-
[show abstract]
[hide abstract]
ABSTRACT: AIM: Unilateral perinatal brain injury may result in recruitment of ipsilateral projections originating in the unaffected hemisphere and development of unilateral spastic cerebral palsy (USCP). The aim of this study was to assess the predictive value of neonatal neuroimaging following perinatal brain injury for recruitment of ipsilateral corticospinal tracts. METHOD: Neonatal magnetic resonance imaging (MRI) and cranial ultrasound scans of 37 children (20 males, 17 females; median [range] gestational age 36 wks(+4) [26(+6) -42wks(+5) ] and birthweight 2312 g ([770-5230g]) with unilateral perinatal arterial ischaemic stroke (n=23) or periventricular haemorrhagic infarction (n=14) were reviewed and scored for involvement of the corticospinal trajectory. Hand function was assessed using the Assisting Hand Assessment (AHA) and transcranial magnetic stimulation (TMS) was performed (age range 7y 4mo-18y and 7mo) to determine the type of cortical motor organization (normal, mixed or ipsilateral). Neuroimaging scores were used to predict TMS patterns. RESULTS: Eighteen children developed USCP with ipsilateral corticospinal tract projections in 13 children (eight mixed, five ipsilateral). AHA scores decreased with increased ipsilateral projections. Asymmetry of the corticospinal tracts seen on neonatal MRI was predictive of development of USCP and recruitment of ipsilateral tracts (positive and negative predictive value of 73% and 91%). INTERPRETATION: Neonatal neuroimaging can predict recruitment of ipsilateral corticospinal tracts. Early knowledge of the expected pattern of cortical motor organization will allow early identification of children eligible for early therapy.
Developmental Medicine & Child Neurology 05/2013; · 2.92 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Patients with severe cerebral palsy (CP) often have poor speech ability but potentially better language comprehension. The arcuate fasciculus and the extreme capsule are two important language tracts between the Wernicke and Broca areas. Using diffusion tensor imaging, we visualized language tracts and pyramidal tracts in both hemispheres in 10 controls (5 to 18 years) and 5 patients (5 to 23 years) with severe CP. Language comprehension was assessed with a recently designed instrument (the Computer-Based instrument for Low motor Language Testing [C-BiLLT]). The language tracts were visualized in all control children and in four CP patients. In one CP patient without any objective language comprehension skills, no language tract could be visualized. Both language and pyramidal tracts were smaller in patients than in controls. These preliminary data indicate a relation between language tracts and language skills. Further research is necessary to study the value of structural integrity of language tracts in predicting language comprehension in CP patients.
Neuropediatrics 04/2013; · 0.94 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: AIM: The aim of this study was to evaluate the long-term effect of selective dorsal rhizotomy (SDR) on the gross motor function of ambulant children with spastic bilateral cerebral palsy (CP), compared with reference centiles. METHOD: The study used a prospective cohort design and participants comprised 29 children classified using the Gross Motor Function Classification System (GMFCS) in level I (n=7), II (n=4), or III (n=18; 18 males, 11 females; median age at time of surgery 6y 4mo; range 2y 10mo-12y 1mo), who were examined 5 years and 10 years after SDR. We used individual centiles based on Gross Motor Function Measure (GMFM-66) scores and age, corresponding to the GMFCS levels. Individual improvement or deterioration was defined as a change of more than 20 centiles. Side effects experienced and additional treatment received after SDR were also recorded. RESULTS: Five years after SDR, 10 out of 28 children showed improvement, and 10 years after SDR 6 out of 20 children had improved. Spinal side effects were noted in two children and hip subluxation in three. Additional treatments included subtalar arthrodesis (n=13), endorotational osteotomy of the tibia (n=5), and botulinum toxin treatment (n=13). INTERPRETATION: None of the children showed deterioration of gross motor function based on centile ranking. Five and 10 years after SDR, gross motor function in some children had improved more than would have been expected according to the reference centiles. This suggests, taking the limitations of this study into account, that the applied criteria for selection were adequate. However, the children still required additional treatment after SDR.
