Porencephaly is an extremely rare

cephalic disorder Cephalic disorders () are Congenital disorder, congenital conditions that stem from damage to, or abnormal development of, the budding nervous system. Cephalic disorders are not necessarily caused by a single factor, but may be influenced by her ...

involving

encephalomalacia Cerebral softening, also known as encephalomalacia, is a localized softening of the substance of the brain, due to bleeding or inflammation. Three varieties, distinguished by their color and representing different stages of the disease progress, ar ...

. It is a

neurological disorder Neurological disorders represent a complex array of medical conditions that fundamentally disrupt the functioning of the nervous system. These disorders affect the brain, spinal cord, and nerve networks, presenting unique diagnosis, treatment, and ...

of the central nervous system characterized by

cysts A cyst is a closed Wikt:sac, sac, having a distinct Cell envelope, envelope and cell division, division compared with the nearby Biological tissue, tissue. Hence, it is a cluster of Cell (biology), cells that have grouped together to form a sac ...

cavities Cavity may refer to: Biology and healthcare *Body cavity, a fluid-filled space in many animals where organs typically develop ** Gastrovascular cavity, the primary organ of digestion and circulation in cnidarians and flatworms * Dental cavity or t ...

within the

cerebral hemisphere 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 ...

.Parker, J. (2004). The official parent's sourcebook on porencephaly: A revised and updated directory for the internet age. ICON Health Publications. Porencephaly was termed by Heschl in 1859 to describe a cavity in the human brain. Derived from

Greek Greek may refer to: Anything of, from, or related to Greece, a country in Southern Europe: *Greeks, an ethnic group *Greek language, a branch of the Indo-European language family **Proto-Greek language, the assumed last common ancestor of all kno ...

roots, the word ''porencephaly'' means 'holes in the brain'. 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. The cysts and cavities cause a wide range of physiological, physical, and neurological symptoms. 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.

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 A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...

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. The following text lists out common signs and symptoms of porencephaly in affected individuals along with a short description of certain terminologies.

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 Cerebral palsy (CP) is a group of movement disorders that appear in early childhood. Signs and symptoms vary among people and over time, but include poor coordination, spasticity, stiff muscles, Paresis, weak muscles, and tremors. There may b ...

or 68% of patients with

epilepsy Epilepsy is a group of Non-communicable disease, non-communicable Neurological disorder, neurological disorders characterized by a tendency for recurrent, unprovoked Seizure, seizures. A seizure is a sudden burst of abnormal electrical activit ...

and congenital vascular

hemiparesis Hemiparesis, also called unilateral paresis, is the weakness of one entire side of the body (''wikt:hemi-#Prefix, hemi-'' means "half"). Hemiplegia, in its most severe form, is the complete paralysis of one entire side of the body. Either hemipar ...

have porencephaly. 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. 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. The following text lists out potential risk factors of developing porencephaly and porencephalic cysts and cavities along with brief description of certain terminologies. 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 The frontal lobe is the largest of the four major lobes of the brain in mammals, and is located at the front of each cerebral hemisphere (in front of the parietal lobe and the temporal lobe). It is parted from the parietal lobe by a Sulcus (neur ...

parietal lobe The parietal lobe is one of the four Lobes of the brain, major lobes of the cerebral cortex in the brain of mammals. The parietal lobe is positioned above the temporal lobe and behind the frontal lobe and central sulcus. The parietal lobe integra ...

forebrain In the anatomy of the brain of vertebrates, the forebrain or prosencephalon is the rostral (forward-most) portion of the brain. The forebrain controls body temperature, reproductive functions, eating, sleeping, and the display of emotions. Ve ...

hindbrain The hindbrain, rhombencephalon (shaped like a rhombus) is a developmental categorization of portions of the central nervous system in vertebrates. It includes the medulla, pons, and cerebellum. Together they support vital bodily processes. Met ...

temporal lobe The temporal lobe is one of the four major lobes of the cerebral cortex in the brain of mammals. The temporal lobe is located beneath the lateral fissure on both cerebral hemispheres of the mammalian brain. The temporal lobe is involved in pr ...

, or virtually anywhere in the

Genetics

From recent studies,

de novo De novo (Latin, , used in English to mean 'from the beginning', 'anew') may refer to: Science and computers * ''De novo'' mutation, a new germline mutation not inherited from either parent * ''De novo'' protein design, the creation of a protei ...

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 In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology (physical form and structure), its developmental processes, its biochemical and physiological properti ...

, including porencephaly, infantile

hemiplegia Hemiparesis, also called unilateral paresis, is the weakness of one entire side of the body ('' hemi-'' means "half"). Hemiplegia, in its most severe form, is the complete paralysis of one entire side of the body. Either hemiparesis or hemiplegia ...

, and cerebral small vessel diseases involving both

stroke Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...

and

infarction Infarction is tissue death (necrosis) due to Ischemia, inadequate blood supply to the affected area. It may be caused by Thrombosis, artery blockages, rupture, mechanical compression, or vasoconstriction. The resulting lesion is referred to as a ...

