There is no known definitive single mechanism that causes colpocephaly. However, researchers believe there are many possible causes of colpocephaly. It is a common symptom of other neurological disorders in newborns, can be caused as a result of shunt treatment of hydrocephalus, developmental disorders in premature infants, due to intrauterine disturbances during pregnancy, genetic disorders, underdevelopment or lack of white matter in the cerebrum, and exposure of the mother and the developing fetus to medications, infections, radiation, or toxic substances. Also, it is usually more common in premature infants than in full-term infants, especially in babies born with hypoxia or lung immaturity.

Some of the central nervous system disorders which are associated with colpocephaly are as follows:

- polymicrogyria

- Periventricular leukomalacia (PVL)

- intraventricular hemorrhage

- Hydrocephalus

- schizencephaly

- microgyria

- microcephaly

- Pierre-Robin syndrome

- Neurofibromatosis

Often colpocephaly occurs as a result of hydrocephalus. Hydrocephalus is the accumulation of cerebrospinal fluid (CSF) in the ventricles or in the subarachnoid space over the brain. The increased pressure due to this condition dilates occipital horns causing colpocephaly.

The most generally accepted theory is that of neuronal migration disorders occurring during the second to fifth months of fetal life. Neuronal migration disorders are caused by abnormal migration, proliferation, and organization of neurons during early brain development. During the seventh week of gestation, neurons start proliferating in the germinal matrix which is located in the subependymal layer of the walls of the lateral ventricles. During the eighth week of gestation, the neurons then start migrating from the germinal zone to cortex along specialized radial glial fibers. Next, neurons organize themselves into layers and form synaptic contacts with other neurons present in the cortex. Under normal conditions, the neurons forming a germinal layer around ventricles migrate to the surface of the brain and form the cerebral cortex and basal ganglia. If this process is abnormal or disturbed it could result in the enlargement of the occipital horns of the lateral ventricles. Common prenatal disturbances that have been shown to disturb the neuronal migration process include the following:

- continuation of oral contraceptives

- exposure to alcohol

- intrauterine malnutrition

- intrauterine infections such as toxoplasmosis

- maternal drug ingestion during early pregnancy such as corticosteroids, salbutamol, and theophylline

Researchers also believe that these factors can cause destruction of neural elements that have previously been normally formed.

It is suggested that the underdevelopment or lack of white matter in the developing fetus could be a cause of colpocephaly. The partial or complete absence of white matter, also known as agenesis of the corpus callosum results in anatomic malformations that can lead to colpocephaly. This starts to occur around the middle of the second month to the fifth month of pregnancy. The lateral ventricles are formed as large cavities of the telencephalic vesicle. The size of the ventricles are decreased in normal development after the formation of the Foramen of Magendie, which decompresses the ventricular cavities. Myelination of the ventricular walls and association fibers of the corpus callosum and the calcarine fissure helps shape the occipital horns. In cases where this developmental process is interrupted, occipital horns are disproportionately enlarged.

Colpocephaly has been associated with chromosomal abnormalities such as trisomy 8 mosaic and trisomy 9 mosaic. A few reports of genetically transmitted colpocephaly are also found in literature. Some of these are of two siblings, monozygotic twins, and non-identical twins. The authors suggest a genetic origin with an autosomal or X-linked recessive inheritance rather than resulting from early prenatal disturbances.

Because pachygyria is a structural defect no treatments are currently available other than symptomatic treatments, especially for associated seizures. Another common treatment is a gastrostomy (insertion of a feeding tube) to reduce possible poor nutrition and repeated aspiration pneumonia.

Colpocephaly is usually non-fatal. There has been relatively little research conducted to improve treatments for colpocephaly, and there is no known definitive treatment of colpocephaly yet. Specific treatment depends on associated symptoms and the degree of dysfunction. Anticonvulsant medications can be given to prevent seizure complications, and physical therapy is used to prevent contractures (shrinkage or shortening of muscles) in patients that have limited mobility. Patients can also undergo surgeries for stiff joints to improve motor function. The prognosis for individuals with colpocephaly depends on the severity of the associated conditions and the degree of abnormal brain development.

A rare case of colpocephaly is described in literature which is associated with macrocephaly instead of microcephaly. Increased intracranial pressure was also found in the condition. Similar symptoms (absence of corpus callosum and increased head circumference) were noted as in the case of colpocephaly that is associated with microcephaly. A bi-ventricular peritoneal shunt was performed, which greatly improved the symptoms of the condition. Ventriculo-peritoneal shunts are used to drain the fluid into the peritoneal cavity.

