Study of a patient population investigated for excessive daytime sleepiness (EDS).

This study included all patients referred to the out-patient department of our sleep disorders centre from 1993 to 1999 on account of excessive daytime sleepiness (EDS). As a first step, patients in whom a diagnosis was established following appropriate polysomnography were excluded: this included sleep apnea syndrome, increased upper airway resistance syndrome, narcolepsy, periodic movements during sleep or other parasomnia, and epilepsy. Patients regularly taking psychotropic substances or with psychiatric disorders were also excluded. Finally, 128 patients remained in whom no clear diagnosis had been established for EDS, 70 women and 58 men, their ages ranging from 16 to 77 years. They underwent a 48-h recording (night 1-MSLT-night 2-continuous day). The aim of the study was to establish, define and characterise different groups of undiagnosed EDS patients using clinical, electrophysiological and immunological data with the help of hierarchical cluster analysis. Eight groups were characterised: group 1: mild hypersomnia type 1 (n = 11); group 2: hypersomnia frequently associated with HLA type DR2-DQw1 (n = 11); group 3: mild hypersomnia type 2 (n = 28); group 4: morning recovery from disrupted sleep (n = 19); group 5: young "long sleepers with difficulty at waking up" (n = 17); group 6: idiopathic hypersomnia (n = 15); group 7: poor or short sleepers since childhood (n = 8); group 8: older poor sleepers with a late onset of symptoms (n = 19). Characteristic features of these different groups provided consistent and objective arguments leading to a more precise diagnosis for these patients, and helped the initiation of appropriate management and treatment.

[Electrophysiologic study in a patient presenting with expanding cerebral lacunae]. / Etude électrophysiologique chez un patient présentant des lacunes cérébrales expansives.

A 42-year-old man was affected with multiple cerebral lesions suggesting expanding lacunae. He had suffered for about 15 years of headaches and blurred vision. Neurological examination showed a Parinaud syndrome and a skew deviation. Magnetic resonance imaging showed an enlargement of the third and lateral ventricles and multiple intraparenchymatous lesions with a signal similar to that of the cerebrospinal fluid. These lesions were located in the mesencephalon and right thalamic region. Important discrepancies between the topography of the lesion and the clinical data were observed. Neurological examination, ocular movements during wake and neuropsychological testing suggested sub-cortical dysfunction. These results suggest functional rather than lesional repercussion of expansive lacunae.

[Effect of modafinil in narcoleptic patients. Electrophysiologic and psychometric studies]. / Effet du modafinil chez des patients narcoleptiques. Etudes électrophysiologique et psychométrique.

Clinical efficiency of Modafinil was clearly demonstrated in narcoleptic patients but only a few electrophysiological studies were carried out to confirm these observations. Since Modafinil did not change the propensy to fall asleep, the aim of this work was to study maintenance of wakefulness and performance levels in treated narcoleptic patients. Of the 16 treated patients, 12 responded as expected to Modafinil. These 12 patients were studied. After a one night polysomnography, electrophysiological tests included: baseline spectral analysis, maintenance of wakefulness tests carried out respectively eyes open in diffused light and eyes closed in darkness during which sleep latency, duration of test and changes in the theta/alpha ratio were measured. Psychometric performances were evaluated using verbal or non verbal tests: visual and auditory reaction time tests. Trail Making Test, Stroop, verbal Fluency and WAIS-R. Modafinil improved the ability of narcoleptic patients to remain awake only when the situation or the environmental conditions were favorable. Some psychometric performances also trended towards on improvement.

Modafinil: a double-blind multicentric study.

Modafinil is a central putative alpha-1 postsynaptic agonist with vigilance-promoting properties. Fifty narcoleptics (33 male and 17 female) participated in a multicentric study aimed at assessing the effects of the compound on night sleep, feeling on awakening, excessive daytime sleepiness and cataplexy. Modafinil was administered in a double-blind cross-over design at a daily dosage of 300 mg versus placebo. The duration of the study was 12 weeks, including a 2-week "run in" period with placebo, a first 4-week treatment period with either modafinil or placebo, a 2-week wash-out period with placebo and a second 4-week treatment period with either placebo or modafinil. Daily evaluation was based on a sleep log, visual analog scales, a sleep questionnaire and a clinical global index. Sleep laboratory evaluation took place on nights 1, 28, 42 and 70. It included 1 night of polysomnography preceded by a questionnaire on therapeutic and side effects, and a maintenance of wakefulness test (MWT). Sleep logs did not show any modification of night sleep, but a reduction of daytime sleepiness and sleep. Feeling on awakening was not modified. An overall benefit was noted by physicians as well as by patients. MWT disclosed a positive effect of modafinil on excessive daytime sleepiness. Cataplexy was not modified.

