HELLP Syndrome with Spontaneous subdural haematoma and intracerebral haemorrhage

A 32-year old primigravida,with prolonged labour and fetal distress, fell unconscious during labour.

Refereed to our neuro institute for further investigation and management. 

No history of trauma. 

On admission MRI Brain shows:

Left fronto parietal subdural haematoma with max with 13mm, T1 bright signals of hematoma attributed to Meth Hb – a sub acute stage blood degradation product.

An associated left frontal intracerebral hematoma. 

Significant mass effect, mid line shift with internal herniation. 

MR Angiography of Brain normal. No obvious aneurysm. 

No abnormal adjacent T2 flow voids to suggest any vascular malformation.

MR Venography of Brain normal, particularly superior sagittal sinus. 

No obvious cortical vein thrombosis on GRE. 

Patient underwent emergency decompressive craniotomy.

Follow up CT shows:

Left anterior craniotomy with evacuation of left fronto parietal subdural hematoma and left frontal intra parenchymal bleed.
Complete reversal of mass effect and mid line shift. No mid brain compression.
Bilateral frontal subdural pneumocephalus noted, which also regressed on subsequent follow studies. 

Patient is clinically improving, residual right hemiparesis. 

During this a diagnosis of HELLP syndrome with Disseminated Intravascular Coagulation (DIC) was made, as her Platelet count was 50,000/μL (low), e/o hemolysis on peripheral blood smear with Serum lactate dehydrogenase : 800 IU/L (Abnormal) and Serum aspartate aminotransferase : 80 IU/L (Abnormal)

HELLP (haemolysis, elevated liver enzymes, and low platelet count) syndrome can result in a fatal intracranial haemorrhage during the perinatal period. 

Patients with HELLP syndrome should be managed as high-risk, which requires an excellent working relationship of the physicians involved. Prompt recognition of intracranial haemorrhagic complications and neurosurgical intervention are particularly important.

CSF shunt imaging

CSF, Cerebrospinal fluid is an ultra-filtrate of plasma, produced by the choroid plexus of the lateral ventricle, fourth ventricle and ependymal lining of the ventricles.
CSF flows from the lateral ventricle through the foramen of Monro into the third ventricle and then into the fourth ventricle through aqueduct.
The CSF exits the ventricular system via the foramina of Luschka (lateral) and Magendie (medial) situated in the fourth ventricle. CSF then ascends into the basal cisterns and around the cerebral convexities where it is reabsorbed by the arachnoid villi which project into the dural venous sinuses.

Hydrocephalus is defined as excess of CSF, primarily caused by obstruction to the flow of CSF within the ventricular system.

Hydrocephalus is primarily classified into two types: communicating and noncommunicating.

Communicating or extraventricular hydrocephalus is caused by extraventricular obstruction at the level of the arachnoid villi and decreased absorption of the CSF mainly caused by prior hemorrhage, meningitis or obstruction of the dural venous sinuses. On imaging lateral ventricles, third ventricles as well as fourth ventricle are equally dilated as level of obstruction is after fourth ventricle.

Non communicating or intraventricular hydrocephalus is induced by obstructive lesions at various levels within the ventricular system due to various causes such as intra ventricular tumors or aqueductal stenosis. Here dilatation is confined to ventricular system proximal to the level of obstruction.

An intra ventricular mass in third ventricle causing non communicating hydrocephalus.
Fourth ventricle is not dilated. 

Csf Diversionary shunts

CSF diversionary procedures like shunt placement are one of the most common pediatric neurosurgical procedures.

Types of shunt include:
ventriculoperitoneal (VP),
ventriculopleural (VPL),
ventriculoatrial (VA),
ventriculolumbar (VL),
ventriculovenous and
Ventriculo-gallbladder.

TheVP shunt is by far the commonest type of shunt used in the pediatric population.
The ventriculolumbar shunts are mainly reserved for adults with normal pressure hydrocephalus and patients with small slit ventricles or recurrent VP shunt malfunction.
Ventriculoatrial shunts have the distal tip in the right atrium. Complications like sepsis, thromboembolic events, shunt nephritis and pulmonary hypertension have led to the decline of their use except as a last resort. Ventriculopleural shunts are also not favored due to inadvertent life-threatening complications like pneumothorax, pleural effusion and infection.
Other proposed shunts have also failed due to various complications and are rarely used in clinical practice.

