Porencephaly

Last updated
Porencephaly
Specialty Medical genetics, neurology   OOjs UI icon edit-ltr-progressive.svg

Porencephaly is an extremely rare cephalic disorder involving encephalomalacia. [1] It is a neurological disorder of the central nervous system characterized by cysts or cavities within the cerebral hemisphere. [2] Porencephaly was termed by Heschl in 1859 to describe a cavity in the human brain. [3] Derived from Greek roots, the word porencephaly means 'holes in the brain'. [4] The cysts and cavities (cystic brain lesions) are more likely to be the result of destructive (encephaloclastic) cause, but can also be from abnormal development (malformative), direct damage, inflammation, or hemorrhage. [5] The cysts and cavities cause a wide range of physiological, physical, and neurological symptoms. [6] Depending on the patient, this disorder may cause only minor neurological problems, without any disruption of intelligence, while others may be severely disabled or die before the second decade of their lives. However, this disorder is far more common within infants, and porencephaly can occur both before or after birth. [2]

Contents

Signs and symptoms

Patients diagnosed with porencephaly display a variety of symptoms, from mild to severe effects on the patient. Patients with severe cases of porencephaly have epileptic seizures and developmental delays, whereas patients with a mild case of porencephaly display little to no seizures and typical neurodevelopment. Infants with extensive defects show symptoms of the disorder shortly after birth, and the diagnosis is usually made before the age of 1. [2] [7]

The following text lists out common signs and symptoms of porencephaly in affected individuals along with a short description of certain terminologies. [2] [6] [7] [8]

Cause

Porencephaly is a rare disorder. The exact prevalence of porencephaly is not known; however, it has been reported that 6.8% of patients with cerebral palsy or 68% of patients with epilepsy and congenital vascular hemiparesis have porencephaly. [5] Porencephaly has a number of different, often unknown, causes including absence of brain development and destruction of brain tissue. With limited research, the most commonly regarded cause of porencephaly is disturbances in blood circulation, ultimately leading to brain damage. [6] However, a number of different and multiple factors such as abnormal brain development or damage to the brain tissue can also affect the development of porencephaly. [2]

The following text lists out potential risk factors of developing porencephaly and porencephalic cysts and cavities along with brief description of certain terminologies. [3] [6] [7] [9]

Cysts or cavities can occur anywhere within the brain and the locations of these cysts depend highly on the patient. Cysts can develop in the frontal lobe, parietal lobe, forebrain, hindbrain, temporal lobe, or virtually anywhere in the cerebral hemisphere. [7]

Genetics

From recent studies, de novo and inherited mutations in the gene COL4A1 , suggesting genetic predisposition within the family, that encodes type IV collagen α1 chain has shown to be associated with and present in patients with porencephaly. COL4A1 mutation causes a variety of phenotypes, including porencephaly, infantile hemiplegia, and cerebral small vessel diseases involving both stroke and infarction. [6] Abnormal gene expression of COL4A1 can contribute to the development of porencephaly. COL4A1 gene expresses a type IV collagen (basement protein) that is present in all tissue and blood vessels and is extremely important for the structural stability of vascular basement membranes. The COL4A1 protein provides a strong layer around blood vessels. [10] The mutation can weaken the blood vessels within the brain, elevating the probability of a hemorrhage, and eventually promoting internal bleeding then leading to porencephaly during neurodevelopment of infantile stage. [6] Therefore, the formation of cavities can be a result of hemorrhages which promote cerebral degeneration. [10] In a mouse model, mouse with COL4A1 mutations displayed cerebral hemorrhage, porencephaly, and abnormal development of vascular basement membranes, such as uneven edges, inconsistent shapes, and highly variable thickness. [6] Purposely causing a mutation in the COL4A1 gene caused several mouse to develop cerebral hemorrhage and porencephaly-like diseases. Though, there is no direct correlation between mutations of the COL4A1 gene, it appears that it has an influential effect on the development of porencephaly. [11] [12] [13]