Modafinil in diurnal sleepiness. A study of 123 patients.

The efficacy of modafinil, a psychostimulant drug acting on postsynaptic alpha-1 adrenergic receptors, as a treatment for excessive daytime sleepiness was studied in 123 patients. Subjects included 94 narcoleptic patients (76 with cataplexy), 23 hypersomnia patients and 6 patients with disrupted nocturnal sleep (DNS) and excessive daytime sleepiness (EDS). Clinical efficacy of the treatment on each symptom (EDS, cataplexy and DNS) was evaluated on a four-point scale from excellent to absent. The effectiveness of modafinil as a treatment for EDS was excellent in 17% of all patients, good in 63%, fair in 17% and absent in 3%. The incidence of side effects was rather low (14 of 123 patients) and most of them disappeared (11 patients) when doses were reduced.

Auditory evoked responses (AER) and augmenting-reducing phenomenon in patients with progressive supranuclear palsy (PSP).

Variations in amplitude and latency of P1, N1 and P2 waves of AER induced by increasing the stimulus intensity (augmenting-reducing) were measured in PSP patients and compared to those observed in normal subjects. The studied population included 17 patients (10 male, 7 female, mean age 66 +/- 8 yr) with a typical PSP symptomatology and 17 normal subjects (10 male, 7 female, mean age 66 +/- 9 yr). All subjects from both the groups showed a normal auditory threshold (less than 30 db SPL or a moderately increased threshold never exceeding 10 db SPL). Nine patients had normal BAER; 4 patients showed an abnormal III wave; 3 patients showed an abnormal V wave. One patient had a poorly individualized BAER. Latencies and amplitudes of P1, N1 and P2 waves derived from Cz and Fz (linked ear reference) were studied with 50, 60, 70 and 80 db intensities and for each patient slopes of amplitude-stimulus intensity and latency-stimulus intensity curves were studied. Although patients showed decreased AER amplitudes, the augmenting-reducing phenomenon was not different from controls regarding either latency or amplitude changes with increasing stimulus intensity. Previous studies had established a negative correlation between the augmenting-reducing responses and HVA levels in the cerebrospinal fluid (CSF). Similarity of augmenting-reducing mechanisms in PSP and normal subjects favors the hypothesis of unimpaired mesocortical and mesolimbic dopaminergic pathways in PSP. This hypothesis is also supported by postmortem studies using biochemical markers.

[Detection and peripheral or central localization of sensory pathway involvement of the lower limbs by somatosensory evoked potentials]. / Détection et localisation périphérique ou centrale des atteintes des voies sensitives par les potentiels évoqués somesthésiques des membres inférieurs.

In the presence of more or less atypical sensory or sensorimotor symptoms the questions that arise most frequently concern the authenticity of the disorders and the precise level of the lesion. In this study, somatosensory evoked potentials (SEPs) to stimulation of the tibial nerve at the ankle were recorded at different levels in 35 healthy subjects and 32 patients with sensory disorders. Recording electrodes were placed at the popliteal fossa (peripheral sensory nerve conduction velocity), at the T12-L1 level (medullary potential: N21) and at the vertex (P40 wave). The spine to cortex time interval was measured. A systematic study of evoked responses to median nerve stimulation was performed. The 32 patients were divided into 4 groups: Group I (3 cases) had slowed sensory conduction velocity (SCV), similar delay in N21 latency and normal N21-P40: peripheral neuropathy. Group II (4 cases) had normal SCV, delayed N21 latency and normal N21-P40: radicular or conus medullaris injury. Group III (19 cases) had normal SCV, normal N21 latency and lengthened N21-P40 interval. A study of responses to median nerve stimulation made it possible to discriminate between spinal and cortical or subcortical impairment. Group IV (6 cases) had abnormalities from any two of the three groups defined above. In 24 out of 32 patients (75 p. 100), further investigations (myelography, MRI, EMG) confirmed the localization determined by evoked responses. In the other 8 patients (25 p. 100) whose clinical picture suggested a medullary or radicular impairment, SEPs alone clearly revealed an injury. SEPs can distinctly show a spinal impairment and determine the choice of further investigations.

