Early and aggressive treatment is important to prevent irreversible neurological damage, hearing loss, or vision loss. Medications used include immunosuppressive agents and corticosteroids such a prednisone, or intravenous immunoglobulins (IVIG). Other drugs that have been used are mycophenolate mofetil (Cellcept), azathioprine (Imuran), cyclophosphamide, rituximab, and anti-TNF therapies.

Hearing aids or cochlear implants may be necessary in the event of hearing loss.

Treatment for Sturge–Weber syndrome is symptomatic. Laser treatment may be used to lighten or remove the birthmark. Anticonvulsant medications may be used to control seizures. Doctors recommend early monitoring for glaucoma, and surgery may be performed on more serious cases. When one side of the brain is affected and anticonvulsants prove ineffective, the standard treatment is neurosurgery to remove or disconnect the affected part of the brain (hemispherectomy). Physical therapy should be considered for infants and children with muscle weakness. Educational therapy is often prescribed for those with mental retardation or developmental delays, but there is no complete treatment for the delays.

Brain surgery involving removing the portion of the brain that is affected by the disorder can be successful in controlling the seizures so that the patient has only a few seizures that are much less intense than pre-surgery. Surgeons may also opt to "switch-off" the affected side of the brain.

Latanoprost (Xalatan), a prostaglandin, may significantly reduce IOP (intraocular pressure) in patients with glaucoma associated with Sturge–Weber syndrome. Latanoprost is commercially formulated as an aqueous solution in a concentration of 0.005% preserved with 0.02% benzalkonium chloride (BAC). The recommended dosage of latanoprost is one drop daily in the evening, which permits better diurnal IOP control than does morning instillation. Its effect is independent of race, gender or age, and it has few to no side effects. Contraindications include a history of CME, epiretinal membrane formation, vitreous loss during cataract surgery, history of macular edema associated with branch retinal vein occlusion, history of anterior uveitis, and diabetes mellitus. It is also wise to advise patients that unilateral treatment can result in heterochromia or hypertrichosis that may become cosmetically objectionable.

Treatment is based

on the stage of the disease. Stage 1 does not

require treatment and

should be observed. 4

Neovascularization

(stage 2) responds well

to laser ablation or

cryotherapy.2,4 Eyes

with retinal detachments (stages

3 through 5) require surgery, with

earlier stages requiring scleral

buckles and later stages ultimately

needing vitrectomy. 2,4

More recently, the efficacy of

anti-VEGF intravitreal injections

has been studied. In one study,

these injections, as an in adjunct

with laser, helped early stages

achieve stabilization, but further

investigation is needed.6

The treatment for Bonnet–Dechaume–Blanc syndrome is controversial due to a lack of consensus on the different therapeutic procedures for treating arteriovenous malformations. The first successful treatment was performed by Morgan et al. They combined intracranial resection, ligation of ophthalmic artery, and selective arterial ligature of the external carotid artery, but the patient did not have retinal vascular malformations.

If lesions are present, they are watched closely for changes in size. Prognosis is best when lesions are less than 3 cm in length. Most complications occur when the lesions are greater than 6 cm in size. Surgical intervention for intracranial lesions has been done successfully. Nonsurgical treatments include embolization, radiation therapy, and continued observation. Arterial vascular malformations may be treated with the cyberknife treatment. Possible treatment for cerebral arterial vascular malformations include stereotactic radiosurgery, endovascular embolization, and microsurgical resection.

When pursuing treatment, it is important to consider the size of the malformations, their locations, and the neurological involvement. Because it is a congenital disorder, there are not preventative steps to take aside from regular follow ups with a doctor to keep an eye on the symptoms so that future complications are avoided.

Treatment for individuals with Dandy–Walker Syndrome generally consists of treating the associated problems, if needed.

A special tube (shunt) to reduce intracranial pressure may be placed inside the skull to control swelling. Endoscopic third ventriculostomy is also an option.

Treatment may also consist of various therapies such as occupational therapy, physiotherapy, speech therapy or specialized education. Services of a teacher of students with blindness/visual impairment may be helpful if the eyes are affected.

