Primary Aberrant Third Nerve Regeneration Dan Boghen, MD, Jean-Pierre Chartrand, MD, Pierre Laflamme, MD, Trevor Kirkham, MD, Jules Hardy, MD, and Marc Aube, M D
The clinical and neuroradiological features in 4 patients with the syndrome of aberrant regeneration of the third nerve are presented. In contrast to what is commonly seen, the syndrome was not preceded by third nerve palsy. A petrous apex-cavernous sinus meningioma was the underlying lesion in all 4 patients. Surgical and pathological confirmation o f the diagnosis was obtained in 3. Regardless of whether the other ocular motor nerves are spared (as in our patients) or involved (as in other cases reported in the literature), primary aberrant regeneration o f the oculomotor nerve appears to be characteristic of a cavernous sinus meningioma. Boghen D , Chartrand J-P, Laflamme P, et al: Primary aberrant third nerve regeneration. Ann Neurol 6:415-418, 1979
The hallmark of the syndrome of aberrant regeneration of the third nerve is retraction of the upper eyelid on attempted downgaze o r adduction of the globe. A segmental contraction of the pupil may occur at the same time as the lid movement. The pupillary light response is impaired. Vertical movements of the globe are usually restricted. The syndrome occurs following an acute third nerve palsy resulting from damage to the nerve by aneurysm o r trauma. Tumor has been considered an unlikely cause [ 101. Recently, on the basis of 4 cases, Shatz e t a1 [7] have suggested that aberrant regeneration of the third nerve, in the absence of a preceding third nerve palsy, may be “diagnostic of an intracavernous meningioma.” A similar case has been described in a report by Trobe, Glaser, and Post [9]. The following 4 cases further consolidate the diagnostic importance of aberrant regeneration of insidious onset.
Case Histories Patient 1 A 60-year-old woman presented in July, 1974, with a four-year history of progressive right lid ptosis; initially she had experienced double vision. She also complained of pain in the area of the right orbit. She suffered from diabetes, for which she was being treated with oral hypoglycemic medication. She also had high blood pressure, hyperlipidemia, and a left anterior bundle-branch block on electrocardiogram. Visual acuity was 20/20 in both eyes, with full fields. There was total right upper lid ptosis. Pupil diameter was 4.5 mm on the right and 3.5 m m on the left.
From the H6pital H&el-Dieu, the University of Montreal Faculty of Medicine, Notre-Dame Hospital, McGill University, and the Montreal Neurological Institute, Montreal, Que, Canada. Accepted for publication Apr 15, 1979.
Reaction to light and near was present but weak in the right eye and normal in the left. Four percent cocaine solution dilated both pupils to 7 mm. There was a 50% reduction in the range of elevation, depression, and adduction of the right eye. The fourth nerve appeared intact. O n attempted adduction and depression of the right eye, partial elevation of the upper lid and reduction in diameter of the pupil occurred on the right side. Exophthalmometry measured 16.5 mm on the right and 14 mm on the left. With the exception of diminished deep sensation in the toes and feet, the remainder of the neurological examination was normal. A skull roentgenogram revealed hyperostosis of the lesser wing of the right sphenoid bone and distortion and medial displacement of the superior portion of the lateral wall of the right sphenoid sinus. Right carotid arteriography showed a tumor blush in the area of the lesser wing of the right sphenoid bone and the right anterior clinoid process. There was encasement of the intracavernous portion of the internal carotid artery, and the supraclinoid portion of that vessel and the middle cerebral artery were elevated. A cavernous sinus-sphenoid wing meningioma was diagnosed. The patient was discharged with plans for regular follow-up. In May, 1975, she was free of headache. While vision in the left eye was still 20/20, vision in the right eye had decreased to 20150. She was then lost to follow-up for two years. In April, 1977, she had finger-counting vision in the right eye. Axial tomography showed an area of enhancement occupying most of the right middle fossa and involving the cavernous sinus (Fig 1). In May, 1978, vision in the right eye had decreased to light perception while visual function in the left eye remained normal; exophthal-
Address reprint requests to Dr Boghen, Neurology Service, H6pital H6tel-Dieu de Montreal, 3840 St. Urbain, Montreal, Que, Canada H2W 1T8.
