Neurosarcoidosis: signs, course and treatment in 35 confirmed cases.

Thirty-five cases of biopsy-proven sarcoidosis with neurologic manifestations are reported. Neurosarcoidosis was the presenting symptom in 31% of cases and the only clinical manifestation in 17%. Mean follow-up time was 48 months. Central nervous system involvement was observed in 37% and meningitis in 40% of patients. Other manifestations were cranial nerve palsies (37%), peripheral neuropathy (40%), and myopathy (26%). Multiple neurologic manifestations were present in 51% of cases. All but 4 were treated with corticosteroids. Another immunosuppressive agent or cerebral irradiation was added in 6 and 2 patients, respectively. Complete recovery was observed in 46%, improvement in 46%, 4% remained stable, and 4% worsened. There were no deaths. We advocate treating neurosarcoidosis with corticosteroids as early as possible. If the patient's condition worsens, additional immunosuppressive agents or cerebral irradiation is warranted.

Value of magnetic resonance imaging-based measurements of hippocampal formations in patients with partial epilepsy.

OBJECTIVE: To determine the occurrence of magnetic resonance imaging-detected hippocampal atrophy (HA) in patients with partial epilepsy (temporal and extratemporal, cryptogenic, or symptomatic). Magnetic resonance imaging-detected HA has been demonstrated to be both sensitive and specific for hippocampal sclerosis in cryptogenic temporal lobe epilepsy. DESIGN: Patients' hippocampal formations were measured on a computerized system using T1-weighted, 5-mm contiguous magnetic resonance coronal images made perpendicular to the hippocampus long axis. Hippocampal atrophy was defined on the basis of a normative asymmetry index and correlated with the epileptogenic focus defined by clinical, electroencephalographic, and magnetic resonance imaging (apart from HA) localizing data. PATIENTS AND CONTROL SUBJECTS: Seventy patients with intractable complex partial seizures of temporal, extratemporal, or undefined origin and 21 healthy control subjects. RESULTS: Hippocampal atrophy was present in 70% of patients with cryptogenic temporal lobe epilepsy (TLE) (n = 40), 44% of patients with symptomatic TLE (n = 9), 29% of patients with extratemporal epilepsy (n = 14), and 6% of unclassified patients (n = 16). In the cryptogenic TLE category, HA was marked and usually concordant (93%) with electroencephalographic lateralization. Hippocampal atrophy was often mild in the extratemporal epilepsy category. With the use of a wider confidence interval (+/- 3.1 SD instead of +/- 2.2 SD), HA specificity for TLE increased to 93%, HA specificity for lateralizing cryptogenic TLE reached 96%, and HA sensitivity for cryptogenic TLE stood almost unchanged (68%). We found a link between early convulsions and HA occurrence. CONCLUSIONS: Hippocampal atrophy is a marker for TLE. Dual pathologic findings are detected in 44% of symptomatic TLE cases. Mild HA is rarely associated with extratemporal epilepsy. Magnetic resonance imaging-based hippocampal volumetric analysis is a useful method to localize the origin of partial complex seizures.

Levorotatory form of 5-hydroxytryptophan in Friedreich's ataxia. Results of a double-blind drug-placebo cooperative study.

OBJECTIVE: To study the effect of the levorotatory form of 5-hydroxytryptophan on the cerebellar symptoms of Friedreich's ataxia. DESIGN: Cooperative double-blind study of the levorotatory form of 5-hydroxytryptophan vs placebo. SETTING: Twelve centers in research hospitals. PATIENTS: Twenty-six patients were included; 19 completed the study (mean +/- SD age of patients, 25.9 +/- 8.1 years). Of these 19 patients, eight were treated with placebo and 11 were treated with the drug. MAIN OUTCOME MEASURES: A semiquantitative scale for kinetic and static ("postural") cerebellar functions and quantitative measurements of time in standard tests that evaluated stance, speech, writing, and drawing. RESULTS: In the active treatment group, a significant decrease of the kinetic score was observed (P = .03), indicating an improvement in coordination. CONCLUSIONS: These results demonstrated that the levorotatory form of 5-hydroxytryptophan is able to modify significantly the cerebellar symptoms in patients with Friedreich's ataxia. However, the effect is only partial and not clinically major.

