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Because of the increasing incidence of primary central nervous system lymphoma (PCNSL), it is essential to recognize this disease in order to start appropriate treatment. We present the characteristic CT and MRI features of this tumour. The findings of 32 CT and 31 MR of 37 immunocompetent patients with biopsy-proved PCNSL are reviewed. The main features are presented and analysed, and are discussed in comparison with proven literature data. Primary central nervous system lymphoma presents as supratentorial solitary lesions in approximately 80% of the patients and multiple lesions in 20%. In contrast to classical data, the lesions are located in deep structures only in one-third of the cases, and involve posterior fossa in 10% of cases. Most of the lesions are hyperdense or isodense (92%) on CT, hypointense or isointense on T1-weighted images, and only about 40% are hyperintense on T2-weighted images. Nearly all the lesions enhance, except after corticosteroid administration. They produce mild oedema and mass effect. Meningeal or ventricular enhancement are rare but suggestive. Calcification, haemorrhage or necrosis are scarce. Although PCNSL in immunocompetent patients have a variable CT and MR appearance, the imaging data often suggest the diagnosis.

Andermann syndrome or Agenesis of the Corpus Callosum with Polyneuropathy (MIM 218000) is an autosomal recessive disease almost exclusively found in Québec. Only few cases have been reported in other populations. The locus for Andermann syndrome was assigned to chromosome 15q13-q15 in French Canadian families. We performed a haplotype analysis with two markers of this chromosomal region in an Algerian consanguineous family with two affected sibs. The children were homozygous for both markers, suggesting genetic homogeneity in Andermann syndrome.

The emergence of a unified cognitive moment relies on the coordination of scattered mosaics of functionally specialized brain regions. Here we review the mechanisms of large-scale integration that counterbalance the distributed anatomical and functional organization of brain activity to enable the emergence of coherent behaviour and cognition. Although the mechanisms involved in large-scale integration are still largely unknown, we argue that the most plausible candidate is the formation of dynamic links mediated by synchrony over multiple frequency bands.

Colorectal carcinoma is one of the most common malignancies in the western world, and although fluorouracil (5-FU) has been used in its treatment for almost 40 years, new agents with significant activity have been introduced recently. Irinotecan (CPT-11, Camptosar), a topoisomerase I inhibitor, administered at 300 to 350 mg/m2 every 3 weeks is significantly more active than continuous-infusion 5-FU in patients who have experienced disease progression after conventional therapy with 5-FU. In comparison to best supportive care, irinotecan improves survival and preserves quality of life despite treatment-related toxicity. Moreover, the combination of irinotecan and 5-FU has been explored in a number of different schedules. In previously untreated patients, overall response rates are high. Irinotecan can also be combined with mitomycin (mitomycin-C [Mutamycin]), oxaliplatin, or raltitrexed (Tomudex). Oxaliplatin is a new-generation platinum compound that has demonstrated activity against colorectal carcinoma in preclinical trials. It has been evaluated as a single agent against advanced colorectal carcinoma in the salvage setting and also in combination with 5-FU as initial therapy for metastatic disease (where it shows significant activity). The toxicity profile of oxaliplatin (chiefly characterized by neurotoxicity) differs from that of irinotecan (primarily producing diarrhea) and the potential, therefore, exists for combining these agents or for exploiting their possible synergy with 5-FU. The introduction of these two new active agents of different pharmacologic classes promises to enable significant improvements in the treatment of patients with colorectal carcinoma.

Changes in presynaptic inhibition of Ia terminals directed to flexor carpi radialis (FCR) motoneurones (MNs) were investigated in normal human subjects at rest and during voluntary wrist flexion and extension. To that end, two independent methods were used: (1) the radial-induced D1 inhibition of the FCR H reflex, which assesses the excitability of PAD (primary afferent depolarisation) interneurones controlling presynaptic inhibition of Ia terminals mediating the afferent volley of the FCR H reflex; and (2) the heteronymous monosynaptic Ia facilitation induced in the FCR H reflex by intrinsic muscle Ia afferent stimulation, which assesses the ongoing presynaptic inhibition of Ia terminals. With respect to results at rest, it was found that at the onset of (and during tonic) voluntary wrist flexion, D1 inhibition was reduced and heteronymous monosynaptic Ia facilitation was increased. This suggests that, as in the lower limb, presynaptic inhibition is decreased on Ia terminals projecting to MNs involved in the voluntary contraction. In contrast with results observed in the lower limb, presynaptic inhibition of Ia terminals to FCR MNs was also found to be reduced at the onset of a voluntary contraction involving the antagonistic wrist extensors, suggesting that presynaptic inhibition of Ia terminals projecting to wrist flexors and extensors might be mediated through the same subsets of PAD interneurones. This is in keeping with other features showing that the organisation of reflex pathways between wrist flexors and extensors differs from that observed at other (elbow, ankle) joints.

We have analyzed with localized proton magnetic resonance spectroscopy (MRS) 31 lesions in 28 patients with multiple sclerosis (MS). The course of the disease was either relapsing remitting, secondary progressive, or primary progressive. Four patients had an isolated neurological syndrome suggestive of MS. The decrease in the NAA/Cre ratio and the raise of the Cho/Cre ratio were more pronounced in patients with an acute isolated neurological syndrome, suggesting the predominance of an inflammatory process, and the presence of an axonal dysfunction in the initial course of the lesion. The NAA/Cre ratio was negatively correlated with clinical disability and thus could be used as an index of disease activity. Patients with a secondary progressive course exhibited a significant increase in the Myo/Cre ratio compared to those with a relapsing remitting course. Thus, there may be an association between the evolution towards a progressive disease and axonal loss or the development of gliosis. The isointense lesions to the cerebrospinal fluid on MRI T1 weighted sequences were characterized by a sharp raise in the Cho/Cre ratio suggesting demyelination and/or intense inflammation. Gadolinium enhanced lesions were not characterized by a specific neurochemical profile.