The term 'pachygyria' does not directly relate to a specific malformation but rather is used to generally describe physical characteristics of the brain in association with several neuronal migration disorders; most commonly disorders relating to varied degrees of lissencephaly. Lissencephaly is present in 1 of 85,470 births and the life span of those affected is short as only a few survive past the age of 20.

Pachygyria is a condition identified by a type of cortical genetic malformation. Clinicians will subjectively determine the malformation based on the degree of malposition and the extent of thickened abnormal grey differentiation present.

Preventing or delaying premature birth is considered the most important step in decreasing the risk of PVL. Common methods for preventing a premature birth include self-care techniques (dietary and lifestyle decisions), bed rest, and prescribed anti-contraction medications. Avoiding premature birth allows the fetus to develop further, strengthening the systems affected during the development of PVL.

An emphasis on prenatal health and regular medical examinations of the mother can also notably decrease the risk of PVL. Prompt diagnosis and treatment of maternal infection during gestation reduces the likelihood of large inflammatory responses. Additionally, treatment of infection with steroids (especially in the 24–34 weeks of gestation) have been indicated in decreasing the risk of PVL.

It has also been suggested that avoiding maternal cocaine usage and any maternal-fetal blood flow alterations can decrease the risk of PVL. Episodes of hypotension or decreased blood flow to the infant can cause white matter damage.

The cause of polymicrogyria is unclear. It is currently classified as resulting from abnormalities during late neuronal migration or early cortical organization of fetal development. Evidence for both genetic and non-genetic causes exists. Polymicrogyria appears to occur around the time of neuronal migration or early cortical development. Non-genetic causes include defects in placental oxygenation and in association with congenital infections, particularly cytomegalovirus.

An association with the gene WDR62 has been identified.

In general, gray matter heterotopia is fixed in both its occurrence and symptoms; that is, once symptoms occur, it does not tend to progress. Varying results from surgical resection of the affected area have been reported. Although such surgery cannot reverse developmental disabilities, it may provide full or partial relief from seizures.

Heterotopia are most commonly isolated anomalies, but may be part of a number of syndromes, including chromosomal abnormalities and fetal exposure to toxins (including alcohol).

Although no treatments have been approved for use in human PVL patients, a significant amount of research is occurring in developing treatments for protection of the nervous system. Researchers have begun to examine the potential of synthetic neuroprotection to minimize the amount of lesioning in patients exposed to ischemic conditions.

The effects of polymicrogyria (PMG) can be either focal or widespread. Although both can have physiological effects on the patient, it is hard to determine PMG as the direct cause because it can be associated with other brain malformations. Most commonly, PMG is associated with Aicardi and Warburg micro syndromes. These syndromes both have frontoparieto polymicrogyria as their anomalies. To ensure proper diagnosis, doctors thus can examine a patient through neuroimaging or neuropathological techniques.

Nasal glial heterotopia is rare, while an encephalocele is uncommon. NGH usually presents in infancy, while encephalocele may present in older children and adults. It is seen in both genders equally.

When seizures are present in any forms of cortical dysplasia, they are resistant to medication. Frontal lobe resection provides significant relief from seizures to a minority of patients with periventricular lesions.

Although surgery is the treatment of choice, it must be preceded by imaging studies to exclude an intracranial connection. Potential complications include meningitis and a cerebrospinal fluid leak. Recurrences or more correctly persistence may be seen in up to 30% of patients if not completely excised.

Recent population-based studies have estimated the prevalence of NPH to be about 0.5% in those over 65 years old, with an incidence of about 5.5 patients per 100,000 of people per year. This is in accordance with comparable findings stating that although normal pressure hydrocephalus can occur in both men and women of any age, it is found more often in the elderly population, with a peak onset generally in the sixth to seventh decades.

Overall, the relative incidence of neonatal encephalopathy is estimated to be between 2 and 9 per 1000 term births. 40% to 60% of affected infants die by 2 years old or have severe disabilities. In 2013 it was estimated to have resulted in 644,000 deaths down from 874,000 deaths in 1990.

If a cause presents itself, the syndrome is referred to as "symptomatic" West syndrome, as the attacks manifest as a symptom of another problem. Almost any cause of brain damage could be associated, and these are divided into prenatal, perinatal, and post-natal. The following is a partial list:

- In around one third of the children, there is evidence of a profound organic disorder of the brain. This includes:

- microcephaly

- cortical dysplasia

- cerebral atrophy

- lissencephaly

- bacterial meningitis

- phakomatoses (e.g. tuberous sclerosis)

- Aicardi syndrome

- cephalhematoma and

- vascular malformation.

