Neuroscience Letters 611 (2016) 59–67

Contents lists available at ScienceDirect

Neuroscience Letters
journal homepage: www.elsevier.com/locate/neulet

Research paper

Longitudinal study of children with perinatal brain damage in whom
early neurohabilitation was applied: Preliminary report
Thalía Harmony ∗ , Jesús Barrera-Reséndiz, María Elena Juárez-Colín,
Cristina Carrillo-Prado, M. del Consuelo Pedraza-Aguilar, Aurora Asprón Ramírez,
Manuel Hinojosa-Rodríguez, Thalía Fernández, Josefina Ricardo-Garcell
Unidad de Investigación en Neurodesarrollo, Departamento de Neurobiología Conductual y Cognitiva, Instituto de Neurobiología, Universidad Nacional
Autónoma de México, Campus Juriquilla, Mexico

h i g h l i g h t s




It is a longitudinal study of perinatal brain damaged children.
Katona’s neurohabilitation procedure was used as treatment.
89% of preterm ≤34 weeks treated had normal neurodevelopment.
Only 20% of non-treated preterm ≤34 weeks had normal neurodevelopment.
Application of neurohabilitation to perinatal brain damaged infants is recommended.

a r t i c l e

i n f o

Article history:
Received 31 March 2015
Received in revised form
26 September 2015
Accepted 10 November 2015
Available online 17 November 2015
Keywords:
Perinatal brain damage
Prenatal risk factors
Neurohabilitation
Preterm encephalopathy
Hypoxic ischemic encephalopathy
MRI

a b s t r a c t
Objective: The neurohabilitation treatment has been shown to be a successful method for decreasing the
sequelae of perinatal brain damage (PBD) in Hungarian population. The goal of this pilot trial was to
introduce this procedure by describing the results of its application in infants with PBD as demonstrated
by clinical, developmental and MRI studies. As this procedure has proved to be useful, according the
declaration of Helsinki, no control clinical trial was permitted.
Participants: Infants younger than 2 months of corrected age (CA) with prenatal and/or perinatal risk factors for brain damage. Two groups were considered. One group was treated using the “neurohabilitation”
method (n = 20), and the other was not treated (n = 13) because treatment was voluntarily discontinued
after the initial evaluation. Evaluations were carried out prior to 2 months of CA and at 6–8 years of age.
All children showed abnormal clinical and MRI characteristics in the first study.
Results: The treated group had a higher percentage (90%) of children with normal outcome than did the
non-treated group (38%; OR = 2.37, CI 95% = 1.2–4.7; p < 0.005). In this latter group, only one out of five
(20%) children born at or before 34 weeks of gestational age had a normal outcome. In contrast, eight out
of nine treated preterm infants had normal outcomes (8/9 = 89%, OR = 4.45, CI 95% = 0.7–26; p = 0.017).
Conclusions: This pilot trial confirms previous studies suggesting that Neurohabilitation decreases the
neurological and cognitive sequelae of preterm and at-term infants with PBD.
© 2015 Elsevier Ireland Ltd. All rights reserved.

1. Introduction
Despite advances in medicine and significant improvements in
the survival of preterm infants over the last 10–20 years, the incidence of births at risk for brain damage has not diminished; in

∗ Corresponding author at: Instituto de Neurobiología, UNAM Campus Juriquilla,
Querétaro 76230, México. Tel.: +52 442 1926101x113.
E-mail address: thaliah@unam.mx (T. Harmony).
http://dx.doi.org/10.1016/j.neulet.2015.11.013
0304-3940/© 2015 Elsevier Ireland Ltd. All rights reserved.

fact, some evidence suggests that disability rates have increased
[1]. Data in the literature also showed that even preterm children
who survive without apparent motor disability, have a substantial
reduction in the mean intelligence quotient (IQ) and an increased
incidence of cognitive and educational difficulties [2–5].
A revision of the literature related to early interventions programs to study high risk premature infants has shown that when
applied to severe low weight preterm babies’ scores [6] or infants
with brain lesions [7] did not show any improvement on neurodevelopment. Neurodevelopmental treatment (NDT) is the method

