Diencephalic syndrome.

A diencephalic syndrome of emaciation in infancy and childhood has constant and most striking feature of this condition is the appearance of emaciation with a uniform loss of body fat. Children with this syndrome often appear muscular because of loss of fat over relatively normal muscles. Linear growth at the time of diagnosis is usually normal or above normal. Rotary nystagmoid eye movements are also striking but are present in only 50 to 60 percent of cases. The nystagmoid eye movements, however, may be the first sign of the central nervous system origin of the "failure to thrive." These children may appear inappropriately happy or even euphoric.

Less consistent clinical features of the diencephalic syndrome are pallor, hyperkinesis, hypertension, hypoglycaemia, and hyperhidrosis. Disproportionately large hands and feet have been described in rare cases. Although optic atrophy is frequently present at the time of diagnosis, visual loss occurs late in the course of the disease. Vomiting, irritability, and an enlarging head due to hydrocephalus are late symptoms. The emaciated appearance. however, is always disproportionate to the anorexia and vomiting.

Most cases has as a common pathologic basis a neoplasm predominantly involving the anterior thalamus. With few if any exceptions, the lesion causing diencephalic syndrome is a tumor involving the anterior hypothalamus and optic chiasm. Some cases of diencephalic syndrome have been reported with lesions in the posterior fossa. However, these lesions have been questioned because of the frequency of anorexia, vomiting, and weight loss associated with posterior fossa tumors. All other reported patients have had tumors in the area of the anterior third ventricle.

Of the cases reported, 80 percent have involved astrocytic tumors. These tumors are usually grossly soft, transparent, and gelatinous in appearance. The most frequent histologic pattern seen is one of moderate cellularity with an open honeycomb background with microcysts. The tumor cells are multipolar, and vascular proliferation is usually minimal. Ependymomas, craniopharyngiomas and  suprasellar germinomas have been reported to produce diencephalic emaciation.

In 95 percent of cases, the onset of symptoms occurs before the age of 2 years. This early onset appears to be significant. The pathophysiology of the lipolysis occurring in this syndrome has not been established.

Growth hormone levels have been elevated in all cases where it has been measured. The response of this elevated growth hormone level to hyperglycemia and hypoglycaemia is inappropriate, and the normal diurnal rhythm is lost. Although the elevated growth hormone level has been implicated in the lipolysis found in the diencephalic syndrome, lipolysis has not been reported in acromegaly or gigantism. Elevated growth hormone levels are also seen in anorexia nervosa and starvation, but the levels correlate closely with the degree of malnutrition and return to normal rapidly when the deficient caloric intake is corrected. The elevated growth hormone level in patients with diencephalic syndrome, on the other hand, does not drop with increased caloric intake and may persist for months after the subcutaneous fat returns.

The diagnostic evaluation of the patient presenting with diencephalic emaciation may include skull films with views of the optic foramina. The optic foramina are enlarged in somewhat less than half the cases. The absence of subcutaneous fat is seen on soft tissue x-ray films. The computed tomography (CT) scan shows a midline suprasellar mass that may be limited to the optic chiasm or optic pathways or may be large, extending subfrontally and temporally. CT bone windows may also show enlarged optic canals. Magnetic resonance imaging (MRI) is usually diagnostic, showing a lesion of the chiasm with extension along the optic pathways and/or involvement of the hypothalamus.

Additional studies provide little further information. Angiography confirms the presence of an avascular suprasellar tumor. Electroencephalography may show diffuse slowing, particularly when the turn or encroaches on the area of the foramen of Monro. The cerebrospinal fluid (CSF) protein content is usually elevated, and tumor cells may occasionally be identified in the CSF. Endocrine evaluation shows elevated growth hormone levels not influenced by hyperglycemia or hypoglycaemia. An inappropriate drop in the growth hormone level following administration of propranolol and L-dopa administration has been reported. Somatomedin values are low or below normal. Adrenocorticotropic hormone stimulation and metyrapone tests indicate an abnormality in the hypothalamic­hypophyseal-adrenocortical axis. Results of thyroid function studies are usually normal.

In the differential diagnosis of the patient with "failure to thrive," inadequate caloric intake and malabsorption problems must be excluded. Inflammatory lesions of the hypothalamic area as a cause of this syndrome are rare. Other suprasellar tumors such as craniopharyngioma, germinoma, and epidermoid or other types of suprasellar cyst rarely produce diencephalic emaciation but do enter into the differential diagnosis of a suprasellar mass.

Histologic confirmation of the lesion has been recommended, but improved imaging techniques now make it unnecessary in most cases. Radiation therapy was recommended in the past; however, because of the deleterious effect of irradiation on the immature brain, chemotherapy is now recommended as the initial therapy.

Regression of the diencephalic syndrome has occurred rarely without therapy. With radiation therapy, return of subcutaneous fat can be noted in 8 to 12 weeks after completion of treatment. Growth hormone levels may drop below normal following treatment, and linear growth may be delayed. Hypothyroidism is frequently found in survivors. Precocious puberty has occurred following treatment. Radiation therapy in the age group of patients who present with the diencephalic syndrome may have additional long-term sequelae, including radionecrosis, leukoencephalopathy, vascular injury, neuropsychological deficits. and secondary malignancies.

Chemotherapy can stabilize or reduce tumor size in young patients harbouring diencephalic tumors without the devastating effects of irradiation. Chemotherapy can allow radiation therapy to be deferred until it can be better tolerated by the central nervous system.

Without treatment, the average survival is between 6 months and 2 years; however,  however, with treatment even after this length of time, tumor regrowth occurs. The long-term efficacy of chemotherapy has not yet been established.