About diencephalic syndrome of emaciation
What is diencephalic syndrome of emaciation?
The diencephalic syndrome is a very rare neurological disorder characterized by failure to thrive, abnormal thinness (emaciation), amnesia, intense sleepiness, unusual eye position and sometimes blindness. It is normally seen in infancy or early childhood but some cases have been reported in older children and even adults. Diencephalic syndrome is usually caused by a brain tumor such as a low-grade glioma or astrocytoma.
What are the symptoms for diencephalic syndrome of emaciation?
The specific symptoms and severity of diencephalic syndrome can vary from one person to another. The disorder can potentially cause severe, even life-threatening complications. Onset is usually in infancy or early childhood. Usually, there is a period of normal development and weight gain, followed by a prolonged period of failure to gain weight and weight loss.
The most striking feature of diencephalic syndrome is profound emaciation including a uniform loss of body fat (adipose tissue). Emaciation occurs despite normal or near normal caloric intake. Emaciation may progressively worsen. Because of the loss of body fat, affected children may appear muscular. Although weight is affected, length (linear growth) may be normal. Emaciation and Failure to thrive may occur following an initial period of normal growth.
Although overall development is slowed, neurological testing is normal. Affected children are usually mentally alert. Some children are overactive and restlessness (hyperkinesia), happy and outgoing, which is not in keeping with their outward appearance. Some affected children are described as intensely excited or happy (euphoric). Others may, in contrast, act irritable.
Rapid, involuntary, “jerky” movements of the eyes (nystagmus) can be seen in children with diencephalic syndrome. Nystagmus is a notable feature of this disorder, but does not occur with every affected individual, it may affect one or both eyes. Additional nonspecific symptoms include pallor, Vomiting (emesis), and headaches. Degeneration of the nerve that transmits visual stimuli from the eyes to the brain (optic nerve) may also occur (optic atrophy). Vision loss can potentially occur in some patients.
Some affected infants and children develop hydrocephalus, a condition in which excessive cerebrospinal fluid (CSF) in the skull causes pressure on the brain, resulting in a variety of symptoms including a head that appears large in comparison to the rest of the body, swelling of the optic disk (papilledema).
Less often, additional symptoms have been reported including Low blood sugar (hypoglycemia), excessive Sweating (hyperhidrosis), and high blood pressure (hypertension). In rare instances, disproportionately large hands and feet have developed.
What are the causes for diencephalic syndrome of emaciation?
Diencephalic syndrome is caused by a tumor, most commonly located in the hypothalamus or the optic chiasm. The hypothalamus is a special area in the brain that is divided into several regions that have different functions. The hypothalamus controls the pituitary gland by controlling’s the gland’s release of certain hormones. The hypothalamus also helps regulate basic functions of the body including sleep, hunger, thirst, and body temperature. The optic chiasm is the region where the optic nerves pass through to the brain.
A glioma or astrocytoma is the most common tumor associated with diencephalic syndrome. An astrocytoma is a tumor that arises from the star-shaped cells (astrocytes) that form the supportive tissue of the brain. Other supportive tissue of the brain includes oligodendrocytes and ependymal cells. Collectively, these cells are known as glial cells and the tissue they form is known as glial tissue. Tumors that arise from the glial tissue are collectively referred to as gliomas. Technically, an astrocytoma is a subtype of gliomas, but occasionally the terms are used interchangeably. Astrocytomas that occur in association with diencephalic syndrome tend to be more aggressive and to develop at an earlier age than other astrocytomas arising in the same area. A juvenile pilocytic astrocytoma is the most common cause of diencephalic syndrome. NORD has a report on this tumor. For more information, choose “juvenile pilocytic astrocytoma” as your search term in the Rare Disease Database. Pediatric low-grade gliomas (grade 1-2) demonstrate specific molecular genetic alterations, such as V600E mutations, activating BRAF-fusions, NF1 gene mutations, CDKN2A/B loss or ATRX mutations, which can be helpful diagnostically and, at times, in guiding therapy.