Two groups of children were considered: the treated and the non-treated groups. persistence and stereotypy and can be divided in two groups: (1) complex chains of movements directed to verticalization of the body and (2) complex movements directed to locomotion [17. / Neuroscience Letters 611 (2016) 59–67 most frequently used for intervention in children with a developmental disorder [8].2. the reticular formation. it is against the Helsinki declaration to leave infants without the treatment in order to have a control trial. this is the first report describing the longitudinal results obtained in the application of neurohabilitation to infants with perinatal brain damage demonstrated by magnetic resonance images (MRI) as well as by clinical and psychological evaluations. These results were obtained in Hungary where this technique has been applied for more than 30 years. Vojta’s procedure showed to normalize more infants than NDT method [14].18. These motor patterns are characterized by a high degree of organization. Katona’s assessment is performed with some of the maneuvers used in the therapy itself. Patients and methods The Ethics Committee of the Instituto de Neurobiología of the Universidad Nacional Autónoma de México approved this study. at 18 months of corrected age (CA). NDT is generally applied later in life. when there are symptoms and signs of brain injury. 32% improved relative to their initial symptoms. These evaluations were repeated according to a time schedule only in the treated group. attention. Vojta methods for the early treatment of cerebral palsy. Harmony et al. The results obtained in Hungary led us to evaluate this procedure in our group of patients in Mexico. the early diagnosis and treatment of brain damage in newborns at risk may also decrease these sequelae. where it has to take into account several evaluation parameters such as: muscle tone (passive and active).25]. (b) Bayley scales [21] (c) Magnetic resonance imaging (MRI) using 1. These early integrated complex movements are chains of processes in which the neck. the following evaluations were performed: (a) neuropediatric examination. during the first 3–4 months after birth. At the . among others). Then. cardiovascular pathology. These risk factors are described in Tables 1 and 2 for each patient. cerebellum. 20 were pseudo-randomly selected [19] from those who had followed the treatment and all the evaluations and who were similar to the non-treated group in terms of age. the effectiveness of the NDT approach and other pediatric therapies is currently an issue generating considerable professional debate [9]. eye tracking and auditory monitoring. hemi bodies symmetry along the maneuver performance. weight at birth. to try to reduce or abolish the neurological sequelae that may result from perinatal brain damage. These 20 children formed the treated group. and each 6 months after 3 years old. In this group the clinical observations were only done before 2 months of corrected age (CA) and at 6-8 years old.16]. MRIs were obtained each year if there was some abnormal finding. gender. In the fourth year WIPPSI scales were used and applied each 6 months and later on. If in the first 3 examinations the child showed normal results. After the fourth year. To our knowledge. from a pool of 1138 treated children from our data base. scissor gait. then her/his outcome was considered “normal”. Nearly all these tracts project to the motor cortex [27]. Bayley’s evaluations and MRIs were done each 4 months during the first year and each 6 months during the second and third year. and (d) Katona’s evaluations [17.3. At these ages MRI was performed using a 3. The same happened with Vojta’s method. Katona based the neurohabilitation procedure on the “elementary neuromotor patterns”. When the children reached 6–8 years of age. each 3 months during the second year. basal ganglia [26]. 2. This Unit currently has a data base with 1138 subjects from 0 to 8 years old. therefore as a rehabilitation procedure. These movements are controlled by the developing subcortical structures and can be activated by determined positions of the head and the body that triggers the activation of the vestibular nuclei and their projections to the spinal cord. 2. 2. The main difference between the two is that neurohabilitatory treatment should begin before the lesion sequelae have been established. or a borderline IQ.60 T. (c) clinical language evaluations [24]. After the infants were discharged from the hospital where they were born. WISC was applied each year. Neuropediatric evaluations were done each month during the first year. irritability. trunk and extremities perform complex and continual movements in certain repetitive patterns. and (d) MRI evaluations. Patients Inclusion criteria: infants during the first 2 months of corrected age (CA) with prenatal and/or perinatal history of risk factors for brain damage.18.0 T Philips equipment. [25]. we looked for children between 6 and 8 years old that voluntarily discontinued the treatment after one month. and they did not have any type of treatment. Katona’s procedure (see Ref. thalamus. as proposed by Ferenc Katona [15–18] to differentiate this process from rehabilitation. brain malformations and/or chromosomal aberrations. it is not well known in other countries. axial hyperextension. and as cognitive sequelae when the clinical psychological evaluation and/or IQ values were abnormal and/or language delays were observed. They comprised the non-treated group. None of five studies that evaluated NDT effects demonstrated a statistically significant effect of intervention in motor development [9–13]. however. On the other hand. and 22% had no change or their symptoms had become worse [15. Although decreasing the number of births at risk for brain damage should be the priority to decrease the neurological and cognitive sequelae. We used these criteria for ethical reasons. risk factors and diagnosis. If it had been shown that the neurohabilitation procedure is useful to improve development even in the case of infants with severe brain lesions [15–18]. presence of genetic factors associated with brain damage. strabismus.0 T GE scanner. (b) clinical psychological evaluations and performance in the WISC-IV test [23]. In a report comparing NDT vs. Exclusion criteria were: infants older than 2 months of CA. 2. The abnormal outcomes were classified as neurological when the last neuropediatric examination showed abnormal findings. Informed written parental consent for participation in this study was obtained for all subjects. The results of the application of this therapy to 2189 infants of less than 6 months old with suspected perinatal brain damage showed. To build a non-treated group who did not undergo treatment but who had initiated the protocol with all the indicated studies. This is the goal of the therapy known as “neurohabilitation”.22]. Apgar. neurological signs of alarm (thumb in fist. their parents were invited to participate in a special project of the Unit for Neurodevelopmental Research at the National Autonomous University of Mexico in Querétaro.1. The parents of 13 children agreed to return to the unit for re-evaluation. that 46% had a normal outcome. Evaluations The initial evaluations were performed in the two groups and they included: (a) Clinical pediatric and neuropediatric examinations [20]. which also complies with the Ethical Principles for Medical Research Involving Human Subjects established by the Helsinki Declaration. data in brief) Katona’s methodology is both diagnostic and therapeutic.

