Chloroma of epidural space

Additional clinical history: Acute leukemia.


Findings

Large anterior epidural mass extending from posterior clinoid to the cervicothoracic junction measuring approx. 6x3x1.5 cm with mass effect on the anterior pons, medulla, and upper cervical cord. No post-contrast imaging obtained.

Differential diagnosis: Epidural mass
- Metastatic disease
- Lymphoma
- Leukemia/chloroma
- Chordoma
- Osteomyelitis/epidural abscess
- Epidural hematoma
- Primary tumor such as neurofibroma/schwannoma


Diagnosis: Chloroma of epidural space


Key points

AKA granulocytic sarcoma, extramedullary myeloblastoma.
Most commonly occurs in the setting of AML.
Can also occur in setting of chronic myelogenous leukemia and other myeloproliferative disorders.
These tumors can involve any part of the body, either concurrently or sequentially.

Imaging characteristics:
- NECT: Isodense or hyper dense to brain or muscle
- MR: Hypo intense or Iso intense on T1-weighted MR images, heterogeneously Iso intense or hyper intense on T2-weighted MR images
- MR+C: Enhance homogeneously after injection of contrast medium

Paraspinal and intraspinal lesions are also thought to arise from perivenous arachnoid spread of leukemic cells. Uncommonly, spinal involvement by granulocytic sarcoma may cause compression of the spinal cord, cauda equina, or nerve roots

Methotrexate neurotoxicity

Additional clinical history: Patient was diagnosed with acute lymphocytic leukemia 2 months previously. He is status post induction therapy with a negative bone marrow biopsy, and is currently receiving consolidation chemotherapy with methotrexate, and presents with right upper extremity weakness.


Findings

MR images of the brain demonstrate a focal area of diffusion restriction involving the left frontoparietal white matter. There is minimal associated T2/FLAIR hyperintensity. No associated enhancement. Remainder of the brain was within normal limits.
Imaging done four months later shows lesion has nearly resolved.


Diagnosis: Methotrexate neurotoxicity


Discussion

Methotrexate is a folic acid analogue. Its cytotoxic effects are carried out through inhibition of the enzyme dihydrofolate reductase, which reduces tetrahydrofolic acid levels, ultimately inhibiting cell division.

From bone marrow cell precursors to the quickly dividing cells of the intestinal tract, methotrexate exerts its effects on all dividing cells in the body. One of its rare side effects is CNS toxicity. The decreased folate levels achieved with methotrexate have implications on metabolism of adenosine, homocysteine, and biopterin. Low folate levels lead to a subsequent decrease in S-adenosyl-methionine(SAM) concentrations. This eventually leads to chronic demyelination and neurologic symptoms.

An additional side effect of MTX is the elevated levels of adenosine in the CSF. Adenosine is a vasodilator, which causes dilatation of cerebral vasculature resulting in neurotoxicity. The increased homocysteine levels caused by MTX have been shown to damage vascular endothelium and lead to subsequent strokes and thromboemboli. Methotrexate has also been found to cause cytotoxic edema, which is the most common cause of lesions that enhance on MRI DWI.

The neurotoxicity caused by MTX can be immediate, acute to subacute, or delayed. Symptoms of the disease can range from headache, nausea, vomiting, and fever, to transient or permanent focal neurologic symptoms. The immediate form occurs within a day of MTX administration and presents as a chemical meningitis. The acute to subacute form presents from days to weeks after administration of MTX, and presents with seizures or focal neurologic symptoms. The delayed form presents as leukoencephalopathy and a generalized decrease in higher cognitive function.


Radiological findings

A case series containing nine cases of MTX neurotoxicity revealed that lesions found in this disease tend to be focal and show up on DWI as well as T2 and FLAIR imaging. These abnormalities can continue to persist on imaging long after the symptoms have resolved. The DWI shows diffusion restriction with T2/FLAIR hyperintensity being less conspicuous.

In another independent case study on MTX neurotoxicity, MRI demonstrated restriction diffusion with no significant T2 or FLAIR signal abnormality. Based on a combination of these imaging findings, it was determined that cytotoxic edema was likely the cause of focal neurologic symptoms on the patient, and demyelination was a less likely cause based on the MRI findings.

A different case study had MRI findings showing subtle signal changes in the left centrum semiovale, with an obviously abnormal area of restricted diffusion, indicating the presence of increased fluid. The authors of this case also mentioned a relation between elevated choline levels in lesion areas with myelin breakdown.

