Case of the Week for April 12, 2019:   4H Leukodystrophy

Clinical Presentation:  11 year old boy with spasticity, ataxia , and dental abnormalities.

Imaging Findings and Discussion: 

•       Typically characterized by the triad of hypomyelination, hypodontia, and hypogonadotropic hypogonadism.
•       The condition is caused by mutations in POLR3A or POLR3B.
•       Clinical hallmarks are early-onset ataxia, delayed dentition, and hypomyelination.  Additional signs are myopia and short stature.
•       MRI findings include a combination of hypomyelination with relative T2 hypointensity of the ventrolateral thalamus, optic radiation, globus pallidus, and dentate nucleus; cerebellar atrophy; and thinning of the corpus callosum.
•       Cerebellar atrophy is present more commonly with POLR3B  mutations, but may not be seen with POLR3A  mutations.
•       There is no specific treatment.
Differential diagnosis:
◦       Hypomyelination and congenital cataract (HCC)
◦       Cockayne syndrome
◦       PCWH syndrome (peripheral demyelinating neuropathy central dysmyelinating leukodystrophy)
◦       Pelizaeus–Merzbacher disease
◦       Vanishing white matter disease


1. Wolf NI, Vanderver A, van Spaendonk RM, Schiffmann R, Brais B, Bugiani M,Sistermans E, Catsman-Berrevoets C, Kros JM, Pinto PS, Pohl D, Tirupathi S,Strømme P, de Grauw T, Fribourg S, Demos M, Pizzino A, Naidu S, Guerrero K, vander Knaap MS, Bernard G; 4H Research Group. Clinical spectrum of 4Hleukodystrophy caused by POLR3A and POLR3B mutations. Neurology. 2014 Nov18;83(21):1898-905.

2. Outteryck O, Devos D, Jissendi P, Boespflug-Tanguy O, Hopes L, Renard D, FerriJ, Vermersch P, Labauge P. 4H syndrome: a rare cause of leukodystrophy. J Neurol.2010 Oct;257(10):1759-61.




Functional Friday Case #17: Answer 4/5/19: CLOVES Syndrome

Clinical presentation: Young woman with overgrowth of the left upper back and extremity since birth; also has linear epidermal nevi

Imaging Findings: Venous malformations within the left mediastinum and upper back musculature, including a phlebolith in the latter. Muscular and lipomatous overgrowth of the left upper back. Arthrogryposis of the left hand.


  • CLOVES syndrome refers to Congenital Lipomatous, Overgrowth, Vascular anomalies, Epidermal nevi, and Scoliosis/spinal deformities.
  • Secondary to sporadic, somatic PIK3CA gene mutation and falls under the PIK3CA-related overgrowth spectrum (PROS). This case was genetically proven. Other PROS disorders include Klippel-Trenaunay (KTS) and fibroadipose vascular anomaly (FAVA).
  • Low flow vascular malformations are commonly present within CLOVES. Spinal AVMs are less common but very characteristic of this entity.
  • Thoracic lipomatous hyperplasia is a key feature of CLOVES, as in this case.
  • Other features include: linear epidermal nevi, lipomas, hand/foot overgrowth, macrodactyly, Wilm tumor

References: Bertino F et al. Congenital Limb Overgrowth Syndromes Associated with Vascular Anomalies. Radiographics 2019.

Functional Friday Case #16 Answer: Chronic recurrent multifocal osteomyelitis (CRMO) AKA chronic recurring multifocal osteomyelitis

  • DWI helpful for distinguishing benign from pathologic compression fractures.
  • Increased water motion in post-traumatic benign compression fractures with low or iso-intense signal on isotropic DWI and high ADC values [1].
  • Pathologic compression fractures related to densely cellular tumors such as lymphoma have restricted diffusion [2].
  • In this case, there is variable diffusion restriction within affected vertebra consistent with acute on chronic disease.
  • Dx: Chronic recurrent multifocal osteomyelitis (CRMO), an autoimmune condition in which PMNs congregate and necrosis develops in the absence of infection [3].

