Neuroradiological Findings in Sickle Cell Disease Excluding Moyamoya

Mauricio Castillo, MD, FACRUniversity of North Carolina at Chapel Hill

Abstract• Purpose: to review lesions other than moyamoya resulting from

sickle cell disease (SCD).• Methods: from our TF we reviewed all SCD cases & identified those

with complications other than moyamoya which form the basis of this review.

• Results: We were able to identify the following complications: spinal cord & bone infarctions, skull infarctions, extramedullary hematopoiesis in paranasal sinuses, intraventricular & micro hemorrhages, intracranial aneurysms, superficial siderosis, PRES, & extracranial carotid stenoses. Imaging findings of all are presented.

• Conclusions: outside of moyamoya, manifestation of SCD are varied & most can be explained by hypoxia & arterial wall damage.

Infection/sepsis Acidosis Hypoxia

Red blood cell sickling

Red blood cell endothelial adhesion

Endothelial damage + vessel occlusion

Arterial Narrowing

Infarction of bone & soft tissues

Event Cascade in SCD

Spine: Vertebral DeformitiesConversion of fatty to red marrow with low T1 signal occurs often. Infarctions of end-plates lead to fractures & subsequent H-shaped or fish-mouth vertebrae (arrows). These findings may result in chronic growth disturbances, osteopenia & osteoporosis with decreased height in children. Marrow hyperplasia may occur outside the bones in the form of extramedullary hematopoiesis & compress the spinal cord. Back pain may be the initial presentation of SCD in children.

Spine: Vertebral InfarctionsBone infarctions affect 12-20% of SCD patients. Infarctions preferentially affect weight-bearing bones & result in areas of lucencies or sclerosis reflected on MRI as T2 bright & T1 low/intermediate zones which enhance with contrast. Aseptic/avascular necrosis leads to pain, vertebral body collapse & vertebrae plana. Repeated blood transfusions may also result in a dark T1/T2 bone marrow.

Spine: Sacral InfarctionsInfarctions of larger bones such as the sacrum result in pain & may evolve into stress fractures. Fat emboli from them has been described. Bone infarctions may become infected leading to osteomyelitis (staphylococcus aureus followed by salmonella). MRI may show bone abnormalities, periosteal reaction, & extension of inflammation into adjacent soft tissues. Infection may extend laterally resulting in SI joint septic arthritis. Bone infections occur in 5-15% of SCD patients.

Spine: Cord Infarction

Spinal cord infarction is rare occurrence in SCD patients. In one autopsied patient, a vertebral artery was filled with clot. These infarcts are not as devastating as those from other etiologies & most SCD patients survive,

many regaining significant function. Unlike the more common idiopathic infarctions, SCD-related ones may affect any part of the cord. (From Marquez JC,

Granados A, Castillo M. Clin Imaging 2011; 36: 595.)

ADC

DWI

Skull: Infarctions

Skull infarctions present high (A) or low radionuclide uptake & CT tends to be negative. On MRI, they show low T1 & high T2 signal

(B & C) with peripheral contrast enhancement (D). They may produce subperiosteal (epidural) hematomas; those ones around

the orbits may result in acute proptosis & vision loss.

A B C D

Skull: Infarctions + Scalp Hematomas

Diffuse swelling & contrast enhancement is present in the subgaleal space (A). Bilateral presumed non enhancing hematomas (*) (B, C) are seen overlying some

of bone marrow hypointensity suggesting marrow infarctions (arrows).

A B C

Skull: Expansion

Skull diploic expansion is 2ry to bone marrow hyperplasia. It affects predominantly the parietal (*) followed by the frontal bones. When

infarctions occur, it is the hyperplastic marrow that is first affected. This changes are more pronounced with the combination of SCD & β

thalassemia which in radiographs has a “hair on end” appearance.

Facial Swelling

Facial swelling may be idiopathic or related to underlying facial bone infarctions & when around the eyes may simulate acute cavernous sinus thrombosis. Subperiosteal hematomas

may be seen (not seen in this patient who shows abnormal signal throughout skin & subcutaneous fat).

Orbital Compression Syndrome

Eye complications in SCD include anterior segment ischemia, glaucoma, & retinopathy. Infarction of the retrobulbar fat with proptosis & compression of nerves

& muscles as shown in this patient may occur. Associated infarction of the greater sphenoid wing with subperiosteal hematomas may occur (not seen in this patient).

Skull: Paranasal Sinuses

Extramedullary hematopoiesis in paranasal sinuses is not uncommon in SCD patients especially those who also have thalassemia. The sphenoid sinus is less commonly involved but the lesion has homogeneous low T2 signal & enhances after Gd as seen in the patient above. Skull base infarctions may have a similar

appearance on CT.

Skull: Paranasal Sinuses

Babies with SCD & thalassemia shows bone marrow replacement of maxillary sinuses. The symmetry & bilateral involvement with reticulated pattern (B: bone

windows) should suggest the diagnosis. Care must be taken to recognize it as such an avoid removal of active bone marrow. (Above: 2 different children with

maxillary (A,B) & ethmoid sinus involvement (C).

A B C

Skull: Temporal Bones

CT (A) shows bone replacement of lateral semicircular canal (arrow). MRI (B) CISS shows obliteration of high signal fluid in right labyrinth when compared to left cochlea, left lateral semicircular canal is also

affected. Sensorineural hearing loss is present in about 50% of adults with SCD and in 4-20% of children & is due to recurrent

occlusion of labyrinth arteries.

A B

Brain: Intracranial Aneurysms

SCD patients have a higher incidence of aneurysms (arrows) than the general population. They tend to be multiple & not associated to other risk factors.

Some articles report an increased prevalence in the posterior circulation & in children. Endothelial ischemia extending to the rest of the arterial wall is thought to be the cause of them & rupture with subsequent SAH occurs.

Brain: Intraventricular Hemorrhage

Intracranial hemorrhage in SCD is more common in children. In adults, parenchymal bleeds have been associated with hypertension

which can be sudden in SCD & thalassemia patients. Bleeds may represent hemorrhagic conversion of infarctions. In adults,

intraventricular bleeds (A,B) are more common than parenchymal ones & DSA shows moyamoya appearance (circle in C).

A B C

Brain: Cerebral Microbleeds

The exact incidence of microbleeds in SCD patients is not known but they are not uncommonly seen at 3.0 &7.0T studies. They tend to be located at the gray-white matter

junctions of brain & cerebellum. They may be due to local thrombosis & subsequent hemorrhage or due to fat embolism from distant bone marrow infarctions. (Above: SWI in

2 different SCD patients.)

Brain: Superficial Siderosis

Pial hemosiderosis (arrows) may be due to SAH from ruptured aneurysm or idiopathic. It has been reported in patients with multiple transfusions & SCD.

Brain: PRES

SCD eventually results in glomerulosclerosis in many patients leading to hypertension. PRES generally happens during a crisis & may be due to altered T cell response with

production of pro-inflammatory proteins changes which may be triggered by superimposed viral infections. Schistocyte formation & lactic acidosis may result in endothelial damage.

Since SCD crises are recurrent, repeated PRES occurs in these patients.

Extracranial Carotid Stenosis

Involvement with narrowing (straight arrows) & occlusions (curve arrow) of the cervical ICAs occurs in up to 10-15% of SCD patients & correlates with embolic cerebral strokes.

This type of involvement happens predominantly in children & anticoagulation is contraindicated due to the expected increased risk of cerebral hemorrhages these

patients already have.

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