**5. Conclusion**

*Spina Bifida and Craniosynostosis - New Perspectives and Clinical Applications*

reflects a long-term disruption of brain development that extends far beyond the neural tube defect [93]. Hydrocephalus associated with the spina bifida is caused by an obstruction of the cerebrospinal fluid flow from IV. ventricular or malformation of the cerebral aqueduct. Ventriculomegaly causes systematic destruction of white matter periventricular axons. Motor, sensory, visual as well as memory systems can be disrupted by stiffening of periventricular structures, including the corpus callosum and the fimbria-fornix pathway. Secondary changes occur in neuronal cell bodies and synapses, with neurons not undergoing apoptosis. The clinical syndrome of hydrocephalic brain dysfunction is caused by subcortical detachment. Some of the brain dysfunctions are reversible due to the restoration of blood flow through the brain and the normalization of the extracellular environment [94]. Diffusion tensor tractography revealed diffusion tensor characteristics of myelination impairment and pathological development as well as abnormalities in intrinsic axonal characteristics and extra-axonal space in the association pathways of children with the development of the spina bifida. The differences in the diffusion metrics are suggestive of the pathological white matter development and persistent degeneration with increased age [95]. Hydrocephalus exerts primarily a linear effect on cognitive and motor outcomes. Deviations from normative standards for volumes of frontal versus posterior regions are associated with reductions in intelligence quotient and fine motor dexterity [3]. With the exception of fine motor skills and small differences in memory and spatial domains, children with spina bifida and arrested or shuntdependent hydrocephalus have similar neuropsychological profiles [96]. Patients with the spina bifida have extensive motor deficits in the trunk, upper limbs, eyes, and speech articulators that correspond to disorders characteristic for cerebellar lesions. The structure and function of the brain correlates with a number of motor dysfunctions. Motor learning is maintained in the spina bifida. Pathological are motor functions that require predictive signals and accurate calibration of motion time signs. This creates a deficit in the coordination of smooth movement and the cerebellar triad - ataxia, dysmetria, and dysarthria. Said motor function in individuals with the spina bifida is impaired phenotypically very similarly to cerebellar lesions. The age-based cerebellar motor plasticity is limited in individuals with this neurodevelopmental disorder [97]. Attention deficit reflecting problems with posterior attention systems involving orienting and arousal mediated by the midbrain, with tectal anomalies directly correlated with the severity of difficulties with stimulus control. Procedural learning and attention functions involving sustained attention and persistence are relatively preserved, possibly reflecting less impairment in frontal-striatal regions and basal ganglia [3, 98]. Impairments in attentional disengagement in the spina bifida are not attributable to the general effects of hydrocephalus but are instead associated with specific midbrain anomalies that are part of the Chiari II malformation [99]. Development of individuals with severe forms of spina bifida throughout the lifetime is strongly affected by neurocognitive and movement disorders. Neurocognitive difficulties cause problems in keeping attention, learning, language comprehension and pragmatics as well as in assimilation of information. Procedural learning, word reading, vocabulary and social activation are usually not affected. Infants with spina bifida do not learn motor contingencies as easily or at the same rate as infants with typical development and are more likely to decrease motor responses when sensory feedback is absent. Intellectual disability is relatively infrequent, affecting perhaps 20–25% of people with the spina bifida and often after complications associated with the hydrocephalus. Status of cognitive functions in spina bifida patients is very variable as well as intelligence quotient scores. Impairment of intelligence and cognitive skills is mostly

associated with presence of possible complications, such as hydrocephalus. Treatment of hydrocephalus is burdened with eventual complications as shunt

**18**

The spina bifida involves congenital problems that result in abnormal bone formation in the spine and spinal cord. Closed spinal dysraphism is the mildest form of the neural tube defects which involves a hidden vertebral defect and minimal neural involvement. Open spinal dysraphism refers to a defect in which neural tissues communicate with the external environment such as meningocele and myelomeningocele. The incidence of neural tube defects has different rates among different ethnicity, geography, gender, and also countries. Various nutritional, maternal and environmental factors play a role in the etiology and pathogenesis of the spina bifida. However, the impact of these factors is ambiguous and further research is needed in this area.
