Monday 29 October 2012

Sinken skin flap syndrome

Syn : Sunken skin flap syndrome, Trephine Syndrome , Syndrome of Trephined skull,Post hemicraniectomy Paradoxical Herniation, 

Sinken skin flap syndrome 
Sinken skin flap syndrome   
An uncommon late post operative complication usually occurs after a month of surgery.
Patient who undergo hemi craniectomy for reasons like malignant MCA Infarction, hemispheric contusion or sub dural hematoma present with new onset of complaints like headaches, seizures, dizziness,easy fatiguability and mood changes. 
On examination often a depressed skin flap that is sunken appearance of the skin flap noted.
On CT / MR imaging a depressed galeal dural complex at the craniectomy site and concave deformity of the underlying brain parenchyma.
In a study of 108 patients who underwent decompressive craniectomy, trephine syndrome was reported in 13% and occurred between 28 and 188 days after surgery (reference : Yang XF, Wen L, Shen F, et al. Surgical complications secondary to decompressive craniectomy in patients with a head injury: a series of 108 consecutive cases. Acta Neurochir Wien) 2008;150(12): 1241–1247;discussion 1248)
Patholophysiology: Exposure of the intracranial contents to atmospheric pressure, which alters CSF hydrodynamics, deforms the brain, and reduces cerebral perfusion. (Reference: Akins PT, Guppy KH  Sinking skin flaps, paradoxical herniation, and external brain tamponade: a review of decompressive craniectomy management.Neurocrit Care 2008;9(2):269–276) 
Management : Some patients may show clinical improvement after the cranial defect repaired with cranioplasty the reason may be improved cerebral blood flow after cranioplasty. 

Paradoxical Herniation
Hemicraniectomy with Paradoxical herniation.
Note the VP shunt tube in situ. 
A very uncommon and further advanced complication of decompressive craniectomy and that is paradoxical internal herniations. Seen in patients with a large craniectomy defect who then undergo CSF drainage by either lumbar puncture or ventriculoperitoneal shunt result in marked decrease in Csf pressure, which leads to reduction in intracranial pressure making intra cranial content vulnerable to atmospheric pressure. This pressure imbalance particularly the negative intara cranial pressure deforms brain and mid line. 
On CT / MR Imaging a significant mid line shift away from the craniectomy side with subfalcine and or transtentorial herniations. Uncal herniation if severe may results in mid brain compression.
Clinically patient present with depressed level of consciousness, autonomic instability, signs of brainstem release, and focal neurologic deficits.
Management: Paradoxical herniation is a neurosurgical emergency and urgent treatment is necessary in order to increase intracranial pressure, to stop any CSF leakage, and restore the continuity of the calvaria.
Options include urgent placing the patient in Trendelenburg position and head inclined towards to craniectomy side, clamping ventricular shunts or drains, administering intravenous fluid. Cranioplasty as soon as possible. Paradoxical herniation also has been reported to be effectively and quickly reversed with a lumbar epidural blood patch or clamping ventricular shunt tube. 

Saturday 27 October 2012

Retrodental Cervical Synovial Cyst MRI

A 30 yo male presented with short history spastic quadriparesis and sensory loss. 
No history of trauma.
No any known caugulopathy.
RA factor negative. 

On admission MRI Cervical spine:

Findings : 
An extra medullary cyst iso intense to Csf causing significant cord compression.
No obvious extension out of adjacent neural foramen.
No any bony spinal canal remodelling.
No any adjacent osseous involvement or altered marrow signals. 
No any associated abnormal soft tissue. 
Cyst non enhancing on post contrast. Normal enhancing epidural venous plexus noted.

Imaging wise possibility given was Arachnoid cyst.
Near complete excision of cyst done by left side posterior laminectomy, appeared extra dural on table. Histopathological diagnosis : Synovial Cyst.