The lesion in this disease is similar in appearance to ischemic stroke, but differs in distribution. The lesions in MTX neurotoxicity can show up in many different patterns, whereas ischemic strokes often follow a vascular distribution, helping differentiate the two.


Radiology

MRI:
MRI with DWI is the gold standard for diagnosis
Will show focal areas of demyelination and/or edema throughout the brain
Can be normal, even in the presence of symptoms
Must perform early to avoid unnecessary workup


CT:
Can be used to rule out other etiologies that may cause focal symptoms, but is not a sensitive test for demyelination and edema found with MTX neurotoxicity
Ultimately need MRI to make diagnosis as CT is often negative
Angiography
Not very useful as it is usually normal

Methotrexate (MTX) induced transient neurotoxicity

14-year-old child with history of Acute Lymphoblastic Leukemia (ALL), on induction chemotherapy complaining of left sided weakness and facial asymmetry of acute onset.





The patient was given supportive treatment and aminophylline, symptoms resolved and an MRI was repeated after 3 days.





Findings

Diffusion weighted images with corresponding ADC maps show restricted diffusion involving bilateral centrum semiovale (Figure 1 and Figure 2).
Diffusion weighted images with corresponding ADC maps, from the MRI done after clinical improvement, show resolution of abnormalities seen on DW and ADC Maps in the initial study (Figure 3 and Figure 4).


Diagnosis: Methotrexate (MTX) induced transient neurotoxicity


With improvements in antileukemic treatment there has been a steady increase in long term survivors of ALL. However a myriad of neurological complications are seen during and after treatment. These maybe broadly categorized into those related to chemotherapeutic agents, radiation therapy, coagulopathy, immunosuppression and marrow transplantation.

Methotrexate is an essential component of treatment regimens in ALL. It can be administered both intravenously and intrathecally. Though hematologic and mucocutaneous consequences are more common, the CNS adverse effects are more worrisome. Chronic leukoencephalopathy as a result of methotrexate and radiotherapy is a well recognized complication and usuallly associated with cognitive deficits rather than focal neurologic deficits although subacuteacute encephalopathy after methotrexate may occur as well and usually presents as headache, confusion, disorientation, seizure, and focal neurologic deficit. A vast majority of patients show hemiparesis and aphasia.

High level of adenosine is thought to be responsible for methotrexate induced toxicity. Statistically the periventricular white matter is the most common area affected. On diffusion weighted imaging these areas show increased signal intensity and hypointensity on corresponding apparent diffusion coefficient (ADC) maps. There may be no abnormality identified on T1, T2, and FLAIR sequences during the acute symptomatic phase.

Clinical resolution is followed by the appearance of residual FLAIR hyperintensities in the involved areas, which show gradual regression. There is no established treatment, however several anecdotes report symptomatic resolution with aminophylline therapy.

Neuroblastoma metastases

Findings

Figure 1: Axial post gadolinium T1 weighted image showing solid enhancing parenchymal lesion in the right temporal lobe with dural and leptomeningeal disease.
Figure 2: Coronal post gadolinium image showing dural enhancement along the tentorium and leptomeningeal enhancement.
Figure 3: Axial susceptibility weighted imaging revealing the hemorrhagic nature of the lesion.


Diagnosis: Neuroblastoma metastases


Neuroblastoma metastatic to the central nervous system is extremely rare, and the reported incidence varies from 1% to 16% at recurrence. Paediatric tumors that metastasise to the brain, in order of frequency, include neuroblastoma, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma and Wilm tumor.

Risk factors for developing intracranial metastases include lumbar puncture at diagnosis, ages 2 to 3 years, bone marrow involvement, and MYCN gene amplification. Newer chemotherapeutic agents with better activity fail to penetrate the blood-brain barrier, thus facilitating a sanctuary for tumor cells within the central nervous system. As a result, the metastases evolve and become extensive before becoming clinically evident. Metastatic spread of tumor cells to central nervous system may occur either via hematogenous or cerebrospinal fluid routes and involve the neuroparenchyma, leptomeninges or dura.

Neuroparenchymal metastases from neuroblastoma have varied appearances. They may be cystic lesions with calcified mural nodules. The wall and mural nodules show intense enhancement with contrast. Metastases may also be solid and hemorrhagic and show homogeneous enhancement. Gradient or susceptibility weighted imaging would help in detecting hemorrhagic components. Leptomeningeal and dural metastatic involvement if present indicates poor prognosis.