Ventriculoperitoneal (VP) shunt

Shunt tube has a proximal intracranial segment inserted through the frontal, parietal or temporal bone, so that the tip and the side holes of the catheter lie within the frontal horn of the lateral ventricle.
Care is taken by the neurosurgeons to avoid proximity of the shunt catheter tip to the choroid plexus, to prevent the occlusion of the catheter by the growth of choroid plexus into the tip and side holes of the shunt catheter. The distal tip of the catheter is tunneled through the skin of the neck, thorax and abdomen into the peritoneal cavity for the drainage of CSF.
Today neurosurgeons have a wide variety of shunts with programmable valves to choose from for a particular patient.
One of the commonly used valves is the Codman Hakim programmable valve which has 18 pressure settings ranging between 30 and 200mmH2O.
The neurosurgeon selects one of the settings at the time of shunt placement and is also able to make precise pressure adjustments to help control intracranial pressure and the ventricle size at any time in the future.

Shunt imaging 

Normal findings
In patients with previous ventricular shunt, the most common and normal finding is an area of Gliosis in the brain along the course of shunt tube (See image)
Diffuse and relatively thin pachymeningeal enhancement along the inner table of the skull and in the dural reflections is a normal finding on post shunt post contrast T1 w MRI images, due to the continued use of the ventricular shunt.
Post shunt Ventricular asymmetry is a known and common finding after ventricular shunting. Asymmetry result due to significantly greater decrease in ventricular size on the side of the ventricular shunt catheter and isolation of the contra lateral ventricle from adequate decompression. Studies have shown that contra lateral placement of tip catheter after perforation of the septum pellucidum that is transeptal placement of catheter would significantly decrease the incidence of post shunting ventricular asymmetry. A special cathter is used which consist of two sets of holes, such that holes are located in both the lateral ventricles. (See Image)

A linear area of Gliosis in right parietal region along the course of shunt tube.

Post shunt mild asymmetry of lateral ventricles, left lateral ventricle wider than right

Shunt malfunction
If a child with a shunt presents acutely with the classical clinical triad of raised ICP with headaches, vomiting and papilledema is need evaluation of shunt for any malfunction.

Causes of shunt malfunction
Mechanical causes leading to inadequate drainage:
○Kinking
○Discontinuity/disconnection
○Break/fracture
○Functional failure of the valve/shunt apparatus
○Migration
Overdrainage:
○Epidural, subdural and intracranial hematoma
○Slit ventricle syndrome
Infection:


INTRACRANIAL COMPLICATIONS

1. Shunt infection.The prevalence of shunt infection is reported in 2.6%-38% of cases. Most infections develop within 2 months from the shunt placement. The common microorganisms are Staphylococcus aureus, Staphylococcus epidermidis, or gram-negative enteric infections.
E/o Ventriculitis and meningitis on CT and MR imaging, are ventriculomegaly, an abnormal enhancement along ventricular ependymal lining and or cerebral cortical sulci. Shunt replacement is usually necessary.
Repeated infections can lead to cerebral venous sinus thrombosis.

2. Shunt obstruction can occur at any time after insertion, and all points along the shunt course. Presents with clinical evidence of raised intracranial pressure.
There two most common locations for obstruction, one is ventricular catheter tip, which can be blocked by ingrowth of choroid plexus, and second is shunt valve, where blood or debris can block the lumen of the valve.
If the ventricular catheter is obstructed by ingrowth of choroid plexus into the lumen of the ventricular catheter tip, its removal is complicated by the risk of bleeding caused by avulsion of choroid plexus if the catheter is forcefully removed.