Retrodental Cervical Synovial Cyst

Spinal synovial cysts are generally found in the lower lumbar spine. Synovial cysts of the cervical spine are
extremely rare. Retro dental / atlanto axial synovial cyst to the best of my knowledge, only thirty-five cases have been documented in the literature.
Often there is an associated CV junction bony abnormalies like hypoplastic dense, Atalnto dental instblity or os odontoideum is reported.
In our case hypo plastic dense with possible atlantoaxial instability appears to be the cause of excess
stress might have produced the synovial cyst.

Presenting symptoms CV Junction usually include signs of cervical myelopathy secondary to cord compression. Treatment is surgical to decompress cord and stabilizing CV junction.

Choroid plexus papilloma MRI

A 3 yo female child presents with vomiting.
MRI Brain
Axial T1w image shows a lobulated, intra ventricular mass in the left lateral ventricle, isointense
to grey matter, left lateral ventricle slightly expanded compared to right. Intense homogenouse enhancement on post contrast T1, frond like surface projections. A single linear vascular flow void noted on Non contrast T1.

Radiological and histopathological diagnosis: Choroid plexus papilloma.

Choroid plexus papilloma

Syn: Choroid plexus papilloma (CPP)
An intraventricular, papillary neoplasm derived from choroid plexus epithelium.

Imaging wise a lobuated well circumscribed intra ventricular Cauliflower-like mass with frond like surface projections intensely and homogenously enhancing on post contrast is a diagnostic clue.
Most common locations, in ~ 50% cases atrium of lateral ventricle, left > right. , followed by fourth ventricle and third ventricle. Multiple masses are also known.
On CT density of mass is iso- or hyperattenuating in ~75% cases with an associated calcification in ~25%.
On MRI Iso intense to cortical grey matter on T1 and iso to hyper intense on T2 with an  associated linear vascular flow voids within the lesion.
Usually larger in size by the time of diagnosis, often associated with overproduction" hydrocephalus".

Choroid plexus carcinoma (CPCA) : Difficult to distinguish CPP from CPCA by imaging findings alone. Often associated with adjacent brain parenchymal invasion.

Clinical Presentation
Most common signs/symptoms: Macrocrania, bulging fontanelle, vomiting, headache, ataxia
Child in first two years of life with signs and symptoms of elevated ICP
Focal neurologic signs and symptoms suggests CPCA.

Benign, slowly growing. May seed CSF pathways (CPP & CPCA)

Total surgical resection.

Reference : Diagnostic imaging Osborn.

Thursday 25 October 2012

Parry Romberg Syndrome

A 54 Year old female with progressive left hemi facial atrophy for last 10 years. 

1.Marked facial asymmetry due to bony left hemi maxillo facial atrophy and hemi mandibular atrophy on CT.  On MRI Atrophy of left sided medial pterygoid, massicator, temporalis and buccinator. An associated atrophy of left hemi facial cutaneous and sub cutaneous soft tissue.
2.Axial Flair screening of brain shows an associated ipsilateral focal left parietal cortical Gliosis. 
3.Left side phthisis bulbi / enophthalmos. An associated left optic nerve and recti atrophy. 

In view of progressive left hemi facial atrophy ‘ Parry–Romberg’ syndrome needs consideration clinically.

Parry Romberg syndrome

Syn: Progressive Hemi facial Atrophy.

First described by Caleb Hillier Parry in 1825,
Second time described by Moritz Heinrich Romberg in 1846.
Term "progressive hemifacial atrophy" used for first time to describe it by German neurologist Albert Eulenburg in 1871

A rare neurocutaneous syndrome characterized by progressive shrinkage and degeneration of skin and sub cutaenous soft tissues usually on only one side of the face that is hemi facial atrophy but occasionally extending to other parts of the body.

Precise etiology and pathogenesis of this acquired disorder remains unknown.
Suggested to be a variant of localized scleroderma with  autoimmune mechanism as an underlying cause as affected individual have shown antinuclear antibodies.
In some reports more than one member of a family has been affected prompting autosomal dominant inheritance.
Other theories are alterations in the peripheral sympathetic nervous system as a result of trauma or infection involving the cervical plexus or sympathetic trunk.

