Megalencephalic leukoencephalopathy with subcortical cysts
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Megalencephalic leukoencephalopathy with subcortical cysts, also known as Van der Knaap disease, refers to a rare inherited autosomal recessive disease characterized by diffuse subcortical leukoencephalopathy associated with white matter cystic degeneration.
The age at symptoms manifestations ranges from birth to 25 years, with a median age of 6 months 5.
In the Indian population, there is an association with the Aggarwal community and thus this condition is sometimes also referred to as Aggarwal's disease 8.
Patients typically present with megalencephaly during the first year of life associated with mild motor developmental delay and seizures 5. There is also a gradual onset of ataxia, spasticity, dysarthria, and sometimes extrapyramidal findings. Mild mental deterioration can be observed late in life.
It is sometimes classified as a megalencephalic leukoencephalopathy.
It is thought to carry an autosomal recessive inheritance, and the gene locus has been mapped as MLC1 gene at chromosome 22q 4,5.
Elevated levels of glycine have been reported in CSF 1.
The hallmarks of radiological diagnosis are the following features:
- diffuse, bilateral and symmetric T2-weighted hyperintensity and T1-weighted hypointensity in the cerebral white matter, giving a characteristic 'swollen' appearance
- there may also be abnormal diffusion signal on DWI
- subcortical white matter involved early in course of disease with involvement of the subcortical U-fibers
- relative sparing of the deep and cerebellar white matter
- bilateral subcortical cysts of CSF intensity affecting the anterior temporal regions and frontoparietal lobes
- eventual cerebral atrophy with increase in size of the subcortical cysts
Treatment and prognosis
The disease is managed by treating the manifestations with antiepileptic drugs to control epileptic seizures and physical therapy to improve motor function.
History and etymology
Although Bhim Sen Singhal (1933-), an Indian neurologist, initially described a megalencephalic leukodystrophy series of cases in 1991 5,6, it is sometimes named after Marjo S van der Knaap (1958-), a Dutch pediatric neurologist, who detailed another series with clinical and radiological features in 1995 4,7.
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- 4. Van der knaap MS, Wevers RA, Kure S et-al. Increased cerebrospinal fluid glycine: a biochemical marker for a leukoencephalopathy with vanishing white matter. J. Child Neurol. 1999;14 (11): 728-31. J. Child Neurol. (citation) - Pubmed citation
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- 6. Singhal BS, Gursahani RD, Biniwale AA, Udani VP. Tokyo, Japan: In Proceedings of the 8th Asian and Oceanian Congress of Neurology; 1991. Megalencephalic leukodystrophy in India; p. 72.
- 7. van der Knaap MS, Barth PG, Stroink H, van Nieuwenhuizen O, Arts WF, Hoogenraad F, Valk J. Leukoencephalopathy with swelling and a discrepantly mild clinical course in eight children. (1995) Annals of neurology. 37 (3): 324-34. doi:10.1002/ana.410370308 - Pubmed
- 8. Gorospe JR, Singhal BS, Kainu T, Wu F, Stephan D, Trent J, Hoffman EP, Naidu S. Indian Agarwal megalencephalic leukodystrophy with cysts is caused by a common MLC1 mutation. Neurology. 2004 Mar 23;62(6):878-82.