Peripheral neuropathies during treatment with almitrine: report of 46 cases.

Almitrine bismesylate is thought to cause sensory peripheral neuropathy. Forty-six patients are reported who received almitrine bismesylate alone for chronic respiratory failure or in combination with raubasine for various cerebrovascular diseases. Polyneuropathy appeared between 9 and 25 months after the onset of treatment. Sensory signs and symptoms were confined to the distal parts of the lower limbs and involved large and small fibres. Histological and electrophysiological findings indicated axonal degeneration. Respiratory failure could have caused the polyneuropathy in some cases but many had no chest disease. Patients began to improve between 3 and 6 months after withdrawal of the drug. Recovery was usually complete after 12 months.

[An experimental study of the psychostimulant action of amantadine]. / Etude expérimentale de l'action psycho-stimulante de l'amantadine

According to previous experimental and clinical data, we have tested the hypothetic psycho-stimulating activity of amantadine on experimental sensitized models. We obtained a strong action on the spontaneous sleep of rats at a dose of 10 mg/kg and a less striking action in diminishing the effects of barbitol on the righting reflex of mice and in reducing the narcosis of rats induced by mebubarbital. This action does not seem to be due to a release of catecholamine because the lesions produced by electrocoagulation in the ascending aminergic pathways or pretreatment by alpha-methylparatyrosine (AMPT) do not block it. It is suggested that there may be a non-aminergic receptor of amantadine which is different from the amphetamine receptor.

PET studies of cortical diaschisis in patients with motor hemi-neglect.

Six patients presenting with multimodal, predominantly motor hemi-neglect, were investigated by 15O2 or 18F-DG and PET to study the local cerebral metabolism in intact regions. All had suffered from an acute right-sided (n = 5) or left-sided (n = 1) focal hemispheric lesion (cortico-subcortical and purely subcortical in three patients each). Frontal and parietal cortices on the side of the lesion were significantly hypometabolic relative to the other side in each case, presumably as a result of diaschisis, whereas thalamic hypometabolism was significant in only 4 patients. Compared to absolute metabolic rates for controls, the uninjured hemisphere showed a trend towards hypometabolism. Hence, true hyperactivity of the contralateral hemisphere with respect to the ipsilateral cerebral cortex was not associated with motor hemineglect in this series. On the contrary, hemineglect was associated with a widespread hypometabolism of the entire ipsilateral cerebral cortex in the context of a moderately reduced metabolism of the ipsilateral thalamus and contralateral cerebral cortex. These findings are consistent with the implication of a cortico-subcortical network serving attention.

Bilateral infarction of the anterior cingulate gyri and of the fornices. Report of a case.

A 70-year-old woman had complex behavioural changes of sudden onset. The symptoms consisted of indifference, docility and inappropriate urination, but predominantly in a lack of attention. She was unable to maintain the attention necessary to perform a goal-directed activity and she was distracted by any stimulus, such as a sound, an object, or a word, which might induce behaviour irrelevant to the preconceived activity. She also exhibited confabulatory-amnestic syndrome. Neuropathological examination of the brain revealed infarcts in th territories of both anterior cerebral arteries. The rostral part of the anterior cingulate gyrus (Acg), small areas of the adjacent medial prefrontal cortex, and the underlying white matter were destroyed bilaterally. Infarction involved the deep territory of the left anterior cerebral artery, with a bilateral lesion of the fornices. This cingulate damage was more restricted than the Acg lesions reported in some cases of akinetic-mutism, which extended more caudally, but was presumably larger than the lesions created in psychosurgery. The impairment of attention was analyzed according to the possible roles of the cingulate and of the fornix lesions as causing a dysfunction between the frontal lobes and the hippocampal formations.

Motor consequences of motor area ablations in man.