Functional Friday Case #15 Answer 3/8/19: Ewing Sarcoma

  • Imaging shows a heterogeneous extra-axial right temporal mass with osseous destruction and extension into the scalp. A well-defined capsule is noted at the medial aspect. Multiple cystic foci are seen on T2 imaging, and there is heterogeneous enhancing septa after contrast administration. Ewing sarcoma was proven after surgical resection.
  • Lesions are considered a type of primitive neuroectodermal tumors; incidence males>females.
  • 2nd most common bone tumor in children (after osteosarcoma), but involvement with the skull is uncommon.
  • Symptoms usually arise from headache and increased intracranial pressure.
  • Imaging differential diagnoses include Langerhans cell histioyctosis, meningioma, solitary fibrous tumor (hemangiopericytoma), and metastasis. LCH does not usually have this large of a solid component. Meningiomas would typically expand the bone though rather than destroy it. SFT usually occurs in adults.

Functional Friday Case #14 – Diagnosis: Maple Syrup Urine Disease

Clinical Presentation: Poor feeding, vomiting , lethargy and developmental delay in early infancy. Characteristic odor of urine.

Etiology: Impaired metabolism of branched-chain amino acids caused by deficiency of alpha-ketoacid dehydrogenase complex

Imaging: Restricted diffusion involving cerebellar white matter, brainstem, Basal ganglia, internal capsules and rolandic white matter. Involvement of optic pathway may occur. Associated with increased T2 signal with affected regions. MRS demonstrates large peak at 0.9 ppm representing branched chain amino acids as well as a lactate peak at 1.3 ppm.

Discussion: Multiple types with classic most common and worst prognosis. Other types include intermittent, and thiamine-responsive.

Functional Friday Case #13 Answer 1/25/19: Acute Flaccid Myelitis from Enterovirus 

  • Polio-like virus responsible for outbreaks in many parts of the world in the past decade. Usually either A-71 or D-68 subtypes.
  • Characteristically involves the anterior horn cells, showing T2 hyperintense signal. Can also demonstrate diffuse cord signal.
  • Intracranial T2 signal can occur in brainstem and cerebellum
  • Contrast can be helpful to assess for ventral nerve root or cranial nerve enhancement
  • Brachial plexus involvement is much less common although present in this case

Functional Friday Case #11 Answer 11/2/18:  Metastatic Neuroblastoma.

The metastatic disease is diffuse, much easier to see on DWI than on any other sequence. But be careful with DWI in children!

  • ADC values variable in kids
  • Red/yellow marrow change with age
  • Water/fat/red blood cell percentages are reflected
  • Hard to quantify ADC values
  • Normal ADC values needed
  • Could ultimately help evaluate treatment response?
  • Reduce reliance on PET to determine active disease?

Functional Friday Case #10 Answer 10/26/18: Disorders of Glycosylation Type 1a (CDG-1a)

CDG-1a is an early-onset neurodegenerative disease with selective hindbrain involvement and highly variable clinical presentation. Classic imaging findings are a hypoplastic cerebellum with T2 hyperintensity in the cerebellar cortex and subcortical white matter. Facilitated diffusion within the cerebellum is common. Small pons with volume loss is progressive. CDG-1a likely results from a combination of cerebellar hypoplasia and atrophy. Cerebellar volume loss with diffuse T2/FLAIR hyperintensity is a unique association in the field of cerebellar atrophies to help in diagnosis.

Functional Friday Case #9 Answer 9/28/18: Acute Demyelinating Plaque.

The differential diagnosis between an acute demyelinating spinal cord plaque and a focal spinal cord tumor can be challenging, even with the assistance of DWI. DTI and fiber tracking can be useful in helping with differentiation. Fibers tend to traverse areas of demyelination while they are displaced by focal masses as the following slide demonstrates.

Functional Friday Case #8 Answer 9/21/18:  SWI showing Brain at Risk.

