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Show Journal of Neuro- Ophthalmology 14( 4): 205- 209, 1994. ) 1994 Raven Press, Ltd., New York Iatrogenic Lateral Rectus Palsies A Series of Five Postmyelographic Cases John A. Bell, M. D., F. R. C. S., F. c. ophth., Gawn G. Mclllwaine, F. R. C. S., F. c. ophth., and Damian O'Neill, F. R. C. S., F. c. ophth. The objective of this study was to assess the etiology of lateral rectus palsies in patients undergoing lumbar myelograms with Iopamidol ( Isovue; ER Squibb and Sons, Princeton, NJ, USA; Niopam, E Merc, UK.). An audit of the departmental orthoptic record revealed two patients who had suffered abducens palsies after myelograms. A further search revealed three additional patients who had suffered similar complications. The incidence of abducens palsy in patients undergoing myelography with the contrast agent Iopamidol was found to be 1 in 500 in around 2,500 myelograms performed under standard conditions. It would appear that lateral rectus palsy in myelography is the result of the lumbar puncture, the neurotoxic effect of the contrast agent, or a combination of the two in patients with an already compromised neu-rophysiologic state. This is the first series to associate this problem with Iopamidol. Although usually a serious neurologic symptom, when associated with contrast myelography using Iopamidol it is important to appreciate that such symptoms usually resolve of their own accord. Key Words: Abducent nerve- Contrast myelography- Iopamidol- Lateral rectus palsy. Modern myelographic contrast media are thought of as being extremely safe, but we report five patients who developed unilateral abducens nerve weakness following myelography with the contrast medium Iopamidol. This is a rare complication of diagnostic lumbar puncture, spinal anesthesia, and myelography. It seems to be more common following the introduction of a material into the thecal space. Iopamidol has shown remarkably few side effects since its introduction, and this is the first report to document a series of cranial nerve palsies in association with its use. The etiology is uncertain, but it seems likely that it is related to the procedure of lumbar puncture ( which alone can cause such side effects), the toxic effects of Iopamidol, or both these factors. This contrast medium has known neurotoxic effects, and possible mechanisms by which these may manifest themselves are discussed. From the Eye Department ( J. A. B.), King's College Hospital, Denmark Hill, London; The Princess Alexandra Eye Pavilion ( G. G. McL), The Royal Infirmary, Edinburgh; Royal Hallam-shire Hospital ( D. O'N.), Glossup Road, Sheffield, United Kingdom. Address correspondence and reprint requests to Dr. John Bell, King's College Hospital, Denmark Hill, London SE5, 9RS, U. K. PATIENTS AND METHODS All patients were well hydrated and were neu-rologically examined before and after myelography. Other conditions that might mimic lateral rectus palsy were eliminated. No patient had Horner syndrome or other cranial nerve involvement that might have indicated a cavernous sinus lesion. A brief resume of the patients is provided in Table 1. Case A A 39- year- old woman had a cervical myelogram for severe back pain and paraesthesia in the left arm. On examination, neck movements were uncomfortable, especially looking to the right, and there were nonspecific sensory changes over the C6 der- 205 206 Patient Age Year of myelogram Side of lateral rectus palsy Indication for myelography Postpuncture symptoms Time of onset of sixth nerve palsy after myelography Time to complete recovery A 39 1986 Left Cervical spondylosis Global headache; dizziness; nausea; 1 episode of vomiting 9 days 6 months J. A. 1 TABLE 1. B 46 1988 Right Low back pain; right- sided sciatica Severe headache; nausea; 1 episode of vomiting 12 days 4 months 1ELL ET AL Patient details C 41 1988 Left Low back pain; right- sided sciatica Mild headache 7 days 3 months D 33 1989 Left Low back pain; right- sided sciatica Severe headache; nausea; pain behind both eyes 1 day 2 weeks E 47 1989 Left Low back pain; previous discectomy at L- 5 Slight headache 5 days 3 months matome. A diagnosis of intermittent nerve root compression was made. Myelography was performed with 10 ml of Niopam 300 introduced via lumbar puncture at L2- 3; the procedure progressed uneventfully. Shortly afterward, she started to complain of global headache and dizziness, followed by a single episode of vomiting. She gradually recovered but felt sufficiently unwell to delay discharge for 6 days. Four days later she was admitted via the casualty department complaining of diplopia, which had come on gradually over the preceding day. She had no other neurologic deficit and a diagnosis of a left sixth nerve palsy was made. This underwent gradual, complete recovery over 6 months. CaseB A 46- year- old woman had been suffering from low back pain and right- sided sciatica for 12 years. Myelography was performed at the L2- 3 level with 10 ml of Niopam 300. Soon afterward, she suffered severe global headache followed by an episode of vomiting. She first noticed diplopia 12 days later. A right sixth nerve palsy was diagnosed, which