What is Schizencephaly?

 

Many sources define Schizencephaly as a very rare cortical malformation that results in grey matter-line clefts that can impact one or both sides of the brain. The brain malformation can occur during the early weeks of pregnancy. Also known as Split Brain disorder, the first documented case of the disorder was dated in 1946 by Yakovlev and Wadsworth. It’s predicted that in 1998, the name Schizencephaly was adopted by the medical community. With only an estimated 7,000 cases reported, Schizencephaly is the second rarest known brain malformation. According to a study in the UK, the probability of having Schizencephaly is 1.48 for every 100,000 births (Stang and Dr. Krucik, 2013). These numbers can vary in different countries where the disorder can often be mis-diagnosed for one of its underlying conditions. Schizencephaly is not degenerative: meaning it will not get worse. The underlying condition associated with Schizencephaly can be varying in degenerative attributes. Muscle tightness, seizures, bone issues and respiratory conditions can often develop as an underlying sometimes degenerative condition(s) to Schizencephaly.

FB_IMG_1468894873945

What causes Schizencephaly?

There are many possible causes to Schizencephaly some medical facilities claim a stroke was involved during the pregnancy. There can be many causes of neurological migration disturbances. The stimulant that causes the damage or in some casesstroke for those cases ranges from folic acid deficiency, CMV,  environmental issues and even genetics.

There are varying arguments over the cause of Schizencephaly.  There are several cases involving gene mutation through extensive genetic testing. There have been cases of trisomy 9 (also linked to Dandy Walker) and chromosome  13 long arm cases. Each child of an individual with a COL4A1-related disorder has about a fifty percent chance of inheriting the mutation from their parent.  It has also been confirmed that mutations in the COL4A1 gene occur in some patients with Porencephaly and Schizencephaly.

For families with concerns you should ask about extensive genetic testing and possible mutations. For others fetal insult to any degree can be a cause (sickness during pregnancy, exposure to toxins, and environmental issues and multiple other complications). Further research is needed to rule out other causes.

Many doctors feel in cases of stroke ( which account for most causes on medical records), the time it happens would be before 13 weeks gestation and account most neural tube defects on folic acid deficiency. But the fact remains, we have a long road to understand Schizencephaly.

 

The spectrum of COL4A1-related disorders includes: small-vessel brain disease of varying severity including porencephaly, variably associated with eye defects (retinal arterial tortuosity, Axenfeld-Rieger anomaly, cataract) and systemic findings (kidney involvement, muscle cramps, cerebral aneurysms, Raynaud phenomenon, cardiac arrhythmia, and hemolytic anemia). On imaging studies, small-vessel brain disease is manifest as diffuse periventricular leukoencephalopathy, lacunar infarcts, microhemorrhage, dilated perivascular spaces, and deep intracerebral hemorrhages. Clinically, small-vessel brain disease manifests as infantile hemiparesis, seizures, single or recurrent hemorrhagic stroke, ischemic stroke, and isolated migraine with aura. Porencephaly (fluid-filled cavities in the brain detected by CT or MRI) is typically manifest as infantile hemiparesis, seizures, and intellectual disability; however, on occasion it can be an incidental finding. HANAC (hereditary angiopathy with nephropathy, aneurysms, and muscle cramps) syndrome usually associates asymptomatic small-vessel brain disease, cerebral large vessel involvement (i.e., aneurysms), and systemic findings involving the kidney, muscle, and small vessels of the eye. Two additional phenotypes include isolated retinal artery tortuosity and nonsyndromic autosomal dominantcongenital cataract.

Links below are informational websites pertaining to Schizencephaly, genetics and resources

Diagnosis/testing.

Diagnosis is based on clinical findings and molecular genetic testing of COL4A1.

Management.

Treatment of manifestations: Supportive care tailored to the individual’s specific medical needs and including practical help and emotional support for affected individuals and their families. Hypertension should be treated to reduce the overall risk of stroke.

Prevention of primary and secondary complications: Avoiding head trauma and anticoagulant exposure may decrease the risk for intracerebral hemorrhage.

Surveillance: Depends on the severity and type of symptoms.

Agents/circumstances to avoid: Smoking and hypertension because these factors increase the risk for stroke; sustained head pressure or physical activities that may cause head trauma; anticoagulant use.