The SWI sequence is a useful clinical tool in the evaluation of cerebrovascular diseases, including detection of intraparenchymal hemorrhage, venous thrombosis and hemorrhagic transformation of stroke, and even assessment of brain tissue at risk of infarction. The presence of prominent veins has been hypothesized to represent an uncoupling between oxygen supply and demand within the hypoperfused tissue, with a relative increase in the deoxyhemoglobin to oxyhemoglobin ratio.Prominent veins on SWI are thought to represent either ischemic penumbra or poor collateralization of arterial supply. (Payabvash S et al. Br J Radiol 89.1068;2016)

Functional Friday Case #8 Answer 8/31/18: Rhabdoid Tumor

  • Large left-sided intraspinal extradural mass extending from the foramen magnum to T1 with neuroforaminal extension in the upper cervical spine extending along the anterior vertebral body of C2 and into the clivus
  • There is heterogeneous enhancement and restricted diffusion within the mass
  • Findings favor Rhabdoid given age and imaging (Confirmed on pathology)
  • Other consideration includes neuroblastoma, which is considered less likely due to the predominance of the mass being intraspinal and not paraspinous
  • Lymphoma is also in the differential. Chordoma is considered less likely due to the T2 signal being hypointense and extension of the mass is primarily intraspinal extending toward the clivus
  • Aggressive soft tissue sarcoma
  • Usually occurs in infancy and childhood (Usually <2 yrs of age)
  • Involvement of the CNS is called Atypical Teratoid Rhabdoid Tumor (AT/RT)
  • Imaging is typically T2 hypointense/Isointense
  • Restricted diffusion and enhancement is common
  • Hemorrhage and CSF dissemination is not uncommon

Functional Friday Case #7 Answer 8/10/18: Acute Wernicke’s Encephalopathy (AWE).

AWE is caused by brain injury secondary to vitamin B1 (thiamine) deficiency. It is most often seen in the setting of adult alcoholism but can occur in children with eating disorders, malignancies, extended ICU stays, obesity treatment, and thiamine transporter-2 deficiency. The classic clinical triad is encephalopathy, opthalmoplegia and gait ataxia. Characteristic signal changes are symmetric hyperintensities in dorsomedial thalamic nuclei, periaqueductal gray, mammilary bodies, and tectal plate (see ASPNR Metabolic Monday Case 7/30/18). DWI can be sensitive in revealing acute changes and additional areas of injury as illustrated in this case. 3D FLAIR imaging nicely demonstrates the signal abnormalities that occur in a characteristic distribution. Histopathologically, edema, demyelination, and hemorrhage in these areas occurs. AWE is an emergency and treatment should be instituted immediately at first suspicion of this disorder without waiting for laboratory confirmation in order to avoid irreversible neurologic injury.

Functional Friday Case #6  Answer 8/3/18: Spontaneous Lateral Sphenoidal Cephalocele (SLSC).

SLSC occurs when temporal lobe parenchyma spontaneously herniates through an area of scalloping or defect in the greater wing of the sphenoid (GWS). These patients will often present with seizures. The SISCOM (Subtraction Ictal Spect Coregistered to MRI) study demonstrates increased uptake of Tc99m-HMPAO in the left temporal lobe. The SLSC (arrow) was identified in retrospect upon focused re-review of the MRI images.

Functional Friday Case #5  Answer 7/27/18.  PHACES Syndrome.

Intracranial (IAC) and extracranial hemangiomas are noted in this case. Marked hyperperfusion of the hemangiomas is nicely demonstrated on arterial spin labeling (ASL) perfusion imaging. There is ipsilateral cerebellar hypoplasia present. Associated anomalies to look for are indicated by the acronym Posterior fossa malformations, Hemangiomas, Arterial anomalies, Cardiac defects, Eye abnormalities, Sternal cleft/ supraumbilical raphe syndrome.

Functional Friday Case #4 Answer 7/20/18. Hemiplegic Migraine.

The hypothesized pathophysiologic mechanism for migraine with aura or hemiplegic migraine is vasospasm. This can be appreciated on brain perfusion studies as a prolongation of transit time in the affected hemisphere. SWI can demonstrate matching increased conspicuity of cortical veins due to the resultant tissue hypo-oxygenation and increase in levels of deoxyhemoglobin. Performing an SWI sequence in suspected acute stroke imaging work-up in children along with DWI can be useful in suggesting the correct diagnosis.