Ulegyria

Arteries supplying the brain

The physical features of ulegyria consist of small radial scars which occupy the cortical sulci.[3] Overall, the physical structure of affected areas in the brain is described as a “mushroom”-like shape in which the gyri are unusually large and the sulci become wider deeper in the cortex. N.C. Bresler, the first person to view a brain with ulegyria in 1899, coined the phrase mushroom gyri. He also named the disorder, basing it off the Latin root ule, meaning scar.[1] This mushroom-like structure is the result of the lower parts of the ulegyria-affected area being more prone to deterioration, while the upper gyri are usually spared.[4] However, the entire affected area shrinks and presents brown coloration as a result of ulegyria. In addition, “islands” of neurons that are relatively unaffected can exist between ulegyria affected neurons.[5] Ulegyria can develop bilaterally or unilaterally, though the former is more commonly diagnosed.[6]

Ulegyria can affect many parts of the brain including the cerebral cortex, parasagittal areas and posterior regions of the brain, such as the parietal and occipital lobes.[1] These areas are situated either near artery rich regions or near a major cerebral artery.[5] For instance, specifically in neonatal children, ulegyria-affected areas are found near the posterior cerebral artery or near the artery rich region between the middle and posterior regions of the brain, often referred to as watershed regions.[1][4][7]

Neurons affected by ulegyria exhibit properties that differ from normally functioning neurons. For instance, ulegyria affected neurons experience gliosis in which glial cells, specifically astrocytes, build up near and around neurons. Ulegyria affected neurons also display decreases in their white matter content, showing signs of sclerosis, which is characterized by the deterioration of myelin in neurons. However, in regions of grey matter, large dense aggregates of myelin are present.[4] Ulegyria affected neurons also display metabolic disorders which could be linked to the disease phenylketonuria and disruptions in the urea cycle.[8] Hypoglycemia and hypoxia are also thought to accompany the symptoms of ulegyria-affected neurons as well.[2][9]

Microphotograph of HE stained section of human brain tissue upon acute ischemic stroke

Ulegyria develops as a result of a brain injury called cerebral ischemia surrounding the time of an infant's birth. Oftentimes, fetal hypoxic-ischemic brain injuries occur as a result of a pregnancy complications such as placental abruption, cord accident, or cardiovascular stress due to a difficult delivery.[10] A lack of oxygen to the brain contributes to the formation of lesions usually near the three main cerebral arteries, located near the parietal lobe and occipital lobes of the brain.[4] The cause of perinatal brain injuries includes:

1. cerebral ischemia

2. cerebral hemorrhage

3. ascending intrauterine infections.[11]

Some risk factors for perinatal brain injuries include: low birth weight, preterm birth, poor perinatal cardiorespiratory fitness, and artificial ventilation.[12]

Ulegyria was found in about 1/3 of patients with defects caused by circulatory disease in the perinatal period.[15] Most clinical observations of the condition report mental retardation, cerebral palsy, and seizures as the main defects.[1][6][8][10][16] However, milder cases have been reported in which patients that exhibit ulegyria develop relatively normally.[1][2] The main movement disorders associated with ulegyria that are classified as cerebral palsy are choreoathetosis, dystonia, and ataxia.[10] It is suspected that ulegyria leads to epilepsy because malformation of the cortex obstructs the differentiation of neurons, glial cells, and synapses.[15] Parietal-occipital lobe epilepsy, which is often synonymous with posterior cortex epilepsy (PCE),[16] is the form of the disease seen in most cases involving ulegyria.[2] This type of epilepsy is very rare, making up about 5% of all reports of epilepsy. This form of the disease involves symptoms that would be expected from damage to the parietal and occipital lobes: seizures with visual hallucinations, visuospatial dysfunction, tingling, numbness, pain, and a burning sensation.[17] In addition to ulegyria, tumors and cortical dysplasia constitute the major causes of PCE.[13] Most of the epilepsy seen in conjunction with ulegyria is classified as medically refractory, meaning it is not responsive to treatment.[7] Patients usually present symptoms of epilepsy at an early age.[1] The severity of epilepsy has been shown to depend on this age of onset as well as the quantity of cortical lesions; earlier onset of epilepsy and a larger extent of lesions tends to mean more severe seizures.[1][7]

Child presenting with seizures likely due to polymicrogyria (seen at arrow).