- Furthermore, other causes increasingly being named in the literature are:

- Incontinentia pigmenti

- Foix-Chavany-Marie syndrome

- Patau syndrome (trisomy 13)

- Sturge-Weber syndrome

- neurometabolic diseases

- congential infections (e.g. Cytomegalovirus)

- hypoglycemia

- brain damage due to asphyxiation or hypoxia (lack of oxygen, e.g. during birth), periventricular leukomalacia, cephalhematoma, cerebrovascular accident or brain damage of various types as well as that caused by premature birth.

West syndrome appears in 1% to 5% of infants with Down syndrome. This form of epilepsy is relatively difficult to treat in children who do not have the chromosomal abnormalities involved in Down syndrome. However, in children with Down syndrome, the syndrome is often far more mild, and the children often react better to medication. The German Down Syndrom InfoCenter noted in 2003 that what was normally a serious epilepsy was in such cases often a relatively benign one.

EEG records for children with Down syndrome are often more symmetrical with fewer unusual findings. Although not all children can become entirely free from attacks with medication, children with Down syndrome are less likely to go on to develop Lennox-Gastaut syndrome or other forms of epilepsy than those without additional hereditary material on the 21st chromosome. The reason why it is easier to treat children with Down syndrome is not known.

If, however, a child with Down syndrome has seizures that are difficult to control, the child should be accessed for autistic spectrum disorder.

HIE is a major predictor of neurodevelopmental disability in term infants. 25 percent have permanent neurological deficits.

It can result in developmental delay or periventricular leukomalacia.

Patients with dementia who are confined to a nursing home and may have undiagnosed NPH can possibly become independent again once treated. So far only one study was able to evaluate the prevalence of NPH, both diagnosed and undiagnosed, among residents of assisted-living facilities, showing a prevalence in 9 to 14% of the residents.

NPH may be relieved by surgically implanting a ventriculoperitoneal shunt to drain excess cerebrospinal fluid to the abdomen where it is absorbed. Once the shunt is in place, the ventricles usually diminish in size in 3 to 4 days, regardless of the duration of the hydrocephalus. Even though the ventricular swelling diminishes, only 21% of patients show a marked improvement in symptoms. The most likely patients to show improvement are those that show only gait disturbance, mild or no incontinence, and mild dementia. A more recent study (2004) found better outcomes, concluding that if patients with idiopathic normal pressure hydrocephalus are correctly identified, shunt insertion yielded beneficial outcomes in 86% of patients, in either gait disturbance (81%), improved continence (70%), or both. They also observed that measurements in the diagnostic clinical triad, the cortical sulci size, and periventricular lucencies were related to outcome. However, other factors such as age of the patient, symptom duration, dilation of ventricles, and the degree of presurgical dementia were unrelated to outcome.

Choristomas, forms of heterotopia, are closely related benign tumors, found in abnormal locations.

It is different from hamartoma. The two can be differentiated as follows: a hamartoma is disorganized overgrowth of tissues in their normal location, (eg, Peutz-Jeghers polyps) while a choristoma is normal tissue growth in an abnormal location (e.g., gastric tissue located in distal ileum in Meckel diverticulum).

Spastic quadriplegia is generally caused by brain damage or disruptions in normal brain development preceding birth. According to the National Institutes of Health, there are four types of brain damage that can cause spastic quadriplegia. These include, damage to the white matter (periventricular leukomalacia), abnormal brain development (cerebral dysgenesis), bleeding in the brain (intracranial hemorrhage), and brain damage due to lack of oxygen (hypoxic-ischemic encephalopathy or intrapartum asphyxia).

The white matter of the brain is especially vulnerable between the 26th and 34th weeks of maturation, and damage to the white matter can interfere with the brain’s ability to transmit signals to the rest of the body. Spastic quadriplegia can be caused by a condition known as periventricular leukomalacia which results in the formation of lesions and holes in the white matter of the brain.

Prior to the 26th week of maturation, the fetal brain is particularly susceptible to various toxins whose effects can ultimately hinder normal development. Exposure of the brain to infectious agents is especially dangerous because they can trigger immune responses that activate cytokines and lead to inflammation of the brain. Some infections that have been linked to the development of spastic quadriplegia include meningitis, herpes, rubella, and encephalitis. A difference in blood types between the mother and the fetus can also initiate a problematic immune response and cause brain damage. Severe jaundice, can also lead to brain damage and spastic quadriplegia due to a buildup of bilirubin in the blood.