twin I. 8/9 7.9 ↑LV ↑↑Subarachnoid space ↑↑LV C7 35/M 2830 gr. average ↑LV ↑↑Subarachnoid space C6 Right central VII palsy. Diffuse leukomalacia ↓↓Corpus callosum ↓↓Corpus callosum C13 39/M 5. low average Cerebral palsy: Right hemiparesia. anemia Hypotonia/hypoxic ischemic encephalopathy Sarnat 2 Hypotonia Preterm encephalopathy Diffuse leukomalacia ↓Corpus callosum Normal C11 40/F 2850 gr. 9/9 5. IQ = 80. IQ = 82. 8/9 5. 61 . IQ = 78.6 Vagina and cervix infections Normal. hyperbilirubinemia Preterm Pre-eclampsia Lung hemorrhage Acute fetal distress Preterm hyperbilirubinemia Generalized hypotonia/hypoxic ischemic encephalopathy Sarnat 2 Hypotonia/Hypoxic ischemic Encephalopathy Sarnat 2 Mixed hypotonia and hypertonia/preterm encephalopathy Normal. 5/6 5.5 Generalized hypotonia/preterm encephalopathy Generalized hypertonia. IQ = 86 low average ↑LV 34/F Generalized hypotonia/preterm encephalopathy Generalized hypotonia/preterm encephalopathy ↑↑Subarachnoid space. Right central VII palsy/ Preterm encephalopathy Severe incoordination problems. probable leukomalacia.3 Oligohydramnios hypoxia ↑↑Subarachnoid space. enterocolitis Preterm. 8/9 9 Seizures. 8/9 6. 8/9 6.46 764/1. icterus.69 4. 9/9 5. hyperbilirubinemia.8 2100 gr. 7/9 4.3 Preterm. ↑Right LV C8 36/M 2260 gr. generalized hypertonic. Adiadochokinesis.1 Chickenpox during pregnancy (3rd Trimester) ↓↓Corpus callosum ↑↑Subarachnoid space Normal X= SD= 35. IQ = 81. learning problems. 9/9 9 Seizures Hypocalcemia C10 29/F 1200 gr. IQ = 79. probable leukomalacia ↓Corpus callosum ↑Left LV Occipital leukomalacia Normal C12 40/F 2375 gr. 7/8 5 Bradycardia Normal development.Table 1 Group without therapy. 8/9 2361/7. Cerebral palsy epilepsy. GA weeks/gender Weight at birth Apgar Age in years in last exam Risk factors Initial clinical findings/diagnosis Outcome final clinical findings WISC total IQ First MRI Final MRI C1 34/F 2100 gr. borderline ↑LV T. IQ = superior Normal.71 Generalized hypertonia Hypoxic ischemic Encephalopathy Sarnat 2 Generalized hypotonia/ hypoxic ischemic Encephalopathy Sarnat 3 Generalized hypertonia Severe neurodevelopmental delay. low average ↑↑Subarachnoid space ↑ LV C5 27/M 1000 gr. attention deficits. / Neuroscience Letters 611 (2016) 59–67 Id. borderline Diffuse white matter damage. IQ = 54. respiratory distress. respiratory distress. IQ = 93. Moderate coordination and fine motor problems Diffuse white matter damage. low average Right frontal and cerebellar arachnoid cysts C9 39/F 3000 gr.8 ↑↑LV2 ↑Frontal SAS ↑↑Subarachnoid space ↑LV C3 38/M 3600 gr. pneumonia. ↑LV C2 Preterm twin II Premature rupture of membranes Preterm twin I Premature rupture of membranes Generalized hypotonia/ Preterm encephalopathy Normal. sepsis. sepsis. IQ = 77. diffuse white matter damage Normal C4 39/F 3280 gr. Dyscalculia. Harmony et al. IQ severe mental retardation Normal. borderline Hearing loss.3 Preterm hyaline membranes. IQ = 121 Superior Moderate coordination problems.13 2375 gr. 7/8 6.4 ↑↑LV 34/M 1725 gr.