Magnetic resonance spectroscopy allows in vivo neurochemical exploration of multiple sclerosis (MS) lesions and normal appearing white matter on MRI. It gives insights into pathophysiology: inflammation (increase of choline), recent demyelination (increase in lipids and choline), axonal dysfunction (decrease of NAA), gliosis (increase of myoinositol). The spectroscopic profile of lesions is not specific to MS. Therefore MRI remains the first investigation to perform when MS is suspected. However, spectroscopy is a sensitive, reproducible, non invasive tool which may provide an index of activity. In the future, spectroscopy may contribute in homogenizing patient selection for clinical trials and might be used, in association with MRI, to evaluate therapeutic efficiency. Spectroscopy might also influence therapeutic choices by identifying the prevailing lesional mechanism: inflammation, demyelination, axonal destruction, or gliosis.

Guidelines for the neuropathological examination of the central nervous system (in adults) are proposed. They include the techniques used for the removal of the brain and spinal cord, the dissection of the skull, the removal of the brain, the fixation of the specimens, the sectioning of the brain, the choice of the blocks for histology, the usual staining methods and the main antibodies to be recommended for immunohistochemistry. Diagrams are given on which the lesions may be drawn and the samples, identified.

Objective: The purpose of this study was to follow changes in superficial veins of the lower extremities during pregnancy and the postpartum period in women with varicose veins., Methods: This was a prospective study with the use of duplex scanning during the first and third trimesters of pregnancy and postpartum period. Competent veins were defined as veins with an absence of reflux, and incompetent veins were defined as veins with reflux. The diameter of the competent or incompetent greater saphenous vein (GSV) and lesser saphenous vein (LSV) was measured. The diameter of the largest varicose dilatations was measured in all three networks: GSV and its tributaries, LSV and its tributaries, and nonsaphenous varicose veins., Results: Sixty-six women were studied prospectively (mean age, 32.2 +/- 4 years; 85 affected extremities). The diameter of competent and incompetent GSVs and competent LSVs increased between the first and third trimester (P <.001) and decreased between the third trimester and the postpartum period (P <.001). The diameter of the largest varicose dilatations of the GSV and its tributaries and nonsaphenous networks increased between the first and third trimester (P <.001) and decreased between the third trimester and the postpartum period (P <.001). No statistically significant variation of the diameter was demonstrated for any of these veins between the first trimester and the postpartum period., Conclusion: The diameters of competent and incompetent superficial veins increased during pregnancy and decreased during the postpartum period to return to their baseline values.

The distribution of monosynaptic and nonmonosynaptic excitation was investigated within flexor carpi radialis (FCR) and extensor carpi radialis (ECR) motoneurone (MN) pools. FCR H reflexes of different size were conditioned by various conditioning stimuli eliciting different effects: (1) musculocutaneous-induced non-monosynaptic excitation of FCR MNs at the onset of biceps contraction, (2) heteronymous monosynaptic Ia facilitation, (3) reciprocal Ia inhibition, and (4) presynaptic inhibition of Ia terminals. Musculocutaneous-induced non-monosynaptic excitation increased continuously with the size of the unconditioned reflex. In contrast, heteronymous monosynaptic Ia excitation first increased and then decreased, with increases in the unconditioned reflex size, reciprocal inhibition and presynaptic inhibition showing an approximately similar tendency. This suggests that the non-monosynaptic excitation is distributed more evenly to early and late recruited MNs than monosynaptic Ia excitation, reciprocal inhibition and presynaptic inhibition. A different pattern of homonymous radial-induced monosynaptic and non-monosynaptic excitation was also found for individual ECR MNs investigated with the poststimulus time histogram (PSTH) method. Whereas the monosynaptic Ia excitation tended to be most marked in lower threshold MUs, the nonmonosynaptic excitation was evenly distributed to lower and higher threshold MUs. We propose that the even distribution of the non-monosynaptic excitation in the motoneuronal pool may be of significance when it is necessary to activate a wide range of MNs more or less simultaneously.

Presynaptic inhibition of Ia terminals and postactivation depression at the Ia fibre-motor neuron (MN) synapses were compared in the upper and lower limbs of both sides in subjects from different populations: 49 spastic patients with hemiplegia [mainly with a lesion in the middle cerebral artery (MCA) area], two tetraplegics and 35 healthy subjects. Presynaptic inhibition was assessed using D1 inhibition of the soleus and the flexor carpi radialis (FCR) H reflexes elicited by electrical stimuli applied to the nerve supplying antagonistic muscles, and postactivation depression was explored by varying the time interval between two consecutive H reflexes. In normal subjects no right-left asymmetry was found in the amount of presynaptic Ia inhibition, homosynaptic depression or the H(max)/M(max) ratio. In the hemiplegic side of patients with MCA area lesions, the H(max)/M(max) ratio was significantly increased in the soleus but not in the FCR. Presynaptic inhibition of Ia terminals, which was significantly reduced at the cervical level on the hemiplegic side (and also, but to a lesser extent, on the unaffected side), was unchanged at the lumbar level. Homosynaptic depression was similarly reduced at the cervical and lumbar levels on the hemiplegic side but not modified on the unaffected side. It is argued that the decrease in presynaptic inhibition of Ia terminals is more a correlate of spasticity than a mechanism underlying it. The decrease in postactivation depression, which very probably contributes to the exaggeration of the stretch reflex characterizing spasticity, might be a consequence of the changes in the pattern of activation of Ia afferents and MNs following the motor impairment.