[Efficacy of uvulopalatopharyngoplasty (UPPP) and modifications in sleep structure in the sleep apnea syndrome (SAS)]. / Efficacité de l'uvulopalatopharyngoplastie (UPPP) et modifications de la structure du sommeil dans le syndrome d'apnée du sommeil (SAS).

Thirty-four patients (32 male, 2 female; mean age 53 +/- 7 years) with confirmed sleep apnea syndrome (SAS) were studied before and after uvulopalatopharyngoplasty (UPPP). Clinical symptoms were tiredness, excessive daytime sleepiness and snoring. All patients were overweight. Patients underwent a thorough physical and oropharyngeal examination and polysomnography before and 3 months after surgery. On the basis of post-operative results, patients are divided into 3 groups: --group 1: 16 cured patients: apnea index (A.I./h) 38 +/- 17 before and 4.4 +/- 4 apneas/h sleep after surgery. Improved nocturnal hypoxemia: mean minimum oxyhemoglobin saturation (SAO2) before and after UPPP in NREM sleep 83 +/- 4% v. 90 +/- 4% in REM sleep 76 +/- 11% v. 85 +/- 7%. Uninterrupted sleep is restored; --group 2: 8 improved patients: A.I./h of 64 +/- 11 before and 20 +/- 6 after UPPP: improved nocturnal hypoxemia: mean minimum SAO2 in NREM sleep 74 +/- 10% before and 86 +/- 6% after UPPP: in REM sleep 59 +/- 9% before and 79 +/- 6% after UPPP, lower amount and percentage of fragmented sleep; --group 3: 10 non-improved patients: A.I./h unchanged 55 +/- 22% before and 50 +/- 20% after UPPP. Persistent nocturnal hypoxemia: mean minimum SAO2 in NREM sleep 76 +/- 13 before and 81 +/- 12% after UPPP: in REM sleep 63 +/- 16% before and 65 +/- 24% after UPPP. Sleep remains fragmented. In this last group patients are more overweight and all suffer from severe SAS with greater nocturnal oxyhemoglobin desaturation. Surgical treatment by UPPP is shown to be effective for 70% of our patients. Better results are obtained when SAS is less severe and overweight less important.

Effect of age on auditory evoked responses (AER) and augmenting-reducing.

Auditory evoked responses (AER) were obtained from Cz and Fz in 30 adults (14 male, 16 female) from 20-80 years old. Sound bursts (1000 Hz-200 msec) of four different intensities were used. Peak to trough amplitudes of P1N1 and N1P2 and latencies of P1, N1 and P2 peaks were measured with increasing stimulus intensity and slopes of amplitude - intensity and latency - intensity curves were analysed for assessment of an age effect. The main result is that the increase in P1N1 amplitude with increasing stimulus intensity is more pronounced in older persons. Previous studies have established a negative correlation between the augmenting-reducing responses and HVA levels in the CSF (with lower amounts of HVA in the CSF of "augmenters"). Decreased dopamine metabolism in old subjects could account for our results, so further studies should focus on patients with pathological dopamine deficiencies.

[Effects after 3 months of uvulopalatopharyngoplasty in the treatment of obstructive sleep apnea syndromes in adults]. / Effets à trois mois de l'uvulopalatopharyngoplastie dans le traitement du syndrome d'apnées obstructives du sommeil de l'adulte.

The results at three months of uvulopalatopharyngoplasty (UPPP) have been evaluated in thirty adult patients with an obstructive sleep apnoea syndrome (SAOS). For the group overall the mean apnoea index (IA) decreased from 57 apnoeas per hour and the mean maximal desaturation decreased to 60% post operatively. However in the overall results different individual facts overlap. 20 of the 30 patients, or 67%, have an IA post operatively of less than 50% of the pre-operative value (responders). 14 of these or 47% have a post operative IA of less than 10 apnoeas per hour, a value considered as non pathological. Finally 33% of the patients have no improvement in their post operative IA (non responders). A stricking diminution of nocturnal desaturation and of the disorganisation of sleep was seen in responders to UPPP. No predictive factor for the results of UPPP could be determined. This study shows that UPPP is an effective treatment in a large number of patients having SAOS at the price of minor and transitory complications.