Another genetic mutation, factor V G1691A mutation, has been reported to show possible association to the development of porencephaly. A mutation in factor V G1691A increases the risk of thrombosis, blood clots, in neonates, infants, and children. [5] Therefore, 76 porencephalic and 76 healthy infants were investigated for factor V G1691A mutation along with other different prothrombotic risk factors. The results indicated that there was higher prevalence of the factor V G1691A mutation in the porencephalic patient group. The prediction that childhood porencephaly is caused by hypercoagulable state, a condition where one has a higher chance of developing blood clots, was supported by the significance of the factor V G1691A mutation. Also, pregnant women in hypercoagulable state can cause the fetus to have the same risks, therefore possibly causing fetal loss, brain damage, lesions, and infections that lead to porencephaly. However, other different prothrombotic risk factors individually did not reach statistical significance to link it to the development of porencephaly, but a combination of multiple prothrombotic risk factors in the porencephaly group was significant. Overall, factor V G1691A mutation has been linked to the development of porencephaly. However, this one mutation is not the cause of porencephaly, and whether further prothrombiotic risk factors are associated with porencephaly still remains unknown. [5]

Cocaine and other street drugs

In utero exposure to cocaine and other street drugs can lead to porencephaly. [14]

Diagnostics

The presence of porencephalic cysts or cavities can be detected using trans-illumination of the skull of infant patients. Porencephaly is usually diagnosed clinically using the patients and families history, clinical observations, or based on the presence of certain characteristic neurological and physiological features of porencephaly. Advanced medical imaging with computed tomography (CT), magnetic resonance imaging (MRI), or with ultrasonography can be used as a method to exclude other possible neurological disorders. The diagnosis can be made antenatally with ultrasound. Other assessments include memory, speech, or intellect testing to help further determine the exact diagnose of the disorder. [2]

Treatments

Currently, there is no cure for porencephaly because of the limited resources and knowledge about the neurological disorder. However, several treatment options are available. Treatment may include physical therapy, rehabilitation, medication for seizures or epilepsy, shunt (medical), or neurosurgery (removal of the cyst). [2] According to the location, extent of the lesion, size of cavities, and severity of the disorder, combinations of treatment methods are imposed. In porencephaly patients, patients achieved good seizure control with appropriate drug therapy including valproate, carbamazepine, and clobazam. [6] [7] Also, anti-epileptic drugs served as another positive method of treatment. [7]

Prognosis

The severity of the symptoms associated with porencephaly varies significantly across the population of those affected, depending on the location of the cyst and damage of the brain. For some patients with porencephaly, only minor neurological problems may develop, and those patients can live normal lives. Therefore, based on the level of severity, self-care is possible, but for the more serious cases lifelong care will be necessary. [2] For those that have severe disability, early diagnosis, medication, participation in rehabilitation related to fine-motor control skills, and communication therapies can significantly improve the symptoms and ability of the patient with porencephaly to live a normal life. Infants with porencephaly that survive, with proper treatment, can display proper communication skills, movement, and live a normal life.[ citation needed ]

Research

Under the United States federal government, the National Institute of Neurological Disorders and Stroke and National Institute of Health are involved in conducting and supporting research related to normal and abnormal brain and nervous system development. Information gained from the research is used to develop understanding of the mechanism of porencephaly and used to offer new methods of treatment and prevention for developmental brain disorders such as porencephaly. [2]

See also

Related Research Articles

<span class="mw-page-title-main">Head injury</span> Serious trauma to the cranium

A head injury is any injury that results in trauma to the skull or brain. The terms traumatic brain injury and head injury are often used interchangeably in the medical literature. Because head injuries cover such a broad scope of injuries, there are many causes—including accidents, falls, physical assault, or traffic accidents—that can cause head injuries.

<span class="mw-page-title-main">Vascular dementia</span> Dementia resulting from stroke

Vascular dementia is dementia caused by a series of strokes. Restricted blood flow due to strokes reduces oxygen and glucose delivery to the brain, causing cell injury and neurological deficits in the affected region. Subtypes of vascular dementia include subcortical vascular dementia, multi-infarct dementia, stroke-related dementia, and mixed dementia.

<span class="mw-page-title-main">Hydranencephaly</span> Medical condition

Hydranencephaly is a condition in which the brain's cerebral hemispheres are absent to a great degree and the remaining cranial cavity is filled with cerebrospinal fluid. "Cephalic" is the scientific term for "head" or "head end of body".

<span class="mw-page-title-main">Schizencephaly</span> Medical condition

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 this malformation include epilepsy, motor deficits, and psychomotor retardation.

<span class="mw-page-title-main">Cerebrovascular disease</span> Condition that affects the arteries that supply the brain

Cerebrovascular disease includes a variety of medical conditions that affect the blood vessels of the brain and the cerebral circulation. Arteries supplying oxygen and nutrients to the brain are often damaged or deformed in these disorders. The most common presentation of cerebrovascular disease is an ischemic stroke or mini-stroke and sometimes a hemorrhagic stroke. Hypertension is the most important contributing risk factor for stroke and cerebrovascular diseases as it can change the structure of blood vessels and result in atherosclerosis. Atherosclerosis narrows blood vessels in the brain, resulting in decreased cerebral perfusion. Other risk factors that contribute to stroke include smoking and diabetes. Narrowed cerebral arteries can lead to ischemic stroke, but continually elevated blood pressure can also cause tearing of vessels, leading to a hemorrhagic stroke.