Background: An association with subcutaneous adipose tissue TNFalpha expression and insulin resistance has been suggested in obesity/type-2 diabetes, but this has not been examined directly. In the first part of the study we investigated whether this association is present in 7 lean, 10 obese nondiabetic and 9 type-2 diabetic men. In the second part of the study we examined the relationship between adipose tissue TNFalpha mRNA levels and BMI in 81 nondiabetic subjects spanning a wide range of BMIs., Methods: Subcutaneous adipose tissue TNFalpha mRNA levels and insulin sensitivity were determined with quantitative RT-competitive PCR and hyperinsulinaemic clamp, respectively., Results: Subcutaneous adipose tissue TNFalpha mRNA levels were similar in 7 lean and 10 obese nondiabetic and 9 type-2 diabetic men (P = 0.68), and did not change in response to 240-min hyperinsulinaemia. TNFalpha mRNA levels and insulin sensitivity were not correlated. Unexpectedly, no correlation between TNFalpha mRNA and BMI was found. The relationship between adipose tissue TNFalpha mRNA and BMI was examined further in 31 male and 50 female nondiabetic subjects. The subcutaneous adipose tissue TNFalpha mRNA level correlated with BMI in all subjects (rS = 0.32, P < 0.01), and in a subgroup analysis in men (rS = 0.55, P < 0.01) but not in women (rS = - 0.08). The correlation in men was dependent on a fourfold higher TNFalpha mRNA level in 5 morbidly obese men while there was no difference in TNFalpha mRNA levels in lean or obese men., Conclusions: Subcutaneous adipose tissue TNFalpha expression does not correlate with insulin sensitivity in nondiabetic or type-2 diabetic men; is not regulated by acute hyperinsulinaemia; and is increased only in morbidly obese men.

Background: Idiopathic torsion dystonia is a clinically and genetically heterogeneous movement disorder. A GAG deletion at position 946 of the DYT1 gene was the first mutation found, in early-onset dystonia, with an autosomal dominant transmission and reduced penetrance., Objective: To evaluate the frequency of the DYT1 mutation in patients with idiopathic torsion dystonia but without a family history., Design: Prospective cohort study., Setting: Four botulinum toxin clinics in the Paris, France, area., Patients: A French population of 100 patients with dystonia., Main Outcome: Frequency of the DYT1 mutation tested by polymerase chain reaction and enzyme restriction analysis for the 946 GAG deletion, and genotype-to-phenotype correlation., Results: Only 5 mutation carriers were identified, 4 of whom were part of a group of 10 patients with generalized dystonia. Onset was between ages 5 and 12 years as in typical early-onset dystonia. All 4 patients had cranial muscle involvement, which is atypical for DYT1 mutation carriers. One had segmental dystonia. Molecular analysis of relatives in 2 families demonstrated that the lack of family history was due to reduced penetrance., Conclusions: For accurate diagnosis and genetic counseling, screening for the DYT1 deletion is of great interest in cases with generalized dystonia without a family history. In other cases, positive results are rare.

The length and complexity of the anatomical course of the facial nerve explains the difficulty of its accurate morphologic evaluation. CT and MR appear to be complementary techniques to precisely depict the nerve from its pontine origin to the parotid gland. Anatomical variations exist in length or thickness of all intrapetrous segments or as frequent dehiscences which can lead to false positive results or at the opposite falsely negative diagnoses. Close relations with the antero-inferior cerebellar artery in the intracisternal and intracanalicular segments must be known. Gadolinium enhancement is usual in the fallopian canal with variable intensity and thickness and should be differentiated from pathological enhancement. Finally the intrapetrous course of the chorda tympani can be precisely displayed on CT in the intra-osseous canal and in the middle ear near the ossicles.

The development and endorsement of the 'El Escorial criteria' by the World Federation of Neurology (WFN) for the diagnosis of amyotrophic lateral sclerosis (ALS) in 1990 and subsequent revision of these guidelines in April 1998 has provided physicians with a much needed tool in the secure diagnosis of ALS. However, even today, over 100 years since ALS was first described by Charcot, when asked to define ALS most neurologists will answer that ALS remains an extremely difficult disease to diagnose early and therefore to manage optimally. Despite the WFN's admirable commitment to optimising the management of ALS the definition of the early stages of ALS is still not clear. To appreciate why this remains so, the development of our understanding of ALS as documented by case reports in the literature will be discussed in this paper.

We describe adjustments in grip force as a consequence of fluctuations in inertial load force during vertical movements of the upper limb in a patient with cerebellar degeneration. Normally grip force is adapted to load-force fluctuations, in particular to the maximum load force, which occurs early in upward movements and late in downward movements. Increased grip force during movement was observed in the patient, but the timing of maximum grip force was not different between upward and downward movements. This suggests impaired cerebellar prediction of the dynamic consequences of voluntary movement.

