Migraine (UK: , US: ) is a common neurological disorder characterized by recurrent headaches. Typically, the associated headache affects one side of the head, is pulsating in nature, may be moderate to severe in intensity, and could last from a few hours to three days. Non-headache symptoms may include nausea, vomiting, and sensitivity to light, sound, or smell. The pain is generally made worse by physical activity during an attack, although regular physical exercise may prevent future attacks. Up to one-third of people affected have aura: typically, it is a short period of visual disturbance that signals that the headache will soon occur. Occasionally, aura can occur with little or no headache following, but not everyone has this symptom.Migraine is believed to be due to a mixture of environmental and genetic factors. About two-thirds of cases run in families. Changing hormone levels may also play a role, as migraine affects slightly more boys than girls before puberty and two to three times more women than men. The risk of migraine usually decreases during pregnancy and after menopause. The underlying mechanisms are not fully known. They are, however, believed to involve the nerves and blood vessels of the brain.Initial recommended treatment is with simple pain medication such as ibuprofen and paracetamol (acetaminophen) for the headache, medication for the nausea, and the avoidance of triggers. Specific medications such as triptans or ergotamines may be used in those for whom simple pain medications are not effective.
Genes shown to cause lissencephaly include both autosomal and X-linked genes. Below, the mutations of LIS1 or DCX genes are discussed as they are most commonly linked to neuronal migration disorders including lissencephaly-pachygyria and subcortical band heterotopia. LIS1
LIS1 is responsible for the autosomal form of lissencephaly. Mutations of the LIS1 gene are associated with about 80% of those affected with lissencephaly. LIS1 was the first human neuronal migration gene to be cloned. It is responsible for encoding the alpha subunit of the intracellular Ib isoform of platelet-activating factor acetylhydrolase. It is located on chromosome 17p13.3 and has 11 exons with a coding region of 1233bp. LIS1 protein appears to interact with tubulin to suppress microtubule dynamics. The protein is highly conserved and studies have shown that it participates in cytoplasmic dynein-mediated nucleokinesis, somal translocation, cell motility, mitosis, and chromosome segregation. LIS1 encodes for a 45kDa protein called PAFAH1B1 that contains seven WD40 repeats required for proper neuronal migration. The LIS1 gene encodes for a protein similar to the β subunit of G proteins responsible for degrading bioactive lipid platelet-activating factor (PAF). This leads to theories that LIS1 might exert its effect on migration through microtubules. Specific concentrations of PAF may be necessary for optimal neuronal migration by influencing cell morphology adhesion properties. Studies have shown that addition of PAF or inhibition of platelet-activating factor acetylhydrolase (PAF-AH) decreases cerebellar granule cell migration in vitro. Addition of PAF to hippocampal cells have shown growth cone collapse and neurite retraction.