Visual neurophysiological dysfunction in infants exposed to hydroxychloroquine in utero.

AIM: Hydroxychloroquine therapy during pregnancy is thought to be safe for foetuses. Normal visual function has been showed on clinical grounds in infants exposed in utero to hydroxychloroquine, but there are few visual neurophysiological data. Our study was designed to assess retina and visual pathways using electroretinogram and visual evoked potentials in a series of infants born to mothers treated by hydroxychloroquine for connective tissue diseases. METHODS: Twenty-one infants (3-7 months of age) were consecutively examined between June 2002 and May 2007. Full-field electroretinogram was recorded by contact lens electrodes and visual evoked potentials were recorded by occipital surface electrodes using flash stimulation in mesopic condition. Analysis was focused on the amplitudes and latencies of the a- and b-waves of electroretinogram and the latency of the P(100) component of visual evoked potentials. RESULTS: Electroretinogram abnormalities were detected in six infants, associated with delayed visual evoked potentials in four of them. CONCLUSION: Early electroretinogram and visual evoked potentials testing evidenced neurophysiological visual disturbances in a subset of infants born to mothers treated by hydroxychloroquine. Systematic clinical and neurophysiological vision testing during childhood is needed to detect possible consequences of antenatal exposure to hydroxychloroquine.

Neurophysiological brainstem investigations in isolated Pierre Robin sequence.

Polysomnography, electromyography (EMG) of the face, tongue, and soft palate, blink reflexes (BRs), EMG during bottle-feeding, and brainstem auditory evoked responses (BAERs) were performed in 25 newborn babies with isolated Pierre Robin sequence (PRS) to aid in evaluation and management. Obstructive apneas were found in 23/24 patients (the 25th having undergone tracheotomy). Number and duration of central respiratory pauses were always normal, as well as electroencephalographic and clinical organization of sleep stages. EMG recruitment pattern in facial and lingual muscles, and BRs were normal in all cases. EMG recruitment pattern in muscles of the soft palate was normal in 14/25 patients, showed a reduced average amplitude with short-duration and low amplitude motor unit potentials in 10/25, and showed signs of denervation in 1/25. EMG during bottle-feeding showed sucking-swallowing disorders in 20/25 patients. BAERs showed a bilateral conductive impairment with increased latencies and thresholds in 5/19 patients, but with normal and symmetric I-III and I-V interpeak latencies in 19/19. These neurophysiological findings suggest that in isolated PRS a dysfunction of the lingual and pharyngeal motor organization exists without any structural impairment in brainstem nuclei and pathways.

Glial and endothelial cell response to a fetal transplant of purified neurons.

Astrocytes, microglia and endothelial cells display very specific phenotypic characteristics in the intact adult CNS, which appear quite versatile when grown in culture without neurons. Indirect evidence from in vitro co-culture studies and analysis of the effects of specific neuronal removal in vivo, does accordingly favour a role of neurons for the phenotypic repression of these cells in the intact brain. In order to provide more direct evidence for such neuronal influence, we attempted to induce, in the rat brain, a reversal of the post-lesional activation of astrocytes, microglia and endothelial cells by transplantation of fetal neurons purified by immunopanning. Host microglial cells which have been activated by the lesion process, penetrated the neuronal graft during the few days after the transplantation. Reactive astrocytes began to appear in the lesioned parenchyma and gathered around the transplant. Thereafter they first sent their processes in the direction of the neuronal graft, before they migrated into the graft a few days later. At this time, which was at the end of the first week post-transplantation, the host endothelial cells sprouted "streamers" of basal lamina within the graft forming small capillaries. During the second week post-transplantation, numerous astrocytes and microglial cells, both displaying a reactive hypertrophied morphology, were observed throughout the grafts. Finally, by the end of the first month, the activated cells differentiated towards a quiescent, resting morphology. At this time the grafts contained a vascular network with morphological characteristics comparable to those observed in the intact brain parenchyma. The results indicate that the interaction of activated astroglia and microglia and endothelial cells with neurons causes the cells to re-differentiate and regain phenotypic features characteristic of intact brain parenchyma, strongly suggesting that neurons play an essential role in the phenotypic restriction of glial and endothelial cells in the adult central nervous system.

