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CASE REPORT
Year : 2021  |  Volume : 69  |  Issue : 6  |  Page : 1785-1788

Chronic Pregabalin Abuse with Subacute Encephalopathy Mimicking Autoimmune Encephalitis


Department of Clinical Neurosciences, Division of Neurology, BRAINS – Brain Spine Centre, #146, Infantry Road, Bangalore, Karnataka, India

Date of Submission09-May-2018
Date of Decision11-Jun-2020
Date of Acceptance15-Feb-2021
Date of Web Publication23-Dec-2021

Correspondence Address:
Dr. Kamble Jayaprakash Harsha
Department of Clinical Neurosciences, Division of Neurology, BRAINS – Brain Spine Centre, #146, Infantry Road, Bangalore - 570 001, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.333486

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 » Abstract 


Pregabalin, a gabapentinoid frequently prescribed for neuropathic pain, also increasingly identified as a drug for abuse. We describe a unique case of 31-year-old man presented with subacute neuro-psychiatric symptoms and a spectrum of movement disorders, suspicious of autoimmune encephalitis. Initial response to IV methylprednisolone followed by recurrence of symptoms strengthened our suspicion for autoimmune encephalitis. His autoimmune encephalitis workup was negative, however, his two MRIs showed parenchymal changes. The patient, finally, confessed to chronic pregabalin abuse. He recovered completely upon stopping pregabalin abuse and remained asymptomatic at follow-up. To the best of our knowledge, we are the first to describe parenchymal changes in MRI mimicking autoimmune encephalitis in a case of pregabalin abuse. Despite the limited number of reports of pregabalin abuse in India, it is time to consider restricting the pregabalin availability, in line with many Western countries. This is particularly relevant to India, where, one legitimate prescription can be used by many to buy medicines at multiple stores without any questions being asked by the pharmacists.


Keywords: Abuse, autoimmune encephalitis, movement disorders, pregabalin, toxicity
Key Messages: Subacute pregabalin toxicity can mimic autoimmune encephalitis.


How to cite this article:
Harsha KJ, Joshy E V, Aravinda RV, Poornima R. Chronic Pregabalin Abuse with Subacute Encephalopathy Mimicking Autoimmune Encephalitis. Neurol India 2021;69:1785-8

How to cite this URL:
Harsha KJ, Joshy E V, Aravinda RV, Poornima R. Chronic Pregabalin Abuse with Subacute Encephalopathy Mimicking Autoimmune Encephalitis. Neurol India [serial online] 2021 [cited 2022 Jan 18];69:1785-8. Available from: https://www.neurologyindia.com/text.asp?2021/69/6/1785/333486




Pregabalin is a gabapentinoid increasingly prescribed for many painful conditions and anxiolysis. Pregabalin toxicity due to acutely consuming large quantities results in reduced consciousness, myoclonic encephalopathy. Pregabalin abuse due to consumption of supratherapeutic dose over months to years leads to self-injury and somnolence. The abuse potential of pregabalin is increasingly identified particularly in western countries, where the drug is listed either for restricted use or in the process of restricting its use. The extent of pregabalin abuse in India is not clear due to lack of high-quality data; however, three previous case reports along with our case report, all reported during 2013 to 2018 indicate increasing pregabalin abuse in India. We report a unique case of chronic pregabalin abuse with subacute neuro-psychiatric symptoms mimicking autoimmune encephalitis.


 » Case History Top


A 31-year-old gentleman, right handed, a PhD scholar as well part-time employee at a start-up company, presented with the history of the involuntary dropping of objects from the hand of two years duration, bizarre behavioral changes of three months duration, intermittent winking of the right eye and abnormal oro-facial movements of three months duration. He also gave a history of abnormal rapid jerky involuntary movements of both hands (R > L). He had unsteady gait with fall tendency to either side of one-month duration. His wife also noticed frequent dropping of objects from his hand during last two years associated with sudden jerky transient movements of the hand.

He has psoriasis since childhood, for which he is not on any medications currently. He also gave a history of recurrent oral ulcers in childhood, had long-term remission, and however recurred with above neurological symptoms. He is a smoker, alcoholic, consumes marijuana occasionally, uncontrolled over-eating. Even on repeated enquiry, he denied any other substance abuse. Personal history is significant for the failure of a previous love affair, erectile dysfunction, and depression. His father also has a history of recurrent oral ulcers and previously had epilepsy His wife was diagnosed with SLE and APLA syndrome.