Leptomeningeal carcinomatosis from esophageal adenocarcinoma

Findings

Figure 1, Figure 2, Figure 3, and Figure 4: Postgadolinium T1 weighted images demonstrate linear contrast enhancement in the subarachnoid space, most notably interdigitating between the folia of the superior cerebellum and in the sulci of the parietal and occipital lobes. The T1 weighted precontrast images are unremarkable.
On FLAIR imaging in Figure 5, there is corresponding hyperintensity in the subarachnoid space.
Chest TC (not shown) demonstrates a high-attenuation central mass within the esophagus, which is expanding the lumen.


Diagnosis: Leptomeningeal carcinomatosis from esophageal adenocarcinoma


The leptomeninges consist of two layers; the pia mater and the arachnoid mater, which enclose the subarachnoid space and the CSF. The leptomeninges are a frequently missed site of metastastic involvement, especially for non-hematologic primary malignancies. There are many proposed routes of entry for tumor cells into the CSF including hematogenous spread via the arachnoid vessels or choroid plexus, direct extension from the skull, vertebrae, dura or retrograde perineural spread via the peripheral or cranial nerves. Once tumor cells reach the CSF, rapid dissemination can occur.

Up to 50% of patients with leptomeningeal metastases present with signs of increased intracranial pressure and/or hydrocephalus including headaches, back pain, nausea, vomiting and dizziness. These symptoms are most likely secondary to obstruction of CSF flow by tumor cells. Other clinical manifestations include seizures, focal cranial nerve deficits and meningeal signs such as nuchal rigidity and photophobia.

CSF cytology is the definitive test for diagnosis of leptomeningeal involvement. However, while highly specific, cytology is often falsely negative. The accuracy of a single lumbar puncture is approximately 50%, which increases to 90% with three LPs. Cytology remains negative in 10-20% of patients, presumably in situations in which the malignant cells are more adherent to the leptomeninges.

Contrast enhanced MR imaging is the diagnostic test of choice as an adjunct to CSF cytology when leptomeningeal metastases are suspected. Gadolinium enhanced MRI is more sensitive than a single lumbar puncture, but is less specific. The most common imaging findings include diffuse leptomeningeal contrast enhancement, multiple masses or nodules within the subarachnoid space and/or hydrocephalus. The diffuse leptomeningeal enhancement pattern has been referred to as sugar-coating or zuckerguss (German for icing or sugar-coating). Studies have shown that contrast-enhanced T1-weighted MR imaging is the most sensitive single sequence for detection of leptomeningeal metastases.

Prognosis for leptomeningeal metastases is poor. Without treatment, the average survival is 1-2 months. Treatment options include corticosteroids, intrathecal chemotherapy and radiation therapy. Despite aggressive therapy, the median survival in most randomized-controlled trials is 3-4 months.

Sarcoidosis involving the lacrimal glands

Findings

Axial (Figure 1) and coronal (Figure 2) non contrast CT images, as well as an axial T2 MRI image (Figure 3), demonstrate symmetrically enlarged lacrimal glands which protrude anterior to the lacrimal fossa bony contours. Homogeneous enhancement is identified on the selected contrast enhanced axial CT image (Figure 4). There is no evidence of adjacent bony orbit invasion. An AP chest radiograph (Figure 6) demonstrates predominantly right hilar lymphadenopathy with “eggshell” calcification and bilateral reticulonodular opacities within the lung parenchyma.


Diagnosis: Sarcoidosis involving the lacrimal glands


20 to 25 percent of patients with systemic sarcoidosis develop ophthalmic manifestations usually between the third and fifth decades. The most common finding is inflammation of the uveal tract. Less commonly, patients will present with inflammation of the optic nerve or orbital involvement including pseudotumor like intraorbital masses, extraocular muscle enlargement, or lacrimal gland infiltration and hypertrophy. Isolated orbital disease is uncommon and usually limited to the lacrimal glands.

Lacrimal gland involvement occurs in approximately 15-28% of patients; usually as painless bilateral gland swelling evident on physical examination. In many cases, lacrimal gland involvement may occur long before lung and other organs are affected, thereby aiding in the early diagnosis of systemic sarcoidosis.

Imaging studies such as orbital CT and MRI are an integral part of early diagnosis. CT findings include symmetric enlargement of the lacrimal glands with diffuse homogeneous post contrast enhancement. There may be associated medial displacement of the optic globes as well as proptosis. Pertinent negative findings include the absence of adjacent bony orbital invasion and destruction. MRI is optimal to evaluate for additional orbital involvement such as optic nerve infiltration which manifests as a thickened and enhancing intraorbital nerve. An MRI of the brain is also recommended to evaluate for extension into the intracranial optic pathways and to exclude findings of coexisting neurosarcoidosis.