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

Treatment of Eales’ disease comprises:

1. Medical treatment:

A course of oral corticosteroids for extended periods is the main stay of treatment

during active inflammation. A course of antitubercular therapy has also been

recommended in selective cases.

2. Laser photocoagulation of the retina is indicated in stage of neovascularizion.

3. Vitreoretinal surgery is required for nonresolving vitreous haemorrhage and tractional retinal detachment.

•If active TB present - treat with ATT

•otherwise manage the vitreous hemorrhage -

Partial h’ge - postural management with propped up position

Total h’ge - Pars Plana Vitrectomy

As of 2014, no treatment strategy has yet been investigated in a randomized clinical trial. Verapamil, nimodipine, and other calcium channel blockers may help reduce the intensity and frequency of the headaches. A clinician may recommend rest and the avoidance of activities or vasoactive drugs which trigger symptoms (see § Causes). Analgesics and anticonvulsants can help manage pain and seizures, respectively.

Overall prognosis for children with amyoplasia is good. Intensive therapies throughout developing years include physical therapy, occupational therapy and multiple orthopedic procedures. Most children require therapy for years, but almost 2/3 are eventually able to walk, with or without braces, and attend school.

Medical management of children with Trisomy 13 is planned on a case-by-case basis and depends on the individual circumstances of the patient. Treatment of Patau syndrome focuses on the particular physical problems with which each child is born. Many infants have difficulty surviving the first few days or weeks due to severe neurological problems or complex heart defects. Surgery may be necessary to repair heart defects or cleft lip and cleft palate. Physical, occupational, and speech therapy will help individuals with Patau syndrome reach their full developmental potential. Surviving children are described as happy and parents report that they enrich their lives. The cited study grouped Edwards syndrome, which is sometimes survivable beyond toddlerhood, along with Patau, hence the median age of 4 at the time of data collection.

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.

Surgery may be necessary to address the congenital deformities frequently occurring in conjunction with arthrogryposis. Surgery on feet, knees, hips, elbows and wrists may also be useful if more range of motion is needed after therapy has achieved maximum results. In some cases, tendon transfers can improve function. Congenital deformities of the feet, hips and spine may require surgical correction at or about one year of age.

Currently, there are no treatments prescribed for PVL. All treatments administered are in response to secondary pathologies that develop as a consequence of the PVL. Because white matter injury in the periventricular region can result in a variety of deficits, neurologists must closely monitor infants diagnosed with PVL in order to determine the severity and extent of their conditions.

Patients are typically treated with an individualized treatment. It is crucial for doctors to observe and maintain organ function: visceral organ failure can potentially occur in untreated patients. Additionally, motor deficits and increased muscle tone are often treated with individualized physical and occupational therapy treatments.

In terms of the treatment of cytomegalovirus retinitis, oral valganciclovir, intravenous ganciclovir, IV foscarnet, and IV cidofovir are all efficient in the treatment of this condition. Also intravitreal injections, an injection of medicine into the vitreous near the retina, of foscarnet in concomitance with oral valganciclovir can be used for treatment as well.

Often individuals with CMV retinitis will need surgery for either retinal detachment or intravitreal instillation of ganciclovir. Retinal detachment occurs in up to 29% of affected eyes, repair being most effective with endolaser and silicone oil endotamponade.Intravitreal ganciclovir implant has the benefit of less systemic toxicity. An adverse effect of this is retinal detachment (and vitreous hemorrhage), also there is no systemic beneficial effect for cytomegalovirus organ disease.

The treatment of arthrogryposis includes occupational therapy, physical therapy, splinting and surgery. The primary long-term goals of these treatments are increasing joint mobility, muscle strength and the development of adaptive use patterns that allow for walking and independence with activities of daily living. Since arthrogryposis includes many different types, the treatment varies between patients depending on the symptoms.

Only a few good articles exist in which a surgical technique that is used to treat arthrogryposis is described. These surgeries are explained below.