0364-5134/79/110415-04$01.25 @ 1978 by Dan Boghen 415
F i g 1 . (Patient 1) Computerized axial tomogramfollowing injection of contrast medium shows an area of abnormal enhancement i n the region of the cavernous sinus. The lesion extends from the superior orbital fissure to the tip of the petrous bone. mometry readings were unchanged. There was complete paralysis of right eye movements in the field of action of the third nerve. Aberrant regeneration could no longer be demonstrated in the right upper lid. Ophthalmoscopy revealed a pale right optic disc and optociliary shunt vessels.
Patient 2 A 60-year-old woman was admitted to the hospital in April, 1978. Twenty years earlier she had been noted to have divergent strabismus of the right eye, for which she was operated on ten years prior to the present admission. A skull roentgenogram performed two years prior to admission revealed an abnormal sella turcica; she refused more complete investigation of this problem. At the time of admission she complained of intense right orbital and retroorbital headache of two months’ duration as well as progressive deterioration of visual function in the right eye. O n examination, visual acuity was 20/300 in the right eye and 20/20 in the left. The visual field was normal on the left, while on the right it was reduced to a nasal island of vision detectable only by the use of highest intensity stimulus. On forward gaze the palpebral fissure measured 7 mm on the right and 10 mm on the left. Left eye movements were normal, while on the right there was limitation of all movements controlled by the third nerve. Attempted adduction of the right eye was accompanied by obvious elevation of the upper lid (Fig 2). Pupil diameter was 4.5 mm on the right and 3.5 mm on the left. Direct and consensual reaction to light and near were absent on the right
F i g 2. (Patient 2) Aberrant regeneration of the third nerve on the right. On attempted gaze to the left there is paralysis of adduction of the right eye and striking elevation of the right upper eyelid. Arrows indicate direction of gaze. side. One percent hydroxyamphetamine dilated both pupils equally. There was pallor of the right optic disc. Cranial nerves IV, V, and VI were intact. Skull roentgenograms and tomograms of the sella showed sloping of the sellar floor downward and to the right and destruction of the right anterior clinoid. Cerebral arteriography demonstrated a tumor blush in the right cavernous area and displacement of the middle cerebral, carotid, and basilar arteries. Computerized axial tomography with contrast enhancement revealed an area of increased density in the right cavernous region that extended into the sella and subtentorially. Following craniotomy, a meningioma measuring 6 cm in diameter was removed from the right middle fossa. The tumor adhered to the lateral wall of the cavernous sinus and surrounded the optic nerve, carotid artery, and third nerve, which had to be sectioned. Laterally the tumor displaced the tip of the temporal lobe. O n follow-up examination in August, 1978, she could only count fingers with the right eye and there was complete right third nerve palsy.
Patient 3 A 40-year-old woman was admitted to the hospital in February, 1978. Two years earlier she had noted right upper lid ptosis. Subsequently, diplopia had developed and the degree of ptosis increased. She complained of moderately intense vertex headache. There was a history of diabetes and high blood pressure. O n examination, visual acuity was 20125 in the right eye
416 Annals of Neurology Vol 6 No 5 November 1979
and 20120 in the left, with full visual fields. The right upper lid descended to the pupillary border. Adduction, elevation, and depression were paralyzed in the right eye. O n gaze to the left, the right lid elevated. Pupil diameter was 2.5 mm on the right and 4 mm on the left. N o pupillary response could be elicited on the right side to either light (direct and consensual) or near. Four percent cocaine produced dilation of both pupils (right, 4 mm, and left, 5 mm). Instillation of methacholine had no effect on either eye. O n the right, the corneal reflex was absent and there was hypoesthesia to pinprick in the second division of the fifth nerve. Plain roentgenograms demonstrated minimal changes, consisting of elevation of the anterior clinoid and hyperostosis of the foramen rotundum on the right side. Cerebral arteriography showed a highly vascularized tumor producing segmental narrowing of the right internal carotid artery, shift of the basilar artery to the left, and elevation of the superior cerebellar artery and the vein of Rosenthal. O n computerized axial tomography there was a large area of increased density centered at the tip of the right petrous bone. The lesion involved the right cavernous sinus and extended from the superior orbital fissure to the posterior fossa, where it compressed the right side of the brainstem. At craniotomy, a meningioma was found originating at the tip of the petrous pyramid. Anteriorly it involved the cavernous sinus. There was invasion of the free margin of the tentorium cerebelli with subtentorial extension. An intracapsular resection was performed.