. 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 basement membrane, also known as base membrane, is a thin, pliable sheet-like type of extracellular matrix that provides cell and tissue support and acts as a platform for complex signalling. The basement membrane sits between epithelial tiss ...

. The ''COL4A1'' protein provides a strong layer around blood vessels. The mutation can weaken the blood vessels within the brain, elevating the probability of a

hemorrhage Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, ...

, and eventually promoting internal bleeding then leading to porencephaly during neurodevelopment of infantile stage. Therefore, the formation of cavities can be a result of hemorrhages which promote cerebral degeneration. In a mouse model, mouse with ''COL4A1'' mutations displayed

cerebral hemorrhage Intracerebral hemorrhage (ICH), also known as hemorrhagic stroke, is a sudden bleeding into the tissues of the brain (i.e. the parenchyma), into its ventricles, or into both. An ICH is a type of bleeding within the skull and one kind of stro ...

, porencephaly, and abnormal development of vascular basement membranes, such as uneven edges, inconsistent shapes, and highly variable thickness. 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. 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 Thrombosis () is the formation of a Thrombus, blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (thrombocytes) and fib ...

, blood clots, in

neonates In common terminology, a baby is the very young offspring of adult human beings, while infant (from the Latin word ''infans'', meaning 'baby' or 'child') is a formal or specialised synonym. The terms may also be used to refer to Juvenile (orga ...

, infants, and children. 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 Thrombophilia (sometimes called hypercoagulability or a prothrombotic state) is an abnormality of blood coagulation that increases the risk of thrombosis (blood clots in blood vessels). Such abnormalities can be identified in 50% of people who ...

, 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.

Cocaine and other street drugs

In utero The uterus (from Latin ''uterus'', : uteri or uteruses) or womb () is the organ in the reproductive system of most female mammals, including humans, that accommodates the embryonic and fetal development of one or more fertilized eggs until bir ...

exposure to

cocaine Cocaine is a tropane alkaloid and central nervous system stimulant, derived primarily from the leaves of two South American coca plants, ''Erythroxylum coca'' and ''Erythroxylum novogranatense, E. novogranatense'', which are cultivated a ...

and other

street drug Recreational drug use is the use of one or more psychoactive drugs to induce an altered state of consciousness, either for pleasure or for some other casual purpose or pastime. When a psychoactive drug enters the user's body, it induces an Sub ...

s can lead to porencephaly.

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 A computed tomography scan (CT scan), formerly called computed axial tomography scan (CAT scan), is a medical imaging technique used to obtain detailed internal images of the body. The personnel that perform CT scans are called radiographers or ...

(CT),

magnetic resonance imaging Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to generate pictures of the anatomy and the physiological processes inside the body. MRI scanners use strong magnetic fields, magnetic field gradients, and ...

(MRI), or with

ultrasonography Medical ultrasound includes diagnostic techniques (mainly imaging) using ultrasound, as well as therapeutic applications of ultrasound. In diagnosis, it is used to create an image of internal body structures such as tendons, muscles, joints, ...

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.

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 A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...

shunt (medical) In medicine, a shunt is a hole or a small passage that moves, or allows movement of, fluid from one part of the body to another. The term may describe either congenital or acquired shunts; acquired shunts (sometimes referred to as iatrogenic ...

, or

neurosurgery Neurosurgery or neurological surgery, known in common parlance as brain surgery, is the specialty (medicine), medical specialty that focuses on the surgical treatment or rehabilitation of disorders which affect any portion of the nervous system ...

(removal of the cyst). 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 Valproate (valproic acid, VPA, sodium valproate, and valproate semisodium forms) are medications primarily used to treat epilepsy and bipolar disorder and prevent migraine headaches. They are useful for the prevention of seizures in those with ...

carbamazepine Carbamazepine, sold under the brand name Tegretol among others, is an anticonvulsant medication used in the treatment of epilepsy and neuropathic pain. It is used as an adjunctive treatment in schizophrenia along with other medications and as ...

, and

clobazam Clobazam, sold under the brand names Frisium, Onfi and others, is a benzodiazepine class medication that was patented in 1968. Clobazam was first synthesized in 1966 and first published in 1969. Clobazam was originally marketed as an anxiosele ...

. Also, anti-epileptic drugs served as another positive method of treatment.

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. 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.

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.

References

External links

Porencephaly Information page, National Institute of Neurological Disorders and Stroke
{{Medical resources , ICD11 = {{ICD11, LA05.60 , ICD10 = {{ICD10, G, 93, 0, g, 90, {{ICD10, Q, 04, 6, q, 00 , ICD9 = {{ICD9, 348.0, {{ICD9, 742.4 , ICDO = , OMIM = 175780 , OMIM_mult = , MedlinePlus = , eMedicineporen , eMedicineTopic = , DiseasesDB = 33031 , SNOMED CT = 38837006 , Orphanet = 2940 Congenital disorders Congenital disorders of nervous system