6 E16 27/M 800 gr. Harmony et al. IQ = 100. IQ = 75. twin II.6 Eclampsia E7 39/F 3950 gr. 9/9 6. twin I. 7/8 E11 39/F 6 E12 35/M 3800 gr. 5/7 9. sepsis. low average ↓↓Corpus callosum Normal Diffuse leukomalacia Normal ↑Left LV ↑LV Generalized hypotonia/preterm encephalopathy Normal IQ = 86. 6/8 5. 8/9 5. maternal urinary infections Preterm premature rupture of membranes. respiratory distress Pre-eclampsia. ↑Subarachnoid space ↑Left LV Normal IQ = 107. attention deficits. borderline Normal IQ = 87. IQ = 40 very low Normal IQ = 82. sepsis E8 36/M 1680 gr. high average Leucoencephalopathy Normal Normal IQ = 88. pre-eclampsia. 8/8 2000 gr. pre-eclampsia.16 1094/8. 5.42 5 5 6. ↑LV Diffuse leukomalacia Normal E3 Generalized hypotonia/preterm encephalopathy Generalized hypotonia/hypoxic-ischemic encephalopathy Sarnat 2 Generalized hypotonia Normal 37/M Preterm. in utero growth restriction Preterm. perinatal asphyxia. RH incompatibility Generalized hypertonia 4 Perinatal asphyxia Generalized hypertonia 1750 gr. acute fetal distress. resuscitation Seizures. icterus.6 Seizures. sepsis. average Delay language development. 5/8 4. low average ↓↓Corpus Callosum ↑Subarachnoid space ↑↑LV Cerebral atrophy Normal Normal IQ = 72. average Normal IQ = 79. apnea Preterm. / Neuroscience Letters 611 (2016) 59–67 35 X= SD= 3. 8/9 2362/7.2 Hypoglycemia.9 5. GA weeks/gender Weight Apgar Age in years in last evaluation Risk factors Initial clinical findings/diagnosis Outcome final clinical findings/total IQ First MRI Final MRI E1 33/F 5. apnea Leucoencephalopathy E2 1950 gr. sepsis Preterm. pre-eclampsia. sepsis Preterm pre-eclampsia.11 Normal. low average Normal IQ = 84.9 . hyperbilirubinemia. sepsis E14 30/F E15 32/F 1400 gr. hyperbilirubinemia. 7/8 E19 32/M E20 33/M 6. 3/7 E13 40/F Preterm pre-eclampsia.98 5. average Leukomalacia Normal Preterm.62 Table 2 Treated group. average Normal. 8/8 6 E9 30/M 6. average Leukomalacia Normal Leukomalacia.11 E4 34/M E5 30/F 2250 gr.8 E17 39/F E18 40/M 2475 gr.2 E10 36/M 1680 gr. 9/10 3775 gr. Periventricular hemorrhage. borderline ↑↑LV ↑Subarachnoid space ↓↓Corpus callosum Atrophy of the parietal cortex Cyst in left cerebellopontine angle Normal IQ = 90. 9/9 E6 39/M 3750 gr. low average Leukoencephalopathy Occipital white matter hyperintensity. 9/9 3100 gr. low average↑ ↑Subarachnoid space Normal Hypoxic-ischemic encephalopathy Sarnat 2 Generalized hypotonia/preterm encephalopathy Normal IQ = 77. respiratory distress 4700 gr. 8/9 1350 gr. Leukomalacia IQ = 70. apnea Condylomatosis. low average Normal IQ = 82. respiratory distress. low average ↑↑Subarachnoid space Normal Normal IQ = 116. 6/9 1250 gr. borderline 39/M 5.4 Preterm. sepsis Mixed hypertonia and hypotonia/preterm encephalopathy Hypertensive encephalopathy 6 Icterus. ↑LV Normal ↑↑LV Normal IQ = 81. twin II. icterus. low average Normal IQ = 87. borderline ↑Subarachnoid space ↓↓Corpus callosum ↑↑LV T. maternal urinary infections Preterm.4 Generalized hypotonia/preterm encephalopathy Generalized hypotonia/preterm encephalopathy Generalized hypotonia/hypoxic-ischemic encephalopathy Sarnat 2 Generalized hypotonia/hypoxic-ischemic encephalopathy Sarnat 2 Hypertonia Hyperbilirubinemic encephalopathy Generalized hypotonia/preterm encephalopathy Generalized hypotonia/preterm encephalopathy Normal IQ = 113. ↓Corpus callosum Leucoencephalopathy Normal Left temporal arachnoidal cyst. acute fetal distress Preterm Leucoencephalopathy. 8/9 1800 gr. 8/9 1550 gr. 5/7 4. pre-eclampsia. borderline Normal IQ = 94.2 Generalized hypotonia/preterm encephalopathy 2240 gr.3 Preterm. Id. acute fetal distress Generalized hypotonia Mixed hypertonia and hypotonia/preterm encephalopathy Moderate language deficits.

