Chronic inhibition of NOS does not prevent plasticity of rat somatosensory (S1) cortex following deafferentation

Nitric oxide (NO) has been proposed as an intercellular messenger mediating postsynaptic to presynaptic information transfer in the induction of long-term potentiation. A number of studies support the possible involvement of NO in synaptic plasticity. NO may have a role in synaptogenesis and synaptic plasticity in developing rat brain and may play a fundamental part in the process of regeneration, plasticity, and retargeting of axons following injury. We examined the possible role of NO on plasticity in the rat first somatosensory cortex with [¹⁴C]2-deoxyglucose (2-DG) autoradiography in rats treated daily with -nitroarginine ( -NA) following neonatal unilateral vibrissae deafferentation. After 6 weeks of -NA treatment, the local cerebral glucose utilization (LCGU) and the spatial extent of the metabolic activation following stimulation of the spared whisker was measured. NOS catalytic activity exhibited significant inhibition throughout the treatment period. Vibrissae deafferentation produced a small but not statistically significant increase of LCGU in the vibrissa activated C3 barrel, and -NA treatment did not alter the activation of LCGU in the deafferented cortex following whisker stimulation. Additionally, -NA treatment did not alter the area of metabolic activation on either the non-deafferented side or the deafferented side. Deafferentation produced a 298% increase in the metabolic representation of the spared C3 barrel following stimulation in the saline treated animals, a 257% increase in the chronically -NA treated animals, and a 256% increase in the short-term treated animals, all with respect to the response in the non-deafferented cortex. Metabolic plasticity in the barrel cortex was not attenuated by -NA treatment. These results show that nitric oxide does not play a major role on developmental cortical plasticity induced by vibrissae deafferentation in the rat.     

Predictors for the benefit of selective dorsal rhizotomy

Selective dorsal rhizotomy (SDR) is a spasticity reducing treatment option for children with spastic cerebral palsy. Selection criteria for this procedure are inconclusive to date. Clinical relevance of the achieved functional improvements and side effects like the negative impact on muscle strength are discussed controversially. In this prospective cohort study one and two year results of 54 children with a mean age of 6.9 (±2.9) years at the time of SDR are analyzed with regard to gross motor function and factors affecting the functional benefit. Only ambulatory children who were able to perform a gross motor function measure test (GMFM-88) were included in this study. Additionally, the modified Ashworth scale (MAS), a manual muscle strength test (MFT), and the body mass index (BMI) were evaluated as possible outcome predictors. MAS of hip adductors and hamstrings decreased significantly (p < 0.001) and stayed reduced after two years, while GMFM improved significantly from 79% to 84% 12 months after SDR (p < 0.001) and another 2% between 12 and 24 months (p = 0.002). Muscle strength did improve significantly concerning knee extension (p = 0.008) and ankle dorsiflexion (p = 0.006). The improvement of function correlated moderately with age at surgery and preoperative GMFM and weakly with the standard deviation score of the BMI, the dorsiflexor and plantarflexor strength preoperatively as well as with the reduction of spasticity of the hamstrings and the preoperative spasticity of the adductors and hamstrings. Correctly indicated SDR reduces spasticity and increases motor skills sustainably in children with spastic cerebral palsy corresponding to clinically relevant changes of GMFM without compromising muscular strength. Outcome correlates to GMFM and age rather than to MAS and maximal strength testing. The data of this evaluation suggest that children who benefit the most from SDR are between 4 and 7 years old and have a preoperative GMFM between 65% and 85%.     

Surgical treatment of spasticity in children: comparison of selective dorsal rhizotomy and intrathecal baclofen pump implantation