Genetic links

COL4A1-related disorders are inherited in an autosomal dominant manner. Most individuals diagnosed with a COL4A1-related disorder have an affected parent. The proportion of cases caused by a de novopathogenic variant is estimated to be at least 27%. Each child of an individual with a COL4A1-related disorder has a 50% chance of inheriting the pathogenic variant. Prenatal diagnosis is possible for pregnancies at increased risk if the pathogenic variant in the family is known.

TUBA1A mutation

Polymicrogyria refers to an excessive number of small gyri separated by shallow sulci, giving the surface of the cortex its characteristic lumpy appearance. Polymicrogyria can be focal or diffuse, unilateral or bilateral. Unilateral involvement may be associated with variable cognitive impairment, congenital hemiparesis, focal seizures83, and visual field defects84. Deletion of 22q11.2 has been found to be associated with polymicrogyria and seems to have a predisposition for the right hemisphere85.

Bilateral involvement of the cortex is frequently seen, with a symmetric or asymmetric distribution, affecting the frontal, fronto-parietal, parieto-occipital, perisylvian, and mesial occipital regions. There is a wide spectrum of clinical manifestations owing to the various locations that are involved. For example, bilateral frontoparietal polymicrogyria is associated with developmental delay, hypertonicity, ataxia, and refractory seizures86. Congenital bilateral perisylvian syndrome (CBPS) is one of the best described syndromes. Affected patients have pseudobulbar palsy, spastic quadriparesis, and epilepsy. Between 50-85% of patients develop seizures, ranging from atypical absence, tonic, atonic, and generalized tonic-clonic seizures87. Imaging of the brain using MRI demonstrates small irregular gyri and an indistinct gray and white matter junction11. The thickness of the cortex may be normal or abnormally thick or thin.

Familial patterns have been recognized in bilateral frontoparietal, bilateral perisylvian, and generalized polymicrogyria. Bilateral frontal and parietal polymicrogyria seem to be associated with mutations in the G-protein-coupled receptor gene (GPR56)88,89. Expression of this gene appears to be highest in the neuronal progenitor cells along the ventricular and subventricular zones. The assumption is that this gene plays a role in regional organization of the brain.

Schizencephaly is classified within the same group as polymicrogyria. Schizencephaly refers to a cleft extending from the cerebral cortex to the ventricle and is typically lined by polymicrogyric cortex. It is in fact considered to be an extreme form of polymicrogyria90. Schizencephaly can be unilateral or bilateral and tends involve the insular, precentral and postcentral regions11. Type I schizencephaly refers to “closed-lip” clefts or small defects that are fused. In contrast, type II schizencephaly refers to “open-lip” clefts or large defects which are filled with fluid. The neurologic manifestations of the disorder depend on the anatomic location and type of the abnormality. Patients with type I lesions tend to be mildly affected and have partial seizures or spastic hemiparesis. On the other hand, patients with type II defects (open cleft) tend to have severe developmental delay, microcephaly, seizures, and spasticity. In particular, those with bilateral involvement have spastic quadriparesis and severe cognitive impairment. Non CNS manifestations have also been reported, such as gastroschisis, and bowel atresias91. Radiographically, in addition to the schizencephaly seen on MRI, an absent or deficient septum pellucidum may be seen and is often associated with temporal or occipital clefts11. The gray matter lining the cleft is nodular, with a polymicrogyric appearance.

Familial cases have been identified and have helped to shed light on the genetic basis of the disorder92. The inheritance pattern is still unclear although the mutations are thought to be autosomal dominant93. Initial reports suggest that EMX2 gene mutations may be associated with type II schizencephaly92; however, this finding needs to be confirmed in additional studies.

Article on mutation

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3547618/

https://academic.oup.com/brain/article/135/5/1348/304670/A-developmental-and-genetic-classification-for

 

22q11.2 Deletion genetic link

https://books.google.com/books?id=Ab9u_AyU9aUC&pg=PA281&lpg=PA281&dq=22q11.2+Deletion+schizencephaly&source=bl&ots=J6CgHuhHGq&sig=f9Ckn93-w7GCZJrHItCYHem0MOE&hl=en&sa=X&ved=0ahUKEwjOpqrvuZDUAhWE4yYKHTGhAOMQ6AEILTAA#v=onepage&q=22q11.2%20Deletion%20schizencephaly&f=false

Article NCBI

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3338922/

explanations of genetic mutations.

http://onlinelibrary.wiley.com/doi/10.1002/ajmg.a.31443/full

 

 

How is Schizencephaly detected?