New methods have been recently developed to explore selectively presynaptic inhibition of Ia afferents in humans. They have allowed us to describe a highly specialized organisation in these pathways. A differential control has been disclosed during voluntary movements among various motoneuronal pools: at the onset of a selective voluntary contraction presynaptic inhibition of Ia afferents projecting to the 'contracting' motoneurons is strongly decreased whereas presynaptic inhibition of Ia afferents to antagonistic or synergistic motoneuronal pools, not involved in the contraction, is increased. Indirect arguments suggested that these modulations are centrally patterned. A differential control has been also disclosed between upper and lower limb pathways. Using transcranial magnetic stimulation to induce a descending corticospinal volley, we have shown that a corticospinal volley inhibits preferentially 'presynaptic interneurons'at the lumbar spinal level, an effect which is strengthened by a cutaneous input whereas it preferentially activates 'presynaptic interneurons' at the cervical spinal level, an effect which is inverted by a cutaneous input.

During the last 40 years, several studies in man have been devoted to the pathophysiological mechanisms underlying spasticity. Spasticity is characterised by a velocity dependent increase in muscle tone. Many spinal pathways control stretch reflex excitability and a malfunction in any one of them could theoretically produce the exaggeration of the stretch reflex. Delwaide showed that the vibration-induced inhibition of Ia fibres is reduced in spastic patients. However, the relation between a decrease in presynaptic Ia inhibition and the pathophysiology of spasticity has been recently questioned since it was argued that homosynaptic depression (or post-activation depression) also contributes to the vibratory-induced depression of monosynaptic reflexes. This paper is thus devoted to a review of the methods recently developed to study selectively presynaptic Ia inhibition in man and to a reevaluation of the relations between modifications in presynaptic Ia inhibition and spasticity in hemiplegic and spinal spastic patients.

The possibility was investigated that human handedness is associated with an asymmetrical cortical and/or peripheral control of the cervical premotoneurones (PreMNs) that have been shown to mediate part of the descending command to motoneurones of forearm muscles. Heteronymous facilitation evoked in the ongoing voluntary extensor carpi radialis (ECR) electromyographic activity (EMG) by weak (0.8 times motor threshold) stimulation of the musculo-cutaneous (MC) nerve was assessed during tonic co-contraction of biceps and ECR. Suppression evoked by stimulation of a cutaneous nerve (superficial radial, SR) at 4 times perception threshold in both the voluntary EMG and in the motor evoked potential (MEP) elicited in ECR by transcranial magnetic stimulation (TMS) was investigated during isolated ECR contraction. Measurements were performed within time windows or at interstimulus intervals where peripheral and cortical inputs may interact at the level of PreMNs. Results obtained on both sides were compared in consistent right- and left-handers. MC-induced facilitation of the voluntary ECR EMG was significantly larger on the preferred side, whereas there was no asymmetry in the SR-evoked depression of the ongoing ECR EMG. In addition, the suppression of the ECR MEP by the same SR stimulation was more pronounced on the dominant side during unilateral, but not during bilateral, ECR contraction. It is argued that (1) asymmetry in MC-induced facilitation of the voluntary EMG reflects a greater efficiency of the peripheral heteronymous volley in facilitating PreMNs on the dominant side; (2) asymmetry in SR-induced suppression of the MEP during unilateral ECR contraction, which is not paralleled by a similar asymmetry of voluntary EMG suppression, reflects a higher excitability of cortical neurones controlling inhibitory spinal pathways to cervical PreMNs on the preferred side.

Transient periods of synchronization of oscillating neuronal discharges in the frequency range 30-80 Hz (gamma oscillations) have been proposed to act as an integrative mechanism that may bring a widely distributed set of neurons together into a coherent ensemble that underlies a cognitive act. Results of several experiments in animals provide support for this idea. In humans, gamma oscillations have been described both on the scalp (measured by electroencephalography and magnetoencephalography) and in intracortical recordings, but no direct participation of synchrony in a cognitive task has been demonstrated so far. Here we record electrical brain activity from subjects who are viewing ambiguous visual stimuli (perceived either as faces or as meaningless shapes). We show for the first time, to our knowledge, that only face perception induces a long-distance pattern of synchronization, corresponding to the moment of perception itself and to the ensuing motor response. A period of strong desynchronization marks the transition between the moment of perception and the motor response. We suggest that this desynchronization reflects a process of active uncoupling of the underlying neural ensembles that is necessary to proceed from one cognitive state to another.

Methods have been developed to investigate recurrent inhibition (RI) in humans. A conditioning reflex discharge is used to evoke in motoneurones (MNs) supplying homonymous and synergistic muscles, an inhibition the characteristics of which are consistent with RI: it appears and increases with the conditioning motor discharge, has a short latency and a long duration, and is enhanced by an agonist of acetylcholine. As in the cat, homonymous RI exists in all explored motor nuclei of the limbs except those of the digits and the pattern of distribution of heteronymous RI closely matches that of monosynaptic Ia excitation. However, striking inter-species differences exist concerning the distribution of heteronymous RI since it is much more widely extended in the human lower limb than in the cat hindlimb, whereas it is more restricted in the upper limb than in the cat forelimb. Changes in transmission in the recurrent pathway have been investigated during various voluntary or postural contractions involving different (homonymous, synergistic, antagonistic) muscles and it has been found that the activation of Renshaw cells (RCs) by the voluntary motor discharge via recurrent collaterals was powerfully controlled by descending tracts: for example, during homonymous contraction, RI evoked by a given conditioning reflex discharge is much smaller during strong than during weak contraction, which suggests that the descending control of RCs might contribute to the regulation of muscle force. The finding that RC inhibition is more marked during phasic than during tonic contraction of similar force of the homonymous muscle is discussed in relation with the projections of RCs to Ia interneurones mediating reciprocal inhibition. Only in patients with progressive paraparesis is there evidence for decreased RI at rest which may contribute to the exaggeration of the passively-induced stretch reflex underlying spasticity. However, despite the seemingly normal RI at rest in most patients, the control of RCs during voluntary movements is disturbed in these patients, which probably contributes to their motor disability.

