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 In anatomy, the meninges (, ''singular:'' meninx ( or ), ) are the three membranes that envelop the brain and spinal cord. In mammals, the meninges are the dura mater, the arachnoid mater, and the pia mater. Cerebrospinal fluid is located in th ...

, or 4) the late stage organization of the neuronal layer in the cortex is disrupted. Abnormal migration ultimately results in abnormal 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 Genetic counseling is the process of investigating individuals and families affected by or at risk of genetic disorders to help them understand and adapt to the medical, psychological and familial implications of genetic contributions to disease; t ...

thus differs greatly between syndromes. *

Lissencephaly Lissencephaly (, meaning "smooth brain") is a set of rare brain disorders whereby the whole or parts of the surface of the brain appear smooth. It is caused by defective neuronal migration during the 12th to 24th weeks of gestation resulting in ...

Microlissencephaly Microlissencephaly (MLIS) is a rare congenital brain disorder that combines severe microcephaly (small head) with lissencephaly (smooth brain surface due to absent sulci and gyri). Microlissencephaly is a heterogeneous disorder, i.e. it has many d ...

Schizencephaly Schizencephaly () is a rare birth defect characterized by abnormal clefts lined with grey matter that form the ependyma of the cerebral ventricles to the pia mater. These clefts can occur bilaterally or unilaterally. Common clinical features of ...

Porencephaly Porencephaly is an extremely rare cephalic disorder involving encephalomalacia. It is a neurological disorder of the central nervous system characterized by cysts or cavities within the cerebral hemisphere.Parker, J. (2004). The official parent ...

Pachygyria Pachygyria (from the Greek "pachy" meaning "thick" or "fat" gyri) is a congenital malformation of the cerebral hemisphere. It results in unusually thick convolutions of the cerebral cortex. Typically, children have developmental delay and seizures, ...

Polymicrogyria Polymicrogyria (PMG) is a condition that affects the development of the human brain by multiple small gyri ( microgyri) creating excessive folding of the brain leading to an abnormally thick cortex. This abnormality can affect either one region o ...

Agyria Lissencephaly (, meaning "smooth brain") is a set of rare brain disorders whereby the whole or parts of the surface of the brain appear smooth. It is caused by Neuronal migration disorder, defective neuronal migration during the 12th to 24th week ...

* Macrogyria *

Microgyria A microgyrus is an area of the cerebral cortex that includes only four cortical layers instead of six. Microgyria are believed by some to be part of the genetic lack of prenatal development which is a cause of, or one of the causes of, dyslexia ...

Micropolygyria Micropolygyria is a neuronal migration disorder, a developmental anomaly of the brain characterized by development of numerous small convolutions ( microgyri), causing intellectual disability and/or other neurological disorders. It is present in a ...

Grey matter heterotopia MRI of a child experiencing seizures. There are small foci of grey matter Heterotopia (medicine)">heterotopia in the corpus callosum, deep to the Cortical dysplasia, dysplastic cortex. (double arrows) Gray matter heterotopias are neurological d ...

* Agenesis of the corpus callosum * Agenesis of the cranial nerves * Band heterotopias Focal

cortical dysplasia Focal cortical dysplasia (FCD) is a congenital abnormality of brain development where the neurons in an area of the brain failed to migrate in the proper formation in utero. ''Focal'' means that it is limited to a focal zone in any lobe. Focal co ...

Miller–Dieker syndrome Miller–Dieker syndrome, Miller–Dieker lissencephaly syndrome (MDLS), and chromosome 17p13.3 deletion syndrome is a micro deletion syndrome characterized by congenital malformations. Congenital malformations are physical defects detectable in a ...

, ,

Fukuyama congenital muscular dystrophy Fukuyama congenital muscular dystrophy (FCMD) is a rare, autosomal recessive form of muscular dystrophy (weakness and breakdown of muscular tissue) mainly described in Japan but also identified in Turkish and Ashkenazi Jewish patients; fifteen case ...

and

Walker–Warburg syndrome Walker–Warburg syndrome (WWS), also called Warburg syndrome, Chemke syndrome, HARD syndrome (Hydrocephalus, Agyria and Retinal Dysplasia), Pagon syndrome, cerebroocular dysgenesis (COD) or cerebroocular dysplasia-muscular dystrophy syndrome (COD- ...

are genetic disorders associated with lissencephaly.

Treatment

Treatment is symptomatic and may include

anti-seizure medication Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of ...

and special or supplemental education consisting of

physical Physical may refer to: *Physical examination In a physical examination, medical examination, or clinical examination, a medical practitioner examines a patient for any possible medical signs or symptoms of a medical condition. It generally co ...

occupational Employment is a relationship between two party (law), parties Regulation, regulating the provision of paid Labour (human activity), labour services. Usually based on a employment contract, contract, one party, the employer, which might be a co ...

and 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 *