Typically appears between 5 – 15 years of age and there after progresses variable course with higher prevalence in females.

A) Skin and connective tissue
Usually starts with an area of the face covered by the temporal or buccinator muscles as an atrophy of the skin and its adnexa. Progressively spreads with resulting atrophy with underlying fat, fascia, cartilage, bones  muscles of one side of the face. Mouth and nose typically deviated towards the affected side.
In frontal region, often begins with a circumscribed patch of scleroderma associated with loss of hair , the appearance of a depressed linear scar is referred to as a "coup de sabre" because it resembles the scar of a wound made by a sabre.
In up to 20% of cases the disease may involve the ipsilateral or contralateral adjacent neck, trunk, arm, or leg. In ~5-10 % has been reported to affect both sides of the face.

B) Neurological
In ~ 45% trigeminal neuralgia and/or migraine.
~10% develop a seizure disorder, seizures are typically Jacksonian in nature (characterized by rapid spasms of a muscle group that subsequently spread to adjacent muscles) and occur on the side contralateral to the affected side of the face.
In ~50 % associated ipsilateral brain parenchymal changes noted like focal cortical Gliosis.

C) Ocular
Enophthalmos is the most common eye abnormality caused by a loss of subcutaneous tissue around the orbit. Other common findings include drooping of the eyelid (ptosis), constriction of the pupil (miosis), redness of the conjunctiva, and decreased sweating (anhidrosis) of the affected side of the face. Collectively, these signs are referred to as Horner's syndrome.

D) Oral
The tissues of the mouth, including the tongue, gingiva, teeth and soft palate are commonly involved.
In ~50% develop ipsilateral dental abnormalities such as delayed eruption, dental root exposure, or resorption of the dental roots.
In ~35% have difficulty or inability to normally open the mouth or other jaw symptoms like temporomandibular joint disorder and spasm of the muscles of mastication on the affected side.

Medical : immunosuppressive drugs such as methotrexate, corticosteroids, cyclophosphamide, and azathioprine.
Surgical : Microsurgical reconstructive surgery to restore near normal contour to the face.
The timing of surgical intervention is controversial; some prefer to wait until the disease has run its course while others recommend early intervention.

Sunday 21 October 2012

Pituitary Microadenoma MRI

A 30 yo female with a history of menstrual irregularities with high levels of prolactin.
Coronal Non contrast T1 and T2
Coronal Post contrast T1
Non contrast coronal T1w image show normal sized pituitary. Coronal T2w image shows an ~ 3mm nodular low signal intensity in left half of pituitary. Dynamic Post contrast study included repeated series of T1w images. The immediate post contrast T1w image show lesion is non enhancing in the background of adjacent normal profusely enhancing pituitary.

Imaging Diagnosis: Pituitary Microadenoma. 


Pituitary adenomas are the most common lesion in the sella, accounting for 10–15% of all intracranial tumors. Lesions less than 10mm are called microadenomas. Lesions greater than 10 mm are macroadenomas. Microadenomas are usually hypointense on precontrast T1 weighted images, and may have variable signal intensity on T2 weighted images. Deviation of the
pituitary stalk has a wide range of normal variation and is difficult to use as a diagnostic sign. Dynamic contrast enhanced images increase the sensitivity of microadenoma detection in immediate post contrast sections seen as non enhancing nodular in the back ground of normal profusely enhancing adjacent pituitary. Delayed post contrast images after ~ 20 minutes may show delayed enhancement of the lesion obscuring it or making it outstaning enhancing lesion where rest of the pituitary is leaves contrast.
The most common endocrinologically active pituitary adenomas are prolactinomas. A serum prolactin level above 200 μg/L is very specific for an adenoma. Growth hormone producing adenomas can produce acromegaly in adults and gigantism in children. ACTH producing adenomas cause Cushing disease.