Gliomas in the hypothalamus or optic chiasm can sometimes be associated with neurofibromatosis type 1, a rare genetic disorder characterized by the development of multiple noncancerous (benign) tumors of the skin and nerves (neurofibromas). The development of a tumor in the hypothalamus and optic chiasm in neurofibromatosis type 1 and the subsequent development of diencephalic syndrome is not common, but does occur.
In some instances, the causative tumor is unclassified. In extremely rare cases, a different type of tumor such as a ependymoma, dysgerminoma, or ganglioma has been associated with diencephalic syndrome.
The exact underlying manner in which these tumors cause the symptoms of diencephalic syndrome is not fully understood.
What are the treatments for diencephalic syndrome of emaciation?
The treatment of diencephalic syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, surgeons, neurologists, oncologists, radiation oncologists, and other healthcare professionals may need to systematically and comprehensively plan an affect child’s treatment.
Specific therapeutic procedures and interventions may vary, depending upon numerous factors, such as disease stage; tumor size and specific location; specific tumor type; the presence or absence of certain symptoms; an individual’s age and general health; and/or other elements. Decisions concerning the use of particular drug regimens and/or other treatments should be made by physicians and other members of the health care team in careful consultation with the patient based upon the specifics of his or her case; a thorough discussion of the potential benefits and risks, including possible side effects and long-term effects; patient preference; and other appropriate factors. Psychosocial support for the entire family is essential as well.
There is no agreed upon consensus for the best treatment for individuals with diencephalic syndrome and there are no standardized treatment protocols or guidelines just for tumor causing the diencephalic syndromes, however, protocols and often clinical trials are available for specific tumor types that cause the syndrome. Various treatments have been reported in the medical literature as part of single patient reports, small series of patients or more extensive, tumor-type based studies. Treatment trials would be very helpful to determine the long-term safety and effectiveness of specific medications and treatments for individuals with diencephalic syndrome.
Surgery, radiation, and chemotherapy alone or in various combinations have been used to treat this diencephalic syndrome. In some cases, physicians may recommend surgical excision and removal of as much as the tumor as possible (resection). However, because of the area of the brain that is usually affected, surgical removal of the entire tumor is often not possible. Additionally, surgery, even to remove only a portion of the tumor, carries risks due to the tumor’s location deep within the brain. However, biopsy is usually indicated to not only determine the histological subtype of the tumor, but its molecular subtype; this is especially useful in low-grade gliomas where molecular findings can guide therapy.
Radiation therapy can be used to directly destroy cancer cells or to destroy cancer cells left over after surgery. However, the potential for serious short and long-term side effects exists. Radiation therapy is especially avoided in children less than 5 years of age because of the potential for serious side effects.
Chemotherapy, the use of one or more anti-cancer drugs, has also been used to treat individuals with diencephalic syndrome, particularly those with low grade gliomas. Chemotherapy may be used instead of radiation in very young children to avoid damage to the developing brain. Chemotherapy may also be administered after radiation in an attempt to destroy any cells that remain or may be given during the course of radiation treatment. The type of chemotherapeutic drug therapy used is determined by a neuro-oncologist who examines the grade of tumor, previous treatment, and current health status of the affected individual. Chemotherapeutic drugs that have been used for diencephalic syndrome include carboplatin, carboplatin-vincristine, carboplatin-vincristine-temador, low dose cisplatin-etoposide, and other drug regimens. Recently, molecularly targeted therapies (biologic therapy) have become available for treatment of low-grade pediatric gliomas. Bevacizumab, which targets vascular endothelial growth factor, has been successfully used for some patients with diencephalic gliomas. Also, agents interfering with RAS-MAPK signaling hold great promise for treatment of diencephalic tumors and prospective clinical trials are underway or soon to open for newly-diagnosed patients. These trials require molecular characterization of the tumor for entry.
What are the risk factors for diencephalic syndrome of emaciation?
Diencephalic syndrome is an extremely rare disorder that affects both males and females. The incidence and prevalence of this disorder in the general population is unknown. The disorder is most often seen in infants or young children, but has also been reported in older children and adults.