I would like to thank Dr. Lee for asking two salient and extremely relevant questions regarding ophthalmoplegic migraine (OM). I will address each in order.
1) In Dr. Carlow's review of the literature did he encounter any ante-mortem or post-mortem examinations of the oculomotor nerve in a patient with OM?
Excluding aneurysm, tumor, brainstem herniation and other explainable causes, only five cases of OM have been autopsied that fulfill the generally accepted clinical criteria for OM.
Weiss (1) reported a case of a 30-year-old woman with repeated episodes of oculomotor paralysis from childhood, who died of tuberculous meningitis in 1885. Gray, warty granulations in the involved third nerve root and at the base of the brain, from which tubercle bacilli were recovered, making this case unhelpful in the quest to understand the pathogenesis of OM.
A second pathologic case was documented in 1887 by Richter (2). A 36-year-old man had a history of recurrent headache and oculomotor paralysis from age 5 years. The involved oculomotor nerve was twice the size of the normal nerve and club-shaped as it passed through the dura. The oculomotor nerve fascicles were separated by connective tissue without nerve fiber degeneration. This thickening was diagnosed as a fibrochondroma; however, there was no documentation of cartilage in the lesion.
Karpus (3) described the third autopsied case of OM. A 43-year-old woman had repeated episodes of headache and oculomotor paresis from age 6 months that ultimately developed into a complete third nerve paralysis. She contracted syphilis at age 18 years and died of periencephalitis chronica, although the meninges were not included in the histopathologic report. A 6 mm thickened oculomotor nerve at the midbrain exit was diagnosed as a neurofibroma with separation and considerable degeneration of the oculomotor nerve fibers.
In 1911, Shionoya (4) reported a case of a 16-year-old boy who died of acute tuberculous meningitis following repeated attacks of headache and oculomotor paralysis dating from age 6 years. The involved third nerve was five times normal size at the nerve root midbrain exit and was surrounded by purulent exudate. Significant strands of connective tissue were intertwined within the oculomotor nerve fascicles, a finding inconsistent with the histopathology of acute tuberculous meningitis.
In 1951, Alpers (5) documented a 23-year-old woman who had had repeated episodes of headache, ptosis, and diplopia for 1 year. Her last admission was prompted by headache, ptosis, and mydriasis without evidence of ophthalmoplegia. A craniotomy was performed and the third cranial nerve on the involved side was observed at surgery to be normal. A microscopic study of the brainstem revealed no abnormalities. The authors concluded that the third nerve was normal. The histopathology of the peripheral oculomotor nerve, especially at the midbrain third nerve root exit, was not included in the report, which allows their conclusion to be questioned.
The histopathology described in three of the above five cases (2–4) could be consistent with oculomotor nerve hypertrophy and scar formation from repeated episodes of demyelination and remyelination and therefore fit with my hypothesis for OM. None of the reports included histopathologic photographs or a detailed microscopic analysis of the involved oculomotor nerve, which will probably be required before the pathophysiology of OM is fully understood.
2) Has there ever been any evidence of hemorrhage using routine MRI or gradient echo imaging in any of these cases or would the lesion be too small to detect blood or an occult vascular malformation within the nerve?
Dr. Lee also wonders whether OM may be associated with a third nerve cavernous angioma. Only four pathologically verified cases of oculomotor cavernous angioma have been reported, two with Robert's syndrome (6–9). Three had only one episode of oculomotor palsy prior to surgery, and one had no history of ophthalmoplegia. None fulfilled the clinical criteria for OM and all had relatively large lesions on CT. One case had an MRI (9) with features consistent with a cavernous angioma.
No case in my series, or in the cases from my literature review, had evidence of hemorrhage using routine MRI. Resolution of the third nerve using routine T2-weighted MRI is suboptimal. A thickened oculomotor nerve in OM was documented in only one case from my literature review and in two cases from my series using T2-weighted MRI. Gradient echo is more sensitive than routine spin echo imaging in detecting very small areas of hemosiderin deposition in intracranial lesions (10). However, resolution is far less than with T1-weighted imaging and was not used in any case from my review or in my series.
Our ability to resolve minute oculomotor nerve vascular malformations, hemorrhage, or hemosiderin is currently inadequate. A dedicated oculomotor nerve midbrain surface coil utilizing 3D T2-weighted fast spin echo imaging or T2-imaging at high field strength (3.0 Tesla) could potentially improve third nerve resolution enough to resolve the problem.
I would like to thank Dr. Mario Kornfeld, professor of Neuropathology at the University of New Mexico, who is fluent in German, for translating and interpreting the German papers referenced.
Thomas J. Carlow, MD
1. Weiss D. Ein fall von periodisch auftretender totaler linksseitiger oculomotoriuslähmung. Wien Med Wschr 1885; 35:521–4.
2. Richter A. Ein fall von typisch recidivierender oculomotoriuslähmung mit sektionsbefund. Arch Psychiat Nervenkr 1887; 18:259–66.
3. Karpus JP. Zur kenntniss der periodischen oculomotoriusllähmung. Wien Klin Wschr 1895; 8:883–5, 901–3, 922–4.
4. Shionoya F. Ein fall von rezidivierender oculomotoriuslähmung (migraine ophtalmoplegique) mit autopsie. Dtsch Z Nervenheilk 1911; 42:155–66.
5. Alpers BJ, Yaskin HE. Pathogenesis of ophthalmoplegic migraine. Arch Ophthalmol 1951; 45:555–66.
6. Scott RM. Third nerve palsy in a 14-year old boy due to cavernous hemangioma of the third nerve. In: Raimondi AJ, ed. Concepts in Pediatric Neurosurgery-3. Basel: Karger, 1983;100–7.
7. Yamada T, Nishio S, Matsunaga M, et al. Cavernous hemangioma in the oculomotor nerve. J Neurol 1986; 233:63–4.
8. Matias-Guiu X, Alejo M, Sole T, et al. Cavernous angiomas of cranial nerves: report of two cases. Neurosurg 1990; 73:620–2.
9. Ogilvy CS, Pakzaban P, Lee JM. Oculomotor nerve cavernous angioma in a patient with Roberts syndrome. Surg Neurol 1993; 40:39–42.
10. Atlas SW, Mark AS, Grossman RI, et al. Intracranial hemorrhage: gradient-echo MR imaging at 1.5 T. Comparison with spin-echo imaging and clinical applications. Radiology 1988; 168:803–7.