18342595_1040826382714770_5910193067518487400_n

As stated earlier, most cases of Schizencephaly goes undetected because it is often overseen by other medical conditions (i.e. Cerebral Palsy, Epilepsy). The symptoms of the disorder can vary depending on the location and amount of under-developed portions of the brain.

Sometimes obstetricians can detect Schizencephaly through ultrasounds. The most accurate way to diagnose the disorder is a MRI. A MRI of the brain can take multiple slices in different angles and depths to determine how advance the malformation. It is our hope to gain earlier ultrasound diagnosis and prevention by teaching about early prenatal care like taking folic acid prior to pregnancy. Possible later epileptic occurrences and delays in advancements cognitively can gear the decision to have MRI imaging done. Many questions our organization gets is from families that never had an MRI done even though they saw and mentioned complications and delays to their childs practitioner.

Upon diagnosis of Schizencephaly parents should consider genetic testing mentioned above to rule out gene mutations.

Symptoms of Schizencephaly

Many people with Schizencephaly have seizures, mild to moderate delays in speech, oral, motor or congnitive function. One side dominance is a very important aspect of diagnosing Schizencephaly.

article about one side dominance is babies.

https://www.babycenter.com/0_your-child-favors-one-hand-or-side-of-his-body_12581.bc

Infant Favoring One Side of the Body

 

Scoliosis

Spinal curvature may begin very early in life. Often after the patient starts supported sitting. Curve may progress rapidly once patient becomes non ambulant (averaging 10 degrees/year)

Spinal curvature may begin very early in life. Often after the patient starts supported sitting. Curve may progress rapidly once patient becomes non ambulant (averaging 10 degrees/year)

physiology-scoliosis-6-638
Scoliosis is an underlying issue of Schizencephaly due to the fact one side of the brain is normally affected more than the other. Causing the child to compensate their usage on the other side of their body can result in over curvature of the spine and severe scoliosis also known as idiopathic curvature.

Many children will be braced for prevention but others will endure spinal surgery and rods to help stop the curvature.

Small Optic Nerves and Blindness

Schizencephaly is often diagnosed by first noticing pale or small optic nerves. It is a characteristic found with Schizencephaly at times. What vision is relayed to the brain is unknown but the brain has amazing healing properties and often children learn ways of seeing with different ways of looking, such as tilting the head to another direction or to the side of the object. Another mystery of Schizencephaly.

When optic nerve hypoplasia occurs in conjunction with midline brain abnormalities, the absence of the septum pellucidum and agenesis or thinning of the corpus callosum, it is known as septo-optic dysplasia or de Morsier’s syndrome.

Diagnosing Septo-Optic Dysplasia – American Academy of …

https://www.aao.org/eyenet/article/diagnosing-septo-optic-dysplasia

Cerebral Palsy

An underlying result of Schizencephaly is tight muscles and atrophy (Cerebral Palsy). Surgeries are needed to remove tightness. Those can range from Botox injections to release stiffness or muscle lengthening and adduct releases ( cuts into the muscles) to allow muscles to grow with the bones.

Due to most children being high tone there is also a need for muscle relaxers to stop muscle spasms and for children with severe tightness the use of a Baclofen pump in necessary. That surgery gives a steady flow of medication to the child through a pump that goes up the spinal cord.

http://www.cerebralpalsy.org/about-cerebral-palsy

 

Weakness or tightness on one side of the body

weakness or paralysis affecting one side of the body), or quadriparesis (weakness or paralysis affecting all four extremities), and may have reduced muscle tone (hypotonia).

Schizencephaly – Wikipedia

This may be one of the first symptoms to emerge.

there should be no ability to favor one side in early months of a childs life.

https://www.gillettechildrens.org/assets/uploads/general/Newsletter_PDFs/Vol18No2.pdf

 

Other symptoms of Schizencephaly

Symptoms of Schizencephaly can include severe gross and fine motor delays,microcephaly ( an abnormally small head), poor muscle tone,  partial to complete paralysis, bone deformity, and muscle atrophy.

Seizures (Epilepsy) are another common symptom of most cephalic disorders, including this one. Hydrocephalus, or a buildup of cerebrospinal fluid in the brain, may also accompany the other symptoms.

Bilateral Schizencephaly means there are abnormal clefts on both sides of the brain. Bilateral is the more severe case of this disorder.