[25].9. (3a) Lift trunk with back support. (1) Lift trunk with hand drive. OR = 4.522–11. CI 95% = 0. Effect size and 95% CI were calculated following Cummings [29] software.171 0. This constant feedback helps in the organization of motor control. p = 0. The therapy was intensive and specific for each infant. Therapy must be integrated to the infant’s schedule and divided into periods according to patterns of sleeping and wakefulness as well as feeding and nursing schedules. CI 95% = −0.483 Table 4B Outcome of the patients with >34 weeks of GA. which send afferent impulses. parents should go daily with the therapist in order to learn how to stimulate the infant under the supervision of the therapist.427–7. Parents learn how to correctly perform the exercises since they are going to treat the infant at home. (3) Lift the trunk with back and hip support. 1–5 show the different maneuvers described in Ref. 2. same time.68.07 to 0. effect size = 0.T. OR CI(95%) P 1. (1a) Double lift trunk with hand drive.955 0. Group Normal outcome Abnormal outcome Total Group Normal outcome Abnormal outcome Total Control ≤ 34 weeks Treated ≤ 34 weeks 1 8 4 1 5 9 Control > 34 weeks Treated > 34 weeks 4 10 4 1 8 11 OR = 4.251 0. Harmony et al. p = 0. During the first 3 months. (2) From lying to sitting. (5) Front protection to support thighs and chest.77 0. A therapeutic program consists of training of a series of neuromotor patterns each day for a certain time. The therapy consists in the elaboration of the individual program.1–22. Odds ratio (OR) and 95% confidence intervals (CI) were calculated for proportions.881 0. of 6–9 sensoromotor patterns such as lift trunk with hand drive [25]. The generation of these movements repeated several times produce brain engrams that improve motor development [28]. CI 95% = 0.4. effect size = 0. specialized therapists conducted the Katona evaluations to obtain a diagnosis and to program the exercises that parents should learn to apply to their infants at home during the first month of therapy. Main maneuvers for verticalization.017.45. Statistics Almost all comparisons between groups were performed using Chi-square statistics. The different positions to generate the specific neuromotor patterns are described in Refs. Each month.50 1. (6) Lateral and anterior protections.436 0. Table 3 MRI Initial findings. At the initiation of the treatment. a session consists in the repetition. 4–8 times. Diagnosis Control Diffuse white matter damage Increased LV volumes Decreased CC volume Cerebral atrophy Treated N % N % 6 5 4 0 46 38 31 0 12 4 4 2 60 20 20 10 Table 4A Outcome of the patients with ≤34 weeks of GA. 1.4.45. As it is known that the outcome of preterm infants with equal or less GA than . (4) Sitting in the air. Figs.355–8. movements generate activation of different receptors. The Student’s t-test was used to compare WISC values between groups. One session has a duration of 45 min and sessions should be repeated 3 or 5 times daily.7–26. CI 95% = 0. / Neuroscience Letters 611 (2016) 59–67 63 Fig. the infant was examined evaluating not only motor performance but also visual and auditory attention and the ages at which the infant mastered various developmental milestones.1–0.7. [22] and [25].75 2.28.

Harmony et al.45. (14) Elementary creeping upward on a slide. In relation to the children with a gestational age (GA) ≤ 34 weeks.7–26.7. Fig. CI 95% = 1. 3. with higher percentage of normal outcomes in the treated than in the non-treated group (OR = 4. effect .2–4.37.5. the results were significantly different between groups.7. 2. CI 95% = 0. p < 0. (11) From kneeling to standing.64 T. Results Tables 1 and 2 describe the characteristics of the treated and non-treated groups. comparisons between treated and non-treated groups were also done separately for infants GA ≤ 34 and GA > 34 weeks. (8) Rolled over with head support. the treated group had a significantly higher percentage of children with normal neurodevelopment (18/20) compared to the non-treated group (5/13 = 38%. All children showed abnormal findings in the first clinical and MRI examinations. 3. (7) Rolling over on a blanket. (12) Elementary horizontal creeping. effect size = 0. Maneuvers to change posture.2–0. / Neuroscience Letters 611 (2016) 59–67 Fig. No significant differences between groups were observed in the initial findings and diagnosis. (15) Shifting support in knees (kneeling creeping). CI 95% = 0. (9) Half roll over. Odds ratio = 2. indicating brain damage (see Table 3). (13) Elementary creeping downward on slide. Maneuvers to creeping.005). 34 weeks (GA ≤ 34) is worst than the outcome of infants with GA greater than 34 weeks (GA > 34). In terms of outcomes. (10) Sitting to four points support.

