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07-161

Van der Knaap Disease, A Megalencephalic


Leukoencephalopathy
KV RAJAGOPAL, RH RAMAKRISHNAIAH, KR AVINASH, BN LAKHKAR

Ind J Radiol Imag 2006 16:4:733-734

Key words : Van der Knaap Disease, Megalencephalic Leukoencephalopathy

Introduction: cysts were noted in anterior temporal lobe and which are
hypointense on T1 (Fig 2A), hyperintense on T2 and
Megalencephalic leukoencephalopathy (MLC) with suppressed on FLAIR images (Fig 2B) consistent with a
subcortical cysts is a rare disease first described by van diagnosis of Megalencephalic leukoencephalopathy.
der Knaap et al, in 1995 [1]. Megalencephalic
leukoencephalopathy with subcortical cysts is a relatively
new entity of neurodegenerative disorder characterized
by infantile onset macrocephaly, cerebral
leucoencephalopathy and mild neurological symptoms
and an extremely slow course of functional deterioration
[1]. Megalencephalic leukoencephalopathy with
subcortical cysts is a rare disease with autosomal
recessive inheritance [2]. The degree of macrocephaly is
variable and can be as much as 4-6 SD above the mean.
Almost all patients have epilepsy from an early age. Some
patients have died in their 2nd and 3rd decades but few
may live till fourth decade. We report a 2-year-old boy
diagnosed to have this disease.

Case report:

A 2 year-old boy, born of non-consanguineous marriage


in a muslim community from Kerala, with uneventful birth
history, presented with progressively increasing head size
noticed from 1 year of age. He attained social smile by 3
months and head control by 7 months of age. He was not
able to sit or walk himself.

On examination, there was macrocephaly with head


circumference of 61 cm. He was not able to comprehend
or speak. Sensory system was normal and there were
no cerebellar signs. Eye examination and abdominal
examination were unremarkable.

MR brain revealed extensive bilaterally symmetrical white


matter changes, which are hypointense on T1 weighted
(Fig 1A) and hyperintense on T2 weighted (Fig 1B) and Fig 1A and Fig 1B: Axial MR shows bilateral symmetrical
FLAIR images suggestive of extensive demyelination. white matter hypointensity on T1 weighted sequence (Fig
1A) and hyperintensity on T2 weighted sequence (Fig 1B)
Additionally, large well defined symmetrical subcortical suggestive of demyelination.

From the Department of Radiodiagnosis and Imaging, Kasturba Medical College, Manipal.

Request for Reprints:Rajagopal K.V, Associate Professor., Department of Radiodiagnosis and Imaging, Kasturba Medical
College. Manipal. Pin:576104 Karnataka State, India.

Received *****; Accepted *****


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734 KV Rajagopal et al IJRI, 16:4, November 2006

dystonia and athetosis, usually as a late finding. Mental


decline occurs later and is much milder than motor
decline. Most patients have epileptic seizures.

In typical cases, the MR findings are often diagnostic of


MLC. MR shows 'swollen white matter' and diffuse
supratentorial symmetrical white matter changes in the
cerebral hemispheres with relative sparing of central white
matter structures like the corpus callosum, internal
capsule, and brain stem. Subcortical cysts are almost
always present in the anterior temporal region and are
also frequently noted in frontoparietal region. Grey matter
is usually spared. Gradually the white matter swelling
decreases and cerebral atrophy may ensue. The
subcortical cysts may increase in size and number.

In India, majority of the patients belong to the Agarwal


community [3]. Our patient did not belong to this
community. Indian patients with megalencephaly and MR
changes that show extensive white matter changes with
temporal cysts should raise suspicion for MLC [3]. This
disease has been assigned to the gene, MLC1, and is
localized on chromosome 22qtel [4]. Moderate decrease
in NAA/ Cr and Choline/Cr ratios have been reported in
patients with MLC on MR spectroscopy [5].

The differential diagnosis of MLC includes Canavan's


disease, Alexander disease, infantile-onset GM2 and GM1
gangliosidosis. These conditions have relentlessly
progressive infantile onset leukoencephalopathy that is
freequently fatal within first decade of life, however MLC
has remarkably slow course of deterioration in neurologic
function. MLC must be included in differential diagnosis
of macrocephaly with early onset leukoencephalopathy
[6].

References:
1. Van Der Knaap MS, Barth PG, Stroink H, van
Nieuwenhuizen O, Arts WF, Hoogenraad F, et al.
Leukoencephalopathy with swelling and a discrepantly
Fig 2A and Fig 2B: Well defined symmetrical subcortical cysts mild clinical course in eight children. Ann Neurol, 1995;
were noted in anterior temporal lobe which are hypointense 37: 324-334.
on T1 (Fig 2A, arrow) and FLAIR sequence (Fig 2B, arrow). 2. Koussa S, Roukoz H, Rizk T, Megarbane A.
Megalencephalic leucoencephalopathy with subcortical
His brother died at the age of 2 years, the cause of which cysts: a study of a Lebanese family and a review of the
literature. Rev Neurol (Paris). 2005 Feb;161(2):183-91
is not known. He was treated symptomatically with use 3. Gorospe JR, Singhal BS, Kainu T, Wu F, Stephan D, Trent
of physiotherapy. J, Hoffman EP, Naidu S. Indian Agarwal megalencephalic
leukodystrophy with cysts is caused by a common MLC1
Discussion: mutation. Neurology. 2004 Mar 23;62(6):878-82.
4. Pascual-Castroviejo I, van der Knaap MS, Pronk JC,
Garcia-Segura JM, Gutierrez-Molina M, Pascual-Pascual
The diagnosis of MLC can be made with confidence in SI. Vacuolating megalencephalic leukoencephalopathy:
patients with typical clinical findings and characteristic 24 year follow-up of two siblings.Neurologia. 2005 Jan-
abnormalities on cranial MR. MLC is known for its mild Feb;20(1):33-40.
5. Brockmann K, Finsterbusch J, Terwey B, Frahm J,
neurological signs and symtoms in the setting of a very Hanefeld F. Megalencephalic leucoencephalopathy with
abnormal MR findings. Macrocephaly is present at birth subcortical cysts in an adult: quantitative proton MR
or, more commonly, develops within the first year of life in spectroscopy and diffusion tensor MRI. Neuroradiology
all patients. Early development is normal or mildly delayed. 2003;45:137-42.
6. Krishnan KH, Pauline CL, Kumaresan G, Mallika TK.
Slow deterioration of motor functions with cerebellar ataxia Megalencephalic leukoencephalopathy with subcortical
and mild spasticity usually starts in early childhood. Some cysts. Indian Pediatr. 2005 Jan;42(1):60-3.
patients have extrapyramidal movement abnormalities with