ESNR 2010 N. Siddiqui, V. Kosaraju, LCH. Cruz, I. Cravo, G. Zuccoli MD NEUROIMAGING FINDINGS IN OSMOTIC DEMYELINATION SYNDROME A REVIEW OF TYPICAL AND ATYPICAL FINDINGS N. Siddiqui, V. Kosaraju, LCH. Cruz, I. Cravo, G. Zuccoli MD “Thank you for attending my talk today – I will be discussing typical and atypical manifestations of osmotic demyleinating syndrome. Before I start I would like to thank my mentor Dr. Zuccoli for his help in this endeavor. “

We have no disclosures “We have no disclosures.”

Background Osmotic demyelination syndrome (ODMS); formally central pontine myelinolysis (CPM) and extrapontine myelinolysis (EPM) ODMS seen with rapid correction of hyponatremia Alcoholics, malnourished, transplant, septic, diabetic, hepatic, HIV, burn and debilitated patients are at risk “Osmotic demyelination syndrome know as ODMS is the combined entity of CPM and EPM It is seen with rapid correction of hyponatremia With the typical pt population being alcoholics, malnourished, transplanted, septic, diabetic, hiv and burn patients – generally anyone in a debilitated state is at risk”

Pathophysiology Rapid adjustment of osmolyte dysfunction results in an osmotic gradient Gradient leads to glial and myelin degradation and/or oligodendroglial apoptosis Pathologically, demyelination characterized by vacuolization and intramyelinitic splitting with rupture of the myelin sheaths “The mechanism of this entity is not completely known – but from we understand, A rapid adjustment of an electrolyte imbalance results in an osmotic gradient which leads to the glial and myelin degradation and the resultant endothelial damage. Pathologically we see vacuolization and rupture of myelin sheaths. This is a demyelination without associated inflammation” change in serum osmolality with intracellular hypotonicity causes endothelial damage and disruption of BBB - accumulation of hypertonic sodium-rich fluid in ECF and release of myelin toxins damages WM with eventual cell death ensues

Purpose The purpose of our study is to delineate the typical and atypical characteristics of ODMS using CT, MRI and Diffusion weighted techniques “The purpose of this study was to delineate the typical and atypical characteristics of osmotic dymyelinating syndrome using CT, MRI and Diffusion weighted techniques”

Methods 2005-2010 Multi-institutional Retrospective Dedicated literature review 90 patients CT, MRI and Diffusion weighted imaging “From 2005 – 2010, a multi-institutional IRB approved retrospective and literature review was performed identifying 90 patients with osmotic demyelinating syndrome evaluated with CT, MRI and diffusion weighted imaging.”

Methods Images and data reviewed by dedicated radiologist for: Signal alterations Location Mass effect Enhancement Restricted Diffusion “Images and data were analyzed for signal alterations, location, mass effect, enhancement and diffusion abnormalities.”

Patient Demographics 54 Patients – Females 36 Patients – Males 65 Patients ≤ 55 years 23 Patients > 55 years Alcoholism: 17% (15/90) “We had 54 female and 36 male patients 65 patients less than 55yrs and 23 patients greater than 55 17% of the population were alcoholics”

Imaging Modalities 90 – MRI 11 – CT 32 – Diffusion weighted imaging “90 MRI’s, 11 CT’s and 32 diffusion weighted sequences were analyzed.”

Presentation Encephalopathy: 73% (66/90) Altered Mental Status: 70% (63/90) Seizures: 63% (57/90) Weakness: 27% (25/90) Dysarthria: 20% (18/90) Hypertension: 14% (13/90) Majority of our patients presented with encephalopathy, altered mental status and siezures A smaller percentage demonstrated weakness, HTN and dysarthria

Presentation Encephalopathy, seizures, altered mental status Typically develop 2-4 days after correction of electrolyte imbalance Rarely can be seen weeks after correction Resolution of symptoms can be seen with electrolyte correction “Typically symptoms began 2-4 days after correction of electrolyte imbalance. However, although rare symptoms can be seen weeks after correction.” Resolution of symptoms can be seen with electrolyte correction”

“Classic axial image from one of our patients showing acute osmotic demyelination affecting the central pons (arrows). Note that the pons is slightly swollen with mild mass effect on the 4th ventricle. “This is a 40-year-old alcoholic woman of ours after rapidly corrected of her hyponatremia. Again demonstrating typical findings of ODMS Sagittal T2-weighted image shows signal prolongation in the pontis (arrow) with Diffusion-weighted imaging and corresponding adc maps demonstrating restricted diffusion (arrows).”