Bleeding in the brain caused by fetal strokes, blood clots, weak and malformed blood vessels, or high maternal blood pressure may also lead to brain damage causing spastic quadriplegia. Maternal infection, most specifically pelvic inflammatory disease, has been shown to increase the risk of fetal stroke.

Hypoxia, lack of oxygen to the brain, can also cause damage in the cerebral motor cortex and other brain regions. This lack of oxygen can be the result of placenta malfunction, womb rupture, umbilical cord damage, low maternal blood pressure or asphyxia during labor and delivery.

Children who experienced many complications during birth, such as, prematurity, insufficient oxygen, low birthweight, aspiration, head injury, or bleeding in the brain have a greater risk of developing spastic quadriplegia. Children whose mothers were ill during the pregnancy or did not receive adequate nutrition are also more likely to develop the disease.

The severity of impairment and related prognosis is dependent on the location and severity of brain lesions. Up to 50% of patients will achieve some degree of ambulation. Speech problems, such as dysarthria, are common to these patients.

Hypoxic-ischemic brain injury (HIBI) is a form of cerebral hypoxia in which oxygen cannot perfuse to cells in the brain. Lesions in the putamen and thalamus caused by HIBI are primary causes of ADCP and can occur during the prenatal period and shortly after. Lesions that arise after this period typically occur as a result of injury or infections of the brain. 40~50% will have intellectual disability.

Hamartomas, while generally benign, can cause problems due to their location. For example, when located on the skin, especially on the face or neck, they can be very disfiguring. Cases have been reported of hamartomas the size of a small orange. They may obstruct practically any organ in the body, such as the colon, eye, etc. They are particularly likely to cause major health issues when located in the hypothalamus, kidneys, lips, or spleen. They can be removed surgically if necessary, and are not likely to recur. Prognosis will depend upon the location and size of the lesion, as well as the overall health of the patient.

In the industrialized world, the incidence of overall cerebral palsy, which includes but is not limited to spastic diplegia, is about 2 per 1000 live births. Thus far, there is no known study recording the incidence of CP in the overall nonindustrialized world. Therefore, it is safe to assume that not all spastic CP individuals are known to science and medicine, especially in areas of the world where healthcare systems are less advanced. Many such individuals may simply live out their lives in their local communities without any medical or orthopedic oversight at all, or with extremely minimal such treatment, so that they are never able to be incorporated into any empirical data that orthopedic surgeons or neurosurgeons might seek to collect. It is shocking to note that—as with people with physical disability overall—some may even find themselves in situations of institutionalization, and thus barely see the outside world at all.

From what "is" known, the incidence of spastic diplegia is higher in males than in females; the Surveillance of Cerebral Palsy in Europe (SCPE), for example, reports a M:F ratio of 1.33:1. Variances in reported rates of incidence across different geographical areas in industrialized countries are thought to be caused primarily by discrepancies in the criteria used for inclusion and exclusion.

When such discrepancies are taken into account in comparing two or more registers of patients with cerebral palsy and also the extent to which children with mild cerebral palsy are included, the incidence rates still converge toward the average rate of 2:1000.

In the United States, approximately 10,000 infants and babies are born with CP each year, and 1200–1500 are diagnosed at preschool age when symptoms become more obvious. It is interesting to note that those with extremely mild spastic CP may not even be aware of their condition until much later in life: Internet chat forums have recorded men and women as old as 30 who were diagnosed only recently with their spastic CP.

Overall, advances in care of pregnant mothers and their babies has not resulted in a noticeable decrease in CP; in fact, because medical advances in areas related to the care of premature babies has resulted in a greater survival rate in recent years, it is actually "more" likely for infants with cerebral palsy to be born into the world now than it would have been in the past. Only the introduction of quality medical care to locations with less-than-adequate medical care has shown any decreases in the incidences of CP; the rest either have shown no change or have actually shown an increase. The incidence of CP increases with premature or very low-weight babies regardless of the quality of care.

Although many perinatal and prenatal risk factors for ONH have been suggested, the predominant, enduring, most frequent risk factors are young maternal age and primiparity (the affected child being the first child born to the mother). Increased frequency of delivery by caesarean section and fetal/neonatal complications, preterm labor, gestational vaginal bleeding, low maternal weight gain, and weight loss during pregnancy are also associated with ONH.