Brain MRI shows vermis atrophy or hypoplasic. Cerebral and cerebellar atrophy with white matter changes in some cases.

People with AMC look their worst at birth. AMC is considered non-progressive, so with proper medical treatment, things can improve. The joint contractures that are present will not get worse than they are at the time of birth. There is no way to completely resolve or cure AMC. But with proper treatment, most children make significant improvements in their range of motion and ability to move their limbs which enables them to do activities of daily life, and live relatively normal lives. Therapeutic interventions that are cornerstone in the treatment of AMC include: stretching and range of motion exercises, physical, occupational, and speech therapy, splinting and serial casting. Surgical intervention may also improve joint mobility and function. Other positive prognostic factors for independent walking were active hips and knees, hip flexion contractures of less than 20 degrees and knee flexion contractures less than 15 degrees without severe scoliosis.

The only effective treatment is prompt delivery of the baby. Several medications have been investigated for the treatment of HELLP syndrome, but evidence is conflicting as to whether magnesium sulfate decreases the risk of seizures and progress to eclampsia. The disseminated intravascular coagulation is treated with fresh frozen plasma to replenish the coagulation proteins, and the anemia may require blood transfusion. In mild cases, corticosteroids and antihypertensives (labetalol, hydralazine, nifedipine) may be sufficient. Intravenous fluids are generally required. Hepatic hemorrhage can be treated with embolization, as well, if life-threatening bleeding ensues.

The University of Mississippi standard protocol for HELLP includes corticosteroids. However, a 2009 review found "no conclusive evidence" supporting corticosteroid therapy, and a 2010 systematic review by the Cochrane Collaboration also found "no clear evidence of any effect of corticosteroids on substantive clinical outcomes" either for the mothers or for the newborns,

Although it is possible for the birthmark and atrophy in the cerebral cortex to be present without symptoms, most infants will develop convulsive seizures during their first year of life. There is a greater likelihood of intellectual impairment when seizures are resistant to treatment. Studies do not support the widely held belief that seizure frequency early in life in patients who have SWS is a prognostic indicator.

Stem cell therapy is considered a very promising treatment for patients with colpocephaly. Oligodendroglial cells can be used which will increase the production of myelin and alleviate symptoms of colpocephaly. Damage to the developing oligodendrocytes near the cerebral ventricles causes cerebral palsy as well as other demyelinating diseases such as multiple sclerosis and leukodystrophies. Demyelination reduces the speed of conduction in affected nerves resulting in disabilities in cognition, sensation, and motor. Therefore, by using oligodendrocyte stem cells the effects of cerebral palsy can be treated and other symptoms of colpocephaly can be alleviated.

Revesz syndrome has so far been observed only in children. There is not much information about the disease because of its low frequency in general population and under reporting of cases.

Autosomal Dominant Retinal Vasculopathy with Cerebral Leukodystrophy (AD-RVCL) (previously known also as Cerebroretinal Vasculopathy, CRV, or Hereditary Vascular Retinopathy, HVR or Hereditary Endotheliopathy, Retinopathy, Nephropathy, and Stroke, HERNS) is an inherited condition resulting from a frameshift mutation to the TREX1 gene. This genetically inherited condition affects the retina and the white matter of the central nervous system, resulting in vision loss, lacunar strokes and ultimately dementia. Symptoms commonly begin in the early to mid-forties, and treatments currently aim to manage or alleviate the symptoms rather than treating the underlying cause. The overall prognosis is poor, and death can sometimes occur within 10 years of the first symptoms appearing.

AD-RVCL (CRV) Acronym

Autosomal Dominance (genetics) means only one copy of the gene is necessary for the symptoms to manifest themselves.

Retinal Vasculopathy means a disorder that is associated with a disease of the blood vessels in the retina.

Cerebral means having to do with the brain.

Leukodystrophy means a degeneration of the white matter of the brain.

Pathogenesis

The main pathologic process centers on small blood vessels that prematurely “drop out” and disappear. The retina of the eye and white matter of the brain are the most sensitive to this pathologic process. Over a five to ten-year period, this vasculopathy (blood vessel pathology) results in vision loss and destructive brain lesions with neurologic deficits and death.

