We report a case of central paraplegia persisting for 3 yr after single-dose intrathecal administration of 400 μg of morphine. Typical causes of such neurological dysfunction do not adequately account for this clinical circumstance.1–11 However, hemiplegic migraine was present when the patient emerged from anesthesia.
Hemiplegic migraine is a disorder associated with reversible vascular impairment of the central nervous system.12 For example, transient spastic motor dysfunction has been reported after a noninjurious interval of spinal cord ischemia in humans and laboratory animals.13,14 We hypothesize that spinal morphine induced a permanent central motor deficit, facilitated by spinal cord vascular dysfunction associated with hemiplegic migraine.
A 29-yr-old woman, height 163 cm, weight 56 kg, underwent rectosigmoid resection and right ovariectomy for deep infiltrating endometriosis. No preoperative functional limitation was recorded. Her preoperative medical examination was unremarkable. Premedication consisted of oral hydroxyzine 100 mg, 120 min before anesthesia. Spinal morphine was administered preoperatively. With the patient in the sitting position and not sedated, the lumbar area was disinfected with a solution of 10% povidone-iodine (Betadine, Viatris Manufacturing, Merignac, France). After removing excess moisture from the disinfected site, spinal puncture was performed at the L3-4 interspace, using a 27-gauge pencil-point-tip needle (B. Braun, Melsungen, Germany). Clear cerebrospinal fluid was observed and aspirated before and after injecting preservative-free morphine 400 μg. Preservative-free morphine sulfate (Lavoisier Laboratory, Paris, France) was provided in an ampoule containing morphine 1 mg, which was further diluted in 0.9% saline 10 mL, before spinal administration. A disposable set, provided in a sealed pack, was used for perineural drug administration (Mediset, Hartman Laboratory, Selestat, France). There was no pain or paresthesia during placement of the needle or drug injection. Standard intraoperative monitoring was used. Surgery was conducted under general anesthesia using propofol, remifentanil, sevoflurane, and atracurium. Throughout the operation, the patient was positioned supine on a vacuum mattress (Vacuform, Schmidt GmbH, Garbsen, Germany) filled with pellets and molded to the patient. The legs were raised 15°. Surgery and the intraoperative anesthetic course were uneventful and lasted for 300 min.
After recovering her alertness, the patient reported inability to move her lower limbs and paresis of the left upper limb. She appeared oriented, with intact speech and intellectual function. Neurological examination disclosed a loss of sensation to light touch and pinprick up to a T11 level on the right side and limited to the inner side of the left knee and leg. Flexion of the left forearm was impossible together with all left hand movements. Bilateral paraplegia, including inability to lift both thighs and to move both legs and both feet, was noted. The plantar reflex was flexion on both sides. Anal sphincter tone was decreased. Reflexes in the knee and ankle joints were bilaterally brisk compared with joint reflexes recorded in the upper limbs, which looked normal. Voiding could not be investigated because a catheter was placed in the bladder.
Cerebral, cervical, thoracolumbar, and sacrococcygeal magnetic resonance imaging (MRI) revealed no abnormalities and excluded acute brain and spinal cord compression or injury. On the first postoperative day, upper left limb motility recovered. On the fifth postoperative day, lower limb sensation had recovered except for saddle anesthesia of the perineum. The patient could move her left foot and lift both thighs. Electromyography, obtained 1 mo, 6 mo, and 1 yr postoperatively, did not show any degree of denervation in the territories of impaired muscles. Six months postoperatively, the patient could not spontaneously void and used a walking aid because of persisting weakness in the left quadriceps. Anal sphincter tone was restored. On the third year assessment, walking was limited to 500 m because of weakness in the left quadriceps, the strength of which was quoted 3 on a 0–5 scale. Lower limb reflexes were bilaterally brisk. Saddle anesthesia of the perineum persisted together with urinary retention requiring intermittent self-catheterization. Urodynamic measurement recorded phasic neurogenic detrusor overactivity during bladder filling showing the central origin of this neurogenic bladder dysfunction.15 MRI examinations performed after 8 days, 6 mo, and 1, 2, and 3 yr were found to be normal.