6CI 95% = 0. p = 0. Maneuvers to crawling. although all the children of both groups had abnormal findings in the initial MRI evaluation. (23) Elementary walk.T. (17) Modified assisted crawling. (20) Crawling in an ascending plane. OR = 2. Interestingly. 4. This child was not taken into account when the mean values of the subtests or the total IQ were compared between groups. / Neuroscience Letters 611 (2016) 59–67 65 Fig. CI 95% = 0. Fig. 5. Total IQ values are shown in Tables 1 and 2.9.85. see Tables 4A and B).32. 6 shows the MRI of two patients. (19) Crawling leg support. 6). (16) Elementary assisted crawling.1–0. However. In the non-treated group there was one child with very severe mental retardation who was not able to perform the WISC test.017 . . in the last MRI study four of thirteen of the non-treated group (31%) and twelve of twenty in the treated group (12/20 = 60%) showed a normal MRI (see Fig. Harmony et al. (21) Crawling a downward slide. size = 0.07–0. (24) Elementary walk on upward slide. No significant differences between groups for the total or the IQ subtests were observed for all the infants and for those subgroups with GA ≤ 34 or GA > 34.75–5. Maneuvers to walking. effect size = 0.15). one of each group.05). no significant differences were observed between the groups in infants with >34 weeks of GA. p = 0. (22) Crawling on stairs. Fig. the difference between groups was not significant (p = 0. The children of both groups who finished the study with normal MRI scans also showed significant differences in outcome: two of four in the non-treated group (50%) and twelve of twelve in the treated group (12/12 = 100%.68CI 95% = 0. (18) Crawling with lateral support.

On the upper line. 6). Patient E-02. the drawbacks of this study should be discussed. in the last MRI study four of thirteen of the non-treated group (31%) and twelve of twenty in the treated group (60%. Thus. there is increased volume of subarachnoidal space. 166772 and 218556 from CONACyT. On the second line at 5.6 years old is normal. p = 0.05).66 T. 5. The repetition of the maneuvers used to generate the sensoromotor response facilitates the performance of normal movements. 4. As our results although preliminary. The finding in the present paper that eight out of nine treated preterm infants born before or at 34 weeks of GA had normal outcomes at school age. 6. These results may imply that the myelination of the corpus callosum and of the white matter surrounding the lateral ventricles not only improves with development but may improve even more with the treatment. Harmony et al.15) showed normal MRI (see Fig. whereas only one of the similar. produces a reorganization of the motor system. It is not a clinical control trial since previous studies have shown the efficacy of the procedure and therefore. Discussion It is well known that premature fetuses and neonates are at increased risk for brain injury compared to term infants. point to be very promising. at 2 months CA. the significant difference observed for the total number of infants in each group was mainly due to the infants with GA ≤ 34. and on the third line the tractographies of the corticospinal tracts (CST) and the corpus callosum (CC) are normal. The MRI at 2 weeks CA. Acknowledgements The authors want to acknowledge all members of the Unidad de Investigación en Neurodesarrollo for their participation in this work (in alphabetical order): Teresa Alvarez-Vázquez. In relation to our results although all the children of both groups had abnormal findings in the initial MRI evaluation. In a national study in Norway of the prevalence of sequelae according to GA [1]. of mental retardation 7. even in adults. the volumes of the LV are normal and the MRI is normal. lateral ventricles (LV) have an abnormal shape and increased volume. The improvement in neurodevelopment of the treated group may be explained by the plastic changes produced by the intensive treatment. For this reason the accompanying data in brief article describe the principal maneuvers used in Kalona’s neurohabilitation. MRIs of patients E-02 and E-15. However. Eduardo Arias-Kanemoto. is a very promising result that suggests the benefits of neurohabilitation in preterm infants. shows PVL and the LV with abnormal shapes. non-treated children did. Paulina Alvarez-García. and there are small periventricular hemorrhages. and the CST and the CC are normal. ethical considerations and the Helsinki Declaration prohibit a control sample with the same type of evaluations across time as those used for the treated group but without treatment. and even structural changes have been reported [30–33]. changing the representations of these movements in the brain. this difference was not significant. Conflicts of interest None. On the second line the MRI at 5. our results although preliminary. and of sensory disabilities 6. In the patients with GA greater than 34 weeks in the non-treated group.8%. The children of both groups who finished the study with normal MRI scans also showed significant differences in outcome: two of four in the non-treated group (50%) and twelve of twelve in the treated group (100%. Barragán-Campos.9 years old. Patient E-15. Conclusion Although there are clear limitations of this study. p = 0. . Funding source This project was partially supported by projects 122547. Gloria AvecillaRamírez. our findings support the results obtained in Hungary with the neurohabilitation procedure and increase our knowledge in relation to the neurological and cognitive sequelae of infants with perinatal brain damage demonstrated by MRI and clinical examinations. Héctor M. / Neuroscience Letters 611 (2016) 59–67 Fig. Therefore. from 1822 infants that were born before or at 34 weeks of GA. the incidence of cerebral palsy was 17%. Financial disclosure The authors have no financial relationships relevant to this article to disclose. Numerous references show that learning motor skills. four out of eight infants had a normal outcome while in the treated group ten out of eleven had a normal outcome. Héctor Belmont-Tamayo. point to be very promising. we propose that other groups apply this procedure early in life in those infants at risk for brain damage to increase our knowledge of this type of therapy. Finally.2%.

