*5.1.2 Road to further research*

*New Insight into Cerebrovascular Diseases - An Updated Comprehensive Review*

*5.1.1 Cisternostomy: the clinical implementation of CSF-shift reversal in TBI*

The corresponding author serendipitously uncovered the fact that opening cisterns in severe head trauma had the effect of abating severe brain swelling while drastically reducing the requirement for decompressive hemicraniectomies [24, 28]. His decade-long work on this led him to believe that CSF was ingressing to the brain through the Virchow Robin spaces, producing a condition which has been recently termed as CSF shift edema. Experimental studies on the glymphatic system by Iliff et al. categorically proved the communication of the CSF with the brain through the Virchow Robin spaces, or paravascular spaces, and that this pathway was critical for clearing the brain of metabolites [5, 6]. Perhaps the biggest clinical implication of this finding is the microsurgical opening of the cisterns: cisternostomy, in cases of moderate to severe head injury in order to reverse CSF shift edema, which is the mainstay of the cascade of the TBI damage. This procedure has been discussed in detail in previous publications and prevents progression to diffuse axonal damage or cortical stretch as otherwise seen in decompressive procedures. The phenomenal prognosis in the patients undergoing cisternostomy led the author to investigate the paravascular system in further depth, as well as CSF shifts, and subsequently the

Today, cisternostomy has shown to be efficacious as a primary surgical intervention in moderate to severe traumatic brain injury. While following the principles of reversal of CSF shift edema, cisternostomy has proven to help in the prognosis by decreasing the rates of morbidities and mortalities [22]. It is now being practiced in many neurosurgical centers around the world [25] and has also been accepted

*(a) Raised cisternal pressure due to the traumatic subarachnoid hemorrhage shifts cerebrospinal fluid into the brain, causing raised intracerebral pressure. (b) Opening of the cisterns reverses the cisternal pressure gradient, causing cerebrospinal fluid to flow back into the cisterns, thus decreasing the brain pressure. (c) Decompressive hemicraniectomy allows extracalvarial herniation, leading to further deterioration due to axonal stretch and* 

acute brain trauma [8, 26].

**5.1 Clinical implication**

perivascular CSF recirculation may be impaired.

likely functionality of the paravascular system (**Figure 8**).

*altered blood flow dynamics. Courtesy: Cherian et al. [24].*

advantages of cisternostomy over decompressive craniectomy, in the treatment of

Decreased intracranial compliance leads to increased intraparenchymal pressure, affecting the arterial perfusion of the brain and promoting venous congestion. On the whole, the kinetics of the fluid in the paravascular spaces is impaired. Should there be a loss of AQP4 localization, as seen in reactive astrogliosis and the aging brain, or following trauma or ischemia, or if the CSF outflow is reduced as a consequence of either CSF flow obstruction, cerebral artery pulsatility inefficiency, cerebrospinal venous insufficiency, or lymphatic disorders [27], the localized

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**Figure 8.**

The paravascular system, its cleaning and cooling properties, and the consequent pathophysiological conditions secondary to the impedance of this system as well as potential treatment measures have not yet been investigated in detail. Reports of an experiment where a bacteriophage is being introduced into the olfactory system of a mouse resulted in the reversal of Alzheimer's symptoms. This could be due to the clearance of the obstructed paravascular system as the phage traveled into the cisterns through the perineural space of the olfactory. This observation opens doors for a paradigm shift in the management of neurodegenerative diseases and warrants extensive research. Further experimental work in this area will include the injection of paramagnetic nanoparticles into the suprasellar cisterns of mice, porcine, or baboon models, where the movement of these nanoparticles may be observed with a T1 W3T MRI.