<span class="mw-page-title-main">Cerebral edema</span> Excess accumulation of fluid (edema) in the intracellular or extracellular spaces of the brain

Cerebral edema is excess accumulation of fluid (edema) in the intracellular or extracellular spaces of the brain. This typically causes impaired nerve function, increased pressure within the skull, and can eventually lead to direct compression of brain tissue and blood vessels. Symptoms vary based on the location and extent of edema and generally include headaches, nausea, vomiting, seizures, drowsiness, visual disturbances, dizziness, and in severe cases, death.

<span class="mw-page-title-main">Hereditary hemorrhagic telangiectasia</span> Medical condition (genetic disorder)

Hereditary hemorrhagic telangiectasia (HHT), also known as Osler–Weber–Rendu disease and Osler–Weber–Rendu syndrome, is a rare autosomal dominant genetic disorder that leads to abnormal blood vessel formation in the skin, mucous membranes, and often in organs such as the lungs, liver, and brain.

A thunderclap headache is a headache that is severe and has a sudden onset. It is defined as a severe headache that takes seconds to minutes to reach maximum intensity. Although approximately 75% are attributed to "primary" headaches—headache disorder, non-specific headache, idiopathic thunderclap headache, or uncertain headache disorder—the remainder are secondary to other causes, which can include some extremely dangerous acute conditions, as well as infections and other conditions. Usually, further investigations are performed to identify the underlying cause.

<span class="mw-page-title-main">Cerebral hypoxia</span> Oxygen shortage of the brain

Cerebral hypoxia is a form of hypoxia, specifically involving the brain; when the brain is completely deprived of oxygen, it is called cerebral anoxia. There are four categories of cerebral hypoxia; they are, in order of increasing severity: diffuse cerebral hypoxia (DCH), focal cerebral ischemia, cerebral infarction, and global cerebral ischemia. Prolonged hypoxia induces neuronal cell death via apoptosis, resulting in a hypoxic brain injury.

<span class="mw-page-title-main">Sturge–Weber syndrome</span> Medical condition

Sturge–Weber syndrome, sometimes referred to as encephalotrigeminal angiomatosis, is a rare congenital neurological and skin disorder. It is one of the phakomatoses and is often associated with port-wine stains of the face, glaucoma, seizures, intellectual disability, and ipsilateral leptomeningeal angioma. Sturge–Weber syndrome can be classified into three different types. Type 1 includes facial and leptomeningeal angiomas as well as the possibility of glaucoma or choroidal lesions. Normally, only one side of the brain is affected. This type is the most common. Type 2 involvement includes a facial angioma with a possibility of glaucoma developing. There is no evidence of brain involvement. Symptoms can show at any time beyond the initial diagnosis of the facial angioma. The symptoms can include glaucoma, cerebral blood flow abnormalities and headaches. More research is needed on this type of Sturge–Weber syndrome. Type 3 has leptomeningeal angioma involvement exclusively. The facial angioma is absent and glaucoma rarely occurs. This type is only diagnosed via brain scan.

<span class="mw-page-title-main">Perivascular space</span>

A perivascular space, also known as a Virchow–Robin space, is a fluid-filled space surrounding certain blood vessels in several organs, including the brain, potentially having an immunological function, but more broadly a dispersive role for neural and blood-derived messengers. The brain pia mater is reflected from the surface of the brain onto the surface of blood vessels in the subarachnoid space. In the brain, perivascular cuffs are regions of leukocyte aggregation in the perivascular spaces, usually found in patients with viral encephalitis.

<span class="mw-page-title-main">Periventricular leukomalacia</span> Degeneration of white matter near the lateral ventricles of the brain

Periventricular leukomalacia (PVL) is a form of white-matter brain injury, characterized by the necrosis of white matter near the lateral ventricles. It can affect newborns and fetuses; premature infants are at the greatest risk of neonatal encephalopathy which may lead to this condition. Affected individuals generally exhibit motor control problems or other developmental delays, and they often develop cerebral palsy or epilepsy later in life. The white matter in preterm born children is particularly vulnerable during the third trimester of pregnancy when white matter developing takes place and the myelination process starts around 30 weeks of gestational age.