Introduction Neurosurgical treatments for spasticity in children include the traditional selective dorsal rhizotomy (SDR) and intrathecal baclofen pumps (ITBPs), which have been widely used in the past decade as an attractive alternative. The purpose of the study was to examine and compare the outcomes of these two procedures in the treatment of children with severe spasticity. Materials and methods A consecutive series of 71 children who underwent SDR for treatment of spasticity was compared with a group of 71 children matched by age and preoperative score on the Gross Motor Function Classification System (GMFCS) who underwent ITBP placement. Change in GMFCS score, lower-extremity tone (based on the Modified Ashworth–Bohannon Scale), and lower-extremity passive range of movement (PROM) at 1 year as well as the need for subsequent orthopedic procedures and parents’ satisfaction were selected as outcome measures. Results At 1 year, both SDR and ITBP decreased tone, increased PROM, and improved function. Both procedures resulted in a high degree of patient satisfaction. Compared with ITBP, SDR provided a larger magnitude of improvement in tone (−2.52 vs −1.23, p < 0.0001), PROM (−0.77 vs −0.39, p = 0.0138), and gross motor function (−0.66 vs −0.08, p < 0.0001). In addition, fewer patients in the SDR group required subsequent orthopedic procedures (19.1 vs 40.8%, p = 0.0106). Conclusions For children with moderate to severe spasticity, SDR and ITBP are both effective surgical treatments. Our results indicate SDR is more effective in reducing the degree of spasticity and improving function than ITBP is in this group of patients.     

Electrophysiologically guided versus non-electrophysiologically guided selective dorsal rhizotomy for spastic cerebral palsy: a comparison of outcomes

Background  The perceived need for electrophysiological guidance (EPG) during selective dorsal rhizotomy (SDR) has limited the frequency with which SDR is performed. The need for EPG during SDR has been questioned. At our institution, of >200 children with SDR for spastic cerebral palsy, 22 children underwent SDR without EPG using clinical guidance (no EPG group). Electrophysiological stimulation was used to distinguish dorsal from ventral roots. The remainder had SDR with EPG. The purpose of this study was to compare outcomes between the groups having SDR with and without EPG. Methods  The 22 patients in the no EPG group were matched with 22 controls in whom EPG was used, with respect to Gross Motor Function Classification System score (GMFCS) and age. The 12-month outcomes with respect to motor function score, hip adductor spasticity (Ashworth), hip abduction range of motion (ROM), quadriceps power [Medical Research Council (MRC)], WeeFIM, Quality of Upper Extremities Skills Test (QUEST), and incidence of complications were compared. Results  There were no statistically significant differences preoperatively with respect to GMFCS, age, gross motor function, Ashworth or MRC scores, joint ROM, WeeFIM, or QUEST. At 1 year after SDR, there were no differences between the groups in the incidence of complications or outcome measures. Percentage of dorsal roots cut was similar, but the duration of surgery was significantly shorter in the no EPG group. Conclusions  There was no advantage of doing SDR with EPG compared to no EPG. SDR can reasonably be done in centers where EPG is not available, but electrophysiological stimulation to distinguish dorsal from ventral roots may be useful in avoiding complications.     

辅加单侧脊神经S2后根选择性切断治疗脑瘫踝痉挛的疗效观察

目的评价脊神经S2后根选择性切断术治疗脑瘫踝痉挛疗效。方法25例痉挛性脑瘫患者均为双下肢受累,对踝痉挛较重的一侧下肢采用L2~S2SPR术,对另一侧踝痉挛相对较轻者采用L2~S1SPR术。术中将各后根分为3~5个小束,采用同心圆电极进行刺激,通过肉眼观察及肌电图记录显示肌肉收缩情况,将肌肉收缩范围明显异常的小束切断。踝痉挛情况按照Ashworth法进行评估,随访16.3±4.9个月,观察疗效并比较两侧肢体踝痉挛改善情况。结果S2后根的切断率为32%。病人术后踝痉挛均明显缓解,行走功能改善,无括约肌功能障碍。手术范围包括S2后根时,该侧踝痉挛改善更佳。结论对踝痉挛严重的脑瘫患者,采用选择性脊神经后根切断术治疗时,手术范围应包括S2后根。     

Predictors of poor outcome after selective dorsal rhizotomy in treatment of spastic cerebral palsy

Objectives The purpose of the study was to determine if there are preoperative clinical characteristics that might be predictive of a poor outcome after selective dorsal rhizotomy (SDR) surgery in children with spastic cerebral palsy (CP).Methods A retrospective analysis was performed on 174 children who had undergone SDR from 1983 to 2001. Patients were divided into two groups according to their outcome at approximately 1 year after surgery: acceptable or poor outcome. As predictors of outcome, the factors compared were age at operation, types of CP (diplegia, quadriplegia), history of prematurity, prior lower limb orthopedic surgeries, history of seizures, dystonic limbs, opisthotonic posturing, lumbar hyperlordosis, truncal hypotonia, preoperative ambulatory function, preoperative Gross Motor Function Classification System (GMFCS) scores, and presence of intellectual delay and speech delay.Results Eleven children (6.3%) had a poor outcome. The type of CP (P<0.001) and intellectual delay (P=0.015) were significant predictors of outcome in the univariate regression analysis, but only the type of CP retained significant predictive power in the multivariate analysis.Conclusion These data suggest that preoperative diagnosis is the strongest predictor of outcome after SDR. Intellectual delay demonstrated predictive power only in the univariate model, suggesting that it might have some prognostic value but less than the diagnosis.     