Ulegyria is often confused with a similar distortion of the cortex known as polymicrogyria.[7] Polymicrogyria is characterized by excessive folding of the surface gyri and a thickening of the cerebral cortex,[18] rather than the sulcal scarring that is typical of ulegyria. In addition to morphological differences, the period in which polmicrogyria and ulegyria emerge is also different. Polymicrogyria typically forms while the embryo's central nervous system is maturing. Ulegyria is acquired later in development during the perinatal period after neuronal migration has already occurred. It is also suspected that polymicrogyra is genetically linked, whereas ulegyria is caused by environmental factors—namely lack of oxygen.[1]

Polymicrogyria can lead to similar conditions that are linked to ulegyria such as mental retardation, cerebral palsy, and epilepsy. It has been observed that patients with polymicrogyria are not receptive to epilepsy surgery. However, responses of patients with ulegyria to similar surgeries are still not fully known, which makes distinction of these two disorders significant. In vivo neuroimaging techniques, namely MRI, have been instrumental in making this distinction. An MRI image of ulegyria is identified by mushroom shaped gyri, deformities in white matter, and localization mainly in the posterior cerebral region.[1] Polymicrogyria is typically recognized by a scalloped appearance at the bordering region between grey and white matter.[18] Although these distinctions have been made with many patients, there is still some difficulty in defining distinct boundaries between these two similar conditions.[7]

Primarily, the main method of detecting ulegyria is through the use of MRI screening for epilepsy. Normally an MRI of an ulegyria affected region will reveal groups of deteriorated neurons with gliosis present. In addition, unaffected gyri are also present in especially bilateral watershed regions indicating delayed effects of perinatal hypoxic damage.[4] However, there are three main criteria for diagnosing ulegyria using MRI in addition to the features mentioned above:[4]

1.The presence of a poorly demarcated lesion

2. Atrophy and thinning of the cortex resulting in the characteristic “mushroom” like shape of ulegyria.

3. Presence of white matter signal abnormalities as a result of FLAIR signaling (fluid attenuated inversion recovery).

Another sign of ulegyria that is visible on an MRI scan is the presence of a widened subarachnoid space, signifying cortex atrophy. FLAIR signaling can help visualize the depths of the parietal-occipital sulci, which also allows ulegyria-affected gyri to be identified.[6] Though there is still confusion in differentiating ulegyria and polymicrogyria in patients, MRI allows for the proper identification in the majority of the cases. In addition, most of the current research regarding ulegyria is focused on improving this identification. Furthermore, MRI can diagnose whether ulegyria presence is unilateral or bilateral.[1] Electroencephalography, EEG, can also be used to screen for ulegyria, though MRI is still preferred. This is mainly done for epilepsy patients as abnormalities in EEG recordings indicate the presence of ulegyria in the area of the brain being tested.[7] For example, when EEG tests in epileptic patients show deviations in the frontal and central-parietal regions, ulegyria can be considered to be present in that area.[7]

Presently, there is no well-defined treatment for ulegyria mainly because of the irreversible ischaemic damage done to neurons of an affected area. However, conditions associated with ulegyria, such as epilepsy and cerebral palsy, can be treated using the appropriate treatment. For instance, seizures caused by epilepsy, due to the presence of ulegyria in the occipital lobe, can be controlled using antiepileptic drugs in some patients.[1] In other patients, such as those who suffer from ulegyria in the posterior cortex, drugs are not effective and surgery of the area causing epilepsy is needed.[1][16] These treatments treat only the conditions but have no effect on the condition of ulegyria itself.