3. Overdrainage refers to when shunt removes more fluid than necessary for that particular patient. Early rapid reduction in ventricular size may result in collapse of the brain and accumulation of extra-axial fluid or results in mid brain compression.
* Slit ventricle syndrome, CT will reveal collapsed converging lateral ventricles (see image)
* Paradoxical herniation and sunken skin flap, very uncommon complication, 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. (see image)
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.

Slit ventricle syndrome

Sunken Skin flap with Paradoxical herniation

EXTRA CRANIAL COMPLICATIONS

1. Abdominal pseudocyst, a pseudocyst is a loculated intra-abdominal fluid collection that develops around the peritoneum and is more common than ascites.
Indicates the presence of a chronic low-grade infection; however, it is common to find sterile fluid within the pseudocyst cavity when it is aspirated.
Symptoms may be consistent with bowel obstruction if the pseudocyst is large.

2. Shunt misplacement can also occur at the distal end of the catheter, including the abdomen, atrium, or pleura. Patients present with abdominal discomfort and eventually may develop headache, nausea, or vomiting. CT scan may discloses, the distal end of the shunt located in the preperitoneal space, resulting in fluid collection under the abdominal incision.

3. Broken shunt. The typical presentation is usually many years after initial insertion and is related to both biomechanical stress as patient's height increases and the inherent degradation of indwelling components because of host reactions. The distal tubing should be free to slide in the subcutaneous tract; however, scar tissue may tether the tubing and produce shear forces that promote fractures as the children grows. The common presentation is that of mildly elevated raised intracranial pressure. It is also common for patients to present with pain, mild erythema, or swelling over the shunt tract often in a location over the shunt fracture.
Shunt series comprising of AP and lateral radiographs of the skull and neck, radiographs of the chest and abdomen are obtained to evaluate for obvious kinks, discontinuity or disconnection. The commonest site of disconnection is between the valve apparatus and the distal shunt tubing.
Most shunts have translucent areas that one should be aware of to avoid being mistaken for abnormal disconnection.
CT scan of the brain is mainly done to assess the size of the ventricles. Worsening hydrocephalus and overdrainage with epidural, subdural and intraventricular hematomas and slit ventricles are easily identified on a CT brain study.

As mentioned earlier, the programmable valves are susceptible to magnetic disturbances due to their ferromagnetic properties, and hence evaluation of valve pressure is necessary after a diagnostic MRI.

Anticancer drug induced Neurotoxicity - Drug induced Leukoencephalopathy

A known case of Ca Cervix, locally advanced cancer.
Offered first-Line Therapy with Radiotherapy
Cisplatin + 5-FU
Days 1 and 29: 4 hrs prior to external-beam radiotherapy: Cisplatin 50mg/m2 IV infusion at 1mg/min with standard hydration, plus
Days 2–5, and 30–33: 5-FU 1000mg/m2 IV continuous infusion over 24 hrs (total dose 4000mg/m2 each course).

Now patient presented with recent sudden onset altered sensorium.
Here is her on admission MRI brain diffusion

This MRI Diffusion shows:
Restricted diffusion involving splenium of corpus callosum and bilateral centrum semi ovale.
Imaging diagnosis : Drug induced Leukoencephalopathy.

Drug induced Leukoencephalopathy

Many chemotherapy drugs are known to cause significant clinical neurotoxicity. Neurotoxicity is a common and often dose-limiting complication of chemotherapy treatment.

It can involve acute alterations in consciousness, seizures, cerebral infarctions, paralysis, neuropathy, and ototoxicity. Sub acute and delayed toxicities also occur. Despite intensive efforts on the management of the neurologic side effects of chemotherapy in patients and the development of chemo protective agents, there is no generally accepted therapy at present.

In a study of effects of paclitaxel (taxol), cisplatin, and methotrexate on primary rat neurons including hippocampal, cortical, and dorsal horn/dorsal root ganglion neuronal cultures found that all of these anti-cancer drugs induce substantial neurotoxicity evidenced by neurite degeneration.
Taxol stabilizes microtubules and prevents cell division in cancer cells but its major side-effect in treatment is neurotoxicity. Cisplatin cross-links DNA which hampers DNA replication and has a long history of inducing peripheral neuropathy but also has been implicated in toxic leukoencephalopathy and ototoxicity. Methotrexate is a folic acid analog that has been shown to produce a number of cognitive deficits and other neurotoxicities in patients, including children.