A syndrome of REM and non-REM sleep reduction and lateral gaze paresis after medial tegmental pontine stroke. Computed tomographic scans and anatomical correlations in four patients.

A common pattern of reduction in both rapid eye movement and non-rapid eye movement sleep associated with various lateral gaze paralyses was present in four cases of brain-stem stroke. From computed tomographic scan data, clinical inferences, and, in two cases, neuropathologic sections, the common lesions were localized in the medial pontine tegmentum, ie, the inner part of the gigantocellular and pontis centralis caudalis nuclei. These data in humans were compared with lesions obtained experimentally in cats.

[Sleep abnormalities and evoked potentials (VEP-BAER-SEP) in progressive supranuclear palsy]. / Etude des anomalies du sommeil et des potentiels évoqués (PEV-PEAp-PES) dans la paralysie supranucléaire progressive (PSP).

Few physiological studies have been performed in PSP. We studied: sleep abnormalities in 36 h polygraphic recordings; changes of PEV after pattern-reversal stimulation, of BAER and of short latency SEP after stimulation of the median nerve. The population was for the 1st group: 18 patients with full typical symptomatology, for the 2nd group: 7 patients with likely diagnose of PSP and for the 3rd group: 10 normal subjects as control sample. All patients of the 1st group had sleep abnormalities: decrease of total sleep time; decrease of the percentage of REM sleep; morphological abnormalities (specially horizontal ocular square wave jerks). Detail is given of the repartition of such abnormalities in the two groups of patients. There is no correlation between sleep abnormalities and the natural history of the disease. The PEV and BAER, abnormalities were present in 50% of the cases. The PES were always normal. The help that can be provided by electrophysiological studies in the diagnose of PSP is discussed (particularly in group 2).

[Sleep and dreams in Korsakoff's amnesia due to alcoholism]. / Sommeil et rêves dans l'amnésie de Korsakoff d'origine alcoolique.

Sleep and dreams in 15 chronic alcoholic patients with amnesia were compared with sleep and dreams of 15 age- and sex-adjusted normal subjects. The patients were subjected to psychological tests in order to determine their I.Q. and their memory disturbances. All subjects had two nights of polygraphic recordings; the first tested the natural sleep organization. During the second night, they were awakened 7 min after the onset of each REM sleep episode, and, at least once, 20 min after the onset of a stage II episode, in order to record on a tape their dream reports according to a standardized protocol. The sleep patterns of the amnesic patients did not show any significant alteration. However, after wakening during the night, patients exhibited a higher tendency to return to REMS than controls. There was still some dream activity in those patients, although noticeably less frequently, and their dream activity had a very poor verbal expression. However, there was no change with respect to the spatio-temporal organization, sensorial perceptions, motor activity and verbalizations during their dreams.

[EEG spectral analysis in sylvian ischemia with normal value tracings]. / Analyse spectrale de l'EEG dans les ischémies sylviennes avec traces standard normales.

The EEG power spectral analysis of 8 patients with a definite sylvian ischemia, the standard EEG of which was normal, was determined in comparison with the date of a control group (N = 14). We calculated the right-left power spectral differences in 4 symmetrical bipolar leads for 5 rhythms (delta: 1.2-3.1 Hz, theta: 3.5-7 Hz, alpha: 7.4-12.3 Hz, beta 1: 12.9-14.1 Hz and beta 2: 15.2-17.2 Hz). For each patient, the spectral difference is measured in comparison with the normal range of the control group with an alpha risk of 5%. There are 54 asymmetries favouring the lesioned side (mostly in 5 patients) and 6 the opposite, without predominance of a particular rhythm with the exception of the beta 2 rhythm which presents no asymmetries.

Two distinct classifications of adult epilepsies: by time of seizures and by sensitivity of the interictal paroxysmal activities to sleep and waking.