Characteristic Findings Appearance Abnormal T2 signal involving the pons, basal ganglia and additional extrapontine sites Pontine involvement spares the periphery and corticospinal tracts Minimal mass effect and effacement Minimal to no enhancement “The characteristic findings of ODMS are abnormal signal involving the pons, basal ganglia and additional extrapontine sites. Pontine involvement often spares the periphery and corticospinal tracts There is usually minimal mass effect and little to no enhancement.”

This patient with ODMS nicely illustrates the confluent hyperintensity in central pons with sparing of periphery and corticospinal tracts As well as the additional typical involvement of the basal ganglia and thalamus

Again confluent hyperintensity involving the pons with minimal mass effect of the fourth ventricle and sparing of the periphery Again not the diffusion hyperintensity

Location – Typical (n=90) Pons 61 (68%) Lentiform Nuclei 59 (66%) Caudate 54 (60%) Thalamus 28 (31%) “We found that the typical locations for ODMS were the pons, basal ganglia and thalamus.”

Axial Flair and diffusion weighted MR images in a hyponatremic, patient with rapid correction of serum sodium showing central pons hyperintensity with sparing the peripheral pontine fibers. And diffuse abnormal T2 signal involving the basal ganglia - again these are typical findings for ODMS.

Appearance Pontine involvement Caudate 25/42 (60%) Putamen 28/42 (67%) Thalamus 18/42 (43%) Splenium 5/42 (12%) “This raises an interesting question of how often and which lesions are seen when the pons is involved. In our study, we found that the basal ganglia was involved roughly 60% of the time and that the thalmus and corpus callosum were involved but to a lesser degree”

Appearance Basal ganglia involvement Pons 27/40 (67%) Thalamus 16/40 (39%) Splenium 2/40 (5%) “Additionally, when the basal ganglia was involved – pontine involvement was seen 67% of the time with the thalamus and splenium involved 39% and 5% of the time, respectively”

“This patient nicely demonstrates the minimal involvement of the pons – but with the very typical involvement of the basal ganglia and thalmus. Note that on post contrasted images no significant abnormal enhancement is seen”

Location – Atypical (n=90) Grey Matter 16 (18%) White Matter 16 (18%) Corpus Callosum 15 (17%) Splenium 12 (13%) Cerebellum 13 (14%) Hippocampus 11 (12%) External Capsule 7 (8%) Midbrain 6 (7%) Subthalamic nuclei 3 (3%) Claustrum 2 (2%) Hypothalamus 2 (2%) Medulla 2 (2%) Amygdala 1 (1%) “Further in our study, we found that atypical lesions affecting patients with ODMS were seen in the grey and white matter 18%, corpus callosum 17%, cerebellum 14% and hippocampus 11% Addditionally lesions were rarely seen involving the midbrain, subthalamic nuclei, claustrum, hypothalamus, medulla and amygdala.”

“These are Flair images from a 51-year-old alcoholic man after rapidly correction of hyponatremia showing both the typical and atypical patterns of ODMS. Note the atypical involvement of the dentate nuclei, red nuclei, cerebral peduncles and mamillary bodies And again the typical involvement of the basal ganglia with additional atypical involvement of the corpus callosum.” A, Axial fluid-attenuated inversion recovery (FLAIR) image reveals selective involvement of facial nerves nuclei (arrows), trigeminal and abducens nuclei (arrowheads), and dentate nuclei of cerebellum (open arrows). B, Oculomotor nerve nuclei and red nuclei (open arrows), cerebral peduncles, mamillary bodies (black arrow), and optic tracts (arrows) show signal intensity alterations. Note that alterations in mamillary bodies are also typical of Wernicke encephalopathy. C, Basal ganglia show high signal intensity alterations bilaterally(arrows). D, Alterations of corpus callosum (arrows) are also noted.

