Central pontine myelinolysis (CPM) is the destruction of myelin sheaths in characteristic places within the brainstem and cerebrum. It was first described pathologically as involving the central part of the basis pontis.1 The most common pattern is an isolated pons lesion, followed by a combined type with central and extrapontine areas of myelinolysis. Sole extrapontine lesions are rare.2 The disorder's various synonyms include osmotic myelinolysis, osmotic demyelination syndrome, and a subtype known as extrapontine myelinolysis (EPM).2-5

Clinical presentation

The classic signs and symptoms of both central and extrapontine myelinolysis are spastic quadriparesis, pseudobulbar palsy, and acute mental status changes which progress to coma and eventual death. It is usually fatal within three months, with survival rates beyond six months only found in 5 to 10% of patients.3-5 Presentation can vary, with symptoms ranging from neurological abnormality to behavioral disorders.6-8

When the pons is involved, MRI generally shows a single large, symmetric central lesion (figure 1). Myelinolysis is now known to occur in extrapontine locations including the basal ganglia, but also in the cerebellar white matter, the thalamus, caudate nucleus, subcortical cerebral white matter, corona radiata, and lateral geniculate body.3,8-10

In surviving patients, serial follow-up has shown early and complete resolution of extrapontine lesions with persistent residual pontine abnormalities. This suggests that there may be some reversibility or healing in certain patients.4,11

Etiology

The underlying etiology and pathogenesis are unknown. Two unifying factors that appear to contribute to the development of these lesions are osmotic insult and metabolic compromise.10 In addition, it has been found that 60 to 70% of cases occur in chronic alcoholics.4,8 The most common osmotic insult involves rapid correction of hyponatremia (>12 mmoles/l/day).10,12

Pathology

Findings for central and extrapontine myelinolysis include destruction of myelin sheaths, though the nerve cells and axis cylinders are spared. Vessels remain patent and unaffected and there generally are no signs of inflammation in or near the lesions.1,4 Osmotic endothelial injury is believed to cause the release of myelin toxic factors and/or edema derived primarily from the more vascular gray matter.12 The basis pontis has the highest gray-white matter apposition in the CNS, providing the appropriate environment for CPM. The basal ganglia, caudate nucleus, thalamus, geniculate bodies, and cortical white matter junction also have a high apposition of gray-white matter and are characteristic sites of extrapontine myelinosis (EPM).12 This theory remains to be proved, but it is consistent with MRI findings in regions of increased water content.4

Computed tomography

Before MRI, CPM remained largely a pathological diagnosis. CT was not a sensitive test and most scans indicated no abnormal findings.5,13 This is understandable as CT reconstruction artifacts in the brainstem routinely cause image degradation. Extrapontine lesions also are easily missed on CT, as exemplified in figure 2. In the proper clinical setting, the absence of mass effect or edema on CT helps exclude the differential diagnosis of tumor, supporting indirectly the diagnosis of CPM.

Magnetic resonance imaging

In regards to central and extrapontine lesions, MRI may show a positive indication as early as 1 to 2 weeks post-onset of signs and symptoms. The CPM lesion appears as a single, symmetric central focus, most commonly trident- shaped (figure 3) or, less commonly, round in the basis pontis. A bat-wing configuration has been described on coronal scans, and a trident shape can be seen on sagittal views.11

MRI demonstrates areas of myelinolysis as hypointense on T1-weighted images and hyperintense on T2-weighted images in the characteristic (pathologic) locations of the central pons and extrapontine sites.4,14 These findings alone are not specific for CPM. However, given the appropriate clinical setting, time frame, characteristic location(s), pattern of involvement, shape, and symmetry of the lesion(s), the diagnosis of CPM is suggested.

Central pons-The characteristic pattern of a midline pons lesion associated with basal ganglia lesions is fairly specific for CPM (figure 4), and narrows the differential diagnosis considerably.4 Similar findings in hypoxia, Leigh's and Wilson's diseases can be differentiated based on the history, clinical, and laboratory findings.