Rossi. New Jersey. Secord. [12] A. Harmony et al. Funct. Effect of early neurodevelopmental therapy in normal and at-risk survivors of neonatal intensive care. Lancet 14 (1985) 1327–1330.L.K. 78 (2009) 13–21. NY. A. 1988. [25] J. W. van der Velde. M. McCarton. M.D. 4th ed. New York. Stein. L. ˜ [23] D. Swanson. Barcelona: Masson S. Filippi. Challenge to Developmental Paradigms: Implications for Theory. ˜ 2005. M. M. [27] J. Semel. [21] N. Kirsch. T. Training-induced structural changes in the adult human brain. PA. WISC-IV.F. D. Evans.D. [26] V. Forgeard.T. Moster. 9 (1967) 373–390. 1st ed. [30] J. Vaughan (Eds. Brain Res. Cartwright.A. Brain Res. T. [8] K.J. Bobath. http://dx. Dev.H. Neurosurgery 70 (2012) 162–169. [24] E. Hallam. Brandt. Goodman. E. Norton. Volpe. 29 (10) (2009) 3019–3025. Paediatr.L.G. Claudia Jiménez-Sánchez. Neuropediatrics 12 (1981) 232–241.A. Scott. Poppeleb. PLoS One 5 (Apr 15(4)) (2010) e10198. D. 19 (2) (2014) 90–96.M. Anderson. Sara Elisa Ponce-Rodríguez. Results through age 5 years from the Infant Health and Development Program. Tyson. A. C.M. Erik Pasayé-Alcaraz. Comi.. 2005. [22] J.C. Ontogenesis of the Human Nervous System (in Hungarian).E.org/10. R. E. [33] K.N. Cooper. [32] M. Rothberg. 4th ed. 1st ed. Engl.M. 24 (1983) 299–314. Effect of an early intervention programme on low birthweight infants with cerebral injuries. Fetal and Neonatal Brain Injury. Alma Janeth Moreno-Aguirre. 1989. An orienting diagnostic system in neonatal and infantile neurology. 2006. Gregg.. México. New York. A. Prematurity and school readiness in a nationally representative sample of Australian children: does typically occurring preschool moderate the relationship? Early Hum. W. Susana Szava for the translation to Spanish from Hungarian of Katona’s book Ontogenesis of the human nervous system. M. in: P. Grune and Stratton. A randomized controlled trial of early physiotherapy for high-risk infants. F. M. [19] J. Clinical Evaluation of Language Fundamentals. Pedraza-Aguilar. Weindling.R. Doyon. et al. New York. Loren. NY. F. Katona. Cartwright. Erat.E. J.T. J. M. 90 (2) (2014) 73–79. T. Distributed neural networks for controlling human locomotion. Delia FigueroaNavarro. V.E. Taylor and Francis Group. [29] G. Silver.P. Dorothy Pless for the revision of the English version of the manuscript. C. [10] M. Schlaug. Winner. J. Claessens.). Stevenson. F. Med.H. New York. Harmony.L. [15] F. Draganski. Philip. Early Identification of Infants with Developmental Disabilities. Espana. Chen. Psychorp. M. / Neuroscience Letters 611 (2016) 59–67 Erika Cruz-Rivero. M. Philadelphia. Lancet 14 (2(8468)) (1985) 1327–1330. Contrasting connectivity of the ventralis intermedius and ventralis oralis posterior nuclei of the motor thalamus demonstrated by probabilistic tractography. T. Bobath. Random Number Generation and Monte Carlo Methods. 85 (1996) 1107–1111.E. Johanna Flores-Arizmendi. NY. Bull. Pagani. 192 (2008) 137–142. Understanding the new statistics.L. Arman. T.I. Cooper. B. pp. Martínez-Matehuala.T. [28] Y. Assessments and Treatment..doi. and Dr. [2] I. J. 2010. Kenka.Z. M.A. Benitz.M. Bernbaum. Ediciones UNAM. in: P. Confidence Intervals. Ertl-Wagner.L. Neurology of the Newborn. Curr.A. Wing. Medicina Konyvkiadó Rt.pone. NY. D. Clinical neurodevelopmental diagnosis and treatment. Early physical therapy effects on the high-risk infant: a randomized controlled trial.doi. [6] J. Hyam. G. Green. Brooks-Gunn.. Motor learning in healthy humans is associated to gray matter changes: a tensor-based morphometry study. Lawrence Erlbaum Hillsdale. Wechsler. 