Patient 4 A 58-year-old woman was admitted to the hospital in May, 1978, for investigation of a generalized seizure that had occurred two months earlier. She had a seventeen-year history of right upper lid ptosis and difficulty in moving the right eye. She also complained of intermittent right frontal headaches. Visual acuity was 20125 in both eyes, and confrontation and Goldmann fields were full. The right upper lid, which was slightly ptotic on primary gaze, retracted on attempted adduction and depression of the right eye. Pupil diameter was 3.5 mm on the right and 4 mm on the left. The right pupil did not dilate in the dark but enlarged to 8 mm (same as the left) when 1% hydroxyamphetamine was instilled in the conjunctival sac. Right eye movements in the field of action of the third nerve were greatly reduced. Exophthalmometry measured 16 mm on the right and 15 mm o n the left. The fundi, other cranial nerves, and remainder of the neurological examination were within normal limits. A skull roentgenogram showed increased density of the right parasellar area and obliteration of the sphenoid sinus. O n cerebral arteriography there was a tumor blush in the right cavernous area, encasement of the intracavernous portion of the right internal carotid artery, and anterior displacement of the sylvian triangle and middle cerebral artery. Computerized tomography with infusion of contrast material showed an area of abnormal enhancement extending from the right cavernous sinus posteriorly along the incisura of the tentorium and displacing the third and lateral ventricles. At surgery a right cavernous sinus meningioma was
found. Excision of the tumor entailed section of the right oculomotor nerve.
Discussion By their anatomical location and clinical features, the tumors in o u r patients are best classified as petrous apex-cavernous sinus meningiomas. These are rare tumors which account for only a small number of the lesions responsible for the cavernous sinus syndrome [4, 81. Their main clinical feature is unilateral involvement of multiple ocular motor nerves. While all o u r patients had headache, this symptom is by n o means constantly present [9].I n 3 patients the headache was frontal o r orbital and o n the same side as t h e lesion. Unilateral visual impairment, found in 2 patients, was o f late occurrence. This is in contrast to what is found in meningiomas of t h e medial sphenoid ridge, in which visual loss is an early manifestation [ l o ] . Proptosis, the earliest sign in the majority of cases of e n plaque meningioma [ 101, is a minor feature of cavernous sinus meningioma. Hypoesthesia in t h e territory of t h e trigeminal nerve was present in 1 of o u r patients. T h e distinction between cavernous sinus meningiomas and aneurysms in t h e same location may be difficult to make o n clinical grounds alone. Definitive diagnosis is based o n t h e characteristic bony changes o n plain roentgenograms and tomographic views, as well as o n the arteriographic findings. Initial plain skull films were interpreted as normal in 50% of t h e cases in t h e literature [ 9 ] ,as well as in 1 of ours. Computerized axial tomography is extremely valuable in demonstrating the presence and extent of t h e lesion; it was positive in all o u r patients. Surgical intervention is best reserved for patients with threatened compression of t h e visual pathways or the brainstem, as it neither allows complete removal of t h e tumor nor brings about clinical improvement. T h e pupils o n t h e involved side were of special interest in o u r patients. Despite minimal o r absent light reaction, they were comparable in diameter to those o n the normal side. Partial or complete sparing of t h e pupils is known to occur with lesions in the cavernous sinus and superior orbital fissure [l] and may be a consequence of concomitant involvement of t h e sympathetic and parasympathetic systems [61. T h e pupil dilation following instillation of 1% hydroxyamphetamine rules out postganglionic sympathetic paralysis and renders this explanation inappropriate in o u r patients. Their relatively normal pupil diameter, coupled with t h e failure t o react to light, may be related to aberrant regeneration of third nerve fibers into t h e iris; recent work [2] supports this possibility. Although t h e pupil was seen to contract o n adduction in only 1 of o u r patients, clinically inapparent aberrant regeneration into the pupil may