<span class="mw-page-title-main">Arachnoid cyst</span> Medical condition

Arachnoid cysts are cerebrospinal fluid covered by arachnoidal cells and collagen that may develop between the surface of the brain and the cranial base or on the arachnoid membrane, one of the three meningeal layers that cover the brain and the spinal cord. Primary arachnoid cysts are a congenital disorder whereas secondary arachnoid cysts are the result of head injury or trauma. Most cases of primary cysts begin during infancy; however, onset may be delayed until adolescence.

<span class="mw-page-title-main">Leukoencephalopathy with vanishing white matter</span> Neurological disease

Leukoencephalopathy with vanishing white matter is an autosomal recessive neurological disease. The cause of the disease are mutations in any of the 5 genes encoding subunits of the translation initiation factor eIF2B: EIF2B1, EIF2B2, EIF2B3, EIF2B4, or EIF2B5. The disease belongs to a family of conditions called the Leukodystrophies.

<span class="mw-page-title-main">Bonnet–Dechaume–Blanc syndrome</span> Medical condition

Bonnet–Dechaume–Blanc syndrome, also known as Wyburn-Mason syndrome, is a rare congenital disorder characterized by arteriovenous malformations of the brain, retina or facial nevi. The syndrome has a number of possible symptoms and can, more rarely, affect the skin, bones, kidneys, muscles, and gastrointestinal tract. When the syndrome affects the brain, people can experience severe headaches, seizures, acute stroke, meningism, and progressive neurological deficits due to acute or chronic ischaemia caused by arteriovenous shunting.

A silent stroke is a stroke that does not have any outward symptoms associated with stroke, and the patient is typically unaware they have suffered a stroke. Despite not causing identifiable symptoms, a silent stroke still causes damage to the brain and places the patient at increased risk for both transient ischemic attack and major stroke in the future. In a broad study in 1998, more than 11 million people were estimated to have experienced a stroke in the United States. Approximately 770,000 of these strokes were symptomatic and 11 million were first-ever silent MRI infarcts or hemorrhages. Silent strokes typically cause lesions which are detected via the use of neuroimaging such as MRI. The risk of silent stroke increases with age but may also affect younger adults. Women appear to be at increased risk for silent stroke, with hypertension and current cigarette smoking being amongst the predisposing factors.

PHACE syndrome is a medical condition involving the uncommon association between large infantile hemangiomas, usually of the face, and birth defects of the brain, heart, eyes, skin and/or arteries. PHACE is an acronym that stands for the medical names of the parts of the body it often impacts:

<span class="mw-page-title-main">Cavernous hemangioma</span> Human disease

Cavernous hemangioma, also called cavernous angioma, venous malformation, or cavernoma, is a type of venous malformation due to endothelial dysmorphogenesis from a lesion which is present at birth. A cavernoma in the brain is called a cerebral cavernous malformation or CCM. Despite its designation as a hemangioma, a cavernous hemangioma is not a tumor as it does not display endothelial hyperplasia. The abnormal tissue causes a slowing of blood flow through the cavities, or "caverns". The blood vessels do not form the necessary junctions with surrounding cells, and the structural support from the smooth muscle is hindered, causing leakage into the surrounding tissue. It is the leakage of blood, referred to as hemorrhage, that causes a variety of symptoms known to be associated with the condition.

<span class="mw-page-title-main">Autosomal dominant porencephaly type I</span> Medical condition

Autosomal dominant porencephaly type I is a rare type of porencephaly that causes cysts to grow on the brain and damage to small blood vessels, which can lead to cognitive impairment, migraines, seizures, and hemiplegia or hemiparesis.

Perinatal stroke is a disease where an infant has a stroke between the 140th day of the gestation period and the 28th postpartum day, affecting up to 1 in 2300 live births. This disease is further divided into three subgroups, namely neonatal arterial ischemic stroke, neonatal cerebral sinovenous ischemic stroke, and presumed perinatal stroke. Several risk factors contribute to perinatal stroke including birth trauma, placental abruption, infections, and the mother's health.