Maturation of the electroretinogram in children: stability of the amplitude ratio a/b.

We report the method and results of mesopic electroretinogram (ERG) recording by corneal electrode in 75 children aged from 0 to 15 years. This method gives an overall evaluation of the electrical activity of the retina in a rapid and acceptable manner, in the awake state and without sedation. The a- and b-waves were present at birth. The amplitude of these waves increased considerably throughout the period studied. The decrease in latencies was statistically significant only for the b-wave between birth and 6 months. The presence of oscillatory potentials increased with age. The amplitude ratio a/b remained constant at about 0.25 in all age groups. This a/b ratio thus constitutes, under the recording conditions described, a criterion of normality that is independent of age.

Segmental myoclonus in a child with spinal cord tumour.

Segmental spinal myoclonus (SSM) involving a child's lower limb revealed the presence of a spinal cord tumour from T8 to T12. The clinical and electrophysiological features of SSM-during the child's development were studied. The presence of this disorder at two months of age did not disturb the development of walking, but did lead to orthopaedic complications. Four electromyographic recordings performed between 23 months and 7 years 10 months of age revealed the topographical extension of the SSM, its passage to rhythmicity, variable frequency and change in the sequence of activation of the muscles. These electroclinical features enable discussion of the pathophysiology of SSM by reference to neonatal motor automatisms and spinal generators.

Night-to-night variability of sleep respiratory pauses in normal infants.

Pneumograms have been recorded for several (6-14) consecutive nights in 11 normal children aged 1-257 days. They enabled to assess greater or equal to 5 seconds respiratory pauses. No statistical differences were found between the number of respiratory pauses per hour recorded during subsequent nights on each subject. Statistically significant (p less than 0.001) differences were found between the children either in the number of pauses or in their intervals. However, the experimental protocol does not allow to assess whether these discrepancies have a genetic, or maturational, or eventually an environmental origin.

Respiratory pauses and periodic breathing assessed by cardio-pneumography in normal infants and in SIDS siblings.

450 cardio-pneumograms (CPG) were performed on two successive nights in 68 controls and 235 SIDS siblings. The number of respiratory pauses greater than or equal to 5 sec and greater than or equal to 10 sec (NP) and the time of periodic breathing (PB) were calculated per 100 minutes of recording. Recordings were arranged into five age groups corresponding to the 1st, 2nd, 3rd, 4th and 5th-6th month of life. No significant differences in NP and PB were found when controls and SIDS siblings were compared separately within each age group, neither as a function of gestational age (less than 40 weeks GA vs greater than or equal to 40 weeks GA), nor as a function of the results of the 1st vs the 2nd night of recording. Nor was any significant difference in NP and PB found when comparing control vs sibling babies within each age group for the 1st or for the 2nd night of recording. In SIDS siblings, there was a significant decrease in the three variables studied between the 1st and the 2nd month of life. No significant decrease was found in controls. We conclude that SIDS siblings are not different from controls of the same age when respiratory variables are studied by CPG recordings.

Polysomnograms and cardiopneumograms in SIDS research.

Polysomnographic (PSG) and cardiopneumographic (CPG) recordings are commonly used in research on sudden infant death syndrome (SIDS). PSG and simultaneous CPG recordings were compared in order to clarify two practical problems: reliability of sleep state evaluation with CPG and comparability of the number of respiratory pauses evaluated by these two recording techniques. This comparison shows that: (1) evaluation of sleep states by CPG technique is only reliable for quiet sleep and (2) there was a significant difference in the number of pauses, the evaluation with PSG being systematically higher than with CPG. The abnormalities found or suspected in CPG home recordings must be confirmed by PSG in the laboratory.

Respiratory frequency during sleep in siblings of sudden infant death syndrome victims. A comparison with control, normal infants.