Developmental Medicine & Child Neurology 04/2013; · 2.92 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: OBJECTIVES:The amino acid glutamine has been shown to reduce the number of serious neonatal infections in very preterm children, which may benefit long-term brain development. The aims of the current follow-up study were to (1) determine the long-term effects of glutamine-enriched feeding in the first month after birth in very preterm children on measures of brain development at school age, and (2) elucidate a potential mediating role of serious neonatal infections.METHODS:Fifty-two very preterm children who originally took part in a randomized controlled trial on enteral glutamine supplementation between day 3 and 30 after birth participated at a mean (SD) age of 8.6 (0.3) years. Measures of brain development included volumetric outcomes of major brain structures, as well as fractional anisotropy (FA) values of major white matter tracts.RESULTS:Glutamine supplementation in the first month was associated with medium-sized increases in white matter (d = 0.54, P = .03), hippocampus (d = 0.47, P = .02), and brain stem (d = 0.54, P = .04) volumes at school age. Exploratory analyses using an uncorrected P value indicated higher FA values of the bilateral cingulum hippocampal tract in the glutamine group. All differences were either strongly associated (hippocampus volume, brain stem volume, and FA values of cingulum hippocampal tract) or completely mediated (white matter volume) by the lower number of serious neonatal infections in the glutamine group.CONCLUSIONS:Short-term glutamine supplementation after birth increases white matter, hippocampus, and brain stem volumes in very preterm children at school age, mediated by a decrease in serious neonatal infections.
PEDIATRICS 10/2012; · 4.47 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The aim of this article was to clarify the impact and consequences of very preterm birth (born <32wks of gestation) and/or very low birthweight ([VLBW], weighing <1500g) on brain volume development throughout childhood and adolescence.
The computerized databases PubMed, Web of Knowledge, and EMBASE were searched for studies that reported volumetric outcomes during childhood or adolescence using magnetic resonance imaging and included a term-born comparison group. Fifteen studies were identified, encompassing 818 very preterm/VLBW children and 450 term-born peers. Average reductions in the total brain volume, white matter volume, grey matter volume, and in the size of the cerebellum, hippocampus, and corpus callosum were investigated using meta-analytic methods.
Very preterm/VLBW children were found to have a significantly smaller total brain volume than the comparison group (d=-0.58; 95% confidence interval [CI] -0.43 to -0.73; p<0.001), smaller white matter volume (d=-0.53; CI -0.40 to -0.67; p<0.001), smaller grey matter volume (d=-0.62; CI -0.48 to -0.76; p<0.001), smaller cerebellum (d=-0.74; CI -0.56 to -0.92; p<0.001), smaller hippocampus (d=-0.47; CI -0.26 to -0.69; p<0.001), and smaller corpus callosum (d=-0.71; CI -0.34 to -1.07; p<0.001). Reductions have been associated with decreased general cognitive functioning, and no relations with age at assessment were found.
Very preterm/VLBW birth is associated with an overall reduction in brain volume, which becomes evident in equally sized reductions in white and grey matter volumes, as well as in volumes of diverse brain structures throughout childhood and adolescence.
Developmental Medicine & Child Neurology 01/2012; 54(4):313-23. · 2.92 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Intrathecal baclofen (ITB) treatment is frequently used for individuals with severe, but non-progressive, spasticity refractory to oral treatment. However, experiences with ITB in patients with progressive neurological disorders of childhood causing spasticity are limited.
To investigate whether ITB is an option in patients with progressive neurological disorders causing spasticity in childhood.
A systematic literature search in Embase, Pubmed and the Cochrane Library was performed.
We identified six eligible studies considering patients with progressive neurological disease in childhood and receiving ITB treatment. The studies included a total of seven paediatric patients and four adult patients. Improvement was reported in spasticity, spasms, pain, gait, activities of daily life and providing care. High satisfaction is described.
ITB has beneficial effects in paediatric patients with progressive neurological disease. However, the level of evidence is limited due to the small number of available studies and due to the poor quality of these studies.