Over the 3 postoperative years, the patient was admitted 5 times to a neurological unit because of acute headache associated with complete left-sided hemiplegia and had therefore several complete additional neurological, otological, ophthalmological, and MRI examinations. Antiinflammatory drug administration was associated with a 24-h recovery. No cause was documented. A posteriori, the patient reported repeated episodes of migraine headaches since adolescence, which had not been reported on preoperative assessment. Neurologists concluded that hemiplegic migraine was the most likely diagnosis of these recurrent attacks.12
We report lower limb sensory-motor deficit and severe bladder dysfunction of central origin, persisting up to 3 yr after single-dose spinal morphine administration.15 Potentially, single spinal morphine administration could be the sole cause of early central neurological deficit. We excluded other potential causes of neurological injuries.1–11 An extended polyradiculoneuritis is a peripheral disorder not consistent with the acute onset and the preservation of all joint reflexes.1 The improper placement of retractors has caused sciatic and femoral neuropathies but cannot account for this extended central neurological impairment.2 The patient had not received any radiation therapy, which is a potential cause of neurological injury.3 Cerebrospinal fluid bleeding or spinal cord compression by an expanding hematoma was excluded in this case by early MRI.4 The patient remained hemodynamically stable.5,6 Aortic clamping was not used.6 Extreme positioning, which may lead to compression of a radicular artery or to increased intraspinal venous pressure and decreased spinal cord perfusion, was prevented by the vacuum mattress.4,5 In 15% of cases, spinal vascularization is provided by iliac arteries.6 However, the surgical approach did not compromise the iliac vascularization. Vasoconstrictors, which may theoretically produce local cord ischemia in patients with microvascular disease, were not used.7 The routine use of disposable syringes and needles and of heat-sterilized local anesthetics eliminated the risk of chemically induced neurological injury.8 Arachnoiditis is a delayed inflammatory response after epidural steroids, blood in the cerebrospinal fluid, trauma, and spinal surgery.9 Coincident postoperative exacerbation of a preexisting neurological disease would have appeared on delayed MRI.10
We hypothesize that spinal morphine induced a central motor deficit, facilitated by spinal cord vascular dysfunction associated with hemiplegic migraine.12 Morphine-induced motor dysfunction has been reported after spinal ischemia in humans and laboratory animals.13,14 Hemiparesis has resulted from spasm of the anterior and middle cerebral artery, which was exacerbated by IV morphine and reversed by naloxone.13,14 In a rat model, neuraxial morphine administration was associated with transient motor dysfunction after a noninjurious interval of spinal ischemia.14
Migraine is an independent risk factor for vascular dysfunction of the central nervous system including ischemic stroke in women younger than 45 yr.12 Local changes in cerebral vessels during attacks including reduced oligemia, activation of the clotting system, vasoconstriction mediated by neural and endothelial alteration lead to vessel embolism, thrombosis, and ischemia.12 Initiation of hemiplegic migraine attack by anesthesia and surgery was reported.16 It is possible that operative stress caused an early postoperative hemiplegic migraine attack associated with vascular dysfunction of the central nervous system resulting in spinal morphine neurotoxicity. Ischemic injury to the spinal cord, including bladder impairment without MRI abnormalities, has been documented.17,18 In one case study, MRI performed soon after and later after the onset of bladder dysfunction of central origin was normal.17 Minor histopathologic changes were observed in the ventral horn of animals subjected to spinal cord ischemia and injected with intrathecal morphine.14 Such limited tissue alteration is likely to be undetected by MRI.18 In view of the frequent prevalence of migraine, further publication of similar unresolved clinical findings is necessary to confirm our hypothesized mechanism of neurodeficits in this patient.
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