References

  1. Gul A, Gungorduk K, Yildirim G, Gedikbasi A, Ceylan Y (2009). "Prenatal diagnosis of porencephaly secondary to maternal carbon monoxide poisoning". Arch. Gynecol. Obstet. 279 (5): 697–700. doi:10.1007/s00404-008-0776-3. PMID   18777036. S2CID   26880094.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  2. 1 2 3 4 5 6 7 8 9 Parker, J. (2004). The official parent's sourcebook on porencephaly: A revised and updated directory for the internet age. ICON Health Publications.
  3. 1 2 Hirowatari C., Kodama R., Sasaki Y., Tanigawa Y., Fujishima J.; et al. (2012). "Porencephaly in a Cynomolgus Monkey ( Macaca Fascicularis )". Journal of Toxicologic Pathology. 25 (1): 45–49. doi: 10.1293/tox.25.45 . PMC   3320157 . PMID   22481858.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. Maria Gieron-Korthals; José Colón (2005). "Hypoxic-ischemic encephalopathy in infants: new challenges". Fetal and Pediatric Pathology. 24 (2). Taylor & Francis. ... Porencephaly (Greek for 'holes in the brain') are hemispheric cavitary lesions that typically communicate with the ventricular system....
  5. 1 2 3 4 Debus O., Kosch A., Strater R., Rossi R., Nowak-Gottl U. (2004). "The Factor V G1691A Mutation is a Risk for Porencephaly: A Case-control Study". Annals of Neurology. 56 (2): 287–290. doi:10.1002/ana.20184. PMID   15293282. S2CID   33972596.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  6. 1 2 3 4 5 6 7 8 Yoneda Y., Haginoya K., Arai H., Yamaoka S., Tsurusaki Y.; et al. (2012). "De Novo and Inherited Mutations in COL4A2, Encoding the Type IV Collagen α2 Chain Cause Porencephaly". Am J Hum Genet. 90 (1): 86–90. doi: 10.1016/j.ajhg.2011.11.016 . PMC   3257897 . PMID   22209246.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  7. 1 2 3 4 5 6 Shimizu M., Maeda T., Izumi T. (2012). "The Differences in Epileptic Characteristics in Patients with Porencephaly and Schizencephaly". Brain Dev. 34 (7): 546–552. doi:10.1016/j.braindev.2011.10.001. PMID   22024697. S2CID   937294.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  8. Gould D., Phalan F., Breedveld G., van Mil S., Smith R.; et al. (2005). "Mutations in Col4a 1 Cause Perinatal Cerebral Hemorrhage and Porencephaly". Science. 308 (5725): 1167–1171. Bibcode:2005Sci...308.1167G. doi:10.1126/science.1109418. PMID   15905400. S2CID   11439477.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  9. Tonni G., Ferrari B., Defelice C., Centini G. (2005). "Neonatal Porencephaly in Very Low Birth Weight Infants: Ultrasound Timing of Asphyxial Injury and Neurodevelopmental Outcome at Two Years of Age". J Matern Fetal Neonatal Med. 18 (6): 361–365. doi:10.1080/14767050400029574. PMID   16390800. S2CID   33117246.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  10. 1 2 Thomas L (2005). "Genetic Mutation Predisposes to Porencephaly". Lancet Neurology. 4 (7): 400. doi:10.1016/s1474-4422(05)70114-9. PMID   15991439. S2CID   19804698.
  11. Schmidt, Martin J.; Klumpp, Stephan; Amort, Kerstin; Jawinski, Sebastian; Kramer, Martin (March 2012). "Porencephaly in dogs and cats: magnetic resonance imaging findings and clinical signs". Veterinary Radiology & Ultrasound. 53 (2): 142–149. doi:10.1111/j.1740-8261.2011.01887.x. ISSN   1058-8183. PMID   22734149.
  12. Meuwissen M., de Vries L., Verbeek H., Lequin M., Govaert P.; et al. (2011). "Sporadic COL4A1 Mutations with Extensive Prenatal Porencephaly Resembling Hydranencephaly". Neurology. 76 (9): 844–846. doi:10.1212/wnl.0b013e31820e7751. PMID   21357838. S2CID   207118938.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  13. Breedveld G., de Coo I., Lequin M., Arts W., Heutink P.; et al. (2006). "Novel Mutations in Three Families Confirm a Major Role of COL4A1 in Hereditary Porencephaly". Journal of Medical Genetics. 43 (6): 490–495. doi:10.1136/jmg.2005.035584. PMC   2593028 . PMID   16107487.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  14. Dominguez, R; Aguirre Vila-Coro, A; Slopis, JM; Bohan, TP (June 1991). "Brain and ocular abnormalities in infants with in utero exposure to cocaine and other street drugs". American Journal of Diseases of Children. 145 (6): 688–95. doi:10.1001/archpedi.1991.02160060106030. PMID   1709777.