Two hundred and thirty-six adult epileptic outpatients were classified twice: firstly according to the time of seizures reported by the patient or his family in diurnal, nocturnal, awaking and diffuse epilepsies (Es) and secondly according to the sensitivity to sleep or waking of the interictal paroxysmal activities (PA) observed during a polysomnographic night session with a sleep PA increase, with a waking PA increase, with PA indifferent to sleep and waking or with few or no PA. The stability of the sensitivity of the PA to sleep and waking was 84%. Patients with diurnal epilepsy have more frequently myoclonic attacks and a lower seizure frequency. Patients with a sleep PA increase have less frequently generalized motor seizures, more frequently partial complex seizures, a higher seizure frequency, higher total night PA density and more frequently the appearance of new PA during sleep. Patients with a waking PA increase had more frequently massive myoclonus, rarely the appearance of new PA during sleep and a high total night PA density. There is no significant relationship between the two classifications. Neither classification succeeds in discriminating the electro-clinical type of the epilepsies.

[Study of early somatosensory evoked potentials by stimulation of the median nerve at the wrist in 6 patients with unilateral thalamic lesions]. / Etude des PES précoces par stimulation du nerf médian au poignet chez 6 patients présentant des lésions thalamiques unilatérales.

Somatosensory evoked potentials were recorded at Erb's point, over the cervical spine (C7) and over the cortex: parietal and frontal electrodes were contralateral and ipsilateral to the stimulus which was applied on the median nerve at the wrist. The stimulation was performed on 2 control groups, the first consisting of 10 subjects (average age: 33.6 years), the second of 16 subjects (average age: 66.2 years) and on 6 patients presenting unilateral thalamic lesions. These lesions were circumscribed, ischaemic or haemorrhagic and were visualized by a scanner. In 5 of our patients, a diffusion of the P14 wave with normal latency and a delay in the N20 cortical wave was obtained at the parietal electrode contralateral to the stimulus and homolateral to the lesion. Normal latencies were observed for the diffusion of the N18 wave recorded at the frontal electrode contralateral to the stimulus. In the 6th patient, the evoked potentials were normal. The results of the somatosensory evoked potentials observed in our patients are discussed in the context of the anatomical lesions.

[Spinal and cortical SEP's in healthy subjects and paraplegics]. / PES médullaires et corticaux chez le sujet normal et paraplégique.

SEPs are evoked by electrical stimulation of tibial nerve in the fossa poplitea. Surface electrodes, located in S1, L4, L2, T12 with a reference in T6, can record lumbar evoked potentials and calculate a peripheral sensitive velocity. Bipolar leads between electrodes located in T12, T9, T6, T3 and C7 record medullary potential and calculate a medullary transit velocity. The cortical potential is monitored between C'z and a non-cephalic reference. 25 controls and 10 paraplegic patients are studied. In controls, sensitive peripheral velocity is 59 m/sec. The lumbar potential is composed of two negative waves, respectively due to the activation of sensitive roots and to the medullary potential. The medullary transit velocity, measured by the increase of the latency of the culmination of this negative wave along the spine, is 60 m/sec. The cortical potential is composed of two stable waves P30 N38 which are observed in every control; these waves are followed by a succession of positive and negative waves. In the 10 paraplegic patients, complete anesthesia observed in 5 cases is associated with an absence of cortical potential, and the hypoesthesia observed in 5 cases is associated with a cortical potential with a reduced amplitude (2 cases) or an increased latency (3 cases). In these last 3 cases, the medullary potential allows to specify the location of slowing of the transit velocity.

Electroencephalographic spectral power and lateralized motor activities.

The powers of the theta (3.5-7 Hz), alpha (7.4-12.3 Hz) and beta 1 (12.9-14.8 Hz) rhythms were analysed in symmetrical derivations. Sixteen right-handed young male adults were observed: at rest, with eyes closed (EC) (4 sequences) and eyes open (EO) (4 sequences); during right then left tonic alternate or sequential movements of the hand and while gazing to the right then to the left. At rest there exists a clear and significant spectral dominance to the right which does not appear in all the rhythms or in all the derivations. As far as the alpha rhythm EC is concerned, individual analysis of the sequences shows that of those which are significantly lateralized, three-quarters are lateralized towards the right. Right motor activity exaggerates, left motor activity diminishes, this right electrical dominance. Lateral gaze is the most powerful activity in this respect. At each derivation, comparison of intensities during right and left activities shows that the contralateral movements diminish the spectral power in the 3 bands studied. This effect seems to be obtained most frequently at the centro-parietal level. The spectral power at rest compared with that during motor activity is higher constantly for theta rhythm, in almost half the cases for the alpha and occasionally for the beta 1.