Most recently, AD-RVCL (CRV) has been renamed. The new name is CHARIOT which stands for Cerebral Hereditary Angiopathy with vascular Retinopathy and Impaired Organ function caused by TREX1 mutations.

Treatment

Currently, there is no therapy to prevent the blood vessel deterioration.

About TREX1

The official name of the TREX1 gene is “three prime repair exonuclease 1.” The normal function of the TREX1 gene is to provide instructions for making the 3-prime repair exonuclease 1 enzyme. This enzyme is a DNA exonuclease, which means it trims molecules of DNA by removing DNA building blocks (nucleotides) from the ends of the molecules. In this way, it breaks down unneeded DNA molecules or fragments that may be generated during genetic material in preparation for cell division, DNA repair, cell death, and other processes.

Changes (mutations) to the TREX1 gene can result in a range of conditions one of which is AD-RVCL. The mutations to the TREX1 gene are believed to prevent the production of the 3-prime repair exonuclease 1 enzyme. Researchers suggest that the absence of this enzyme may result in an accumulation of unneeded DNA and RNA in cells. These DNA and RNA molecules may be mistaken by cells for those of viral invaders, triggering immune system reactions that result in the symptoms of AD-RVCL.

Mutations in the TREX1 gene have also been identified in people with other disorders involving the immune system. These disorders include a chronic inflammatory disease called systemic lupus erythematosus (SLE), including a rare form of SLE called chilblain lupus that mainly affects the skin.

The TREX1 gene is located on chromosome 3: base pairs 48,465,519 to 48,467,644

The immune system.

- The immune system is composed of white blood cells or leukocytes.

- There are 5 different types of leukocytes.

- Combined, the 5 different leukocytes represent the 2 types of immune systems (The general or innate immune system and the adaptive or acquired immune system).

- The adaptive immune system is composed of two types of cells (B-cells which release antibodies and T-cells which destroy abnormal and cancerous cells).

How the immune system becomes part of the condition.

During mitosis, tiny fragments of “scrap” single strand DNA naturally occur inside the cell. Enzymes find and destroy the “scrap” DNA. The TREX1 gene provides the information necessary to create the enzyme that destroys this single strand “scrap” DNA. A mutation in the TREX1 gene causes the enzyme that would destroy the single strand DNA to be less than completely effective. The less than completely effective nature of the enzyme allows “scrap” single strand DNA to build up in the cell. The buildup of “scrap” single strand DNA alerts the immune system that the cell is abnormal.

The abnormality of the cells with the high concentration of “scrap” DNA triggers a T-cell response and the abnormal cells are destroyed. Because the TREX1 gene is identical in all of the cells in the body the ineffective enzyme allows the accumulation of “scrap” single strand DNA in all of the cells in the body. Eventually, the immune system has destroyed enough of the cells in the walls of the blood vessels that the capillaries burst open. The capillary bursting happens throughout the body but is most recognizable when it happens in the eyes and brain because these are the two places where capillary bursting has the most pronounced effect.

Characteristics of AD-RVCL

- No recognizable symptoms until after age 40.

- No environmental toxins have been found to be attributable to the condition.

- The condition is primarily localized to the brain and eyes.

- Optically correctable, but continuous, deterioration of visual acuity due to extensive multifocal microvascular abnormalities and retinal neovascularization leading, ultimately, to a loss of vision.

- Elevated levels of alkaline phosphatase.

- Subtle vascular changes in the retina resembling telangiectasia (spider veins) in the parafovea circulation.

- Bilateral capillary occlusions involving the perifovea vessels as well as other isolated foci of occlusion in the posterior pole of the retina.

- Headaches due to papilledema.

- Mental confusion, loss of cognitive function, loss of memory, slowing of speech and hemiparesis due to “firm masses” and white, granular, firm lesions in the brain.

- Jacksonian seizures and grand mal seizure disorder.

- Progressive neurologic deterioration unresponsive to systemic corticosteroid therapy.