Selective posterior rhizotomy: experience of 30 cases

The increasing interest in selective posterior rhizotomy for reduction of spasticity in children with cerebral palsy and other neurological disorders comes from the selectivity that this procedure has achieved with intra-operative electromyographic monitoring. Thirty patients were operated on between April 1989 and October 1991. Spasticity was of cerebral origin in 27 cases and secondary to spinal cord lesion in 3 others. A reduction in the abnormally high muscle tone was observed in all cases, mainly in the lower extremities, but also, to a lesser degree, in the upper extremities. All patients showed functional improvements that depended on the individual preoperative condition.Even severely disabled patients with quadriplegia and intellectual impairment, whose spasticity interfered with their daily care, had a significantly improved quality of life after rhizotomy. These patients became much looser, with better swallowing and less drooling, and were much more easily managed by their caretakers. Preliminary results with follow-up from 1 to 30 months indicates that selective posterior rhizotomy is a safe procedure which contributes to significant functional improvement in spastic patients.The clinical aspect of this paper was presented at the XIII Congress of the European Society for Paediatric Neurosurgery, Berlin 1992, and the surgical aspect and results were presented at the XX Annual Meeting of the International Society for Pediatric Neurosurgery, Prague 1992     

Two cases of improvement of smooth pursuit eye movements after selective posterior rhizotomy

Objective  Selective posterior rhizotomy (SPR) represents a standard neurosurgical approach in the treatment of spasticity in children with cerebral palsy (CP). Beside the reduction of spasticity in lower limbs, SPR may have suprasegmental effects, considerably above the surgery site. In this communication, we report on the improvement of smooth pursuit eye movements (SPEM) in two children after SPR. Material and methods  Four children with CP underwent SPR. Eye movements were registered by infrared video-oculography before and after the surgery. Results  The analysis of SPEM showed the improvement of the correlation coefficient of the eye response to the stimulus after SPR in two subjects. Improvement of SPEM performance was largely due to suppression of spontaneous fixation nystagmus. Conclusion  SPR may lead to the improvement of SPEM in children with CP. The influence of SPEM improvement on quality of life in a group of severely disabled nonambulant children with CP remains to be assessed.     

Plasticity of the synaptic contact zone following loss of synapses in the cerebral cortex of aging humans

Quantitative ultrastructural analyses of ethanolic phosphotungstic acid-stained human layer 1 precentral mortor cortex (Brodmann's area 4) and layer 1 postcentral somatosensory cortex (Brodmann's area 3) were undertaken to determine the nature of synaptic changes occurring over a series of ages (45–84 years) of a normal aging human population. In the precentral cortex, a significant decrease in the number of synapses was accompanied by an increase in mean length of the postsynaptic contact zone and a decrease in the mean width of the presynaptic paramembranous density. The frequency of mature type A and immature type E synaptic profiles decreased with age. There were no changes in the width of the postsynaptic paramembranous density, cleft width or the number of presynaptic dense projections per synapse. In the postcentral cortex there were no significant changes in synaptic number or in any of the synaptic parameters measured. The present study demonstrates that age-related synapse loss in the human cerebral cortex may be confined to specific cortical regions. The data suggest that in the precentral cortex the plasticity of the synaptic contact zone may be a compensatory response by the remaining synapses to age-related synapse loss.     