A study is reported of the relations between vestibular sensitivity and vection chronometry in healthy human adults. Twenty-three subjects were examined. For both vestibular and vection investigations, the subjects were seated in an armchair with the spinal axis aligned with the earth vertical and the head normally erect. The subjects' vestibular thresholds for detection of vertical upward accelerations were assessed by a double-staircase psychophysical method. The subjects' vection onset latencies were measured for both upward and downward directions. Since the vection onset latencies are presumed to be shortened by the decrease of the conflict between visual and vestibular afferents, the less-vestibular-sensitive subjects were hypothesised to have shorter vection onset latencies than the more-vestibular-sensitive ones. As expected, the results indicate a negative correlation between vestibular thresholds and vection onset latencies: the higher the vestibular thresholds, the lower the vection onset latencies.

The N1 component of the auditory brain evoked potential was used as a direct electrophysiological index, to study how the perception of pitch for complex periodic tones can be influenced by the phase of the harmonics that make up a sound, according to their ranks. Results showed that in the low pitch and/or high spectra region, N1 latency was modified by phase, whereas it was not in the high pitch and low spectra region. These data help bring evidence towards a dual mechanism for pitch perception, and demonstrate that these processes take place within 110 ms following stimulus onset. Results are compatible with a model based on the resolvability of components and on the bandwidth of auditory filters.

Due to the recent regulations generated by the diversity of infectious risks, autologous bone is the standard graft material in maxillofacial surgery. Although synthetic biomaterials can be useful, they remain insufficient in many situations. Among the many sites offering graft material, monocortical parietal bone which is accessible within the craniocephalic operative field has distinguishing characteristics due to its membranous embryological origin and its mode of direct ossification which does not include a cartilaginous stage. The proportion of cancellous bone per unit volume is much higher than in enchondral bone (iliac bone, ribs...). These factors are undoubtedly the source of its main qualities--very little resorption and excellent capacity for bony integration--motivating its increasingly widespread use over the past twenty years. We present our experience in a series of patients who underwent surgery between 1992 and 1997. Parietal bone was used for orthognathic, pre-implant or reconstruction surgery after trauma or carcinological trauma. We present a description of the surgical procedures together with morbidity results and compare our findings with those found in large series in the literature, particularly concerning rare neuromeningeal complications. We discuss indications for parietal grafts and their course at the receiver site.

The effect of transcranial magnetic stimulation was investigated on presynaptic inhibition of Ia terminals in the human upper and lower limb. Presynaptic inhibition of Ia afferents was assessed by three different and independent methods: (1) heteronymous Ia facilitation of the H-reflex (assessing ongoing presynaptic inhibition of Ia afferents in the conditioning volley); (2) long-lasting inhibition of the H-reflex by a group I volley (D1 inhibition, assessing presynaptic inhibition on Ia afferents in the test volley); (3) measurement of the monosynaptic Ia peak evoked in single motor units by a homonymous or heteronymous volley (post stimulus time histogram method). The first two methods were used on the lower limb; the last two on the upper limb. Provided that the corticospinal volley and the explored Ia volley were directed to the same target motoneurones, cortical stimulation evoked significant and congruent changes: (1) In the lower limb, transcranial stimulation provided increased heteronymous Ia facilitation and decreased D1 inhibition, both of which suggest a decrease in presynaptic inhibition of Ia afferents; (2) in the upper limb, transcranial stimulation provided an increase in the radial-induced inhibition of the wrist flexor H-reflex and a decrease in the peak of monosynaptic Ia excitation in single units, both of which suggest an increase in presynaptic inhibition. Selectivity of corticospinal effects was explored by testing presynaptic inhibition of Ia afferents to soleus motoneurones and focusing the transcranial stimulation to excite preferentially different motor nuclei (soleus, quadriceps and tibialis anterior). A cortical-induced decrease in presynaptic inhibition of Ia afferents was seen when, and only when, cortical and peripheral Ia volleys were directed to the same motor nucleus.

Malformations of the cranio-cervical junction represent a complex entity, comprising neuro-meningeal and bone anomalies. Malformations of the central nervous system are nowadays easily explored using magnetic resonance imaging (MRI), while osseous malformations are classically assessed with standard radiographic techniques, which can give only incomplete information, and are often difficult to realize and analyse. We report a retrospective study of 10 patients with a Chiari malformation operated on in our department at La Salpêtrière hospital, between July 1995 and December 1996 (1 man, 9 women; mean of age: 35 years; postoperative median follow-up: 6 months; 70% of improvement and 20% of stabilisation), and we underline the interest of the systematic pre-operative realization of a 3D CT and angio-CT studies of the cranio-cervical junction. This examination offers advantages of: a precise analysis of the more complex osseous malformations; a study of the relationships between vascular and bony structures; a study of the relationships between neuraxis and spinal and cranial structures; and an optimal planning of the surgical procedure, adapted to the anatomical particularities of the patient.