Boghen et al: Primary Aberrant Nerve Regeneration
417
well have been present in oi-hers as well. While such inapparent aberrant regeneration may be responsible for pupillary findings in other lesions of the cavernous sinus-superior orbital fissure, it would not explain cases in which the pupillary reaction to light is entirely normal [ 11 or those in which various degrees of pupillary sparing occur in the context of an acutely presenting intracavernous aneurysm [3]. Based on the findings in some of their patients, Trobe, Glaser, and Post [9] suggested that “relative pupil sparing in cavernous sinus lesions may, in part, reflect sparing of the inferior division of the third nerve.” Aberrant regeneration of the third nerve usually follows an acute third nerve palsy and is due to either trauma to the nerve or compression of the nerve by an aneurysm of the posterior communicating artery. Rarely the syndrome may present insidiously and without a history of preceding third nerve palsy. In only 2 such cases has the underlying lesion been aneurysmal. An intracavernous aneurysm was present in 1 of these [9], and in the other, a patient with evidence of axonal neoformation in the third nerve, a large posterior communicating aneurysm was found
[51. Recently, on the basis of 4 cases, Schatz et a1 [71 suggested that primary aberrant regeneration of the third nerve is diagnostic of intracavernous meningioma. The syndrome was thought to occur because the slowly growing meningioma allows concomitant subclinical destruction and regeneration of third nerve fibers. Trobe e t a1 [9] reported an identical case. Although i t would appear that in rare instances the syndrome may be caused by an aneurysm, our 4 cases support the suggestion put forward by Schatz et a1 and establish a meningioma involving the cavernous sinus as the main consideration in the presence of aberrant third nerve regeneration not preceded by third nerve palsy. In contrast to cases in the litera-
418
Annals of Neurology
Vol 6 No 5
ture, the oculomotor involvement in o u r patients was confined to the third nerve. T h e progression of aberrant regeneration to complete third nerve palsy without intervening surgery, which occurred in Patient 1, has not been reported previously. T h e fact that 3 of our cases were seen over a period of a few months may indicate that aberrant third nerve regeneration is more frequent than the paucity of previous reports would suggest. The entity should be specifically sought in patients who present with a partial and persistent third nerve palsy. Grateful acknowledgment is made to Dr Michel Laflamme, who referred Patient 1, and to Drs Jacques Lesage and Roger Maltais for their help with the neuroradiological interpretation.
References 1. Cogan DG: Neurology of the Ocular Muscles. Springfield, IL, Thomas, 1956, p 176 2. Czarnecki JSC, Thompson HS: The iris sphincter in aberrant regeneration of the third nerve. Arch Ophthalmol 96: 16061610, 1778 3. Jefferson G : O n the saccular aneurysms of the internal carotid artery in the cavernous sinus. Br J Surg 26:267-302, 1938 4. Jefferson G: The Bowman Lecture: concerning injuries, aneurysms and tumors involving the cavernous sinus. Trans Ophthalmol SOCUK 73:117-152, 1953 5. Levin PM: Intracranial aneurysms. Arch Neurol Psychiatry 67:7J1-786, 1952 6. Meadows SP: Intracavernous aneurysms of the internal carotid artery. Arch Ophthalmol 70:757-77 1, 1963 7. Schatz NJ, Savino PJ, Corbett JJ: Primary aberrant oculomotor regeneration: a sign of intracavernous meningioma. Arch Neurol 34:29-32, 1777 8. Thomas JE, Yoss RE: The parasellar syndrome: problems in determining etiology. Mayo Clin Proc 45:617-623, 1970 9. Trobe JD, Glaser JS, Post JD: Meningiomas and aneurysms of the cavernous sinus: neuro-ophthalmological features. Arch Ophthalmol 96:457-467, 1978 10. Walsh FB, Hoyt WF: Clinical Neuro-ophthalmology. Baltimore, Williams & Wilkins, 1969, pp 2266-2268
November 1979