Cavernous sinus Meningioma encasing ICA

A 50 yo female with a known sellar para sellar tumor in previous CT. MRI performed for further evaluation and follow up imaging. On clinical examination multiple left sided cranial nerve palsies.
Axial T1 and Coronal T2
Axial and Coronal Post contrast T1

Axial T1w and Coronal T2w image show a sellar left para sellar well circumscribed mass lesion obliterating left cavernous sinus, encasing left ICA. Lesion is iso intense to cortical Grey matter on T1 and T2 images. Homogenous enhancement on axial and coronal post contrast T1w images. Encased Left ICA narrowed. Lesion is extending in sellar and supra sellar region. Left temporal lobe Gliosis as an e/o previous attempt of excision / biopsy.

Radiological and Histopathological Diagnosis: Cavernous sinus Meningioma encasing ICA.


A meningioma that originates in the cavernous sinus can invade the sella. Meningiomas classically encase and narrow vessels while a pituitary adenoma would not. Cavernous sinus Meningiomas that encase and narrow the carotid artery are difficult to resect surgically or completely non resectable. Obliteration of left sided cavernous sinus explains multiple cranial nerve palsies namely 3rd 4th and 6th CN traversing left side cavernous sinus.

Lipoid Proteinosis

A 40 yo married female with history of recent seizure, the reason for her this neurological consultation for first time.  According to her this was second episode of seizure.

CT study of brain shows bilateral symmetrical horn like calcification of medial temporal lobes.
Rest of the brain parenchyma unremarkable.
In this case the imaging findings being very typical assisted in clinical diagnosis of Lipoid proteinosis. The retro grade clinical examination revealed an associated skin lesions as thick rough skin, blapherosis, papules, hoarseness of voice which is progressive as per history with episodes of seizures.

Lipoid proteinosis

Syn : Urbach-Wiethe disease, initially described by Urbach and Wiethe in 1929 as “hyalinosis cutis et mucosae”.
A rare genodermatosis characterized by multisystem involvement due to intracellular deposition of an amorphous hyaline material.
Caused by mutations in the ECM1 gene on chromosome 1q21.
Normally EMC1 gene is expressed in the dermis, basal keratinocytes, endothelial cells and developing bones and is linked to keratinocyte differentiation, basement membrane regulation, collagen composition, and growth-factor binding. The mutated ECM1 gene gives rise to hyaline material deposition in the dermis and thickening of the skin and mucous basement membrane around blood vessels and adnexal epithelia.
The patient may present with abnormal scarring and wound healing. Premature skin aging, skin and mucosal thickening usually the first clinical manifestation. Moniliform blepharosis is considered a pathognomonic finding present in 50% of patients.

Associated hoarseness is present at birth or in the early infancy in two-thirds of patients, due to early hyaline material larynx infiltration, progressing with time.

When CNS is affected, a wide variety of neurologic abnormalities may be present. The hallmark findings are calcifications, mostly occurring in the amygdalae, hippocampus, parahippocampal gyrus, or even the striatum.
CNS infiltration occurs predominantly around the hippocampal capillaries, resulting in wall thickening, which later progresses to perivascular calcium deposition.
Neurologic manifestations range from migraine, variable degrees of mental retardation, seizures, depression, anxiety, and panic attacks to disturbances in decision making, memory, and abnormal social interaction patterns.

In half of cases imaging assist in the diagnosis and gives clue to the diagnosis because there are few diseases that can manifest such a typical pattern of bilateral and symmetrical calcification occurring in the medial temporal lobes. Amygdalae involvement is considered pathognomonic.
The other commonly affected sites are the amygdalae, hippocampus, parahippocampal gyrus, or even the striatum. The calcification pattern described is dense curvilinear horn-shaped well depicted by CT in the amygdaloid bodies. In MR imaging, such lesions are hypointense in all pulse sequences, especially in GRE T2*

Reference : American journal of Neuroradiology, Amygdalae and Striatum Calcification in Lipoid Proteinosis F.G. Gonçalvesa,b, M.B. de Meloa,  V. de L. Matosa, F.R. Barraa and R.E. Figueroac.