completely resolved over 4 months. Case C A 41- year- old woman presented with a 6- year history of episodic low back pain with right- sided sciatica. She had an absent right ankle reflex. A myelogram was performed by lumbar injection of 10 ml Niopam 300. This proceeded satisfactorily and a possible disc prolapse at L5- S1 was noted. She suffered a mild headache after the myelogram but was sufficiently well to be discharged the next day. However, she developed diplopia on left gaze 7 days later and consulted her doctor some 6 days after that, as the diplopia appeared to be worsening. A diagnosis of a partial left sixth nerve palsy was made, but she was not seen in the Eye Department until some 3 weeks after the myelogram. At that time, a left sixth nerve palsy was confirmed. She had no other neurologic deficit, and over a 3- month period she made a complete recovery. CaseD A 33- year- old woman complained of low back pain, which radiated down to her left ankle following trauma 2 years previously. Examination was normal. Myelography was performed with 10 ml Niopam 300 injected via lumbar puncture. The myelogram proceeded uneventfully and was subsequently found to be normal. The patient complained of severe headache and nausea within a few hours of the investigation and the next morning developed pain behind both eyes, A few hours later she noticed progressive double vision, and on examination was found to have an isolated left ab-ducens nerve palsy. This was treated with oral dexamethasone 2 mg four times daily and diaze- / Neuro- OphtMmol, Vol 14, No. 4, 1994 IATROGENIC LATERAL RECTUS PALSY 207 pam 5 mg twice daily for 3 days. By 2 weeks later the lateral rectus weakness had completely resolved. Case E A 47- year- old woman underwent a microdiscec-tomy at the L- 5 level, but after a few weeks her symptoms returned. A lumbar myelogram was carried out with 10 ml Niopam 300. This showed a minor central disc protrusion at the L4- 5 level but no other abnormality. No symptoms attributable to the myelogram were recorded at this time. Two years later, a repeat myelogram was performed. Again she had no significant immediate postpuncture symptoms, but 5 days later she noticed slight double vision. She attended the Eye Department 5 weeks later, at which time a partial left lateral rectus weakness was noted; this had completely resolved 3 months after the myelogram. She had no other neurologic findings. DISCUSSION This is the first series to document lateral rectus palsies following the use of Iopamidol in contrast myelography, although individual cases have been described from this group as it was assembled ( 1- 3). An extensive search failed to reveal reports of similar complications with Iopamidol. Isolated abducens nerve palsies are rare and may be harbingers of serious intracranial disease or a nonspecific indicator of raised intracranial pressure. They have little localizing value, although in a series of 90 tumors involving the sixth nerve, 80 were infratentorial ( 4). The most common reported causes of sixth nerve palsies include trauma, neoplasms, and vascular accidents. However, the single most common category is idiopathic; despite the advent of computed tomography this seems to have changed little over the years- 30% in 1958 ( 5), very close to the 32% found in a similar study ( 6) in 1981. Procedures involving lumbar puncture are unusual causes of lateral rectus palsy: in a series of 409 patients with an abducens palsy, 1 case ( 0.23%) was found ( 5), and in another study of 515 lateral rectus palsies, again only 1 case ( 0.19%) was found to follow lumbar puncture ( 4). In a later study Rush and colleagues ( 6) found the incidence of abducens palsy following lumbar puncture or myelography to be more than four times as high, and in a series limited to adults under 50 years of age, an incidence of 4% of all cases of lateral rectus palsy was attributed to procedures involving lumbar puncture ( 6). Either procedures involving lumbar punctures are increasing as a cause of lateral rectus palsy or their importance is more often recognized. The incidence of abducens nerve palsies following procedures that involve breaching the theca is uncertain. The most authoritative account is that of Thorsen ( 8), who collected a large number of patients from his own practice and from the literature. Of 324 patients with cranial nerve palsies following diagnostic lumbar puncture or spinal anaesthetic, 299 had sixth nerve involvement alone. He estimated that the incidence of cranial nerve palsies following spinal anesthesia was 1 in 400. It is difficult to estimate the incidence of lateral rectus palsies associated with myelograms using Iopamidol. This study has been entirely retrospective and was first instigated as a result of an audit of orthoptic records. A careful trawl of that record suggests an incidence of at least 1 in 500. It seems likely that many similar events are missed. As the symptoms described typically occur around the tenth day ( 9), it is possible that patients who develop lateral rectus palsies or similar subtotal lesions are coping on their own, being treated by their family doctor or being managed at other eye units. The etiology of