European journal of paediatric neurology: EJPN: official journal of the European Paediatric Neurology Society 10/2011; 16(3):279-84. · 2.01 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To assess the long-term outcome and adverse events of selective dorsal rhizotomy (SDR) in children with spastic cerebral palsy (CP).
Studies were selected based on the following inclusion criteria: children with CP that underwent SDR with a follow-up period of at least 5 years. The following databases were searched: MEDLINE, Web of Science, Embase, PEDro, and the Cochrane library. Studies meeting the inclusion criteria were scored by two reviewers, who graded the level of evidence and the quality/conduct of the studies. Outcomes were classified according to the International Classification of Functioning, Disability and Health (ICF).
Only three of the 21 studies who met the inclusion criteria allowed a tentative conclusion on outcome. There is moderate evidence that SDR has a positive long-term influence on the ICF body structure and body function domains but there is no evidence that SDR has an influence on the ICF activity and participation domains. Spinal abnormalities seem to be common, but no conclusion can be drawn about their relation to SDR.
There is lack of evidence concerning the long-term outcomes after SDR. Future studies need to clarify the long-term influence of SDR - especially in the ICF domains of activity and participation.
Developmental Medicine & Child Neurology 06/2011; 53(6):490-8. · 2.92 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Treatment options for dystonic cerebral palsy (CP) are limited. Our aims were to determine whether intrathecal baclofen (ITB) improves daily care, decreases dystonia and decreases pain in patients with dystonic CP.
Patients received randomized blinded treatment with ITB or placebo. Scores on problems of daily care were recorded and dystonia, pain and comfort were assessed.
Four patients (three males, average age 12 years 6 months) were included (all Gross Motor Function Classification System level V). During the trial period problem scores and dystonia scores decreased in all four patients.
In this pilot study we report positive functional effects of ITB trial treatment in four patients with dystonic CP. A randomized trial with a larger cohort is needed to verify these results.
European journal of paediatric neurology: EJPN: official journal of the European Paediatric Neurology Society 05/2011; 15(6):539-43. · 2.01 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The primary aim of this prospective cohort study was to evaluate the short-term (1 year) and long-term (mean 6 years) effects of selective dorsal rhizotomy (SDR) on gross motor function and spasticity in ambulatory children with spastic diplegia. Secondary aims were to investigate side effects, additional treatment during follow-up (botulinum toxin type A injections or orthopedic surgery), and parental satisfaction.
Thirty-three children who had undergone SDR at a mean age of 6 years and 7 months (± 2 years) were included. There were 7 children at Gross Motor Function Classification System (GMFCS) Level I, 7 at Level II, and 19 at Level III. Gross motor function was assessed with the Gross Motor Function Measure-66 (GMFM-66). Spasticity was measured according to a modified Tardieu scale. Side effects, additional treatment, and parental satisfaction were recorded using a parental questionnaire and medical records.
At 1-year follow-up, mean GMFM-66 scores improved significantly by 4.3 ± 4.1 points. Children at GMFCS Levels I and II showed significantly more improvement (7.2 points) on the GMFM-66 compared with children at GMFCS Level III (2.9 points). On long-term follow-up (mean 6 years ± 22 months), mean GMFM-66 scores improved significantly by 6.5 ± 5.9 points, without a difference between children at GMFCS Levels I and II and Level III. No relapse of spasticity was noted. Ten children (30%) needed orthopedic surgery and 13 children (39%) received botulinum toxin type A treatment after SDR. Twenty (91%) of the 22 parents who answered the questionnaire at long-term follow-up believed that their child's functioning had improved after SDR.
Selective dorsal rhizotomy resulted in short- and long-term improvements in gross motor function, without relapse of spasticity. However, the majority of the children still needed additional surgery or botulinum toxin A treatment.