We report clinical and neurophysiological characteristics of six patients (five women and one man) presenting a pure motor bilateral asymmetric proximal and distal weakness in the setting of radiation therapy for Hodgkin's lymphoma in four cases, carcinoma of the uterus in one, and cancer of the ovary in one. Motor deficit, amyotrophy, cramps, fasciculations and tendinous areflexia were confined to the lower limbs in five patients and to the upper limbs in one. No sensory or sphincter disturbance was noted. The progression of the disease was slow with sometimes secondary stabilization. In some patients, CSF showed a slight increase in protein content with no cell. Blood and MRI medullary examination were normal. Delay between radiation therapy and onset of neurological symptoms range from 6 to 24 years (mean 15). Neurophysiological findings suggest ventral roots proximal conduction blocks. We found an increase F-waves latency, a complete distal palsy contrasting with persistent muscle action potential after distal stimulation, in most of the patients; and an evidence of a conduction block between the erb point and the cervical roots using magnetic stimulation in the patient with upper limbs involvement. Mechanisms and sites of nerve radiation injury remains still unclear. These data could indicate, as it was already reported, a proximal damage involving predominantly the motor roots.

Deep facial spaces are anatomically delineated by the layers of deep cervical fascia. They are located between the skull base and the hyoid bone. Each space contains specific anatomic structures, which can be responsible for specific pathologic processes. Deep facial spaces can be divided in two medial odd spaces (pharyngeal mucosal and retropharyngeal spaces), and in three lateral even spaces (retrostylian, prestylian, and masticator spaces). The dividing of these core tissues are useful for the analysis of the lesions found in this area. CT scan and MRI (with axial and coronal views) provide precise analysis. The main lesions are: -medially, adenoidal hyperplasias and squamous cell carcinomas (pharyngeal mucosal space), adenopathies and abscess (retropharyngeal space). -laterally, salivary tumors (prestylian space), adenopathies, schwannomas and paragangliomas (retrostylian space). Masticator space (and especially pterygopalatine fossa) is an important way of communication and is often involved by the extension of locoregional pathologic processes.

Different methods, based on different principles, have been proposed to estimate changes in presynaptic inhibition of Ia terminals (accompanied by primary afferent depolarization, (PAD)) during voluntary contraction in humans. (i) A discrepancy between the H-reflex amplitude, at an equal level of EMG activity, in two situations (e.g., walking and standing) may be taken as suggesting a different control of PAD interneurones in the two cases. (ii) A conditioning stimulation (vibration or electrical stimulation) is used to activate PAD interneurones and to evoke presynaptic inhibition of the afferent volley of the test reflex. The resulting long-lasting depression of the reflex depends on the excitability of PAD interneurones, but can be contaminated by long-lasting post-synaptic effects. (iii) The amount of reflex facilitation evoked by a purely monosynaptic Ia volley varies inversely with the on-going presynaptic inhibition of Ia afferents mediating the conditioning volley, and can be used to assess this on-going presynaptic inhibition. None of these methods can provide by itself unequivocal evidence for a change in presynaptic inhibition of Ia terminals, but reasonably reliable interpretations may be proposed when congruent results are obtained with different methods. Thus it has been shown that, during selective voluntary contraction, presynaptic inhibition is decreased on Ia afferents projecting on motoneurones of the contracting muscle and increased on Ia afferents projecting on motor nuclei not involved in the contraction.

We studied subdural recordings from a patient with an unusually focal and stable occipito-temporal epileptic discharge under four experimental conditions. The series of time intervals between successive spike discharges displayed a few (3-5) clusters of periodic values representing statistically significant short-term periodicities when tested against surrogate data. This short-term predictability was modulated during the different experimental conditions by periodicity shifts of the order of 15-30 ms. Correspondingly, there was an increased gamma-band (30-70 Hz) coherence between the epileptic focus and surrounding recording sites. We conclude that the focal epileptic activity is part of an extended network of neural activities which exert a fast modulation reflected in changes of transiently periodic activities.

The EMG activity of the cricothyroid muscle (CT) and the three extrinsic laryngeal muscles (thyohyoid, TH; sternothyroid, ST, and sternohyoid, SH) were recorded throughout the voice range of one female and one male subject, both untrained singers. The voice range was examined using rising and falling glissandos (production of a sustained sound with progressive and continuous variation of fundamental frequency). Muscle activity was observed at various pitches during the glissandos. The strap muscle activity during the production of glissandos appears to be synergistic. At the lowest frequency, the CT is inactive but strap muscles (TH, ST, SH) are active. As frequency increases, strap muscle activity decreases while the CT controls frequency in the middle of the range. At higher frequencies the strap muscles once again become active. This activity might depend on the vocal vibratory mechanism involved. The role of the strap muscles at high pitches is a widely debated point but it seems that in some way they control the phenomena relevant to the rising pitch. The phasic-type strap muscle activity contrasts with the tonic-type activity of the CT. The CT closely controls the frequency, while the straps are not directly linked to the pitch but rather to the evolution of the frequency of voice production (speaking voice, singing voice, held notes, glissandos, trillo, vibrato, etc.).