Saturday 20 October 2012

Imaging of Neck vasculature with emphasis of non contrast MR Angiography

In Neck atherosclerosis of the carotid arteries accounts for the majority of cervical vascular pathology and the most common indications for imaging include transient ischemic attack (TIA), ischemic stroke or carotid bruit. 
Different imaging modalities which are commonly used for evaluation of neck vasculature include DSA, Doppler, CT Angiography (CTA) and MR Angiography (MRA).
Each modality has its own pro and con, however DSA remains the gold standard.

Doppler is most commonly used screening test for carotid stenosis, due in part to the superficial location of the cervical carotid arteries and the ability of doppler to provide functional information. Again its relatively inexpensive, easily available, rapid and safe. Its main disadvantage is Operator and equipment dependent.

CT Angiography has rapidly evolved over the past decade with the advent of multidetector row CT scanners. CT Angiography can be performed at high spatial resolution and is better at detecting calcification than DSA or the MRA. Further, CTA does not suffer from the flow-related artifacts that can affect MRA interpretation. Unlike MRA, CTA is not limited by the presence of implanted devices such as cardiac pacemakers. Most patients can tolerate the short scan times of CTA. The main disadvantages of CTA are contrast-based technique and ionizing radiation. 

Magnetic Resonance Angiography
There are two main techniques TOF and PC, among them TOF is most commonly used.
We use non contrast 3 D TOF for brain as well as Neck as a routine screening along with parenchymal sequences for Brain, let's see the technical details in brief.

Time-of-flight (TOF) imaging, is based on differences in the excitation of flowing protons in blood and the stationary protons in background tissues, can be performed as 2D TOF as well as 3D TOF technique. 2 D TOF is rapid but susceptible to stair-step artifacts due to motion between the two adjacent slices. 3 D TOF technique offers ability to achieve a smaller voxel size, resulting in higher resolution, as compared to 2D TOF. However, the smaller voxels result in lower signal-to-noise ratio (SNR), and the use of a larger imaging volume predisposes the technique to signal loss from saturation effects. In addition, 3D TOF imaging offers a shorter allowable echo time (TE), which can minimize signal losses from phase dispersion.

Phase contrast (PC) imaging uses two gradients of equal strength but opposite polarity to induce a phase change in excited protons.  PC can thus measure flow velocity as well as directionality. Technical limitations and issues related to scan time limit the clinical application of this technique for neck angio.

Contrast-enhanced magnetic resonance angiography (CE MRA) refers to the injection of an intravascular contrast agent, to shorten the T1 of blood and thus provide contrast against surrounding tissue. A fixed delay time, a timing run, an acquisition triggered off detecting the arrival of contrast and temporally resolved strategies can all be employed.

Artifact and Signal Loss
Two major sources of artifact and signal loss in MRA are saturation effects and phase dispersion. The different MRA techniques have their own particular strengths and weakness is as well as differing susceptibility to the saturation and dephasing effects.

Saturation Effects
Slower blood protons may become saturated and lead to a signal loss. This effect is important for clinical assessment as it can simulate near-occlusive stenosis as complete occlusion. A similar phenomenon is noted in areas where blood recirculates or produce edie's current, as in the carotid bulb. The third example of such saturation effect is signal dropout from in-plane blood flow when blood is flowing parallel to the imaging plane rather than perpendicular to it, the blood will be within the imaging slice for a longer period of time, resulting in loss of signal. Such saturation effects can be minimized by making the imaging slice thinner or to increase the TR to prolong the time between excitation pulses. The ability of 2 D TOF to obtain a thin slice has an important advantage over 3 D TOF in demonstrating slow flow. However, a thinner slices will require more slices to cover a similar anatomic area of interest and has the potential to increase sensitivity to motion and, thus, stair-step artifacts. Prolonging the TR is problematic, as this will decrease the degree to which the signal from background stationary tissue is suppressed. MOTSA (multiple overlapping thin-slab acquisition) is a 3D TOF technique that uses a relatively thin-slab thickness to minimize signal loss from saturation while maintaining the other advantages of 3D TOF imaging. TONE (titled optimized nonsaturating excitation), is another technique used to reduce signal loss from saturation, which uses a variable flip angle to reduce the saturating effect of the excitation pulse as protons enter the image volume. The use of iv contrast in CE MRA is another very effective means of reducing saturation effect by shortening the T1 of the blood, allows for the use of thick-slab without the consequence of saturation. Therefore, a very large field of view (FOV) can be acquired parallel to the vessels of interest, such as a coronal acquisition to cover the aortic arch to the intracranial extent of the cervical arteries without signal loss from in-plane flow. 

