Journal of Addiction & Addictive Disorders Category: Clinical Type: Case Report
Restoration of Consciousness with Zolpidem in a Patient with Sporadic Creutzfeldt - Jakob Disease (sCJD)
- Roshan Sutar1*, Abhinav Nahar1, Seby Seby Kurthukulangara1, Ravinder Jeet Singh Sidhu2, Harish T1, Jitender Saini3, Ravi Yadav4, Santosh Chaturvedi1
- 1 Department Of Psychiatry, National Institute Of Mental Health And Neurosciences, Bangalore, India
- 2 Department Of Neurology, National Institute Of Mental Health And Neurosciences, Bangalore, India
- 3 Department Of Neuroradiology, National Institute Of Mental Health And Neurosciences, Bangalore, India
- 4 Department Of Neurology, National Institute Of Mental Health And Neurosciences, , Bangalore, India
*Corresponding Author:Roshan Sutar
Department Of Psychiatry, National Institute Of Mental Health And Neurosciences, Bangalore, India
Received Date: Jun 13, 2016 Accepted Date: Aug 24, 2016 Published Date: Sep 08, 2016
On examination she was awake and was opening eyes spontaneously with no verbal output. She was not obeying simple commands but would localize pain. She had severe rigidity of all limbs (lower limbs slightly more than upper limbs), intermittent myoclonic jerks which were not stimulus sensitive, and brisk deep tendon reflexes with bilaterally extensor plantar reflex. Grasp reflexes were present bilaterally.
Investigations including CBC, metabolic panel, thyroid profile and serum B12 levels were normal. TPO antibody, autoimmune encephalitis workup for antibodies against NMDA, AMPA 1 and 2, VGKC (LGI-1 and CASPR), GABA 1 and 2, and autoimmune panel for vasculitis were negative. MRI Brain (Figure 1) showed cortical ribbon sign with bilateral involvement of caudate and putamen, which was highly suggestive of prion disease like CJD. EEG showed frequent bilateral periodic triphasic discharges with diffuse slowing of background activity. Patient met diagnostic criteria for probable CJD by World Health Organization (Figure 2).
Figure 1: MRI brain picture showing cortical ribbon sign and bilateral involvement of caudate and putamen in our patient with sporadic Creutzfeldt - Jakob disease.
Patient had not responded earlier to trials of L-dopa, donepezil, memantine, amantadine and a course of methyl prednisolone. Care givers reported earlier noticing a marked improvement in her responsiveness when she was given tablet zolpidem for insomnia for two nights. Based on this history, a trial of immediate release tablet zolpidem 5 mg HS was started. Response was noticed 7 hours after the first dose in the form of patient spontaneously getting up from the bed, attempting to walk with assistance and taking food orally by self-removal of nasogastric tube. She also started initiating verbal communication with care givers. This response was maintained on regular dosing of zolpidem 5 mg BD without any noticeable side effects. There was no further requirement of nasogastric tube feeding. She was shortly discharged with advice to continue Tab zolpidem 5 mg BD. She did not come for follow up. A telephonic enquiry 3 months later revealed that, after a few days of sustained improvement, she again progressively deteriorated to a vegetative state despite taking zolpidem, which was then discontinued.
Zolpidem preferentially acts on omega 1-GABA-A receptors within the GABA receptor - chloride channel complex. Arousal appears to be specific to zolpidem unlike other non - specific benzodiazepines due to possible differential receptor affinity, but exact mechanism is still unclear. One hypothesis is that reduced arousal in patients following brain disease leads to alteration in the number of GABA receptors as a mechanism of neuroprotection. Zolpidem appears to reverse it by reactivation of dormant brain neural networks. Another hypothesis claims that zolpidem may activate limbic loops modulating motivational processes thus leading to disinhibition and thalamocortical overactivity . Paradoxical restoration of consciousness by CNS depressants is thought to be by functional restoration of certain networks like reticular activating system, cortico - cortical loop and cortico - thalamo-cortical loop as suggested by functional neuroimaging studies [3,6,7]. However, not all patients with disorders of consciousness respond to zolpidem as noted in a placebo controlled trial .
In conclusion, zolpidem appears to have a role in improving consciousness in some patients with disorders of consciousness such as CJD. Though response is likely to be only for a short period, the very fact that improvement albeit transient is possible, in rapidly progressive neurodegenerative diseases otherwise deemed to be irreversible, merits further studies which may also further our understanding of neurobiology of consciousness .
We thank to Department of Neurology, Neuro-radiology and Consultation liaison psychiatry for assistance in writing this report.
CONFLICT OF INTEREST
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Citation: Sutar R, Nahar A, Kurthukulangara S, Sidhu RJS, Harish T, et al. (2016) Restoration of Consciousness with Zolpidem in a Patient with Sporadic Creutzfeldt - Jakob disease (sCJD). J Addict Addictv Disord 3: 010.
Copyright: © 2016 Roshan Sutar, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.