Though the medical community states many children with Bilateral Schizencephaly will have uncontrollable seizures, limited mobility and wheelchair bound. We learned through the members of our organization that many children with Bilateral Schizencephaly are able to sustain mobility. The children are able use walkers and other equipment to move without parental assistance. In addition, parents have controlled seizure activity through the use of finding the appropriate medication

Bilateral Schizencephaly

Mykka Beson Bilateral schizencephaly

Mykka Beson
Bilateral schizencephaly

Bilateral clefts tend to cause more serious symptoms than unilateral clefts. … They can also cause problems with movement due to poor communication between your brain and spinal cord. Other symptoms of schizencephaly can include: poor muscle tone.Jul 27, 2016

Schizencephaly: Definition and Patient Education – Healthline

www.healthline.com/health/schizencephaly

Unilateral Schizencephaly

Unilateral Schizencephaly is a term where a cleft is located on only one side of the brain. Whatever side the cleft is on would affect the opposite side of the body. Many people can live with Unilateral Schizencephaly to adulthood and beyond. But they may have cognitive and motor issues and many will still have seizures.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3611921/

http://www.neurology.org/content/48/5/1427

Morphological Types

Whether a person has Unilateral or Bilateral Schizencephaly, they will either have what’s called an open or closed lip.

https://www.ncbi.nlm.nih.gov/pubmed/12012128

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4253694/

https://radiopaedia.org/articles/schizencephaly

Open Lip

Open lip means the cleft walls are separated and filled with cerebrospinal fluid (CSF). It is the most common morphological type in bilateral cases.

http://www.ajnr.org/content/ajnr/13/1/85.full.pdf

Close Lip

Close lip is most common in Unilateral Schizencephaly. The cleft walls are in apposition. (Dr. Bickle and Dr. Gaillard)

Hydranencephaly (severe bilateral cases)

In hydranencephaly, the cerebral hemispheres are replaced by a thin-walled, fluid-filled cyst. The aqueduct is usually atretic, and increased fluid pressure causes the cyst (and the head) to enlarge. There is variable preservation of the inferior frontal, temporal, and occipital lobes, and of the basal ganglia and diencephalon. The brainstem and cerebellum are usually preserved. Hydranencephaly is not a malformation, but a disruption caused probably by ischemia in utero in the territories of the carotid arteries. Some cases of perinatal HIE come close to hydranencephaly. Babies with hydranencephaly may appear normal initially because the brainstem is intact. The empty cranial cavity transilluminates.

https://rarediseases.info.nih.gov/diseases/6681/hydranencephaly
Holoprosencephaly– failure of the prosencephalon (the embryonic forebrain) to sufficiently divide into the double lobes of the cerebral hemispheres. The result is a single-lobed brain structure and severe skull and facial defects.

 

Hydranencephaly-a clear fluid that surrounds the brain and spinal cord. The excessive accumulation of CSF results in an abnormal widening of spaces in the brain called ventricles

information on this condition

https://rarediseases.org/rare-diseases/hydranencephaly/

http://www.hydranencephaly.com/

http://www.pediatricbrainfoundation.org/educate/disorder/hydranencephaly

Monoventricular -cavity with a single midline thalamic mass. Midline facial anomalies.

Near complete absence of the cerebrum. Intact meninges and cranial vault.

Porencephaly-characterized by cysts or cavities within the cerebral hemisphere

https://en.wikipedia.org/wiki/Porencephaly

http://neuropathology-web.org/chapter3/chapter3fPorencephaly.html

Arachnoid cysts-cerebrospinal fluid-filled sacs that are located between the brain or spinal cord and the arachoid membrane, one of the three membranes that cover the brain and spinal cord

https://rarediseases.org/rare-diseases/arachnoid-cysts/

http://www.skullbaseinstitute.com/arachnoid-cyst/

May appear similar to schizencephaly if bilateral and near the sylvian fissures (CT and MR may demonstrate lack of gray matter lined cleft).

Less likely to be symmetric. Typically do not communicate with lateral ventricle.

Muscle Atrophy– decrease in the mass of the muscle; it can be a partial or complete wasting away of muscle

https://www.healthgrades.com/symptoms/muscle-atrophy

Speech delay– when a child’s language is developing in the right sequence, but at a slower rate. Speech and language disorder describes abnormal language development. Delayed speech or language development is the most common developmental problem.

5 Reasons Why Speech & Language Therapy is Crucial for a Non-Verbal Child

http://www.sertomacenter.org/importance-of-speech-therapy/

Hydranencephaly

Hydranencephaly

 

 

Is there a Cure?

Presently, there is no cure for Schizencephaly; however, there is great interest in medications such as stem cell regeneration medications that shows great hope in repairing brain damage. However, it is currently not available in the United States and many other countries.