The clinical and neuroradiological features in 4 patients with the syndrome of aberrant regeneration of the third nerve are presented. In contrast to what is commonly seen, the syndrome was not preceded by third nerve palsy. A petrous apex-cavernous sinus meningioma was the underlying lesion in all 4 patients. Surgical and pathological confirmation o f the diagnosis was obtained in 3. Regardless of whether the other ocular motor nerves are spared (as in our patients) or involved (as in other cases reported in the literature), primary aberrant regeneration o f the oculomotor nerve appears to be characteristic of a cavernous sinus meningioma. Boghen D , Chartrand J-P, Laflamme P, et al: Primary aberrant third nerve regeneration. Ann Neurol 6:415-418, 1979
The hallmark of the syndrome of aberrant regeneration of the third nerve is retraction of the upper eyelid on attempted downgaze o r adduction of the globe. A segmental contraction of the pupil may occur at the same time as the lid movement. The pupillary light response is impaired. Vertical movements of the globe are usually restricted. The syndrome occurs following an acute third nerve palsy resulting from damage to the nerve by aneurysm o r trauma. Tumor has been considered an unlikely cause [ 101. Recently, on the basis of 4 cases, Shatz e t a1 [7] have suggested that aberrant regeneration of the third nerve, in the absence of a preceding third nerve palsy, may be “diagnostic of an intracavernous meningioma.” A similar case has been described in a report by Trobe, Glaser, and Post [9]. The following 4 cases further consolidate the diagnostic importance of aberrant regeneration of insidious onset.
Case Histories Patient 1 A 60-year-old woman presented in July, 1974, with a four-year history of progressive right lid ptosis; initially she had experienced double vision. She also complained of pain in the area of the right orbit. She suffered from diabetes, for which she was being treated with oral hypoglycemic medication. She also had high blood pressure, hyperlipidemia, and a left anterior bundle-branch block on electrocardiogram. Visual acuity was 20/20 in both eyes, with full fields. There was total right upper lid ptosis. Pupil diameter was 4.5 mm on the right and 3.5 m m on the left.
From the H6pital H&el-Dieu, the University of Montreal Faculty of Medicine, Notre-Dame Hospital, McGill University, and the Montreal Neurological Institute, Montreal, Que, Canada. Accepted for publication Apr 15, 1979.
Reaction to light and near was present but weak in the right eye and normal in the left. Four percent cocaine solution dilated both pupils to 7 mm. There was a 50% reduction in the range of elevation, depression, and adduction of the right eye. The fourth nerve appeared intact. O n attempted adduction and depression of the right eye, partial elevation of the upper lid and reduction in diameter of the pupil occurred on the right side. Exophthalmometry measured 16.5 mm on the right and 14 mm on the left. With the exception of diminished deep sensation in the toes and feet, the remainder of the neurological examination was normal. A skull roentgenogram revealed hyperostosis of the lesser wing of the right sphenoid bone and distortion and medial displacement of the superior portion of the lateral wall of the right sphenoid sinus. Right carotid arteriography showed a tumor blush in the area of the lesser wing of the right sphenoid bone and the right anterior clinoid process. There was encasement of the intracavernous portion of the internal carotid artery, and the supraclinoid portion of that vessel and the middle cerebral artery were elevated. A cavernous sinus-sphenoid wing meningioma was diagnosed. The patient was discharged with plans for regular follow-up. In May, 1975, she was free of headache. While vision in the left eye was still 20/20, vision in the right eye had decreased to 20150. She was then lost to follow-up for two years. In April, 1977, she had finger-counting vision in the right eye. Axial tomography showed an area of enhancement occupying most of the right middle fossa and involving the cavernous sinus (Fig 1). In May, 1978, vision in the right eye had decreased to light perception while visual function in the left eye remained normal; exophthal-
Address reprint requests to Dr Boghen, Neurology Service, H6pital H6tel-Dieu de Montreal, 3840 St. Urbain, Montreal, Que, Canada H2W 1T8.