While diagnostic imaging tests may reveal findings highly suggestive of lacrimal gland sarcoidosis; definitive diagnosis requires biopsy of the glandular tissue and histopathologic assessment. Noncaseating granulomas characterized by clustered epithelial cells, central giant cells and abundant surrounding lymphocytes are characteristic.

The mainstay of therapy is high dose systemic steroids, usually oral prednisolone for approximately two weeks, followed by gradual tapering after the inflammation appears controlled. Some patients may require maintenance doses for several weeks to months.

Lhermitte-Duclos disease

Findings

There is a small amount of increased signal on FLAIR and T2-weighted images with mild post contrast enhancement in the right cerebellar hemisphere. No mass effect is seen. Contrast images show an incidentally noted venous developmental anomaly on the right draining into the sylvian vein.

Differential diagnosis for the cerebellar lesion:
- Low-grade glioma
- Medulloblastoma
- Pilocytic astrocytoma
- Ganglioglioma
- Lhermitte-Duclos disease
- Cerebellar stroke


Diagnosis: Lhermitte-Duclos disease (dysplastic gangliocytoma of the cerebellum)


Key points

Lhermitte-Duclos disease (LDD) is a very rare benign cerebellar mass
Often associated with Cowden Syndrome–macrocephaly; benign breast, skin, and thyroid lesions; oral papillomas; GI tract hamartomas/polyps; cataracts; genitourinary neoplasia
Lesions grow very slowly or not at all
May cause obstructive hydrocephalus–presentation is usually vague neurologic symptoms related to hydrocephalus
Most commonly present at age 30-40, but can present from birth to age 60
Treatment–surgery for symptomatic patients
Rare recurrence, although complete resection is almost never possible
If confirmed LDD, no followup is needed unless patient is symptomatic

Radiologic appearance
- Well-defined cerebellar mass with striated or "gyriform" appearance
- CT–hypo dense cerebellar mass with hyper dense striations, rare enhancement
- MR
Striated mass with increased T2 and FLAIR signal +/- contrast enhancement
Bright on diffusion weighted images without signal decrease on ADC
MR Spectroscopy–decreased NAA, increased lactate, increased or normal choline
May use MRS to confirm LDD over glioma

CHARGE syndrome

Findings

Posterior orbital globe defects of bilateral colobomas (Figure 1).
Bilateral choanal atresia, predominantly osseous component (Figure 2). Notice the bilateral air-fluid levels within the nasal cavity, which is classic for choanal atresia as fluid cannot drain posteriorly into the nasopharynx. There is deformity of both pinnae (Figure 3 and Figure 4).
Deformities of the semicircular canals (Figure 5).


Diagnosis: CHARGE syndrome

CHARGE is an acronym for the major clinical features of the syndrome (ocular Coloboma (75-90%), Heart defects (50-85%), Atresia of nasal choanae (35-65%), Retardation of growth/development, Genital anomalies (50-70% with male predominance), Ear anomalies (>90%). Additional associated features include facial dysmorphism, anosmia, auditory and vestibular anomalies, hypothalamo-hypophyseal dysfunction, and urinary tract anomalies. CHARGE syndrome occurs sporadically with an estimated prevalence of 1:10,000. Many patients with CHARGE syndrome have been genetically linked to mutations in the CHD7 gene, which encodes a protein within the chromodomain helicase DNA-binding (CHD) family of proteins responsible for gene expression regulation via chromatin remodeling. The ubiquitous expression of CHD7 protein helps explain the pleiotropic effects of patients with CHARGE syndrome.

Diagnosis of CHARGE syndrome initially required 4 of the cardinal 6 signs described by its acronym, with at least one sign being choanal atresia or coloboma. The diagnostic criteria were updated by Blake et al in 1998 to include brainstem anomalies, facial dysmorphism, and characteristic ear anomalies. More recently, and relying on the clinical triad of Coloboma-Choanal Atresia-semicircular Canal Anomalies, Verloes has proposed dividing the syndrome into typical, partial/incomplete, and atypical CHARGE syndromes based on 3 major signs (ocular coloboma, choanal atresia, hypoplastic semi-circular canals) and 5 minor signs (rhombencephalic dysfunction, hypothalamo-hypophyseal dysfunction, abnormal middle/external ear, mediastinal organ malformation, mental retardation).