Medical Care

Since the degree of symptoms from Schizencephaly can vary, the type of medical care provided can differ.

Therapy

Therapy is essential and key to helping children with Schizencephaly. Early intervention is available to children between birth to three years old and that is a critical time for development. Normal therapy options include behavioral, feeding, physical and occupational but we are going to provide additional therapy options which have proven success.

Conductive Education

Conductive education has shown positive results on children with Schizencephaly. Their programs can be found across the US and is based out of Hungary. The technique is similar to patterning in that the brain is taught to know specific time to do things, eating, physical walking, playing. It is very hands on and has shown huge strides for children with cerebral palsy. (CECO)

http://conductivelearningcenter.org/about/what-is-conductive-education/

Hippotherapy

Hippotherapy has been used to treat patients with neurological or other disabilities, such as autism, cerebral palsy, arthritis, multiple sclerosis, head injury, stroke, spinal cord injury, behavioral disorders and psychiatric disorders. The effectiveness of hippotherapy for many of these indications is unclear, and more research has been recommended. (Wikipedia)

http://www.cerebralpalsy.org/about-cerebral-palsy/treatment/therapy/hippotherapy

Hydrotherapy

Hydrotherapy is considered an effective method for the relief and treatment of multiple conditions, including wound care, increasing circulation, reducing inflammation and swelling and boosting immune system function. Hydrotherapy comes in many forms, including warm or cool water, steam, vapor or ice. Some forms of hydrotherapy direct firm streams of water toward areas of the body damaged by injury or disease to relieve pain and invigorate the area with gentle massaging pressure that helps loosen muscles, tendons and ligaments. (Stern, 2011)

https://www.nemours.org/service/medical/cerebralpalsy.html?gclid=CjwKEAjwl9DIBRCG_e3DwsKsizsSJADMmJ11vmrRB8If0GXpj4y19qBQ8SqU8FY4yK0YzHDbLPBNyxoCj63w_wcB

Island Dolphin Care

Island Dolphin Care, Inc. (IDC) was developed to help children with special needs and their families who are dealing with developmental and/or physical disabilities, emotional challenges, and critical, chronic or terminal illness. Island Dolphin Care, Inc., was created by Ms. Deena Hoagland, LCSW, after witnessing the remarkable recovery of her son, Joe, after he began swimming with dolphins at the age of three. A variety of children with special needs could experience therapeutic success in an environment less threatening than standard medical settings.

http://www.islanddolphincare.org/

Stroke Therapy

Stroke therapy focuses on repetitive motions to train the functional part of the brain to compensate for the abnormal portion. Although it is mostly used for adult stroke victims, it has proven to be very beneficial for children with Schizencephaly.

https://en.wikipedia.org/wiki/Constraint-induced_movement_therapy

Shunts

Often times a person with Schizencephaly brain can tell the body to not function properly. In these cases, especially those that are complicated by hydrocephalus, a surgically implanted tube called a shunt is used to divert fluid to another area of the body where it can be absorbed.

Surgery -A temporal lobe resection is a surgery performed on the brain to control seizures. In this procedure, brain tissue in the temporal lobe is resected, or cut away, to remove the seizure focus. The anterior (front) and mesial (deep middle) portions of the temporal lobe are the areas most often involved. ( webMD)

Supporting the Need for Research

There is little to no information available for parents dealing with Schizencephaly and many are left learning from other parents. The medical field has made slow advancements in cases especially research. There is simply not enough research and education happening.

WeAreR.A.R.E is working to change that. Currently we spend a vast amount of time talking with hospitals around the world so we can not only train then and provide more information to grief counselors but also to become the first point of contact for new parents seeking accurate information not being provided. Research is crucial in finding answers and helping to prevent disruptions of the brain formation.

Sources:
Debra Stang and George Krucik, MD, MBA – RiskFactors
Dr Ian Bickle and Dr Frank Gaillard – Types of Schizencephaly
Conduction Education Center of Orlando (CECO) – Conductive Education
Denise Stern – Hydrotherapy
Wikipedia – Hippotherapy
Deena Hoagland – Island Dolphin Care, Inc
Phenotypic spectrum of COL4A1 mutations: porencephaly to schizencephaly”. Ann. Neurol.Wikipedia
 WebMD http://www.webmd.com/epilepsy/guide/temporal-lobe-resection

This site is optimized for Chrome, Safari, FireFox, and Internet Explorer 9 and 10 (does not support Internet Explorer 6, or 7).