Phase Dispersion
Phase dispersion, also referred to as dephasing artifact, is another source of signal loss in MRA. One solution to phase dispersion artifact is to decrease the size of the voxel so that each voxel contains a smaller range of velocities of flowing blood protons. The smaller distribution of velocities will result in less intravoxel signal loss from dephasing. Another approach to decreasing the dephasing artifact is to decrease TE. Among TOF techniques, a 3 D technique offers smaller voxels and shorter TE values than are generally achievable with 2 D techniques. Administering gadolinium compensates for the signal loss in 3D TOF imaging from the saturation effects described earlier while compensating for signal losses from dephasing.

Imaging of vessels that have undergone stenting. 
Both MRA and CTA will suffer from artifacts from stents. MRI-incompatible stents may demonstrate complete dropout of signal along the stented segment of vessel. Thin-section CTA can visualize the contents of a stented vessel, though the stent will cause streak artifact. CTA will overestimate the degree of in-stent stenosis and that CTA cannot reliably determine patency of a stent smaller than 4 mm in diameter.

Reference : CT and MR Angiography: Comprehensive Vascular Assessment edited by Geoffrey D. Rubin, Neil M. Rofsky.

Wednesday 17 October 2012

Intraventricular Cavernoma

A 30 yo female with giddiness.

Non contrast CT shows a solitary round to ovoid well circumscribed intra ventricular mass attached to left lateral ventricle. Hyper dense specks of calcification. No significant mass effect or hydrocephalus. On MRI lesion shows low signal intensity blooming on GRE, thin rim of hemosiderin on T2. Diffusion non contributory as expected. Very minimal enhancement on post contrast T1. No significant mass effect. Perilesional odema in adjacent brain parenchyma.

Imaging wise : Intraventricular cavernoma possible, all the imaging findings of a typical cavernoma may not be expected. Histopathological evaluation followed by endoscopic biopsy mentions findings favoring cavernous malformation.


Intraventricular masses represent ~ 10% of all CNS neoplasms, DDs are based on imaging findings, location, and age of the patient. Symptoms are usually non-specific and are related to mass effect and or hydrocephalus.
IVCs are rare entities. The prevalence rate of IVC varies between 2.5% to 10.8%.
44% of intraventricular cavernomas located in third ventricle, 27% in the lateral ventricle, 20% in the trigone, and 9% in the fourth ventricle.
Clinical presentation is usually non-specific often secondary to increased intracranial pressure with resultant mass effect. May have intermittent or fluctuating symptoms attributed to secondary to minor intra ventricular bleed. Hydrocephalus not present in majority of cases, depends on location.
On imaging,IVCs may show a similar appearance to that of intraparenchymal cavernoma. IVCs have been found to be more voluminous than their intra parenchymal counterparts, can measure up to several centimetres attributed to the lack of restriction from adjacent brain parenchyma allows for more unrestrictive growth.
On CT they are hyperdense well circumscribed round to ovoid masses, specks of calcification. Enhancement vary from none to avid. On MRI a well-defined mass with heterogeneous signal intensity on both T1W and T2W sequences due to areas of calcification and T1 bright methemoglobin. A hypointense peripheral hemosiderin rim on T2W images. GRE imaging is very sensitive in demonstrating the susceptibility effect of hemosiderin and in identifying the multiplicity of the lesion and therefore supporting the diagnosis of IVC.
On imaging, DDs include other intraventricular lesions including intraventricular arteriovenous malformations, low-grade astrocytomas, meningiomas, teratomas, or neurocytomas. Lack of surrounding edema on FLAIR or T2W imaging, peripheral hemosiderin, and lack of enhancement make tumor less likely and favor atypical vascular malformation. But on MRI, central hyperintensity,due to methemoglobin and peripheral hemosiderin rim, limits the differentials. Contrast enhancement does not help much in differentiation. GRE may be extremely helpful.