Bilateral choanal atresia is usually osseous but may be membraneous and is usually detected in the newborn since neonates are obligate nose-breathers during feeding. Treatment is surgical with a transnasal or transpalatal approach to open the choanae. Ocular colobomas are often small and may only be detected via a funduscope. Vision is usually not impaired. Semicircular canal aplasia/dysplasia results in loss of nystagmus response to auditory caloric stimuli.

Hemolytic uremic syndrome

Findings

CT head: Low attenuation in the bilateral basal ganglia
MRI brain: There are small focal areas of diffusion restriction in the periventricular white matter, bilateral thalami and putamen. There is T2 prolongation affecting the basal ganglia, corpus callosum (genu and splenium), external capsules, and corona radiata.


Diagnosis: Hemolytic uremic syndrome


Key points

Most common pathogen is E. Coli O157:H7 verotoxin.
Clinical: acute renal failure, microangiopathic hemolytic anemia, thrombocytopenia, and neurologic symptoms
Neurologic complications occur in 20-50%. Symptoms include seizures, visual changes, altered consciousness and brainstem findings.
Neurologic findings most likely due to verotoxin affecting the microvascular endothelium leading to small vessel infarction and/or hemorrhage.
Patients with neurologic symptoms should undergo CT and MRI evaluation.
Treatment: fluid replacement, plasmapheresis. Avoid antibiotics which can worsen HUS.


Imaging (MRI)

Basal ganglia T2 hyper intensity is the most common finding, particularly the dorsal lateral lentiform nuclei.
Involvement of the basal ganglia is associated with a good clinical outcome.
T2 weighted hyper intensities have been reported to involved the thalamus, internal and external capsules, dorsal brainstem, corpus callosum, posterior leukoencephalopathy syndrome. Findings likely related to edema.
Diffusion restriction in the basal ganglia and thalami has been reported.
Areas of T1 hyper intensity should raise the possibility of hemorrhage.
Areas of hemorrhage are most likely to result in neurologic sequela.

Tuberous sclerosis with subependymal giant cell astrocytoma

Findings

Head CT shows a heterogeneous soft tissue mass in right lateral ventricle at right foramen of Monro. Heterogeneous contrast enhancement. Nodular ependymal calcifications. Hydrocephalus.
MR confirms heterogeneously enhancing mass at R foramen of Monro. T2 hyper intensity surrounding R frontal horn representing transependymal CSF resorption. Additional sub-ependymal nodule in L frontal horn.


Diagnosis: Tuberous sclerosis with subependymal giant cell astrocytoma.


Key points

TS is an inherited disorder of multiple hamartomatous lesions.
Classic clinical triad: Mental retardation, facial angiofibroma, seizure.
Subependymal nodules (SEN) (98%) 50% calcify. 30-80% enhance.
Enlarging SEN at foramen of Monro = Subependymal giant cell astrocytoma (SGCA)
Ventriculomegaly common, even in absence of obstructing SEN / SGCA.
Cortical / subcortical tubers (70-95%) cause thickening of cortex, gyral enlargement.
Number of tubers corresponds with degree of mental retardation.
White matter lesions – linear, wedge-shaped T2/FLAIR hyper intensities.
Extra cerebral TS: Renal angiomyolipoma / cysts (40-80%), cardiac rhabdomyoma (50-65%), lung LAM, subungual fibromas (15-20%), skin "ash-leaf spots," shagreen patches.

Ocular Wegener’s granulomatosis

Findings


There is an extraconal mass within the right medial orbit, adjacent to the lamina papyracea, extending in an arc like fashion from the superomedial aspect to the inferolateral aspect of the right orbit. Mass extends into the intraconal space and splays the medial and inferior rectus muscles. Mass is hypointense to cortex on T2 weighted images and isointense to cortex on T1-weighted images. Mass demonstrates homogeneous post contrast enhancement. There is associated proptosis of the right globe. There are extensive postoperative changes of the paranasal sinuses and mucosal thickening involving all of the paranasal sinuses, predominately the ethmoid air cells.