Plexiform Neurofibroma MRI

A 20 y o female.
MRI Pelvis
Sequences: Cor STIR, T1WI. Axial STIR and T2WI.

This MRI study reveals T2 hyper intense multi lobulated / conglomerate masses along right sided exiting sacral nerve roots in pre sacral region, extending along sacral nerve at greater sciatic notch deep to Gluteal muscles.

Imaging wise possible diagnosis: Plexiform Neurofibroma.

Excisional biopsy done.

Histo pathology Report

Gross appearance : The specimen consist of multiple fusiform, globular yellowish white nodular tissue together measuring 6x4cm. The nodules appear encapsulated with overall rubbery consistency. The cut section shows dull yellowish white appearance. Representative sections are submitted for processing. Codes A and B.

Microscopy : Sections A and B both show benign encapsulated neoplasm of peripheral nerve sheath origin, comprising interlacing fascicles. whorls and bundles of slender - spindle shaped cells having wavy elongated nuclei and scanty eosinophilic cytoplasm. The interstitial stroma shows variable myxoid change along with fatty tissue, congested blood vessels and residual mononuclear inflammatory infiltrates. There is no evidence of malignancy.

Final diagnosis : Neural Plexiform lesion_ Plexiform Neurofibroma.

Sellar Suprasellar mass DDs

A 49 yo male.
Non contrast CT, MRI Brain with contrast

Non contrast CT

FLAIR

T2

Non contrast T1

Non contrast T1

Post contrast T1 MRI

MRI BRAIN

This MRI study shows:
A well-demarcated sellar supra sellar solid mass with right para sellar component.
Expansion of right half of Sella. No direct Sphenoid sinus extension.
Size of the mass 46mm width, 30mm AP, and height 48mm.
Mass is multi lobulated, Cysts around the lesion can be attributed to areas of cystic degeneration or an associated adjacent meningeal cysts. Signals are homogeneously isointense on T1w and T2w images. Homogeneous enhancement on post contrast T1.
A tissue resembling Pituitary is seen at the floor of left half of hypophyseal fossa on Sagittal T1 and Post contrast T1 sections.
Extension and mass effect _ Prepontine cistern extension causing Basilar compression and encasement. Mid brain and Pons compressed. Right para sellar component causing encasement of right ICA. Optic Chiasma, Optic nerve significantly compressed.
Low signal intensity hemosiderin staining along sub arachnoid space on T2* GRE attributed to superficial siderosis.
Moderate communicating hydrocephalus.

Imaging wise possible DDs: Meningioma more likely than Macro adenoma as pituitary seen separately.

Operated with right sub frontal approach.

Histopathology Report

Gross appearance : The Specimen consist of friable pieces of dull grey tan tissue. The entire tissue submitted for processing. 

Microscopy : Section shows fragmented bits of hyper cellular neoplasm of probable meningothelial cell origin. Tumour consist largely of cohesive sheets of intermediate sized round to oval cells having modestly hyper chromatic nuclei with delicate - irregularly condensed chromatin and scantly eosinophillic to clear cytoplasm having indistinct cytoplasmic membranes. Many neoplastic cells display nucleoli. Overall the tissue reveals 1 to 2 mitosis per 10 HPF. The interstitial stroma shows numerous congested blood vessels. The adjacent stroma shows foci of hyalinised blood vessels. There is no e/o vascular space invasion. Couple of foci show areas of tumor hemorrhage with focal coagulative necrosis. There is no e/o brain invasion. 

Final Diagnosis : Atypical Meningioma Grade II of III (as per  WHO Classification)

Fourth ventricular mass MRI

A 7 y o female.

MRI BRAIN WITH MR SPECTROSCOPY
Sequences planned are FSE T1W, FSE T2W, FLAIR, T2w *GRE and DW images.
Post contrast T1w.
Axial T2w localizer taken and Single voxel MR Spectroscopy performed. The voxel of size 2x2cm placed over the lesion. Water suppression obtained was 99% with optimum spectral waveform obtained at short as well as long TE.
Non contrast CT.