Host immunity to Epstein-Barr Virus Patterns of Epstein-Barr Virus latent gene expression in EBV posttransplantation lymphoproliferative disorders Cytokines network in posttransplantation lymphoproliferative disorders associated with EBV Lymphomagenesis and EBV Morphology and clonality of posttransplantation lymphoproliferative disorders associated with EBV Treatment of posttransplantation lymphoproliferative disorders associated with EBV.

Segmentation of the neural tube has been clearly shown in the forebrain and caudal hindbrain but has never been demonstrated within the midbrain/hindbrain domain. Since the homeobox-containing gene Otx2 has a caudal limit of expression in this region, we examined, mainly in chick embryos, the possibility that this limit could represent an interneuromeric boundary separating either two cerebellar domains or the mesencephalic and cerebellar primordia. In situ hybridisation with chick or mouse Otx2 probes showed the existence of a transient Otx2-negative area in the caudal mesencephalic vesicle, between stages HH10 and HH17/18 in chick, and at embryonic day 9.5 in mice. The first post-mitotic neurons of the mesencephalon sensu stricto, as labelled with an anti-beta-tubulin antibody, overlay the Otx2-positive neuroepithelium with a perfect match of the caudal limits of these two markers at all embryonic stages analysed (until stage HH20). Chick/quail homotopic grafts of various portions of the midbrain/hindbrain domain have shown that the progeny of the cells located in the caudal mesencephalic vesicle at stage HH10 are found within the rhombomere 1 as early as stage HH14. Furthermore, our results indicate that the cells forming the HH20 constriction (coinciding with the caudal Otx2 limit) are the progeny of those located at the caudal Otx2 limit at stage HH10 (within the mesencephalic vesicle). As a result, the Otx2-positive portion of the HH10 mesencephalic vesicle gives rise to the HH20 mesencephalon, while the Otx2-negative portion gives rise to the HH20 rostral rhombomere 1. Long-survival analysis allowing the recognition of the various grisea of the chimeric brains strongly supports the view that, as early as stage HH10, the caudal limit of Otx2 expression separates mesencephalic from isthmo/cerebellar territories. Finally, this study revealed unexpected rostrocaudal morphogenetic movements taking place between stages HH10 and HH16 in the mediodorsal part of the caudal Otx2-positive domain.

In human beings of both sexes, dehydroepiandrosterone sulfate (DHEAS) circulating in blood is mostly an adrenally secreted steroid whose serum concentration (in the micromolar range and 30-50% higher in men than in women) decreases with age, toward approximately 20-10% of its value in young adults during the 8th and 9th decades. The mechanism of action of DHEA and DHEAS is poorly known and may include partial transformation into sex steroids, increase of bioavailable insulin-like growth factor 1, and effects on neurotransmitter receptors. Whether there is a cause-to-effect relationship between the decreasing levels of DHEAS with age and physiological and pathological manifestations of aging is still undecided, but this is of obvious theoretical and practical interest in view of the easy restoration by DHEA administration. Here we report on 622 subjects over 65 years of age, studied for the 4 years since DHEAS baseline values had been obtained, in the frame of the PAQUID program, analyzing the functional, psychological, and mental status of a community-based population in the south-west of France. We confirm the continuing decrease of DHEAS serum concentration with age, more in men than in women, even if men retain higher levels. Significantly lower values of baseline DHEAS were recorded in women in cases of functional limitation (Instrumental Activities of Daily Living), confinement, dyspnea, depressive symptomatology, poor subjective perception of health and life satisfaction, and usage of various medications. In men, there was a trend for the same correlations, even though not statistically significant in most categories. No differences in DHEAS levels were found in cases of incident dementia in the following 4 years. In men (but not in women), lower DHEAS was significantly associated with increased short-term mortality at 2 and 4 years after baseline measurement. These results, statistically established by taking into account corrections for age, sex, and health indicators, suggest the need for further careful trials of the administration of replacement doses of DHEA in aging humans. Indeed, the first noted results of such "treatment" are consistent with correlations observed here between functional and psychological status and endogenous steroid serum concentrations.

Neural progenitors are thought to be multipotent cells whose adult phenotype is determined by extrinsic influences acting during and immediately after their last mitosis. To test this hypothesis, postnatal cerebellar precursor cells were placed in the heterochronic cellular environment of the embryonic mouse cerebellar anlage and the resulting phenotypes were determined. To identify the cells arising from postnatal precursors, tissue fragments taken from 3- to 8-day-old cerebellum of several transgenic mouse lines (each expressing the lacZ reporter gene in different sets of neuronal populations) were mixed with fragments taken from the wild-type cerebellar primordium of 12- or 13-day-old embryos. The fragments were dissociated and grafted into the cerebellum of adult mice. The phenotype acquired by postnatal precursors in the mixed grafts was determined by their morphology and ultrastructural features and by the expression of specific markers. Only two adult phenotypes were generated by these precursors: granule cells and molecular layer interneurons. Most granule cells were well integrated in the trilaminated cortex of the graft, being positioned in their proper layer both during development and after complete maturation. By contrast, basket and stellate cells were always ectopic, remaining outside the molecular layer. These results indicate that at least two distinct progenitor cells are present in the postnatal cerebellar cortex under the experimental conditions of this study. Both progenitors appear to be strictly specified at the time of grafting, and neither their identify nor the expression of their major distinctive features are significantly influenced by local signals emerging from the cellular environment of the embryonic cerebellar anlage.