脊神经部分切断联合肌腱延长治疗痉挛型脑瘫

目的探讨选择性脊神经后根部分切断术,同期联合肌腱延长术治疗下肢痉挛型脑瘫的方法和疗效。方法下肢痉挛型脑瘫患者23例,选择性脊神经后根部分切断,同期对伴有的下肢肌腱部分挛缩行肌腱延长术治疗。分别于手术前、术后6个月、12个月行神经功能评估。结果所有病例随访12～17个月,平均14个月。术后肌张力明显降低,痉挛及挛缩状态明显缓解,髋、膝、踝关节活动范围明显改善。术后经康复训练,运动能力改善效果明显,有效率81％,无明显手术并发症。结论选择性脊神经后根部分切断术同期联合肌腱延长术治疗下肢痉挛型脑瘫,可有效的改善痉挛状态,纠正肢体部分挛缩畸形,降低患者残障程度,提高患者的生活质量。     

Comparative assessment of therapeutic response to physiotherapy with or without botulinum toxin injection using diffusion tensor tractography and clinical scores in term diplegic cerebral palsy children

The present study was to compare the effects of combined therapy [botulinum (BTX) plus physiotherapy] with physiotherapy alone using diffusion tensor imaging (DTI) derived fractional anisotropy (FA) values of motor and sensory fiber bundles and clinical grade of the disability to see the value of BTX in term children with spastic diplegic cerebral palsy (CP). Clinically diagnosed 36 children participated in the study. All these children were born at term, and had no history of seizures. The study was randomly categorized into two groups: group I (n = 18) – physiotherapy alone and group II (n = 18) – physiotherapy plus BTX injection. Quantitative diffusion tensor tractography on all these children was performed on motor and sensory fiber bundles on baseline as well as after 6 months of therapy. Motor function and clinical grades were also measured by gross motor function measures (GMFM) scale on both occasions. We observed significant change in FA value in motor and sensory fiber bundle as well as in GMFM scores at 6 months compared to baseline study in both the groups. However, delta change and relative delta change in FA values of sensory and motor fiber bundle as well as GMFM score between group I and group II was statistically insignificant. We conclude that addition of BTX to physiotherapy regimen does not influence the outcome at 6 months with similar insult in children with term diplegic spastic CP. This information may influence management of diplegic CP especially in developing countries, where BTX is beyond the reach of these children.     

选择性颈段脊神经后根部分切断术治疗脑瘫性上肢痉挛状态(附17例报告)

目的探讨选择性颈段脊神经后根部分切断术治疗脑瘫性上肢痉挛状态的疗效。方法回顾性分析17例脑瘫性上肢痉挛病人的临床资料．均采用选择性颈段脊神经后根部分切断术。平均随访38、7个月。结果94．1％的病人术后即刻痉挛状态缓解．随访期间缓解率为88．2％：术后6周内运动功能改善率为52．9％．随访期间为76．5％：生活质量提高率在随访期间为82．4％。术后发生上肢感觉障碍20侧（58．8％），肌力下降13侧（38．2％），随访期间均见好转。随访期间复发2例（11．8％）。结论选择性颈段脊神经后根部分切断术是治疗脑瘫性上肢肌群广泛痉挛有效的手术方法。选择合适病例．熟悉局部解剖．掌握显微手术技巧和术后坚持长期正规康复训练等．是保证疗效的关键。     

Aberrant high-gamma oscillations in the somatosensory cortex of children with cerebral palsy: a meg study

Objective: Our study is to investigate somatosensory dysfunction in children with spastic cerebral palsy (CP) using magnetoencephalography (MEG) and synthetic aperture magnetometry (SAM). Methods: Six children with spastic CP and six age- and gender-matched typically developing children were studied using a 275-channel MEG system while their left and right index fingers were stimulated in random order. The latency and amplitude of somatosensory evoked magnetic fields were analyzed at sensor level. The patterns of high-gamma oscillations were investigated with SAM at source level. Results: In comparison to the children with typical development, the latency of the first response of somatosensory evoked magnetic fields (SEFs) in the children with spastic CP was significantly delayed (p < 0.05). High-gamma oscillations were identified in the somatosensory cortex in both children with CP and typical developing children. Interestingly, children with spastic CP had significantly higher incidence of ipsilateral activation in the somatosensory cortex following right and left finger stimulation, compared to typically developing children (p = 0.05). Conclusion: The results suggest that children with spastic CP have a measurable delay of SEFs and high-gamma oscillations. The high rates of ipsilateral cortical activation imply the impairments of functional lateralization in the developing brain. This is the first MEG study to demonstrate abnormal high-gamma oscillations of somatosensory cortices representing the finger in children with spastic CP.     