He had consulted many physicians; was diagnosed previously as a psychiatric disorder and started on SSRI and antipsychotics. He underwent MRI during his previous consultation, reported as normal. He came to our hospital seeking the second opinion. His parents showed several recorded videos during the course of this new onset illness, which revealed different kinds of abnormal movements in him. During the examination, several myoclonic jerky movements witnessed involving both upper and lower limbs, as well oro-facial muscles. He was profusely sweating during all his visits to outpatient department, throughout in-patient period. He had bilateral gaze-evoked nystagmus (L > R), impaired tandem gait, generalized brisk deep tendon reflexes. His previous MR imaging reviewed, which showed subtle T2/FLAIR hyperintensities of right cerebellar white matter, right cingulate gyrus, left posterior limb of internal capsule [Figure 1]. He was satisfying the diagnostic criteria for possible autoimmune encephalitis (subacute onset of altered mental status/psychiatric symptoms, MRI features suggestive of encephalitis and reasonable exclusion of alternative causes[1]). In view of the history of psoriasis and recurrent oral ulcers, family history of recurrent oral ulcers, autoimmune encephalitis was first among the differential diagnoses.
Figure 1: Initial cerebral Magnetic Resonance Imaging (MRI). (a and b) Axial FLAIR image showing subtle hyperintensity in right cerebellar white matter, corresponding negative image depicting abnormality better. (c and d) Axial FLAIR image showing abnormal hyperintensity in right cingulated gyrus (circle) and left posterior limb of internal capsule (left arrow), corresponding negative image depicting abnormality better

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He was advised admission and detailed evaluation including repeat MRI during his first visit. Though he was admitted to the hospital, immediately after reaching ward he reported paranoid ideas and absconded from the hospital on the same day. He was advised 1 gram of methylprednisolone IV injection for 5 days. His parents were able to convince the patient to carry out the injectable treatment, to which he was highly reluctant but could not avoid parents' request.

After the fifth dose of IV methylprednisolone, his symptoms reduced significantly, hence his parents convinced him to seek medical attention promptly. Excellent response to steroids strengthened our suspicion for autoimmune encephalitis in him. He was admitted to hospital for the second time, underwent extensive autoimmune workup (blood and CSF studies), repeat high-resolution MRI. The follow-up MRI did at an interval of 2 weeks showed subtle T2/FLAIR hyperintensity involving left cerebellar hemisphere white matter, left middle cerebellar peduncle, left parieto-occipital white matter [Figure 2], left thalamus. After discharge from the hospital, he had a recurrence with worsening of symptoms, frequent falls, became severely disabled and not able to carry out his daily activities. He revisited outpatient department, and was clinically diagnosed as paroxysmal kinesiogenic dyskinesia. Sodium valproate was started with reasonable improvement in symptoms. While awaiting blood, CSF reports, and PET scan, he finally admitted to consuming 30 tablets of 75 mg pregabalin daily (total dose of 2,250 mg/day) since last 2 years. He claims to feel 'psychedelic effects' (he revealed that he had gathered information about the pregabalin drug on internet), 'high' while on medication, makes him calm, and can slip to sleep easily during the night. He claims no such neuropsychological symptoms since he started pregabalin abuse. His all blood and CSF investigations, PET-CT and EEG were normal. Serum pregabalin levels were not done. He stopped pregabalin abuse abruptly and was observed in the hospital for three days during which time he was completely asymptomatic. He and his family members underwent several sessions of counselling. During one-month follow-up, he had successfully abstained from the drug abuse and remained asymptomatic.
Figure 2: Follow up cerebral MRI. (a and b). Axial FLAIR image showing subtle hyperintensity involving left cerebellar hemisphere and middle cerebellar peduncle, corresponding negative image depicting abnormality better. (c and d) Axial FLAIR image showing subtle hyperintensity involving left temporo-occipital lobe cortex and white matter, corresponding negative image depicting abnormality better

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 » Discussion Top


Pregabalin is a drug approved for many disabling long-term conditions like epilepsy, post-herpetic neuralgia, fibromyalgia, neuropathic pain, diabetic neuropathy, and generalized anxiety disorder. Acute pregabalin toxicity/acute self-poisoning is a clinical syndrome secondary to consumption of the supratherapeutic dose of pregabalin in short duration. The dosage for acute pregabalin toxicity described in the literature varies from 600mg[2] to 11.5 g.[3] Chronic pregabalin toxicity/pregabalin abuse is due to un-indicated long-term consumption of the therapeutic/supratherapeutic dose of pregabalin.

Pregabalin has a relatively simple pharmacokinetic profile, rapidly and extensively absorbed with the oral bioavailability of more than 90%, is not bound to plasma protein, undergoes negligible metabolism, excreted primarily by renal excretion. While acute pregabalin accumulation reported in renal failure patients,[4] its accumulation in healthy adults not reported.[5] We describe a case of chronic pregabalin abuse since two years, developing neuro-psychiatric syndrome due to subacute (3 months duration) toxicity. To the best of our knowledge, we are first to describe changes in brain parenchyma in MR imaging, mimicking autoimmune encephalitis. Myoclonic encephalopathy secondary to pregabalin toxicity is previously described; however, we describe a case with varied abnormal movement disorders, which include – tremor, asterixis, tics, fasciculations, dyskinesia, choreoathetosis, ataxia. The subacute (3 months) onset of neuro-psychiatric symptoms in our patient who used to abuse the same dosage of the drug since 2 years remains elusive.