0364-5134/79/110415-04$01.25 @ 1978 by Dan Boghen 415
F i g 1 . (Patient 1) Computerized axial tomogramfollowing injection of contrast medium shows an area of abnormal enhancement i n the region of the cavernous sinus. The lesion extends from the superior orbital fissure to the tip of the petrous bone. mometry readings were unchanged. There was complete paralysis of right eye movements in the field of action of the third nerve. Aberrant regeneration could no longer be demonstrated in the right upper lid. Ophthalmoscopy revealed a pale right optic disc and optociliary shunt vessels.
Patient 2 A 60-year-old woman was admitted to the hospital in April, 1978. Twenty years earlier she had been noted to have divergent strabismus of the right eye, for which she was operated on ten years prior to the present admission. A skull roentgenogram performed two years prior to admission revealed an abnormal sella turcica; she refused more complete investigation of this problem. At the time of admission she complained of intense right orbital and retroorbital headache of two months’ duration as well as progressive deterioration of visual function in the right eye. O n examination, visual acuity was 20/300 in the right eye and 20/20 in the left. The visual field was normal on the left, while on the right it was reduced to a nasal island of vision detectable only by the use of highest intensity stimulus. On forward gaze the palpebral fissure measured 7 mm on the right and 10 mm on the left. Left eye movements were normal, while on the right there was limitation of all movements controlled by the third nerve. Attempted adduction of the right eye was accompanied by obvious elevation of the upper lid (Fig 2). Pupil diameter was 4.5 mm on the right and 3.5 mm on the left. Direct and consensual reaction to light and near were absent on the right
F i g 2. (Patient 2) Aberrant regeneration of the third nerve on the right. On attempted gaze to the left there is paralysis of adduction of the right eye and striking elevation of the right upper eyelid. Arrows indicate direction of gaze. side. One percent hydroxyamphetamine dilated both pupils equally. There was pallor of the right optic disc. Cranial nerves IV, V, and VI were intact. Skull roentgenograms and tomograms of the sella showed sloping of the sellar floor downward and to the right and destruction of the right anterior clinoid. Cerebral arteriography demonstrated a tumor blush in the right cavernous area and displacement of the middle cerebral, carotid, and basilar arteries. Computerized axial tomography with contrast enhancement revealed an area of increased density in the right cavernous region that extended into the sella and subtentorially. Following craniotomy, a meningioma measuring 6 cm in diameter was removed from the right middle fossa. The tumor adhered to the lateral wall of the cavernous sinus and surrounded the optic nerve, carotid artery, and third nerve, which had to be sectioned. Laterally the tumor displaced the tip of the temporal lobe. O n follow-up examination in August, 1978, she could only count fingers with the right eye and there was complete right third nerve palsy.
Patient 3 A 40-year-old woman was admitted to the hospital in February, 1978. Two years earlier she had noted right upper lid ptosis. Subsequently, diplopia had developed and the degree of ptosis increased. She complained of moderately intense vertex headache. There was a history of diabetes and high blood pressure. O n examination, visual acuity was 20125 in the right eye
416 Annals of Neurology Vol 6 No 5 November 1979
and 20120 in the left, with full visual fields. The right upper lid descended to the pupillary border. Adduction, elevation, and depression were paralyzed in the right eye. O n gaze to the left, the right lid elevated. Pupil diameter was 2.5 mm on the right and 4 mm on the left. N o pupillary response could be elicited on the right side to either light (direct and consensual) or near. Four percent cocaine produced dilation of both pupils (right, 4 mm, and left, 5 mm). Instillation of methacholine had no effect on either eye. O n the right, the corneal reflex was absent and there was hypoesthesia to pinprick in the second division of the fifth nerve. Plain roentgenograms demonstrated minimal changes, consisting of elevation of the anterior clinoid and hyperostosis of the foramen rotundum on the right side. Cerebral arteriography showed a highly vascularized tumor producing segmental narrowing of the right internal carotid artery, shift of the basilar artery to the left, and elevation of the superior cerebellar artery and the vein of Rosenthal. O n computerized axial tomography there was a large area of increased density centered at the tip of the right petrous bone. The lesion involved the right cavernous sinus and extended from the superior orbital fissure to the posterior fossa, where it compressed the right side of the brainstem. At craniotomy, a meningioma was found originating at the tip of the petrous pyramid. Anteriorly it involved the cavernous sinus. There was invasion of the free margin of the tentorium cerebelli with subtentorial extension. An intracapsular resection was performed.
