Neuronal migration disorder (NMD) refers to a heterogenous group of disorders that, it is supposed, share the same etiopathological mechanism: a variable degree of disruption in the migration of

neuroblast In vertebrates, a neuroblast or primitive nerve cell is a postmitotic cell that does not divide further, and which will develop into a neuron after a migration phase. In invertebrates such as ''Drosophila,'' neuroblasts are neural progenitor cell ...

s during neurogenesis. The

neuronal migration The development of the nervous system, or neural development (neurodevelopment), refers to the processes that generate, shape, and reshape the nervous system of animals, from the earliest stages of embryonic development to adulthood. The fiel ...

disorders are termed cerebral dysgenesis disorders, brain malformations caused by primary alterations during neurogenesis; on the other hand, brain malformations are highly diverse and refer to any insult to the brain during its formation and maturation due to intrinsic or extrinsic causes that ultimately will alter the normal brain anatomy. However, there is some controversy in the terminology because virtually any malformation will involve neuroblast migration, either primarily or secondarily.

Symptoms and signs

Symptoms vary according to the abnormality, but often feature poor muscle tone and motor function,

seizures An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with l ...

developmental delay Global developmental delay is an umbrella term used when children are significantly delayed in their cognitive and physical development. It can be diagnosed when a child is delayed in one or more milestones, categorised into motor skills, speech ...

mental retardation Intellectual disability (ID), also known as general learning disability in the United Kingdom and formerly mental retardation, Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010). is a generalized neurodevelopmental disorder characterized by signifi ...

, failure to grow and thrive, difficulties with feeding, swelling in the extremities, and a smaller than normal head. Most infants with an NMD appear normal, but some disorders have characteristic facial or skull features that can be recognized by a neurologist.

Cause

In the developing brain, neural stem cells must migrate from the areas where they are born to the areas where they will settle into their proper neural circuits. Neuronal migration, which occurs as early as the second month of gestation, is controlled by a complex assortment of chemical guides and signals. When these signals are absent or incorrect, neurons do not end up where they belong. This can result in structurally abnormal or missing areas of the brain in the

cerebral hemispheres The vertebrate cerebrum (brain) is formed by two cerebral hemispheres that are separated by a groove, the longitudinal fissure. The brain can thus be described as being divided into left and right cerebral hemispheres. Each of these hemispheres ...

, cerebellum, brainstem, or

hippocampus The hippocampus (via Latin from Greek , ' seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, ...

. Several

genetic abnormalities A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...

in children with NMDs have been identified. Defects in genes that are involved in neuronal migration have been associated with NMDs, but the role they play in the development of these disorders is not yet well understood. A study in Sweden investigated the impact of environmental factors on NMDs. The study indicated that there might be an impact of low or subnormal maternal BMI before and during

pregnancy Pregnancy is the time during which one or more offspring develops (gestation, gestates) inside a woman, woman's uterus (womb). A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occur ...

, maternal infection, such as rubella, and maternal smoking on fetal brain development, including neuronal migration. The roles of maternal BMI and congenital infections should be tested in future analytical studies. NMDs occur in the instance that 1) neuroblasts do not migrate from all of the ventricles or migrate only part of the way, 2) only some of the neuroblasts reach the

cortical layer The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. The cerebral cortex mostly consists of the six-layered neocortex, with just 10% consisting of ...

, 3) neuroblasts overshoot the appropriate cortical layer and protrude into the subarachnoid space, or 4) the late stage organization of the neuronal layer in the cortex is disrupted. Abnormal migration ultimately results in abnormal Gyrus, gyral formation.

Diagnosis

Types of NMD syndromes

More than 25 syndromes resulting from abnormal neuronal migration have been described. Among them are syndromes with several different patterns of inheritance; genetic counseling thus differs greatly between syndromes. * Lissencephaly * Microlissencephaly * Schizencephaly * Porencephaly * Pachygyria * Polymicrogyria * Agyria * Macrogyria * Microgyria * Micropolygyria * Grey matter heterotopia * Agenesis of the corpus callosum * Agenesis of the cranial nerves * Gray matter heterotopia, Band heterotopias Focal cortical dysplasia, Miller–Dieker syndrome, , Fukuyama congenital muscular dystrophy and Walker–Warburg syndrome are genetic disorders associated with lissencephaly.

Treatment

Treatment is symptomatic and may include Anti-seizure medications, anti-seizure medication and special or supplemental education consisting of Physical therapy, physical, Occupational therapy, occupational and Speech therapy, speech therapies.

Prognosis

The prognosis for children with NMDs varies depending on the specific disorder and the degree of brain abnormality and subsequent neurological signs and symptoms.

References

{{reflist, 2 Neurological disorders Neuronal migration disorders, *