Motor disorders reported in the present paper do not result from cortical ablations stricto sensu since some white matter was excised in every patient. However they appear to suggest that, as suggested by Walshe (1935), the central region and premotor area are a functional entity, i.e. they work as a whole. The extensive lesions of the premotor area, leaving untouched the motor region, have the same motor and tonic consequences as lesions limited to the central region. This point which appears specific for man does not imply that the premotor region subserves activities similar to those subserved by the central region. Rather it may suggest a deafferentiation of the central region, the consequences of which would be more important than is generally assumed. Extensive central or premotor lesions determine various tonic disorders: a well known spasticity, with exaggeration of the stretch reflex, associated with an increase in passive swinging of segments of limbs and in extensibility of joints. These two latter phenomena are usually defined as hypotonia. With premotor and precentral lesions the hypotonia disappears and a hemiplegic posture is observed. This hemiplegic posture is a dystonia which apparently does not result directly from the exaggeration of the stretch reflex. Anatomically it appears to result from lesions of both central and premotor regions. This is in agreement with Denny-Brown's (1966) contention that an extrapyramidal region lies rostral to the prerolandic sulcus. As suggested by Evarts (1973) motor regions appear to control automatic as well as voluntary movements. They probably play a role in the trophic function of muscle, since, despite rehabilitation, amyotrophy was present in every case reported in the present paper.

Clinical consequences of corticectomies involving the supplementary motor area in man.

Three patients with well-mapped, circumscribed ablations of the medial part of the frontal lobe are reported. A specific clinical evolution in 3 stages was observed: (1) post-operatively there was global akinesia, more prominent contralaterally, with an arrest of speech; (2) recovery occurred suddenly but even then there was severe reduction of spontaneous motor activity contralaterally, an emotional type facial palsy and a reduction of spontaneous speech; (3) long after the operation the only sequela was disturbance of the alternating movements of the hands. The anatomical basis of these disorders appears to be a lesion of the supplementary motor area (SMA). Three main points have been discussed, namely: (1) the nature of the motor disorder which may be a disturbance of the function of the SMA in initiating and sustaining spontaneous and automatic motor activity; (2) the nature of the arrest of speech which appears not to be aphasic; the studies reported in the present paper do not support a left cerebral dominance for the SMA as suggested by previous studies; (3) the method of clinical examination appears to be important in distinguishing between spontaneous and voluntary motor and speech performance. Differences in method may account for differences between our findings and those reported in previous studies.

Excessive glutamine sensitivity in Alzheimer's disease and Down syndrome lymphocytes.

In addition to clinical and neuropathological similarities between Alzheimer's disease and Down syndrome there are genetic and biochemical data which suggest common disease mechanism. Using an in vitro assay examining variations of the mitotic index in the presence or absence of various inhibitors or metabolites of purine and/or pyrimidine synthesis, we studied 19 Alzheimer disease patients and 16 patients with both Down syndrome and Alzheimer type dementia. A highly significant decrease in mitotic index in the presence of exogenous glutamine was noted in patients presenting an Alzheimer type dementia with or without associated Down syndrome. These findings suggest that glutamine sensitivity or some dysregulation of the glutamine/glutamate pathway may play a role in the pathogenesis of Alzheimer's disease. If these findings are confirmed, they would have important implications in the development of preventive strategies.

Thought and language.

From aphasics' self records, common experience, changes in signification of sentences according to a verbal or non-verbal context, animals and non speaking children performances, it seems possible to get some evidence that thought is distinct from language even though there is a permanent interaction between both in normal adult human beings. Some considerations on formalisation of language suggests that the more formalised it is, the less information it contains. If it is true, it is not reasonable to hope that a formalised language like that used by computers may be a model for thought. Finally, the lack of status of thought, as far as it is a subjective experience and the impossibility of giving it a definition as far as it exceeds language, make it clear that in spite of progress in scientific psychology, thought, per se, is not an object for science.

Use of introspection in scientific psychological research.

The use of introspection is unavoidable even in psychological research on animals. Difficulties may arise from the absence of reliable introspective data; it is suggested that this could be the case for the so-called "reward system". In other circumstances confusion comes from using introspection without being aware of it: speaking and thinking have for many years been considered as the same operation, but the reason for this belief is not clearly documented and it may be suspected of being only introspection. Amongst other evidence, a careful and conscious use of introspection demonstrated by auto-analyses of former aphasic patients strongly suggests that language and thought are quite distinct entities.

