The disrupted brainstem can lead to decorticate posture, respiratory center depression and death. Other possibilities resulting from brain stem distortion include lethargy, slow heart rate, and pupil dilation.Uncal herniation may advance to central herniation. The sliding uncus syndrome represents uncal herniation without alteration in the level of consciousness and other sequelae mentioned above. Central herniation
In central herniation, the diencephalon and parts of the temporal lobes of both of the cerebral hemispheres are squeezed through a notch in the tentorium cerebelli. Transtentorial herniation can occur when the brain moves either up or down across the tentorium, called ascending and descending transtentorial herniation respectively; however descending herniation is much more common. Downward herniation can stretch branches of the basilar artery (pontine arteries), causing them to tear and bleed, known as a Duret hemorrhage. The result is usually fatal. Other symptoms of this type of herniation include small, fixed pupils with paralysis of upward eye movement giving the characteristic appearance of "sunset eyes". Also found in these patients, often as a terminal complication is the development of diabetes insipidus due to the compression of the pituitary stalk. Radiographically, downward herniation is characterized by obliteration of the suprasellar cistern from temporal lobe herniation into the tentorial hiatus with associated compression on the cerebral peduncles. Upwards herniation, on the other hand, can be radiographically characterized by obliteration of the quadrigeminal cistern. Intracranial hypotension syndrome has been known to mimic downwards transtentorial herniation.
In the late stages of the disease, patients have been noted to develop impaired coordination, overresponsive reflexes, and even seizures. MRI testing is used to study and diagnose patients with this disease. A study conducted on four patients with this disease yielded similar MRI results despite their slightly differing symptoms. Genetic testing can show whether or not the individual has a mutation in the MLC1 gene, which accounts for 75% of all cases. Management
There currently is not a known cure for this disease. However, there are treatment options to mitigate the effects of symptoms that come with this disease. The drug Carbamazepine is an anticonvulsant drug commonly used to treat seizures and nerve pain. A case with a 5-year-old girl indicated the ability of this drug to reduce the effects of seizures linked to this disease. Epidemiology
Most of the cases were studied in Turkish families who were part of consanguineous marriages (getting married to relatives or the “same blood”). Nonetheless, Megalencephalic leukoencephalopathy with subcortical cysts does not show genetic heterogeneity which means that there are no mutations in other loci expressing similar phenotypes. History
A series of cases with megalencephalic leukodystrophy were described by the Indian neurologist Bhim Sen Singhal (1933-)in 1991. However, it is sometimes referred to as Van der Knaap disease after the Dutch neurologist Marjo van der Knaap who described another series of cases with clinical and radiological features in 1995. References
External links

GeneReview/NIH/UW entry on Megalencephalic Leukoencephalopathy with Subcortical Cysts