To gain insight into cellular and molecular mechanisms subserving neuronal cell migration in the adult mouse forebrain, we have first investigated the cellular composition of the subventricular zone-olfactory bulb pathway (SVZ-OB). The pathway was essentially composed of cells with neuronal and astrocytic identities, neuronal cells being four times more numerous than astrocytes. Neuronal cells (precursors and some young postmitotic neurons) formed continuous cellular strands of migratory cells from the anterior horn of the lateral ventricle to the olfactory bulb. These chains of migrating cells moved within channels formed by the processes of a special subpopulation of astrocytes. The neuronal cells expressed the embryonic form of polysialic acid neural cell adhesion molecule, and the astrocytes were tenascin-C positive, thus preserving an embryonic cellular environment. Through transplantation experiments, the second part of this study attempted to analyze the functional properties of the adult SVZ-OB pathway. Early postnatal (P2-13) cerebellar progenitor cells, taken from a transgenic mouse line in which cerebellar granule cells and molecular layer interneurons (basket/stellate cells) expressed the reporter gene lacZ, were implanted in the SVZ-OB pathway of adult wild-type mice. Unlike grafted SVZ cells that migrate all along the pathway, none of the cerebellar precursors reached the olfactory bulb, although some of them were able to migrate along the caudal one-third of the pathway. The majority (over 67%) of the migrating cells were progenitors that acquired the phenotype of basket/stellate cells. Granule cell progenitors and most granule cells did not survive transplantation. These results show that the adult SVZ-OB pathway is not a "passive generic guidance" for all classes of premigratory neurons. From the two types of grafted cerebellar progenitors, only those with migratory capability and that do not follow radial glial axes are able to translocate along the SVZ-OB pathway. Furthermore, the basket/stellate cell progenitors are specified at the time of grafting: Neither their identity nor the pace of expression of their major distinctive features are influenced by local signals emanating from the adult forebrain.

Seven patients suffering from Parkinson's disease (PD) with severely disabling dyskinesia received low-dose propranolol as an adjunct to the currently used medical treatment. There was a significant 40% improvement in the dyskinesia score without increase of parkinsonian motor disability. Ballistic and choreic dyskinesia were markedly ameliorated, whereas dystonia was not. This study suggests that administration of low doses of beta-blockers may improve levodopa-induced ballistic and choreic dyskinesia in PD.

Script analysis was investigated in patients with lesions in the prefrontal (n = 10) and posterior (n = 8) cortical regions, and in normal subjects (n = 15). The selection and temporal organization of relevant actions belonging to different pre-established sequences were studied in three different situations: (A) script with headers, (B) script with headers and distractors, and (C) scripts without headers. Contrarily to Normals and Posterior patients, Frontal patients committed sequence and boundary errors, and failed to eliminate distractors elements. The analysis of errors suggests two different cognitive modes of representing actions: (1) One using temporal contiguity between actions, that would be mainly under the control of the posterior associative areas; (2) the other, using the goal of the action and its consequences as a binding element between script and context, that would require the intervention of prefrontal cortex.

A study was conducted in Paris among primary care physicians as part of a World Health Organization study entitled Psychological Problems in General Health Care. Though social phobia is associated with significant impairment and drug use, the level of problem recognition by general practitioners was low. Social phobia (n = 38) was identified as a psychological case in 53% of the patients in whom social phobia was not comorbid with depression, and in 66% when comorbid with depression. This low level of recognition was comparable to that observed for depression where only 66% of the depressed patients (n = 121) were recognized as psychological cases. Psychotropic drug use was high: 61% of patients with social phobia had taken at least one psychotropic drug in the last month, compared to only 32% of those without social phobia. This difference was explained by a significant difference in the use of anxiolytics (45.4 versus 12.1%). The use of psychotropic drugs was twice as frequent in patients with social phobia who were depressed than in those not depressed. The results of this study emphasize the crucial need for primary care physician training in the recognition and treatment of mental disorders.

Complex tones such as vowels expressed by the human voice vary both in fundamental pitch (harmonic periodicity) and spectrum shape (vowel type). Three different pitches and spectra were combined into nine auditory stimuli. Latencies of cerebral evoked potential components decreased significantly as pitch increased, whereas they remained constant with spectrum shape. Because the fundamental (direct clue about pitch value) was purposely omitted from stimuli, these results reflect feature extraction processes. They also demonstrate that brain potentials can be used as objective indexes of perceived pitch.

In man there is now strong evidence for the existence of a system of cervical propriospinal premotoneurons interposed in the corticospinal pathway to upper limb motoneurons. The relevant neurons are located rostral to upper limb motoneurons. They receive both weak excitation and strong inhibition from low threshold afferents in the upper limb. Ongoing EMG activity recorded in wrist and elbow extensors during voluntary movements of different types (tonic contraction, reaching) is suppressed by a cutaneous volley evoked by stimulation of the superficial radial nerve. There is evidence that this cutaneous-induced suppression is due to inhibition of transmission of the cortical command in the system of cervical propriospinal premotoneurons, thus indicating that part of the descending command for movement reaches the relevant motoneurons via these premotoneurons. In patients with hemiplegia, the cutaneous-induced depression of ongoing EMG activity is significantly larger on the hemiplegic side. This suggests that the mechanisms underlying residual motricity after a lesion of the corticospinal tract involve the system of propriospinal premotoneurons.