[Epistemological remarks on the question of cerebral organization]. / Réflexions épistémologiques sur la question de l'organisation cérébrale.

Two complementary models of brain organization are nowadays offered: one anatomical and functional, the other computational. The first model implies a subdivision of brain functions in order to find the corresponding brain areas. It is easy to show that this cutting up can only be artificial and is influenced by some kind of "folk psychology", thereby raising suspicion on the "top down" method. On the other hand, it seems impossible to do without any psychological and even any subjective reference and work only according to the bottom up way. It must therefore be concluded that our subdivisions of brain functions must always be regarded as provisional as long as the two methods do not exactly overlap. The computational model uses either the conventional method or the parallel distributed processing. It can be shown that the conventional language utilized impoverishes the normal language and even more thought and is therefore unable to yield more than restricted results. It is suggested that the main advantage of parallel distributed processing is precisely to erase the formalization of language and it is then possible to expect from it much more interesting models. Although it seems possible to improve continuously our understanding of the functional conditions required for consciousness to appear, there seems to be theoretical limits to a complete scientific explanation of self awareness.

[Obsessive-compulsive disorders caused by basal ganglia diseases]. / Obsessions et compulsions par lésions des noyaux gris centraux.

CT scan and magnetic resonance imaging in patients with bilateral lesions of the lenticular nuclei, especially the pallidum, have demonstrated a relationship between these lesions and obsessive-compulsive behaviours. Typical behaviour may satisfy the DSM III criteria for obsessive-compulsive disorders, but in some patients signs are limited to elementary stereotyped movements or thoughts, either together or separately. The same patient may exhibit several kinds of behaviour. The range of disorders suggests that circuits running through the striatum and pallidum participate in regulatory and unification processes of sensori-motor and mental systems. Neuropsychological and metabolic tests suggest that frontal circuits involving the pallidum are especially important in this process. Similar disorders may be observed in patients with frontal or bilateral lesions of the caudate. Obsessive-compulsive behaviour is often associated with a loss of psychic self-activation, but there are exceptions. This evidence suggests a similarity between obsessions related to demonstrated lesions of the basal ganglia and other diseases displaying obsessive-compulsive behaviour, including Gilles de la Tourette disease and the former obsessive neurosis, currently termed obsessive-compulsive trouble. As after von Economo encephalitis, these pathological and clinical features should be considered in the current interpretation of the mechanisms of obsession-compulsion. It appears to be easier to apply Charcot's intuitions about neuroses to obsessive-compulsive behaviour than to hysteria.

[Loss of psychic self-activation]. / La perte d'auto-activation psychique.

Loss of motivation is a well-known disorder in patients with frontal lesions or, as more recently described, with bipallidal lesions. Some of these patients also report a kind of fading of their mental life when they are without exogenous stimulation. Yet their performances return to normal (or almost normal) levels under the influence of a social stimulation. It is this dissociation which we propose to call "loss of psychic self-activation" (LPSA). Comparisons with disorders produced by similar lesions suggest that this is not an "all or none" phenomenon. The purpose of this paper is to discuss the originality, usefulness and validity of the loss of psychic self-activation concept and to evaluate its heuristic value, notably in its application to Janet's psychasthenia and to obsessional neurosis. An interpretation of this disorder based on the available anatomical data is also tentatively proposed.

[Is there a correlation between motor neglect and unilateral sensory neglect]. / La négligence motrice a-t-elle un rapport avec la négligence sensorielle unilatérale?

Similarities between motor neglect and unilateral sensorial neglect are so striking that their mechanisms are likely to be almost the same. As the attentional interpretation is no longer possible for motor neglect, and the intentional interpretation may be dismissed in man because of the loss of automatic movements, the psychological interpretation must be abandoned. A purely physiological hypothesis is put forward for motor neglect. When applied to unilateral neglect, it suggests that sensorial signals treated by the right hemisphere do not reach a significant functional level. In such case, the left hemisphere assumed to be dominant for awareness of body and space would receive from the right hemisphere a message interpreted as nul and would neglect information coming from the left.

[Affective disorders due to the loss of mental self-activation. Comparison with athymhormia]. / Les troubles affectifs de la perte d'auto-activation psychique. Comparaison avec ceux de l'athymhormie.

