrocytes, along with a certain amount of neuronal loss. Surmised pathological mechanisms and applied therapy are briefly reviewed. For an appraisal of therapeutic results, perennial hepatic encephalopathies should be set apart from both the acute varieties and the usual chronic variety with its succession of recurrent exacerbations and remissions.

[The role of evoked potentials in the diagnosis of multiple sclerosis]. / La place des potentiels évoqués dans le diagnostic de la sclérose en plaques.

Diagnosis of multiple sclerosis is based mainly upon evidence of inflammation in the cerebrospinal fluid and of diffuse neurological involvement. The second feature is often lacking at onset. It is important to establish the diagnosis as early as possible. In this respect, evoked potentials (visual, auditive or somatosensory) in the brainstem are useful to demonstrate asymptomatic lesions. Our recordings taken in 43 patients are conclusive. The diagnostic reliability of simultaneous recordings of all three types of evoked potentials is similar to that of the study of cerebrospinal fluid.

[Involvement of the peripheral and pyramidal nervous system in Crohn disease. Determining role of folic acid deficiency]. / Atteinte des systèmes nerveux périphérique et pyramidal au cours d'une maladie de Crohn. Rôle déterminant d'une carence folique.

We report on the case of a 16-year-old male patient who presented with a peripheral neuropathy remarkable by the severity of pain, the proximal involvement and the association with an underlying myelopathy. All these symptoms coincided with an acute exacerbation of Crohn disease (regional enteritis) involving mainly the duodenojejunal segment, and were ascribed to a major folic acid deficiency, with total recovery following supplementation. In this connection we recall the various neurological symptoms induced by folic acid deficiency. We point out how difficult it is to prove the responsibility of such deficiencies in the production of neurologic diseases, mainly because of the possible intrication with other pathogenic factors: combined deficiencies or direct action of the factor responsible for the deficiency on the nervous system. Guidelines for solving these difficulties are suggested.

[Occlusive arteriopathy of the circle of Willis with outlined "Moya-Moya" network in a woman with migraine under oral contraception. Regressive course]. / Artériopathie occlusive du polygone de Willis avec ébauche de réseau "Moya-Moya" survenue chez une jeune femme migraineuse sous médication contraceptive. Evolution régressive.

A 19-year-old woman with migraine under contraceptive therapy had transient right hemiparesis due to a minor lesion in the left hemisphere, which was probably hemorrhagic rather than ischemic. On the left side, angiography showed nearly complete obstruction of the terminal portion of the internal carotid artery, extending to the initial portion of its terminal branches, with an outlined "Moya-Moya" network. On the right side, moderate annular stenosis of the cervical portion of the internal carotid was visible. On subsequent angiographies, done 7 and 19 months later, blood flow was reestablished in the left internal carotid artery as well as in its terminal branches, but with persistent segmental stenosis. Since the stroke, the symptomatology of migrainous attacks has been altered, pointing to a left hemispheric spreading.

PIP: A 19-year old woman with a migraine who had been taking oral contraceptives (OCs) had transient right hemiparesis due to a minor lesion in the left hemisphere, probably hemorrhagic rather than ischemic. On the left side, angiography showed nearly complete obstruction of the terminal portion of the internal carotid artery, extending to the initial portion of its terminal branches with an outlined "Moya-Moya" network. On the right side, moderate annular stenosis of the cervical portion of the internal carotid was visible. On subsequent angiographies, done 7 and 19 months later, blood flow was reestablished in the left internal carotid artery as well as in its terminal branches, but with persistent segmental stenosis. Since the stroke, the symptomatology of migrainous attacks has been altered, pointing to a left hemispheric spreading. (author's modified)

[Incomplete regressive obstruction of the internal carotid artery in a female patient with fibromuscular dysplasia]. / Obstruction incomplète de la carotide interne d'évolution régressive chez une malade atteinte de dysplasie fibro-musculaire.

The authors report on the case of a 48-year-old woman, with no history of cardiovascular disease, presenting with a progressive right cerebral deficiency syndrome predominating in the parietal region. X-ray, arteriography and CT scan findings led to the diagnosis of right middle cerebral artery ischemic stroke, in the proximal territory, due to a practically complete occlusion of the right internal carotid artery. The patient recovered and a right carotid arteriography performed 8 months after the initial one showed repermeation of the carotid artery, as well as evidence of fibromuscular dysplasia (FMD). The authors then reviewed the literature dealing with cervico-cephalic FMD and concluded that FMD only exceptionally leads to arterial occlusion, whether by arterial dissection, intimal hyperplasia or thrombosis. This case is remarkable by its favorable outcome: the thrombus, which was unquestionably responsible for the clinical picture, dissolved spontaneously.