Patient 4 A 58-year-old woman was admitted to the hospital in May, 1978, for investigation of a generalized seizure that had occurred two months earlier. She had a seventeen-year history of right upper lid ptosis and difficulty in moving the right eye. She also complained of intermittent right frontal headaches. Visual acuity was 20125 in both eyes, and confrontation and Goldmann fields were full. The right upper lid, which was slightly ptotic on primary gaze, retracted on attempted adduction and depression of the right eye. Pupil diameter was 3.5 mm on the right and 4 mm on the left. The right pupil did not dilate in the dark but enlarged to 8 mm (same as the left) when 1% hydroxyamphetamine was instilled in the conjunctival sac. Right eye movements in the field of action of the third nerve were greatly reduced. Exophthalmometry measured 16 mm on the right and 15 mm o n the left. The fundi, other cranial nerves, and remainder of the neurological examination were within normal limits. A skull roentgenogram showed increased density of the right parasellar area and obliteration of the sphenoid sinus. O n cerebral arteriography there was a tumor blush in the right cavernous area, encasement of the intracavernous portion of the right internal carotid artery, and anterior displacement of the sylvian triangle and middle cerebral artery. Computerized tomography with infusion of contrast material showed an area of abnormal enhancement extending from the right cavernous sinus posteriorly along the incisura of the tentorium and displacing the third and lateral ventricles. At surgery a right cavernous sinus meningioma was
found. Excision of the tumor entailed section of the right oculomotor nerve.
Discussion By their anatomical location and clinical features, the tumors in o u r patients are best classified as petrous apex-cavernous sinus meningiomas. These are rare tumors which account for only a small number of the lesions responsible for the cavernous sinus syndrome [4, 81. Their main clinical feature is unilateral involvement of multiple ocular motor nerves. While all o u r patients had headache, this symptom is by n o means constantly present [9].I n 3 patients the headache was frontal o r orbital and o n the same side as t h e lesion. Unilateral visual impairment, found in 2 patients, was o f late occurrence. This is in contrast to what is found in meningiomas of t h e medial sphenoid ridge, in which visual loss is an early manifestation [ l o ] . Proptosis, the earliest sign in the majority of cases of e n plaque meningioma [ 101, is a minor feature of cavernous sinus meningioma. Hypoesthesia in t h e territory of t h e trigeminal nerve was present in 1 of o u r patients. T h e distinction between cavernous sinus meningiomas and aneurysms in t h e same location may be difficult to make o n clinical grounds alone. Definitive diagnosis is based o n t h e characteristic bony changes o n plain roentgenograms and tomographic views, as well as o n the arteriographic findings. Initial plain skull films were interpreted as normal in 50% of t h e cases in t h e literature [ 9 ] ,as well as in 1 of ours. Computerized axial tomography is extremely valuable in demonstrating the presence and extent of t h e lesion; it was positive in all o u r patients. Surgical intervention is best reserved for patients with threatened compression of t h e visual pathways or the brainstem, as it neither allows complete removal of t h e tumor nor brings about clinical improvement. T h e pupils o n t h e involved side were of special interest in o u r patients. Despite minimal o r absent light reaction, they were comparable in diameter to those o n the normal side. Partial or complete sparing of t h e pupils is known to occur with lesions in the cavernous sinus and superior orbital fissure [l] and may be a consequence of concomitant involvement of t h e sympathetic and parasympathetic systems [61. T h e pupil dilation following instillation of 1% hydroxyamphetamine rules out postganglionic sympathetic paralysis and renders this explanation inappropriate in o u r patients. Their relatively normal pupil diameter, coupled with t h e failure t o react to light, may be related to aberrant regeneration of third nerve fibers into t h e iris; recent work [2] supports this possibility. Although t h e pupil was seen to contract o n adduction in only 1 of o u r patients, clinically inapparent aberrant regeneration into the pupil may