Mapping of secondary somatosensory cortex activation induced by vibrational stimulation: an fMRI study

Sensory functional MRI was performed in seven normal volunteers at 1. 5 T using a vibratory stimulus applied to the pad of the first finger of the left hand. The data was normalized to a standard atlas, and individual and group statistical parametric maps were computed. Robust bilateral activation was demonstrated in the secondary somatosensory cortex (SII), indicating a bilateral representation of SII in humans. Greater maxima and activation volumes were achieved in contralateral SII as compared to SI. Sensory fMRI can provide a sensitive assay for probing the nature and function of SII in vivo.     

Effect of observation of simple hand movement on brain activations in patients with unilateral cerebral palsy: an fMRI study

The aim of this functional magnetic resonance imaging (fMRI) study was to examine and compare brain activation in patients with unilateral cerebral palsy (CP) during observation of simple hand movement performed by the paretic and nonparetic hand. Nineteen patients with clinical unilateral CP (14 male, mean age 14 years, 7–21 years) participated in the study. Hand motor impairment was assessed using the sequential finger opposition task. Using fMRI block design, brain activation was examined following observation at rest of a simple opening-closing hand movement, performed by either the left or right hand of an actor. Eighteen fMRI dataset were analyzed. Observing hand movement produced large bilateral activations in temporo-parieto-fronto-occipital network, comprising most of the nodes of the well described action-observation network. For either side, observing hand movements recruits the primary motor cortex (M1), contralateral to the viewed hand, as would be expected in healthy persons. Viewing movement performed by an actor's hand representing the paretic side of patients activated more strongly ipsilesional M1 than viewing movement performed by an actor's hand representing the nonparetic side of patients. Observation of hand movement in patients with CP engaged the motor execution network regardless of the degree of motor impairment.     

The effect of video-guidance on passive movement in patients with cerebral palsy: fMRI study

In patients with cerebral palsy (CP), neuroimaging studies have demonstrated that passive movement and action–observation tasks have in common to share neuronal activation in all or part of areas involved in motor system. Action observation with simultaneous congruent passive movements may have additional effects in the recruitment of brain motor areas. The aim of this functional magnetic resonance imaging (fMRI) study was to examine brain activation in patients with unilateral CP during passive movement with and without simultaneous observation of simple hand movement. Eighteen patients with unilateral CP (fourteen male, mean age 14 years and 2 months) participated in the study. Using fMRI block design, brain activation following passive simple opening–closing hand movement of either the paretic or nonparetic hand with and without simultaneous observation of a similar movement performed by either the left or right hand of an actor was compared. Passive movement of the paretic hand performed simultaneously to the observation of congruent movement activated more “higher motor areas” including contralesional pre-supplementary motor area, superior frontal gyrus (extending to premotor cortex), and superior and inferior parietal regions than nonvideo-guided passive movement of the paretic hand. Passive movement of the paretic hand recruited more ipsilesional sensorimotor areas compared to passive movement of the nonparetic hand. Our study showed that the combination of observation of congruent hand movement simultaneously to passive movement of the paretic hand recruits more motor areas, giving neuronal substrate to propose video-guided passive movement of paretic hand in CP rehabilitation.     

肛门括约肌肌电图监测下双侧L2～S2选择性脊神经后根切断术治疗痉挛性脑瘫

目的为提高手术安全性,在L2～S2选择性脊神经后根切断(SPR)手术时,对肛门括约肌进行肌电图(EMG)监测,并评价其作用。方法在SPR手术监测中,当对S2后根小束进行电刺激时,采用针状电极记录双侧肛门括约肌的反应情况,有明显反应的后根小束予以保留。手术后随访患者踝痉挛改善情况和括约肌功能变化情况。结果所有患者手术后踝痉挛均有明显改善,无大小便功能障碍发生。结论SPR手术包括S2后根时,术中括约肌EMG监测对保证疗效,保护括约肌功能,提高手术安全,具有重要意义。     

Loss and spontaneous recovery of forelimb evoked potentials in both the adult rat cuneate nucleus and somatosensory cortex following contusive cervical spinal cord injury