Description of findings:

An ~50x40mm solid hyper dense well defined mass in the region of fourth ventricle on non contrast CT. Lesion is iso intense on T2 and FLAIR. High signal on Dw images. Avid enhancement on post contrast T1 marked at periphery.
Significant mass effect _ moderate obstructive hydrocephalus with mild peri ventricular ooze of Csf. Brain stem compressed.

MRI SPECTROSCOPY performed over lesion.
On short TE of 35ms and TR of 1500ms.
From right to left.
At 2.01ppm - short peak of NAA. NAA is reduced.
At 3.03ppm - short peak of Creatinine.
At 3.2ppm - sharp and long peak of Choline. High choline.
A peak of lactate at 1.4.
NAA/ Creatinine ratio is 1:1
Choline/ Creatinine ratio is 2:1

Imaging possible diagnosis: Medulloblastoma. 

Operated, posterior fossa craniotomy done.

Histopathology report 

Gross specimen : specimen consist of multiple irregular soft to friable pieces of dull – gray tan tissue. Representative sections submitted for processing. Codes : A and B.

Microscopy : sections A and B show a cellular neoplasm composed of medium sized cells with indistinct outlines and round oval or angular hyperchromatic nuclei varying in size. The larger nuclei show clumped chromatin. A fine fibrillary background is discerned between the cells at many places. Peri vascular arrangement of tumor cells with fibrillary processes arising from the cells and extending towards the blood vessels in the center are seen. The tumor is vascular and shows areas of hemorrhage.

Histopathological Diagnosis: Medulloblastoma. 

Similar cases of Medulloblastoma. 
Case 1 : Medulloblastoma MR Spectroscopy 
Case 2 : Medullobastoma lateral origin

MEDULLOBLASTOMA

Syn: MB, Posterior fossa PNET, PNET – MB,
A highly cellular embryonal cell tumor.
Age group : common in children, ~75% diagnosed by 10 years.
3 times more common in males.

Location:
Intraventricular – 4th ventricular roof is a typical and most common location. A most common posterior fossa tumour in children.
Lateral origin – Cerebellar hemisphere is an atypical location common in older children and adults.

Size vary, average size ranges between 3- 5cm at the time of presentation.
On Non contrast CT, solid 4th ventricle mass, hyperdense, calcifcaiton seen in ~20% cases, small intra tumoural cysts, necrosis in ~50% cases.
On MR signal on T1 iso - hypo intense to cortical grey matter on T1 , iso – hyperintense on T2w and FLAIR. High signal on diffusion attributed to its dense, highly cellular nature.
An associated Obstructive hydrocephalus is common seen in ~ 95% cases.
Usually mild to moderate and homogenous enhancement, may show patchy heterogeneous enhancement due to areas of necrosis.

On MR Spectroscopy, NAA reduced or absent as it’s a non neuronal tumour, raised choline.

Posterior Fossa Arachnoid cyst MRI

MRI Brain

Seq planned are Axial FLAIR, T2, Sag T2, Axial Diffusion. 

This MRI study of Brain shows:
Wide posterior fossa with scalloping.
Posterior fossa cyst iso intense to Csf. No restricted diffusion on Dw images. Cyst non communicating with fourth ventricle. Fourth ventricle normal sized.
An associated hypoplastic left cerebellar hemisphere.

An associated Dysgenesis of posterior portion of Corpus callosum with Colpocephaly.
Cerebellar tonsils protruding down across foramen magnum_ Arnold chiari type i malformation with an associated cervical cord syrinx.

Imaging wise diagnosis : Posterior fossa Arachnoid cyst.

DDs ruled out are Dandy walker and other cerebellar malformation as Cyst non communicating with fourth ventricle. Epidermoid Cyst ruled out as no restricted diffusion on Dw images.

Operated and excisional biopsy done.