Boghen et al: Primary Aberrant Nerve Regeneration
417
well have been present in oi-hers as well. While such inapparent aberrant regeneration may be responsible for pupillary findings in other lesions of the cavernous sinus-superior orbital fissure, it would not explain cases in which the pupillary reaction to light is entirely normal [ 11 or those in which various degrees of pupillary sparing occur in the context of an acutely presenting intracavernous aneurysm [3]. Based on the findings in some of their patients, Trobe, Glaser, and Post [9] suggested that “relative pupil sparing in cavernous sinus lesions may, in part, reflect sparing of the inferior division of the third nerve.” Aberrant regeneration of the third nerve usually follows an acute third nerve palsy and is due to either trauma to the nerve or compression of the nerve by an aneurysm of the posterior communicating artery. Rarely the syndrome may present insidiously and without a history of preceding third nerve palsy. In only 2 such cases has the underlying lesion been aneurysmal. An intracavernous aneurysm was present in 1 of these [9], and in the other, a patient with evidence of axonal neoformation in the third nerve, a large posterior communicating aneurysm was found
[51. Recently, on the basis of 4 cases, Schatz et a1 [71 suggested that primary aberrant regeneration of the third nerve is diagnostic of intracavernous meningioma. The syndrome was thought to occur because the slowly growing meningioma allows concomitant subclinical destruction and regeneration of third nerve fibers. Trobe e t a1 [9] reported an identical case. Although i t would appear that in rare instances the syndrome may be caused by an aneurysm, our 4 cases support the suggestion put forward by Schatz et a1 and establish a meningioma involving the cavernous sinus as the main consideration in the presence of aberrant third nerve regeneration not preceded by third nerve palsy. In contrast to cases in the litera-
418
Annals of Neurology
Vol 6 No 5
ture, the oculomotor involvement in o u r patients was confined to the third nerve. T h e progression of aberrant regeneration to complete third nerve palsy without intervening surgery, which occurred in Patient 1, has not been reported previously. T h e fact that 3 of our cases were seen over a period of a few months may indicate that aberrant third nerve regeneration is more frequent than the paucity of previous reports would suggest. The entity should be specifically sought in patients who present with a partial and persistent third nerve palsy. Grateful acknowledgment is made to Dr Michel Laflamme, who referred Patient 1, and to Drs Jacques Lesage and Roger Maltais for their help with the neuroradiological interpretation.
References 1. Cogan DG: Neurology of the Ocular Muscles. Springfield, IL, Thomas, 1956, p 176 2. Czarnecki JSC, Thompson HS: The iris sphincter in aberrant regeneration of the third nerve. Arch Ophthalmol 96: 16061610, 1778 3. Jefferson G : O n the saccular aneurysms of the internal carotid artery in the cavernous sinus. Br J Surg 26:267-302, 1938 4. Jefferson G: The Bowman Lecture: concerning injuries, aneurysms and tumors involving the cavernous sinus. Trans Ophthalmol SOCUK 73:117-152, 1953 5. Levin PM: Intracranial aneurysms. Arch Neurol Psychiatry 67:7J1-786, 1952 6. Meadows SP: Intracavernous aneurysms of the internal carotid artery. Arch Ophthalmol 70:757-77 1, 1963 7. Schatz NJ, Savino PJ, Corbett JJ: Primary aberrant oculomotor regeneration: a sign of intracavernous meningioma. Arch Neurol 34:29-32, 1777 8. Thomas JE, Yoss RE: The parasellar syndrome: problems in determining etiology. Mayo Clin Proc 45:617-623, 1970 9. Trobe JD, Glaser JS, Post JD: Meningiomas and aneurysms of the cavernous sinus: neuro-ophthalmological features. Arch Ophthalmol 96:457-467, 1978 10. Walsh FB, Hoyt WF: Clinical Neuro-ophthalmology. Baltimore, Williams & Wilkins, 1969, pp 2266-2268
November 1979
