Neurology India
menu-bar5 Open access journal indexed with Index Medicus
  Users online: 289  
 Home | Login 
About Editorial board Articlesmenu-bullet NSI Publicationsmenu-bullet Search Instructions Online Submission Subscribe Videos Etcetera Contact
  Navigate Here 
 Resource Links
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
    Article in PDF (489 KB)
    Citation Manager
    Access Statistics
    Reader Comments
    Email Alert *
    Add to My List *
* Registration required (free)  

  In this Article

 Article Access Statistics
    PDF Downloaded16    
    Comments [Add]    

Recommend this journal


Table of Contents    
Year : 2021  |  Volume : 69  |  Issue : 3  |  Page : 753-754

The Impact of Aneurysmal Subarachnoid Hemorrhage on Blood Brain Barrier Permeability: What We Learnt?

Department of Pharmacology, All India Institute of Medical Sciences, Raipur, Chhattisgarh, India

Date of Submission05-Sep-2020
Date of Decision17-Mar-2021
Date of Acceptance31-Mar-2021
Date of Web Publication24-Jun-2021

Correspondence Address:
Dr. Alok Singh
Department of Pharmacology, All India Institute of Medical Sciences, Raipur - 492 099, Chhattisgarh
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.319205

Rights and Permissions

How to cite this article:
Kumar B M, Gupta D, Singh A. The Impact of Aneurysmal Subarachnoid Hemorrhage on Blood Brain Barrier Permeability: What We Learnt?. Neurol India 2021;69:753-4

How to cite this URL:
Kumar B M, Gupta D, Singh A. The Impact of Aneurysmal Subarachnoid Hemorrhage on Blood Brain Barrier Permeability: What We Learnt?. Neurol India [serial online] 2021 [cited 2021 Oct 17];69:753-4. Available from:


We read the article with immense interest titled as “Aneurysmal subarachnoid hemorrhage: Impact on Phenytoin permeability across the Blood-Brain Barrier”[1] published in your esteemed journal.

The pragmatic study aimed at evaluating the clinical dilemma that has been in the long run in the neurosurgery practice had a well-established background and research question. Though a pilot study with relatively smaller sample size, matching between cases and controls was done with great efforts to mimic the pathophysiology and clinical features in both the groups. Even though aneurysmal subarachnoid hemorrhage is a surgical emergency, steps taken to explain the study's nature and purpose to the participants for getting informed written consent was remarkable one. Usage of liquid chromatography-mass spectrometry for phenytoin estimation for better sensitivity of the results and appropriate statistical analysis were added gems to the crown.

By careful and curious reading, a few questions remained unanswered and needed further clarification. Being a pilot study, we assume that convenient sampling technique was employed in the study. The matching of cases and controls could have been further redefined. As in the case of the aneurysmal subarachnoid hemorrhage group, the condition is a surgical emergency, whereas it was not the same in the control group. Cerebral salt wasting syndrome leading to hyponatremia and resultant seizures were more common in the case group, and it is almost rare in the control group.[2] If the severity is the ground for recruiting subjects with Fisher grade 3 and 4 aneurysmal subarachnoid hemorrhage in the case group, including one participant with astrocytoma grade-1 in the control group remains unclear. The sampling in the cases group was done within ten days following the ictus event, but that is the most crucial period for the reactive cerebral vasospasm to occur, and this might contribute as a potential confounding factor. Though phenytoin's administration timing was not mentioned, phenytoin was given at an appropriate dose and rate to prevent cardiac adverse events. Furthermore, the authors could have included about the preparatory procedure for phenytoin infusion, as phenytoin sodium is known to precipitate in all glucose-containing solutions.[3] Surprisingly, the median plasma concentration of phenytoin in both cases and control group lies within the therapeutic concentration for preventing seizures even after giving phenytoin in 5% dextrose leads to further query whether agents like hydroxypropyl-β-cyclodextrin was added or any other micron filter was used in the infusion pump.[4] Data regarding the duration and number of phenytoin doses given for maintenance also lacked in the literature. As phenytoin follows saturation kinetics, the authors did not indicate about the point at which samples were harvested from patients of either groups. In the discussion, it was mentioned that peri-pathological tissues were extracted from both the cases and the control groups. Extraction of the peri-pathological tissues in cases of aneurysmal subarachnoid hemorrhage group remains questionable since it may result in neurological deficits in the subjects. Being a prospective observational study, if the patient's outcomes in cases and control group in terms of seizure occurrence and deaths at least in the post-operative period were mentioned, would yield a much better data regarding the safety of phenytoin as a prophylactic antiepileptic for patients undergoing neurosurgery.

In the era of evidence-based medicine, author's effort to prove the long-run dilemma with laboratory evidence existing in the neurosurgical practice are remarkable. With no doubt, this study would pave the way for different areas of exploration in the management of aneurysmal subarachnoid hemorrhage.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Dhir N, Attri SV, Pattanaik S, Kumar MP, Gill NK, Patial A, et al. Aneurysmal subarachnoid hemorrhage: Impact on phenytoin permeability across the blood–brain barrier. Neurology India 2020;68:588.  Back to cited text no. 1
K. Petridis A, A. Kamp M, F. Cornelius J, Beez T, Beseoglu K, Turowski B, et al. Aneurysmal subarachnoid hemorrhage. Dtsch Arztebl Int 2017;114:226-36.  Back to cited text no. 2
Parenteral Dilantin. Available from: [Last accessed on 2020 Aug 08].  Back to cited text no. 3
McDonald C, Muzumdar PP. Prevention of precipitation of phenytoin in an infusion fluid by hydroxypropyl beta-cyclodextrin. J Clin Pharm Ther 1998;23:235-9.  Back to cited text no. 4


Print this article  Email this article
Online since 20th March '04
Published by Wolters Kluwer - Medknow