Intraventricular cavernoma, John D. Nguyen, MD, Sangam Kanekar, MD, and Annilyn S. Purayidom, MD applied radiology Journal Volume 39, Number 11, November 2010

Tuesday 16 October 2012

Van der Knaap Leukoencephalopathy MRI

A 2 year old male presented with relatively larger head size for further evaluation. Previous CT study shows diffuse low attenuating white matter. No hydrocephalus. 
Clinical and neurological examination shows delayed milestones, walking imbalance. 
MRI study of brain shows:
Diffuses white matter involvement. 
Sub cortical white matter involved early shows cystic areas iso intense to Csf representing white matter paucity in fronto parietal and temporal regions. 
Basal ganglia and internal capsules spared.
Cerebral cortical atrophy. 
Relatively spared cerebellum. 

Imaging findings of bilateral diffuse white matter disease, involvement sub cortical white matter with cysts, sparing basal ganglia and internal capsules with Macrocephaly clinically goes in favour of Van der Knaap disease. 

Vander Knaap Leukoencephalopathy

Abbreviations and Syn: 
1. MLC: Megaloencephalic leukoencephalopathy with subcortical cysts, formerly known as Vacuolating megaloencephalic leukoencephalopathy with benign, slowly progressive course.
2. VWM: Leukoencephalopathy with Vanishing white matter (WM), Alternatively called CACH (Childhood ataxia central hypomyelination)
3. WML: White matter disease with lactate.
4. H-ABC: Hypomyelination with atrophy of the basal ganglia (BG) and cerebellum.

Imaging findings and diagnostic clues: 
Swollen WM involvement is diffuse, includes subcortical U-fibers.
Subcortical cysts makred in anterior temporal and fronto parietal white matter.
Spares internal capsules, BG, thalami
Cerebellar involvement subtle. 
WM replaced by CSF signal, involvement is diffuse WM, includes subcortical U-fibers.
BG and thalami not involved.
Trackt-like ventral trigeminothalamic and central tegmental tract demyelination in brain stem
Cerebellar WM involved.
Diffuse periventricular, deep cerebral WM.
Spared subcortical U-fibers.
Posterior corpus callosum and posterior limb of internal capsule involved.
In Brainstem cerebral Peduncles, pyramidal tracts, medial lemniscus, intraparenchymal trajectories of trigeminal nerves, anterior spinocerebellar tracts involved.
Cerebellar WM involved later, but then notably abnormal.
Spinal involvement an important feature. In spine dorsal columns and lateral corticospinal tracts involvement is typical.
Atrophy of BG and cerebellum.
Diffuse hypomyelination of cerebral WM.
Subcortical U-fibers involved.

In all varieties involved WM show reduced attenuation. No contrast-enhancement.
In all involved WM show decreased signal on Tl WI and increased signal on T2WI
In MLC: Anterotemporal and frontoparietal subcortical cysts approximate CSF signal.
In VWM: Involved WM approximates CSF signal.
DWI: both MLC and WML on DTI shows decreased anisotropy and increased ADC values
No contrast-enhancement on post contrast study.
On MR spectroscopy in MLC all metabolites decreased in cystic regions with reduced NAA in
WM, +/- lactate. In VWM: All metabolites of affected WM disappear as the WM disappears; +/-lactate , glucose signals. In WML: Positive lactate peak; normal to mildly increased Cho,
reduced NAA, increased myo-inositol. In H-ABC: Increased Myo-inositol and creatine (gliosis) in WM;reduced frontal NAA, but otherwise NAA relatively normal

Differential Diagnosis: 

DDs of macrocephaly with   diffuse leukoencephalopathy is limited includes Canavan disease, Alexander disease, infantile-onset GM2 gangliosidosis and laminin alpha-2 (merosin) deficiency.