2003. Saunders Elsevier.C. Dr. Bayley. Med. Ivanenkoa. JAMA 26272 (16) (1994) 1257–1262. A. Review. Fetal Neonatal Med. (Bayley-III). Hernández-Corona.E. [11] A. Kunos. UK. Vietze. N. 167–186. Cambridge University Press. Lacquanitia. Ramsay.org/10. Barrera-Reséndiz. Kringelbach. M. Tonatzin Pineda-Martínez. Neurosci. McCormick. van der Velde. Philadelphia. Msall. P. Stefanelli. Bayley Scales of Infant and Toddler Development. Early physiotherapy ad modum Vojta or Bobath in infants with suspected neuromotor disturbance. R. 121–144. Bennett. Lie.C. Keeser. Hergenroeder. Neurobiol. Jacklin. Data in brief Submitted 2015. Goodman. P.C. D. and Meta-Analysis. pp. Piper. Ohgi. Juan José Ortiz-Reséndiz. Pediatrics 78 (1986) 216–224.1007/s00429-014-0971-x. R. Hintz. E. Rosenbloom. Semin. References [1] D.. Antonio Fernández-Bouzas †. J. Mazer. Juárez-Colín. Neurología perinatal. D. T. Dieterich. Effect of early neurodevelopmental therapy in normal and at-risk survivors of neonatal intensive care. Lerch. B.E. Reorganization and plasticity in the adult brain during learning of motor skills. Pediatrics 88 (1991) 547–552. Amaya SoberónGarcía and Angeles Zavala. K.G.C. Hutton. Zelazo. Katona. Structural and functional connectivity mapping of the vestibular circuitry from human brainstem to cortex. Terapia Neurohabilitatoria.J. Routledge. Budapest. Barrera-Reséndiz. H. Rosa M.. J. 2009. Musical training shapes structural brain development. http:// dx. Escala de Inteligencia de Wechsler para ninos—IV. Jenkinson. B. Long-term medical and social consequences of preterm birth. 15 (2005) 161–167. P. [4] J. Psychorp. Opin. Benali. A. Brain Struct. Authors also acknowledge the anonymous reviewer for his/her suggestions..D. N. [13] M. Barr (Eds. M. Gatti. A. Casey. [5] P. in: Effect Sizes. . Oxford. P.D. [31] B. Description of the principal maneuvers of Katona’s neurohabilitatory treatment as an early intervention program for perinatal brain damage infants. Child Health 40 (2004) 689–695. J.A. Verónica Guidobono-Radesca. Madrid.M. M.L. Acta Paediatr. L. Lessons from normal and SCI subjects. A.E. 2009. 67 [14] M.0010198. P. [18] F. Six-year follow-up of early physiotherapy intervention in very low birth weight infants. Developmental clinical neurology and neurohabilitation in the secondary prevention of pre and perinatal injuries of the brain. [7] F. Cummings. 2001. Druzin. J. Aziz. G. Dev. Carrillo-Prado. T. Amiel-Tison. J. J.L.A. A. The very early treatment of cerebral palsy.R. 2001.1371/journal. [17] F. A.C.J. Willis.M. 3rd ed. D’Avignon.G.). Hyde. Houston-McMillan. Acta Paediatr. M. S. [9] J. J. R. H. Falini. Berta González-Frankenberger †. (2015). [3] J. C. 2012. H.E. Springer. Bauer. Katona.R. Rothberg. Neuropsychological outcomes of children born very preterm. N. May.A. Hung.A. 5th ed. Gentle. Eneida Porras-Kattz. Akiyama. Behav. [16] F. Sunshine. Early intervention in low-birth-weight premature infants. Ceccarelli. Child Neurol. L. Rocca. [20] C. Owen. Katona. Markestad. 359 (2008) 262–273. S.