A systematic review by Schjerning O, et al., in 2016 described nine cases of pregabalin abuse consuming supra-therapeutic dosage, with the mean age of 34 years (age range 19-47 years), most were diagnosed with psychiatric disease.[6] Pregabalin also found to be a co-abuse substance along with other abusive drugs, particularly heroin.

Concern for abuse/misuse of pregabalin rose due to a recently increased prescription of pregabalin.[7],[8] The United States of America (USA) and the United Kingdom (UK) have identified the problem of pregabalin abuse and taking appropriate step to control its misuse. The United States Drug Enforcement Administration (DEA) placed pregabalin and all products containing pregabalin into Schedule V of the Controlled Substances Act in 2005. Both Pregabalin and gabapentin misuse are increasingly being reported in the UK, which has led to the proposal by Advisory Council on the Misuse of Drugs (ACMD) to classify these drugs as Class C drugs (i.e., controlled drugs). Similar trends reported from other countries like Germany, Finland, and USA. Realizing the abuse potential and increasing reports of the misuse of the drug, pregabalin was agenda Item 5.1 in thirty-ninth meeting of WHO Expert Committee on Drug Dependence in November 2017. Ojanpera I, et al., noted clearly increasing trend in fatal toxicity index (FTI) with pregabalin in Finland, they also identified pregabalin as emerging drug of abuse.[9]

There are only three cases of pregabalin misuse/abuse reported from India so far [Table 1]. The prevalence of pregabalin abuse is probably undermined. Low level of suspicion among neurologists/psychiatrists/emergency physicians could be one of the contributory factors for non-detection of pregabalin toxicity/abuse. Even with a limited number of reports of increasing abuse of pregabalin, the Drug Controller General of India (DGCI) should consider restricting the availability of this medicine to reduce misuse. This is increasingly relevant to India, as one legitimate prescription can be used by many to buy medicines at multiple stores on the same day without any questions being asked by the issuing pharmacists. An alternative suggestion would be to stamp “drugs delivered” on the prescription by pharmacists, so that same prescription cannot be misused.[10],[11],[12]
Table 1: Case reports of pregabalin toxicity in India

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Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initial s will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 » References Top

1.
Graus F, Titulaer MJ, Balu R, Benseler S, Bien CG, Cellucci T, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 2016;15:391-404.  Back to cited text no. 1
    
2.
Wood DM, Berry DJ, Glover G, Eastwood J, Dargan PI. Significant pregabalin toxicity managed with supportive care alone. J Med Toxicol 2010;6:435-7.  Back to cited text no. 2
    
3.
Braga AJ, Chidley K. Self-poisoning with lamotrigine and pregabalin. Anaesthesia 2007;62:524-7.  Back to cited text no. 3
    
4.
Courtois F, Borrey D, Haufroid V, Hantson P. Pregabalin-associated myoclonic encephalopathy without evidence of drug accumulation in a patient with acute renal failure. Indian J Nephrol 2014;24:48-50.  Back to cited text no. 4
[PUBMED]  [Full text]  
5.
Toth C. Pregabalin: Latest safety evidence and clinical implications for the management of neuropathic pain. Ther Adv Drug Saf 2014;5:38-56.  Back to cited text no. 5
    
6.
Schjerning O, Rosenzweig M, Pottegård A, Damkier P, Nielsen J. Abuse potential of pregabalin: A systematic review. CNS Drugs 2016;30:9-25.  Back to cited text no. 6
    
7.
Goodman CW, Brett AS. Gabapentin and pregabalin for pain-Is increased prescribing a cause for concern? N Engl J Med 2017;377:411-4.  Back to cited text no. 7
    
8.
Evoy KE, Morrison MD, Saklad SR. Abuse and misuse of pregabalin and gabapentin. Drugs 2017;77:403-26.  Back to cited text no. 8
    
9.
Ojanperä I, Kriikku P, Vuori E. Fatal toxicity index of medicinal drugs based on a comprehensive toxicology database. Int J Legal Med 2016;130:1209-16.  Back to cited text no. 9
    
10.
Tandon VR, Mahajan V, Gillani ZH, Mahajan A. Pregabalin-induced self-harm behavior. Indian J Pharmacol 2013;45:638-9.  Back to cited text no. 10
[PUBMED]  [Full text]  
11.
Ashwini S, Amit DR, Ivan NS, Alka PV. Pregabalin dependence with pregabalin induced intentional self-harm behavior: A case report. Indian J Psychiatry 2015;57:110-1.  Back to cited text no. 11
[PUBMED]  [Full text]  
12.
Parekh M, Dash GK, Ahamed I. Pregabalin toxicity manifesting as reversible encephalopathy with continuous triphasic waves in electroencephalogram. Clin Neuropharmacol 2017;40:226-8.  Back to cited text no. 12
    


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