Histopathology Report

Gross appearance : The specimen consist of thin pearly white soft membranous cystic tissue. The entire tissue submitted for processing.
Microscopy : Sections shows thin undulating delicate fibro collagenous cyst wall lined by meningothelial cells, at places seen to form focal aggregates. There is no e/o cytotological atypia.

Final Diagnosis : Arachnoid cyst.

Intraventricular Arachnoid cyst MRI

A 30 years old female with history of progressive headache, giddiness and vomiting.

Here is Non contrast CT Brain, MRI Brain with axial T2, T2*GRE, Diffusion and post contrast T1w images. 

Findings:

Non contrast CT Brain : Marked dilatation of fourth ventricle iso dense to Csf. Mild non communicating hydrocephalus. Dilated outlet foramen of fourth ventricle. 

Diffuse cerebral edema.

MRI Brain : Fourth ventricular lesion is iso intense to Csf, non enhancing on post contrast T1.l
No restricted diffusion on Dw images.
No low signal intensity hemosiderin staining or calcification on GRE.

Posterior fossa craniotomy done.
Intra operative finding is Intra ventricular Arachnoid cyst. 

Van Der Knaap Leukoencephalopathy MRI

A 3 year old female, larger head relative to rest of the body.

Product of non consanguineous marriage. 

Clinical and neurological examination shows delayed milestones, walking imbalance. 

History of similar illness in elder sister. 

MRI study of brain shows:
Diffuses cerebral white matter involvement. Early involvement of sub cortical white matter. Sub cortical white matter cysts iso intense to Csf representing white matter paucity in temporal regions.
Basal ganglia and internal capsules spared.
Cerebral cortical atrophy.
Minimal involvement of Cerebellar white matter.

On MRS reduced NAA and slightly raised Choline peak.

Impression:
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: 
MLC:
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.
VWM:
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.
WML:
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.
H-ABC:
Atrophy of BG and cerebellum.
Diffuse hypomyelination of cerebral WM.
Subcortical U-fibers involved.

CT
In all varieties involved WM show reduced attenuation. No contrast-enhancement.
MRI
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

Genetics: 
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)

Etiology: 
All are inborn genetic errors

Epidemiology
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.

Age
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.

Management

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.

Similar case of Van Der Knaap Leukoencephalopathy Click here

Superficial Siderosis MRI Brain

A known case of Sellar Supra sellar mass with right para sellar component causing encasement of right ICA on MRI. Here are his Axial T2*GRE images. 

Axial T2 *GRE images of brain reveals low signal intensity hemosiderin staining along tentorium, sylvian fissures and hemispheric cortical sulci suggestive of Superficial siderosis, not at all obvious on any other parenchymal sequences implies to highest sensitivity of GRE to blood degradation product.

Superficial Siderosis

A rare condition characterised by abnormal hemosiderin staining of sub arachonid space, may be diffuse or focal, commonly overlying cerebral and cerebellar convexity, basal cisterns, ventral surface of brain stem on T2*GRE, results from excessive and repetitive subarachonid bleed.
An associated staining along cranial nerves particularly i, ii and viii CNs.
May see an associated atrophy of cerebellar hemispheres and vermis, lepto meningeal thickening with enhancement.
CT usually normal may show faint hyperdense layering.
Differential diagnosis is none, it has a pathognomonic appearace on T2*GRE.

Superficial siderosis is not a final diagnosis but an important finding indicating a remote or recurrent intra cranial bleed in subarachnoid space. Further imaging evaluation should be directed towards source of bleeding like MR Angiography to rule out aneurysm or any other vascular malformation.
The issue is cause of bleed. In ~25% cases cause in not found.

Clinically common symptoms are ataxia, hearing loss, anosmia, dementia; in long standing cases adjacent brain parenchymal atrophy ensues with altered cognition.
Treatment directed towards finding and removing cause of bleeding. Iron chelating agents.

Reference: Teaching atlas of brain imaging: By Nancy J. Fischbein, William P. Dillon, A. James Barkovich : Dural and lepto meningeal processes, Case 65, page  231.

To see other cases of Superficial Siderosis :
Case 1: Click here
Case 2: Click here