Extrapontine sites-The extrapontine lesions (with or without pontine involvement) are seen on MRI as bilateral, symmetric, and well demarcated. The basal ganglia is the most common extrapontine lesion and often is seen in association with other extrapontine sites.2,9 Recently, we have seen two cases with lesions that are solely extrapontine (figure 5).

Extrapontine myelinolysis does not follow a typical vascular distribution, and this helps differentiate it from cerebrovascular accidents. Dementing illnesses with EPM findings have characteristic histories and usually appear as normal on T1-weighted images. Toxins (methanol, carbon monoxide, trichloroethane) can cause extrapontine changes, but the T1-weighted images demonstrate increased signal, rather than the decreased signal seen in CPM.15

Conclusion

MR is the optimal tool for imaging CPM and its EPM variants. In the proper clinical setting, characteristic findings can be used to suggest the diagnosis early in the disease process. Early diagnosis is important, as this appears to be a potentially reversible condition in a small percentage of patients. Although the etiology is unknown, the standard of care is to promptly correct osmotic and metabolic abnormalities, as well as to provide general clinical support. AR

References

1. Adams RD, Victor M, Manacle EL: Central pontine myelinolysis: A hither to undescribed disease occurring in alcoholic and malnourished patients. Arch Neurol Psychiatry 181:154-172, 1959.

2. Gocht A, Colmant HJ: Central pontine and extrapontine myelinolysis: A report of fifty-eight cases. Clin Neuropathol 6:262-270, 1987.

3. Kalnins RM, Berkovic SF, Bladin PF: Central pontine myelinolysis with wide spread extrapontine lesions: A report of two cases. Clin Exp Neurol 189-202, 1984.

4. Ho VB, Fitz CR, Yoder CC, Geyer CA: Resolving MR features in osmotic myelinolysis (Central pontine and extrapontine myelinolysis). AJNR 14:163-167, 1993.

5. Sterns RH, Riggs JE, Schocet SF: Osmotic demyelination syndrome following correction of hyponatremia. N Engl J Med 314:1535-1542, 1986.

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373-386, 1976.

7. Price BH, Mesululam MM: Behavioral manifestations of central pontine myelinolysis. Arch Neurol 44:671-973, 1987.

8. Wijdicks EFM, Blue PR, Steers JL, Wisner RH: Central pontine myelinolysis with stupor alone after orthotopic liver transplantation. Liver Transpl Surg 2:14-16, 1996.

9. Dickoff DJ, Rapps M, Yahr MB: Striatal syndrome following hyponatremia and its rapid correction. Arch Neurol 45:112-114, 1988.

10. McKee AC, Winkelman MD, Yeager BQ: Central pontine myelinolysis in severely burned patients: Relationship to serum hyperosmolality. Neurology 38:1211-1217, 1988.

11. Miller GM, Baker HL, Okazaki H, Wisnant JP: Central pontine myelinolysis and its imitators: MR findings. Radiology 168:795-802, 1988.

12. Norenberg MD, Leslie KO, Robertson AF: Association between rise in serum sodium and central pontine myelinolysis. Ann Neurol 11:128-135, 1982.

13. DeWitt DL, Buonanno FS, Kistler JP, et al: Central pontine myelinolysis: Demonstration by nuclear magnetic resonance. Neurol 34:570-576, 1984.

14. Brunner JE, Redman JM, Haggar AM, Kruger TF, Aliath FB: Central pontine myelinolysis and pontine lesions after rapid correction of hyponatremia: A prospect of magnetic resonance imaging study. Ann Neurol 27:61-66, 1990.

15. del Amo M, Berenguer J, Pujol T, Marcader JM: MR in trichloroethane poisoning. AJNR 17:1180-1182, 1996.

Dr. McCurdy and Dr. Francis Hahn are with the Department of Radiology at the University of Nebraska Medical Center in Omaha. Dr. Paul Hahn is with the Department of Radiology at the University of Iowa Hospital in Iowa City.