- Discrete, often confluent, foci of coagulation necrosis in the cerebral white matter with intermittent findings of fine calcium deposition within the necrotic foci.

- Vasculopathic changes involving both arteries and veins of medium and small caliber present in the cerebral white matter.

- Fibroid necrosis of vessel walls with extravasation of fibrinoid material into adjacent parenchyma present in both necrotic and non-necrotic tissue.

- Obliterative fibrosis in all the layers of many vessel walls.

- Parivascular, adventitial fibrosis with limited intimal thickening.

Conditions with similar symptoms that AD-RVCL can be misdiagnosed as:

- Brain tumors

- Diabetes

- Macular degeneration

- Telangiectasia (Spider veins)

- Hemiparesis (Stroke)

- Glaucoma

- Hypertension (high blood pressure)

- Systemic Lupus Erythematosus (SLE (same original pathogenic gene, but definitely a different disease because of a different mutation in TREX1))

- Polyarteritis nodosa

- Granulomatosis with polyangiitis

- Behçet's disease

- Lymphomatoid granulomatosis

- Vasculitis

Clinical Associations

- Raynaud's phenomenon

- Anemia

- Hypertension

- Normocytic anemia

- Normochromic anemia

- Gastrointestinal bleeding or telangiectasias

- Elevated alkaline phosphatase

Definitions

- Coagulation necrosis

- Endothelium

- Fibrinoid

- Fibrinoid necrosis

- Frameshift mutation

- Hemiparesis

- Jacksonian seizure

- Necrotic

- Necrosis

- Papilledema

- Perivascular

- Retinopathy

- Telangiectasia

- Vasculopathy

- Vascular

What AD-RVCL is not:

- Infection

- Cancer

- Diabetes

- Glaucoma

- Hypertension

- A neurological disorder

- Muscular dystrophy

- Systemic Lupus Erythematosis (SLE)

- Vasculitis

Things that have been tried but turned out to be ineffective or even make things worse:

- Antibiotics

- Steroids

- X-Ray therapy

- Immunosuppression

History of AD-RVCL (CRV)

- 1985 – 1988: CRV (Cerebral Retinal Vasculopathy) was discovered by John P. Atkinson, MD at Washington University School of Medicine in St. Louis, MO

- 1988: 10 families worldwide were identified as having CRV

- 1991: Related disease reported, HERNS (Hereditary Endiotheliopathy with Retinopathy, Nephropathy and Stroke – UCLA

- 1998: Related disease reported, HRV (Hereditary Retinal Vasculopathy) – Leiden University, Netherlands

- 2001: Localized to Chromosome 3.

- 2007: The specific genetic defect in all of these families was discovered in a single gene called TREX1

- 2008: Name changed to AD-RVCL Autosomal Dominant-Retinal Vasculopathy with Cerebral Leukodystrophy

- 2009: Testing for the disease available to persons 21 and older

- 2011: 20 families worldwide were identified as having CRV

- 2012: Obtained mouse models for further research and to test therapeutic agents

In the early stages, there are a few treatment options. Laser surgery or cryotherapy (freezing) can be used to destroy the abnormal blood vessels, thus halting progression of the disease. However, if the leaking blood vessels are clustered around the optic nerve, this treatment is not recommended as accidental damage to the nerve itself can result in permanent blindness. Although Coats' disease tends to progress to visual loss, it may stop progressing on its own, either temporarily or permanently. Cases have been documented in which the condition even reverses itself. However, once total retinal detachment occurs, sight loss is permanent in most cases. Removal of the eye (enucleation) is an option if pain or further complications arise.

Revesz syndrome is a fatal disease that causes exudative retinopathy and bone marrow failure. Other symptoms include severe aplastic anemia, intrauterine growth retardation, fine sparse hair, fine reticulate skin pigmentation, ataxia due to cerebellar hypoplasia, and cerebral calcifications. Its effects are similar to that of Hoyeraal-Hreidarsson syndrome. It is a variant of dyskeratosis congenita.

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.