Again T2 weighted and flair images demonstrating the atypical involvement of the dentate nuclei

This is another patient with osmotic demyelinating syndrome demonstrating the typical involvement of the pons with sparing of the periphery and restricted diffusion. However in addition to this the patient had atypical symmetic involvement of the cortical grey matter – a rare but associated finding in ODMS

Discussion Positive CT findings in 36% Restricted diffusion in 78% Minimal to no enhancement Can be seen in normonatremic patients Subacute presentation Subtle hyperintensities May completely resolved “Interestingly, we found that CT was only positive in 36% of our cases, thus indicating the far greater sensitivity of MRI for ODMS. We saw restricted diffusion in 78% of our cases and minimal to no enhancement. We believe that for adequate evaluation with MRI – Flair, DWI and post T1 images are essential to include or exclude this diagnosis Additionally, we found that ODMS can be seen in normonatremic patients - it appears to be a heterogeneous disorder with a common etiology of osmotic stress. Finally in the subacute setting, findings can be subtle or may have completely resolved.” Enhancement - change in serum osmolality with intracellular hypotonicity causes endothelial damage and disruption of BBB Can be seen in normonatremic patients - heterogeneous disorder with common etiology of osmotic stress Osmotic derangement with azotemia, hyperglycemia, hypokalemia, ketoacidosis

“This is another patient of ours who demonstrates both typical and atypical findings consistent with the diagnosis of ODMS. We see involvement of the pons and midbrain with sparing of the corticospinal tracts However, interestingly on repeat imaging a few days later, we see complete resolution of the hyperintense lesions; thus indicating the difficulty of this diagnosis in the subacute setting.” In subacute setting, hyperintensity often normalizes, may resolve completely No consensus on treatment; no "optimal" correction rate for hyponatremia Self-correction (fluid restriction, discontinue diuretics) if possible Plasmapheresis, steroids, glucose infusions being studied

Discussion Pontine involvement in 68% of patients Basal ganglia involvement in 66% of patients Pontine and basal ganglia involvement in 33% of patients Pons involved, basal ganglia lesions seen 67% Atypical lesions, can be seen without basal ganglia or pontine involvement 16% (14/90) “Approximately 70% of out patients demonstrated involvement of the pons or basal ganglia; and involvement of both was seen in 33% of our cases Interestingly, when the pons was involved we saw concurrent involvement of the basal ganglia in 67% of our patients Finally atypical lesions were not seen without basal ganglia or pontine involvement”

“This is an interesting patient of ours who presented with an abnormal lesion in the pons; note the slight asymmetric involvement. Although the lesion may be confused with ODMS, it is the post contrast images which demonstrate the abnormal ring type enhancement giving the diagnosis away. These findings were consistent with metastatic disease from the pt’s primary lung malignancy.”

Differential Diagnosis Neoplasm – Metastases and astrocytoma Pontine infarction Demyelinating disease Metabolic Syndromes Wilson’s Disease Leigh’s Disease Diabetes Hypertensive encephalopathy “This transitions us into differential considerations for ODMS as mentioned include metastatic disease or pontine glioma – these lesions are usually asymmetric and demonstrate ring enhancement ‘pontine glioma’ are typically seen in the pediatric/young adult patients and that Pons is a rare site for solitary metastasis Pontine infarct - Often asymmetric involving both corticospinal tracts and peripheral pontine fibers – be careful for these lesions when considering basilar artery infarcts Demyelinating disease; typical lesions are seen elsewhere in the brain and have an incomplete ring of enhancement Metabolic disease; you can see pons and basal ganglia involvement in Wilson’s, Leigh’s and HTN encephalopathy – these lesions typically do not spare the peripheral pontine fibers” Basal ganglia > pons in Wilson disease Basal ganglia, midbrain in Leigh disease Parieto-occipital lobes = most common site in hypertensive encephalopathy Pontine hypertensive encephalopathy – typically does not spare peripheral fibers

Conclusion Setting of encephalopathy, seizures, altered mental status T2 hyperintense signal involving the pons and basal ganglia Atypical lesion can be seen without pontine or basal ganglia involvement Restricted diffusion and minimal to no enhancement Subacute stage, abnormal signal may improve or completely resolve “In conclusion, one should maintain a high degree of suspicion for ODMS in the setting of encephalopathy, siezures and altered mental status Abnormal T2 signal involves the pons and/or the basal ganglia; atypical lesions are not seen without involvement of the basal ganglia or pons Lesions can demonstrate restricted diffusion and have minimal to no enhancement. In the subacute stage, findings may be subtle or may have completely resolved.”