The present study was carried out on 76 polygraphic recordings performed on 38 siblings of sudden infant death syndrome victims and on 38 control (2 days to 18 weeks old) infants. Each sibling corresponded to a control infant according to gender, gestational age at birth and postnatal age criteria. We found that in siblings as in controls, respiratory frequency (RF) was higher in active sleep (AS) compared to quiet sleep (QS) state (P less than 0.05 for 11-18 week siblings, p less than 0.01 for the other groups). During the transitional sleep (TS), RF was on an intermediate level (AS greater than TS greater than QS). There were no significant differences between RF of siblings compared to controls, except that RF during QS in 6-10 week control infants was higher than in siblings of the same age (P less than 0.05). We found a wide variability between RF of different individuals within all the age groups of siblings and of controls (P less than 0.001). However, a high correlation was usually noted between RF found in different sleep states: some infants (siblings or controls) breathed more rapidly and others more slowly in all states studied. In siblings, as previously described in other groups of normal infants, RF seems to be an individual characteristic. In addition, the present work shows that according to RF criterion, healthy siblings are similar to normal infants.

Sleep apneas in normal neonates and infants during the first 3 months of life.

Sleep polygraphic recording was carried out on 52 normal full-term babies. 16 infants were recorded at 2 - 7 days of age, 14 at 2 to 5 weeks, 13 at 6 to 9 weeks and 9 at 10 - 13 weeks. Central apneas of 2 sec and over were analysed in Active Sleep (AS), Quiet Sleep (QS) and Transitional Sleep (TS). Apnea Index (AI, percent of non-breathing) and Number of Apneas (NA) per 100 min of sleep state (for 2 - 4 sec, greater than or equal to 5 sec, greater than or equal to 6 sec and greater than or equal to 10 sec apneas) were determined. Obstructive and mixed apneas were tabulated separately. % of Periodic Breathing (PB) was also determined. These results were statistically tested using different methods. AI and number of less than 5 sec apneas are higher in AS than in QS during the period studied. A decrease of AI and NA occurs before the end of the 2nd month both in AS and QS. During the first five weeks of postnatal life the AI, the NA and the % of PB are higher in infants born at 38 - 39 weeks of Gestational Age (GA) than in infants born at 40 - 42 weeks. A positive correlation between short apneas (less than 5 sec) and apneas greater than or equal to 5 sec was found in AS and in total sleep. Obstructive and mixed apneas were very infrequent. Apneas are not affected by recording technique, sex or sleeping position of infants. There is a great interindividual variability of NA, particularly during the first month of life. Little normative data has been published so far concerning the incidence of respiratory apneas during day sleep in full-term infants recorded by polygraphy.

Respiratory pauses in normal infants and in siblings of victims of the sudden infant death syndrome.

Sleep polygraphic recording was carried out on 57 normal infants and on 100 SIDS siblings during morning naps between birth and the 4th month of life. Total sleep time and duration of sleep stages were determined. Central apnoeas of 2 sec and longer duration were analysed in AS, QS and IS. Apnoea index and number of apnoeas per 100 min of sleep stage were determined. Obstructive and mixed apnoeas were tabulated separately. Percentage of periodic breathing was also determined. Control babies and SIDS siblings were compared on these parameters, using the Mann-Whitney test. Between the 6th and 13th weeks of life respiratory pauses were significantly more frequent in SIDS siblings than in control subjects. The difference disappeared after the 13th week. The roles that peripheral afferents and the circadian organization of respiratory pauses play in determining the results are discussed. This technique does not appear to permit estimation of the risk of subsequent apnoeic episodes.

[The value and reliability of auditory evoked potentials in the detection of deafness in early childhood (author's transl)]. / Intérêt et fiabilité des potentiels évoqués acoustiques dans la détection des surdités de la petite enfance.

The authors have carried out a study on 472 subjects using auditory evoked response techniques in the evaluation of hearing difficulties and deafness in the child. They were able to demonstrate excellent correlation between the technique used and the clinical data and its additional prognostic value. Furthermore because of its safety and its ability to assess high tones it can be recommended whenever a hearing deficit is suspected in the neonate or toddler.

[Maturation of somesthetic evoked potentials in man]. / La maturation des potentiels evoques somesthesiques (PES) chez l'homme

Somaesthetic evoked potentials (SEPs) have been recorded on the parietal scalp of 375 normal and awake children to brief electrical stimulation (0.5 msec) applied to the contralateral median nerve at the wrist. Each SEP was obtained by summation of the responses to 150 stimuli delivered at a frequency of 1/sec. The population studied has been divided in five age groups, each one corresponding to a recognizable stage of maturation of the responses.