Journal of Neurosurgery Pediatrics 05/2011; 7(5):557-62. · 1.53 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Beare-Stevenson syndrome (BSS) is a rare autosomal-dominant condition characterized by cutis gyrata, craniosynostosis, acanthosis nigricans, anogenital anomalies, and a prominent umbilical stump. In 1996, two mutations in the fibroblast growth factor receptor 2 gene were found to cause this syndrome, thereby including BSS in the fibroblast growth factor receptor gene-related craniosynostosis spectrum. Until now, 12 patients with fibroblast growth factor receptor 2 gene-related BSS have been described. We report what is to our knowledge the first 2 Dutch patients with this syndrome, both caused by the mutation Tyr375Cys in the fibroblast growth factor receptor 2 gene. The patients exhibited a simplified gyral pattern, an abnormal posterior fossa, and an abnormal hippocampus on cranial magnetic resonance imaging. We discuss the clinical and radiologic findings in fibroblast growth factor receptor 2 gene-related BSS.
Pediatric Neurology 04/2011; 44(4):303-7. · 1.52 Impact Factor
-
Florieke J Berfelo,
Karina J Kersbergen,
C H Heleen van Ommen,
Paul Govaert,
H L M Irma van Straaten,
Bwee-Tien Poll-The,
Gerda van Wezel-Meijler, R Jeroen Vermeulen,
Floris Groenendaal,
Linda S de Vries,
Timo R de Haan
[show abstract]
[hide abstract]
ABSTRACT: Cerebral sinovenous thrombosis is a rare disease with severe neurological sequelae. The aim of this retrospective multicenter study was to investigate the clinical course, possible risk factors, and outcome of a cohort of neonatal patients with sinovenous thrombosis and, second, to estimate the incidence in The Netherlands.
From January 1999 to March 2009, a review of all neonatal patients with sinovenous thrombosis from 6 tertiary neonatal intensive care units was performed. Population characteristics, clinical presentation, (prothrombotic) risk factors, neuroimaging, interventions, and neurodevelopment were evaluated. An estimated incidence was calculated based on the Netherlands Perinatal Registry.
Fifty-two neonates were included (39 boys) with a median gestational age of 39 weeks (range, 30 to 42 weeks; 5 preterm). An assisted or complicated delivery occurred in 32 of 52. Presenting symptoms developed at a median postnatal age of 1.5 days (range, 0 to 28 days) and consisted mainly of seizures (29 of 52). All sinovenous thrombosis cases were confirmed with MRI/MR venography. Multisinus thrombosis was most common followed by superior sagittal sinus thrombosis. FII G20210A mutation was present in 2 of 18 tested neonates (11%). Anticoagulation therapy (in 22 of 52) did not result in hemorrhagic complications. At follow-up (median age, 19 months; range, 3 to 72 months), moderate to severe neurological sequelae were present in 38%. The mortality was 10 of 52 (19%). A variable, although high yearly incidence of 1.4 to 12 per 100 000 term newborns was found.
Neonatal sinovenous thrombosis is a multifactorial disease. The estimated incidence in The Netherlands seems higher than reported elsewhere.
Stroke 07/2010; 41(7):1382-8. · 5.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This paper describes the development of an instrument to assess comprehension of spoken language in children with severe cerebral palsy (CP) who cannot speak, and for whom standard language assessment measures are not appropriate due to severe motor impairment. This instrument, the Computer-Based instrument for Low motor Language Testing (C-BiLLT), was administered to 42 children without disabilities (aged 14 months to 60 months) and to 18 children with severe CP (age 19 months to 71 months). Preliminary data showed that the instrument was acceptable to the children. Convergent validity was investigated by correlating C-BiLLT scores with test results on the well-established Reynell Developmental Language Scales (RDLS). Clinical implications and recommendations for future research are discussed.