the association between procedures involving lumbar puncture and sixth nerve palsies is uncertain. The postpuncture triad of headache, auditory manifestations, and ocular symptoms has been called the syndrome of decreased intracranial pressure ( 10). As a result of dural sheath puncture, a gradual cerebrospinal fluid leak, producing a volume deficit, a progressive caudal shift of the brain, and traction on its supporting structures is experienced as headache. As the cerebrospinal fluid cushion to the brain leaks away, a compensatory dilatation in the cerebral veins leads to a secondary increase in brain volume, thereby reinforcing the tendency of the brain to shift caudally ( 8). Collier ( 11) thought that a shift backward of the brainstem is responsible for cranial nerve palsies, and the nerves most likely to be affected are those that are most frontocaudal in direction. Thus the sixth and the third cranial nerves, followed by the seventh and the eighth, might be expected to be the most commonly affected. Most of the cranial nerves can be affected, but by far the most common is the sixth ( 8). Combinations of nerve palsies may occur and total unilateral ophthalmoplegia has been reported in association with spinal anesthesia ( 12). / Neuro- Ophthalmol, Vol. 14, No. 4, 1994 208 J. A. BELL ET AL One explanation of the particular liability of the sixth nerve to palsy may lie in its anatomy. Its course within the subarachnoid space renders it more susceptible to damage than other cranial nerves. From its emergence from the lower border of the pons, the nerve runs steeply upward between pons and clivus. It is crossed by branches of the basilar artery, most of which lie between the clivus and the nerve, although some lie between pons and nerve. Occasionally, the nerve is penetrated by the anterior inferior cerebellar artery. The nerve breaks through the dura while still on the clivus, and, at the sharp rim of the pyramidal apex, it turns almost at a right angle in a horizontal and sagittal direction, entering the cavernous sinus ( 13). As a result of increased intracranial pressure, and, thus, downward shift of the brain, the anterior inferior cerebellar artery may press on and groove the nerve ( 14). Similar pressure may be produced by the inferior auditory artery, and stretching at the sharp bony petrous temporal bony ridge may entirely, or in part, contribute to nerve paresis ( 15). Bilateral lateral rectus palsy can be seen following myelography. Miller and coworkers ( 16) reported three cases following myelograms with water- soluble contrast medium, and Seyfert and Mager ( 9) included one case in their series of five. However, all the cases in this report are unilateral, and in the literature in general there is an overwhelming incidence of unilateral involvement. This may be due to anatomic asymmetry. It is well known that the petrous bones may be asymmetrical, and, in other conditions, such as trigeminal neuralgia, this has been postulated as an explanation for unilaterality ( 9). It may be that the diagnostic procedure hastens the progress of already existing pathology, Fincham and associates ( 17) reported the progress of neurologic symptoms in four patients after myelograms, and attributed their symptoms to an interruption in the vascular supply, which was in a tenuous or submarginal state. Such a mechanism could apply to all the patients in this study who had neurologic symptoms ( and therefore presumably pathology) from 2 to 12 years with an average duration of 6.4 years prior to myelography. The contrast medium Iopamidol is a highly water- soluble, iodinated, monomeric, nonionic, low osmolar material used in a variety of radiologic procedures ( 18). Side effects, such as headache and nausea, are common but transient ( 19). More serious side effects, including aseptic meningitis ( 20,21) and optic neuritis ( 22), are far less common. Accidental injection into the spinal cord, causing hemorrhagic necrosis of the gray matter, which contributed to death, has been reported ( 23). Iopamidol has a significant neurotoxicity ( 24), which can cause changes in visually evoked responses ( VER) ( 25,26), and significant electroen-cephalographic changes ( 27- 29). It can also induce more subtle neurophysiologic changes, such as deterioration in memory function ( 30). Mechanisms that influence neurotoxicity are poorly understood but include binding of proteins, effects on cell memebranes, blocking of enzymes, or a combination of all of these ( 31). The frequency of cerebral side effects is related to the amount of contrast medium coming into contact with the cerebral cortex ( 32,33). A direct neurotoxic effect on the abducens nucleus has been suggested to account for lateral rectus palsy after spinal anesthesia ( 34). This seems unlikely, as the closely related facial nucleus has not been implicated in any case in this series and there has been no associated gaze palsy. It is possible that the etiology of the palsies in most of the patients in this series lies in a partial physiologic compromise of the sixth nerve in its subarachnoid portion, secondary to the neurotoxic effects of Iopamidol. 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