Laminin alpha 2 deficiency: The white matter disease in laminin alpha-2 deficiency most closely resembles that observed in MLC; however, the typical subcortical cysts of van der Knaap are lacking. Individuals with laminin alpha-2 deficiency have prominent weakness and hypotonia, not seen with MLC - van der Knaap. Molecular genetic testing will be confirmative.
Canavan disease: Typically shows involvement of the thalamus and globus pallidus with relative sparing of Putamen and caudate nucleus. The globus pallidus and thalamus are not involved in MLC. The white matter may be cystic in Canavan disease, but the typical subcortical cysts seen in MLC are lacking. Confrmation of Canavan disease possible by demonstration of very high concentration of NAA in the urine and/or molecular genetic testing of ASPA.
Alexander disease: Megalencephaly and leukoencephalopathy with frontal predominance on MRI is typical with contrast enhancement of particular brain structures  not a feature of MLC. Cystic degeneration may occur in Alexander disease, but the location of the cysts is frontal. Alexander disease can be confirmed by molecular genetic testing of GFAP.
Infantile GM2 gangliosidosis: MRI characterized by prominent involvement of the basal ganglia and thalami in addition to the white matter abnormalities. Demonstration of assaying hexosaminidase A and B in serum, leukocytes, or cultured skin fibroblast will be confirmtative.

General Features: None have systemic or other organ involvement

MLC: Autosomal recessive; gene localized on chr22q(tel); 26 different mutations of MLCI gene. Encodes putative CNS membrane transporter
VWM: Recessive inheritance; gene on 3q27,mutations in genes that encode eIF2B subunits: EIF2Bl-S.
WML: Autosomal recessive inheritance likely.
H-ABC: Unknown, 7 cases in literature (no sibling pairs, so inheritance unknown)

All are inborn genetic errors

All are extremely rare
MLC and VWM rare, but carrier rate is high in some communities with high levels consanguinity.
Common MLC mutations in specific Indian community (Agarwal), Libyan Jewish, and Turkish populations due to founder effect.
Common VWM mutations in certain regions of Netherlands.

MLC: Macrocephaly before the age of 1year
VWM: Young children (slower progression of older onset of symptoms)
WML: Older children, adolescents, young adults
H-ABC: 1-20 years.

Clinical Presentation
Most common signs/symptoms
MLC: Macrocephaly. Delayed onset slow motor deterioration. Slower cognitive decline.Cerebellar ataxia and pyramidal tract involvement, motor deterioration, seizures.
VWM: Episodes of major deterioration and coma following infection or minor head trauma. Relatively preserved cognition.
WML: Slowly progressive pyramidal, cerebellar and dorsal column dysfunction. Spasticity and ataxia. preserved cognitionr
H-ABC: Progressive extrapyramidal symptom like ataxia.


Establish the extent of disease in an individual diagnosed with megalencephalic leukoencephalopathy with subcortical cysts (MLC) by
Neurologic examination
Brain MRI
Physical therapy/occupational therapy assessment
Assessment of cognitive dysfunction (neuropsychological testing)

Supportive therapy includes the following:
Antiepileptic drugs (AED) if epileptic seizures are present
Physical therapy to improve motor function
Special education
Speech therapy as needed

Prevention of Secondary Complications from minor head trauma.
Evaluation of Relatives at Risk with Genetic Counseling.

Reference : Diagnostic Imaging Osborn.

Click here for similar case of Van der Knaap Leukoencephalopathy