Augmentative and alternative communication (Baltimore, Md.: 1985) 06/2010; 26(2):97-107. · 0.94 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We evaluated the use of a mock scanner training protocol as an alternative for sedation and for preparing young children for (functional) magnetic resonance imaging (MRI). Children with severe mental retardation or developmental disorders were excluded. A group of 90 children (median age 6.5 years, range 3.65-14.5 years) participated in this study. Children were referred to the actual MRI investigation only when they passed the training. We assessed the pass rate of the mock scanner training sessions. In addition, the quality of both structural and functional MRI (fMRI) scans was rated on a semi-quantitative scale. The overall pass rate of the mock scanner training sessions was 85/90. Structural scans of diagnostic quality were obtained in 81/90 children, and fMRI scans with sufficient quality for further analysis were obtained in 30/43 of the children. Even in children under 7 years of age, who are generally sedated, the success rate of structural scans with diagnostic quality was 53/60. FMRI scans with sufficient quality were obtained in 23/36 of the children in this younger age group. The association between age and proportion of children with fMRI scans of sufficient quality was not statistically significant. We conclude that a mock MRI scanner training protocol can be useful to prepare children for a diagnostic MRI scan. It may reduce the need for sedation in young children undergoing MRI. Our protocol is also effective in preparing young children to participate in fMRI investigations.
European Journal of Pediatrics 03/2010; 169(9):1079-85. · 1.88 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To develop subjective (visual) and objective (morphometric) rating scales for the classification of MRI in infants who had microcephaly with a simplified gyral pattern (MSGP) and to validate the first by the latter.
We compared the MRI of 12 patients with MSGP and of 5 term-born control infants. Visual rating and morphometric analysis was performed for gyration and associated brain abnormalities of basal ganglia, lateral ventricles, pons, cerebellum, and corpus callosum.
Gyral pattern was rated reliably as normal in the control infants, simplified in 6 patients, and severely simplified in the other 6 patients. Associated brain abnormalities were reported in 10 of 12 patients. Visual rating correlated well with the morphometric measures.
Our visual rating scale for a simplified gyral pattern proved to be sensitive and reliable. Associated brain abnormalities are frequent, which underlines the need for a consistent scoring in these patients.
Neurology 02/2010; 74(5):386-91. · 8.31 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To investigate the predictive value of motor testing at 1 year for motor and mental outcome at 2 years after perinatal hypoxic-ischaemic encephalopathy (HIE) in term neonates.
Motor and mental outcome at 2 years was assessed with the Bayley Scales of Infant Development, 2nd edition (BSID-II) in 32 surviving children (20 males, 12 females; mean gestational age 40.2 wk, SD 1.4; mean birthweight 3217g, SD 435) participating in a prospective cohort study of HIE. The predictive value of three motor tests (Alberta Infant Motor Scale [AIMS], BSID-II, and the Neurological Optimality Score [NOS]) at 1 year was analysed, in addition to predictions based on neonatal Sarnat staging and magnetic resonance imaging (MRI). Poor motor test results were defined as an AIMS z-score of <-2, a psychomotor developmental index of the BSID-II of <70, or a NOS of <26. Poor motor and poor mental outcome at 2 years was defined as a psychomotor developmental index or mental developmental index of the BSID-II of <70.
Twelve children, all with Sarnat grade II, had a poor motor outcome and 12 children, of whom one had Sarnat grade I, had a poor mental outcome at 2 years. Nine children had cerebral palsy, of whom five had quadriplegia, three had dyskinesia, and one had hemiplegia. Poor motor tests at 1 year increased the probability of a poor motor outcome from 71% (range 92 to 100%), and a poor mental outcome from 59% (range 77 to 100%) in children with Sarnat grade II and abnormal MRI, assessed with the AIMS and BSID-II or NOS respectively.
Additional motor testing at 1 year improves the prediction of motor and mental outcome at 2 years in children with Sarnat grade II and abnormal MRI.
Developmental Medicine & Child Neurology 03/2009; 52(1):54-9. · 2.92 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To establish the supplemental value of diffusion-weighted (DW) magnetic resonance (MR) imaging beyond conventional MR to predict clinical outcome after neonatal hypoxic ischemia (HI) at 2 years of age.
Forty-six infants with neonatal HI were enrolled in this prospective study, after approval by the local ethical committee and informed consent of the parents. Neonatal MR imaging ranged from 1 to 45 days after birth. Apparent diffusion coefficient (ADC) was measured in 14 brain regions. DW and conventional images were qualitatively scored for abnormalities, resulting in cumulative scores and patterns of damage. Surviving infants were scored for motor outcome at the age of 2 years, and outcome was classified as poor if the motor score was less than 70 or in case of death. Analyses were performed for the whole group, with additional analyses for the early (0-4 days after birth) and late (>4 days after birth) imaging groups.
