Title : Vertiginous giddiness and upbeat nystagmus in pregabalin treatment
Abstract:
Pregabalin has been recommended as a first-line treatment for neuropathic pain, such as diabetic peripheral neuropathy, post-herpetic neuralgia, spinal cord injury, and radiculopathies. Experience and studies have shown that pregabalin is well tolerated for the management of neuropathic pain. The most commonly noted adverse effects of pregabalin include sedation, dizziness, peripheral edema and dry mouth. Oculomotor manifestations associated with pregabalin have rarely been reported. Positional upbeat nystagmus caused by pregabalin has not been reported. Herein, I report a case of patient who developed vertiginous giddiness and upbeat nystagmus during treatment with pregabalin.
Case Report: A 36-year-old female patient with medical history of asthma, hepatic steatosis, left knee osteochondral defect of femoral condyle and recent lumbar intervertebral disc surgeries was admitted to my department for inpatient rehabilitation and pain management. She presented to orthopedic surgery with left foot numbness and foot drop 5 months prior to this admission. Lumbar spine magnetic resonance image showed large diffuse disc bulge at L4-L5 causing severe narrowing of the spinal canal and lateral recesses with crowding of the cauda equina (Fig 1). She underwent left L4/5 posterior decompression. Her left foot numbness and foot drop were improved after surgery. However, she developed right lower limb radiating pain and numbness 2 months later from the first spine surgery. She underwent L4 to L5 posterior decompression and discectomy. She still complained of severe low back pain and right lower limb radiating even after the second spine surgery. She had been treated with pregabalin 150-150mg daily since the second spine surgery. Pregabalin dose was increased 150-50-150mg daily by pain team 20 days prior to this admission to optimize pain control. She had been taken tramadol 50-50-50mg daily and oxycodone 5mg with naloxone 2.5mg daily as well. She complained of severe vertiginous giddiness during turning her head to left and getting up from bed on the day of admission. Bilateral severe upbeat nystagmus was noted during roll test with 2 seconds of latency. Upbeat nystagmus was also noted on left side-lying test with 3 seconds of latency. Both side Dix-Hallpike test induced vertigo. The laboratory tests were unremarkable. Brain magnetic resonance image was normal as well. On suspicion of adverse effect of pregabalin, dose of pregabalin was reduced to 150-150mg daily. Vertiginous giddiness and upbeat nystagmus were resolved within 2 days of reducing pregabalin dose.
Discussion: There have been some case reports of vestibulocerebellar dysfunction with pregabalin. Two cases were reported for downbeat nystagmus related pregabalin and pregabalin dosage range in the cases was 150mg daily to 300mg daily. One case was reported for positive horizontal head impulse test and pregabalin dosage was 150-150-150mg.
The mechanisms of pregabalin related vestibulocerebellar disorder are not yet well understood. The pharmacological studies in rat model suggested that pregabalin binds to the α2 δ-1 and α2 δ-2 subunit of voltage-gated calcium channels, which are expressed in the brain and spinal cord. It is known that α2 δ-1 is present in cerebral cortex, hippocampus and cerebellum, and α2 δ-2 is concentrated in the cerebellum. Decreased excitatory inputs from brain, especially cerebellum by pregabalin may result in functional disturbance of the cerebellum. In addition, one animal study with albino rat showed acute and chronic pregabalin intoxication caused dystrophic changes in cerebral cortes and cerebellum.
Adverse effects of pregabalin have shown dose-response relationship. The total daily dose of pregabalin in this case during adverse effects was 350mg which was lower than the usual recommended maximum daily dose for neuropathy, 600mg. However, there are large interindividual differences in pregabalin-induced toxicity.
Conclusion: This case demonstrates that pregabalin can induce vestibulocerebellar symptoms. Clinician should be aware that vestibulocerebellar adverse effects may occur with the usual dose of pregabalin and proper neurologic or vestibular evaluation is necessary to rule out other possible causes of symptoms and signs.