The affective state of the patients suffering from loss of psychic autoactivation (LPA) is preserved and is dampered as exhibited by a subtle examination, but depends on the same activation by the surrounding people as cognitive thought: it fades if the patient is not stimulated. This affectivity disorder cannot be responsible for LPA, but rather is part of its expression. The empty mind, characteristic of LPA, is not incompatible with the painful mood of the depression contrarily to our intuitive notion. In other words, the mood (or thymia) of patients with LPA is not neutral or null as suggested by the term "athymia". The term "anhormia" would describe rather well part but only a part of the disorder, the loss of drive. Furthermore, the term "self activation" has the advantage of highlighting, by contrast, the preserved heteroactivation, an essential part of the clinical picture. The heuristic value of this distinction is illustrated by the division it suggests between the so called "will" or "motivation" and of the circuitry supporting the two components. The term of LPA leads also to the description of a new state of conscious awareness, a consciousness devoid of any content.

[The debate over "hysteria"]. / Le débat sur l'hystérie.

The debate on hysteria at the "Société de Neurologie" in 1908 signed the official death certificate for Charcot's hysteria, which even in his day had started to come under attack. The article by Babinski in 1901 had delivered the "coup de grâce". The debate paints an astonishing picture of the medical world of the day, and also of hysteria, which would never again present the spectacular clinical picture seen up to that point. Babinski, dominating the debate with his strong personality, prevented a discussion on the mental basis for hysteria, requested by several participants, in favour of pithiatism, which in his view offered an acceptable definition of hysteria. It is surprising that more was not made of the contradiction in terms in the expression "auto-suggestion", and of the fact that Babinski was begging the question when he asserted that it could not be asserted that a patient had been subject to suggestion! This debate effectively banished hysteria from the columns of the neurological press, whose pages it had tended to overburden. It cannot however be blamed for not having made a positive contribution to our understanding of this neurosis which, even today, remains enigmatic. It does our Society credit to have ruled out "for ethical reasons" the hypothesis of simulation.

[Side effects of antiepileptic therapy. Study of 197 cases]. / Les effets secondaires des traitements antiépileptiques. Etude de 197 cas.

A study of 197 epileptic outpatients consecutively observed by one Neurologist allowed a prospective study of the side effects of antiepileptic drugs. This study shows essentially that a clinical improvement comparable to that generally reported can be obtained with side effects limited in their number and intensity. The main principle is the routine search of these effects which are not always spontaneously mentioned by the patients, especially intellectual slowness and loss of sexual activity. The detection of the side effects through history and physical examination is far more fruitful than are plasma concentrations of drugs which can be doubly misleading: some plasma concentrations lower than recognized therapeutical levels are efficient however while others are higher and nevertheless necessary and well tolerated. Among the side effects specific to certain antiepileptic drugs, shoulder-hand syndrome due to phenobarbital was noted in 10 per cent of the cases. Furthermore, the frequency of scapulo-humeral periarthritis was significantly higher in the epileptic group than in the controls. Dupuytren's disease was less frequent (8 per cent) and the difference with the controls was not significant. Among the non-specific side effects, nystagmus is a somewhat useful sign in treatments by phenytoin but as with drugs dosages, it must be weighed within the whole clinical picture.

[Motor neglect of thalamic origin]. / Négligence motrice d'origine thalamique.

The clinical picture of thalamic motor neglect is identical to those of motor neglect in general, the major symptom of which being an underutilization of one side of the body in the absence of sensory-motor defect. Several thalamic nuclei can be implicated on the grounds of pathological and experimental data, most frequently the ventro-lateral nucleus. The prevalence of left neglect is not so obvious in the case of thalamic than in the case of other sites of lesions. Motor neglect appears as a disorder in the triggering of the brain structures network which program and prepare movement in several circumstances; attentional tasks are only a particular circumstance. Some thalamic nuclei are the site of hypoactivity in the case of frontal motor neglect in the monkey, as shown by anatomical and functional studies; this emphasizes the strong participation of thalamus to the motor network, the dysfunction of which can induce a motor neglect.