Twenty-five infants had a good outcome and 21 had a poor outcome. Only in the early imaging group, the infants with poor outcome had significantly lowered ADC values in several brain areas, with the posterior limb of the internal capsule being the most predictive (Wald score = 5.7; P = .017). Cumulative scores of DW imaging were the best predictor of poor motor outcome at the age of 2 years (Wald score = 7.2, P < .01). The basal ganglia and central cortex and the diffuse pattern of brain damage were highly associated with poor outcome (Fisher exact test = 29.8; P < .001).
In neonatal HI, DW imaging is a useful additional MR technique to predict the motor outcome at 2 years. Local ADC values had a limited value. Recognition of the patterns of brain damage with DW and conventional MR imaging can be used as a diagnostic tool in neonatal HI.
Radiology 10/2008; 249(2):631-9. · 5.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Selective dorsal rhizotomy at the lumbar level is a neurosurgical procedure, which reduces spasticity in the legs. Its effect has mainly been studied in children with spastic cerebral palsy. Little is known about the outcome of selective dorsal rhizotomy in patients with neurodegenerative disorders. We report the clinical course after selective dorsal rhizotomy in 2 patients with progressive spasticity. Leg spasticity was effectively and persistently reduced in both patients, facilitating care and improving sitting comfort. However, spasticity of the arms and other motor disturbances, such as spontaneous extension spasms and the ataxia, increased gradually in time. Selective dorsal rhizotomy leads to a disappearance of leg spasticity in patients with a neurodegenerative disease. Other motor signs are not influenced and may increase due to the progressive nature of the underlying disease.
Journal of child neurology 07/2008; 23(7):818-22. · 1.59 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To determine the effect of neonatal glutamine-enriched enteral nutrition in very low birth weight (VLBW) infants on neurodevelopmental outcome at 2 years of age.
Eighty-eight out of one hundred two infants participating in the initial study were eligible for the follow-up study (13 died, one exclusion due to a chromosomal abnormality). Neurodevelopmental outcome (neurologic status, vision, hearing and Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) of the Bayley Scales of Infant Development II) was evaluated at the corrected age of 2 years. To adjust for potential confounders, data were analyzed by multiple linear or logistic regression (for continuous and dichotomous variables, respectively)
Seventy-two out of eighty-eight (82%) infants participated in the follow-up study: 40 and 32 infants in glutamine-supplemented and control groups, respectively. The incidence of neither an MDI nor a PDI <or= 85 was different in glutamine-supplemented and control groups (MDI <or= 85: 27 and 19%, p = 0.17; PDI <or= 85: 28 and 16% p = 0.16, respectively). The incidence of neurodevelopmental impairment was not different between both groups (OR: 2.16, 95% CI: 0.64-7.28).
A positive effect of neonatal glutamine-enriched enteral nutrition in VLBW infants on neurodevelopmental outcome at 2 years of age was not found in this study.
Acta Paediatrica 05/2008; 97(5):562-7. · 2.07 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: An infant with pneumococcal meningitis developed signs of raised intracranial pressure during the progression of the disease, including loss of consciousness, hypertension, bradycardia, and respiratory depression. However, both the emergency computed tomography scan findings and intracranial pressure measured by lumbar puncture were normal. Diffusion-weighted magnetic resonance imaging identified multiple lesions with restricted diffusion suggestive of ischemia in the brainstem, explaining the signs observed in the patient. These lesions could not be identified on T(2)-weighted images at that time.
Pediatric Neurology 05/2008; 38(4):276-8. · 1.52 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We present a case of Pott's disease, where the patient presented with neurological impairment due to vertebral granulomatous necrosis, needing immediate decompression and later stabilizing and reconstructive orthopaedic surgery, in order to create awareness for TB in general, especially this forgotten form of spinal tuberculosis.
European Journal of Pediatrics 11/2007; 166(10):1071-3. · 1.88 Impact Factor