Varying degrees of neurologic function spontaneously recovers in humans and animals during the days and months after spinal cord injury (SCI). For example, abolished upper limb somatosensory potentials (SSEPs) and cutaneous sensations can recover in persons post-contusive cervical SCI. To maximize recovery and the development/evaluation of repair strategies, a better understanding of the anatomical locations and physiological processes underlying spontaneous recovery after SCI is needed. As an initial step, the present study examined whether recovery of upper limb SSEPs after contusive cervical SCI was due to the integrity of some spared dorsal column primary afferents that terminate within the cuneate nucleus and not one of several alternate routes. C5-6 contusions were performed on male adult rats. Electrophysiological techniques were used in the same rat to determine forelimb evoked neuronal responses in both cortex (SSEPs) and the cuneate nucleus (terminal extracellular recordings). SSEPs were not evoked 2 days post-SCI but were found at 7 days and beyond, with an observed change in latencies between 7 and 14 days (suggestive of spared axon remyelination). Forelimb evoked activity in the cuneate nucleus at 15 but not 3 days post-injury occurred despite dorsal column damage throughout the cervical injury (as seen histologically). Neuroanatomical tracing (using 1% unconjugated cholera toxin B subunit) confirmed that upper limb primary afferent terminals remained within the cuneate nuclei. Taken together, these results indicate that neural transmission between dorsal column primary afferents and cuneate nuclei neurons is likely involved in the recovery of upper limb SSEPs after contusive cervical SCI.     

Mapping the effects of motor cortex stimulation on somatosensory relay neurons in the rat thalamus: Direct responses and afferent modulation

Single unit recordings were used to map the spatial distribution of motor (MI) cortical influences on thalamic somatosensory relay nuclei in the rat. A total of 215 microelectrode penetrations were made to record single neurons in tracks through the medial and lateral ventroposterior (VPM and VPL), ventrolateral (VL), reticular (nRt), and posterior (Po) thalamic nuclei. Single units were classified according to their: 1) location within the nuclei, 2) receptive fields, and 3) response to standardized microstimulation in deep layers of the forepaw-forelimb areas of MI cortex. For mapping purposes, only short latency (1-7 msec) excitatory neuronal responses to the MI cortex stimulation were considered. Percentages of recorded thalamic neurons responsive to the MI stimulation varied considerably across nuclei: VL: 42.6%, nRt: 23.0%, VPL: 15.7%, VPM: 9.3%, and Po: 3.9%. Within the VPL, most responsive neurons were found in "border" regions, i.e., areas adjacent to the VL, and (to a lesser extent) the nRt and Po thalamic nuclei. The same parameters of MI cortical stimulation were used in studies of corticofugal modulation of afferent transmission through the VPL thalamus. A condition-test (C-T) paradigm was implemented in which the cortical stimulation (C) was delivered at a range of time intervals before test (T) mechanical vibratory stimulation was applied to digit No. 4 of the contralateral forepaw. The time course of MI cortical effects was analyzed by measuring the averaged evoked unit responses of the thalamic neurons to the T stimuli, and plotting them as a function of C-T intervals from 5-50 msec. Of the 30 VPL neurons tested during MI stimulation, the average response to T stimulation was decreased a mean 43%, with the suppression peaking at about 30 msec after the C stimulus. This suppression was more pronounced in the VPL border areas (-52% in areas adjacent to VL and nRt) than in the VPL center (-25%).     

Different effects of anoxia and hind-limb immobilization on sensorimotor development and cell numbers in the somatosensory cortex in rats

Cerebral palsy (CP) is a group of movement and posture disorders attributed to insults in the developing brain. In rats, CP-like motor deficits can be induced by early hind-limb sensorimotor restriction (SR; from postnatal days P2 to P28), associated or otherwise with perinatal anoxia (PA; on P0 and P1). In this study, we address the question of whether PA, early SR or a combination of both produces alterations to sensorimotor development. Developmental milestones (surface righting, cliff aversion, stability on an inclined surface, proprioceptive placing, auditory startle, eye opening) were assessed daily from P3 to P14. Motor skills (horizontal ladder and beam walking) were evaluated weekly (from P31 to P52). In addition, on P52, the thickness of the somatosensory (S1) and cerebellar cortices, and corpus callosum were measured, and the neuronal and glial cell numbers in S1 were counted. SR (with or without PA) significantly delayed the stability on an inclined surface and hastened the appearance of the placing reflex and impaired motor skills. No significant differences were found in the thickness measurements between the groups. Quantitative histology of S1 showed that PA, either alone or associated with SR, increased the number of glial cells, while SR alone reduced neuronal cell numbers. Finally, the combination of PA and SR increased the size of neuronal somata. We conclude that SR impairs the achievement of developmental milestones and motor skills. Moreover, both SR and PA induce histological alterations in the S1 cortex, which may contribute to sensorimotor deficits.