Differential diagnosis:
- Sarcoidosis
- Lymphoma
- Vasculitis / angiitis (e.g., Wegener's granulomatosis)
- Subperiosteal abscess


Diagnosis: Ocular Wegener’s granulomatosis (favored diagnosis: the patient was known for Wegener’s granulomatosis)


Discussion

Wegener's granulomatosis is a multisystem disease classically characterized by necrotizing granulomatous inflammation of the upper and lower respiratory tract and the kidneys and necrotizing vasculitis of the small and medium sized vessels. Patients typically present between 35-55 years of age. The nose and sinuses are most commonly affected, and patients may present with sinus headaches and nasal drainage. The lungs are affected in 85% of patients, and kidneys are involved in 75% patients. Most of the morbidity of the disease is usually related to the renal component.

Wegener's involvement of the eye is not uncommon, occurring in 30-60% of cases. Approximately 8-16% of patients with Wegener's granulomatosis initially present with ophthalmic disease. Ocular manifestations can be diverse, ranging from mild conjunctivitis to episcleritis, uveitis, ciliary vessel vasculitis, and retro-orbital mass lesions. Vision loss can occur secondary to mass effect, ischemia, or vasculitis of the optic nerve or occlusion of the retinal artery.

Several medication regimens utilizing immunosuppressants are given to patients with Wegener's granulomatosis. Commonly used drugs include steroids, cyclophosphamide, azathioprine, and methotrexate.


Key radiology findings in Wegener's granulomatosis (head and neck)

Paranasal sinus inflammatory disease associated with nodular soft tissue mass in the nasal cavity.
Destructive/erosion changes of the nasal septum; nasal septum perforation is common.
Orbital invasion is the most common site of paranasal sinus disease extension.
Orbital findings can vary but may include, retro-orbital soft tissue mass resulting in compression of adjacent structures. Although rare, orbital granulomata can calcify.

Non-ketotic, hyperglycemic, hemichorea

Findings

Figure 1: CT scan reveals unilateral hyperdensity of the left lentiform nucleus and the head of the left caudate nucleus with sparing of the intervening internal capsule that corresponds to abnormal gemistocytic astrocyte production. No significant abnormal enhancement is identified.
Figure 2: MR images demonstrate hyperintense T1 and hypointense T2 and diffusion weighted image signals in the same distribution as the CT abnormality. There is no significant abnormal enhancement and no mass effect.
Figure 3: Follow-up imaging performed 14 weeks after initial presentation demonstrates preserved high signal in the left basal ganglia without mass effect or enhancement. T2-weighted signal has changed from low to high intensity, perhaps representing interval gliosis.


Diagnosis: Non-ketotic, hyperglycemic, hemichorea


The differential diagnosis for the new-onset hemichorea includes: stroke, hemorrhage, tumor, infectious disease, neurodegenerative disorders and non-ketotic, hyperglycemic hemichorea.
Particular to the diagnosis of NHH, the characteristically unilateral transient extrapyramidal motions resolve following glycemic control.
Cerebral images of these patients consistently have shown unilateral CT hyperattenuation and unilateral MRI T1-weighted hyperintensity in the striatum contralateral to the side of the transient, extrapyramidal motion disorder.
Typically, an elderly diabetic patient presents with new-onset hemichorea as well as glucose levels ranging from 400 to 600 mg/dl with an HBA1c greater than 13%.

Non-ketotic, hyperglycemic hemichorea (NHH) was first described by Rector, et al. in 1982. Thirty-three cases of NHH have been identified in our recent review of literature. The most commonly reported location of a lesion has been in the putamen. Kumral, et al. have suggested that the anterior putamen needs to be involved for transient extrapyramidal motions to occur. The distinct imaging findings are hyperattenuation on CT and hyperintensity on T1-weighted MRI. This Case in Point’s images concur with these distinct image findings.

The onset of NHH has been attributed to petechial hemorrhage with blood-brain barrier breakdown, cerebral ischemia leading to dysfunction of the GABAnergic projection neurons and gliosis. Blood glucose levels of 159 to 647 mg/dl have initiated non-ketotic hyperglycemia resulting in hemichorea. More commonly reported values exceed 500 mg/dl.

There is accumulating consensus on the pathophysiology of NHH. Human autopsy, animal studies, human biopsy and MR spectroscopy evidence that NHH results in mild infarction with gliosis and concurrent accumulation of pathologically swollen, nucleus-eccentric astrocytes, known as gemistocytes. MRI findings have been attributed to gemistocyte deposition along axons. Rat model and human autopsy histopathology have revealed T1-weighted, hyperintense, gliotic brain tissue with abundant gemistocytes.

This Case in Point documents new hyperintensity in the areas of previous hypointensity on follow-up T2-weighted MRI and FLAIR images. It is plausible such images represent areas of delayed gliosis or scar tissue formation.