Anosmia after anterior communicating artery aneurysm surgery

Anosmia after anterior communicating artery aneurysm surgery

For Bor et al. anosmia occurs after coiling in 1 of every 6 SAH patients, but has a good prognosis in most patients. The cause of anosmia after coiling for ruptured aneurysms remains elusive; severity of the initial hemorrhage or long lasting hydrocephalus may be contributing factors 1).

In patients with subarachnoid hemorrhage (SAH), anosmia has mainly been reported after surgery for anterior communicating artery aneurysms. Olfactory dysfunction after SAH caused by rupture of the ACoA are very frequent and were present in both treatment groups (aneurysmal clip placement and coil embolization).

Cerebral vasospasm and frontal lobe lesions are related to worse performance on an olfactory test in patients undergoing endovascular coil embolization 2).

Both clip treatment and SAH contribute to the occurrence of anosmia, with different chances of improvement. Olfactory dysfunction occurs in almost all patients on the side of surgery and can occur subclinically after coil deployment 3).

Its occurrence after coiling suggests not only damage to the olfactory nerve by clipping but also that the SAH itself plays a role in its pathogenesis 4).


The highest incidence of olfactory dysfunction following a pterional approach and its modifications for an intracranial aneurysm has been reported in cases of anterior communicating artery (ACoA) aneurysms. The radiological characteristics of unruptured ACoA aneurysms affecting the extent of retraction of the frontal lobe and olfactory nerve were investigated as risk factors for postoperative olfactory dysfunction. In cases of unruptured ACoA aneurysm surgery, the height of the aneurysm neck and the estimated extent of brain retraction were both found to be powerful predictors of the occurrence of postoperative olfactory dysfunction. 5).


Wongsuriyanan and Sriamornrattanakul published that the interhemispheric approach provided an excellent surgical corridor for clipping anterior communicating artery aneurysms (AcoAAs). However, an important disadvantage of the approach is obtaining proximal control at A1 in the last stage of dissection, especially in anterior or superior projecting AcoAAs and ruptured cases.

Postoperative anosmia was detected in 22.7% 6).


For Ito et al. the causes of postoperative anosmia in subfrontal and interhemispheric approach were as follows: sectioning of olfactory tracts intentionally or not, avulsion of olfactory bulbs and probability of ischemic or minor mechanical insults to olfactory tracts. However, these matters rarely occur in posterior interhemispheric approach because of little exposure of olfactory nerves. The mechanisms of postoperative anosmia in posterior interhemispheric approach were considered to be as follows: sinking of frontal lobes due to excessive drainage of cerebrospinal fluid and over-retraction of frontal lobes. The incidence of postoperative anosmia decreased from 27.0% via subfrontal and interhemispheric approach to 5.5% via posterior interhemispheric approach 7).

Superior direction of aneurysm appears associated with postoperative olfactory dysfunction. Olfactory protection using gelfoam and fibrin glue could be a simple, safe, and useful method to preserve olfactory function during A-com aneurysm surgery. 8).


For Aydin et al. the functions of olfactory nerve could be preserved at a relatively high rate of 85 per cent. This high rate resulted from the microtechnique employed as well as the relatively cautious frontal lobe retraction which was less than 1.5 cm 9).



For Fujiwara et al. Unilateral dural incision and unilateral brain retraction without elevation of the frontal lobe from the frontal base are important, because frontal lobe depression and elevation during surgery may injure the olfactory nerve 10).

Olfactory dysfunction has an important impact on quality of life. Recovery after traumatic anosmia has been recorded up to 5 years after injury. Nevertheless, the authors believe that the damage is permanent when lasting 35 months or longer 11).

The interhemispheric approach (IHA) provides an excellent surgical corridor for clipping anterior communicating artery aneurysms (AcoAAs). However, an important disadvantage of the approach is obtaining proximal control at A1 in the last stage of dissection, especially in anterior or superior projecting AcoAAs and ruptured cases. Wongsuriyanan and Sriamornrattanakul described and evaluated the microsurgical clipping of AcoAAs using the IHA with early A1 exposure.

This was a retrospective descriptive study in patients with AcoAA who received microsurgical clipping through the IHA with early A1 exposure between April 2016 and May 2019. Aneurysm morphology, projection, completeness of clipping, surgical complications, and outcomes were collected from medical records.

Twenty-five patients with AcoAA received microsurgical clipping via the IHA with early A1 exposure. Twenty-three patients (92%) presented with subarachnoid hemorrhage. Intraoperative rupture while dissecting the interhemispheric fissure occurred in 2 cases, for which proximal control via subfrontal route was effectively performed. Of the patients, 100% achieved complete obliteration of their aneurysms. Postoperative anosmia was detected in 22.7%. In ruptured cases, 16 (88.9%) of the good grade patients achieved a good outcome (Glasgow Outcome Scale scores of 4 and 5) at 3 months after the operation.

The IHA with early A1 is safe and effective for clipping AcoAAs. 12).


Hendrix et al. assessed the risk for olfactory dysfunction following surgical treatment of unruptured cerebral aneurysm via the supraorbital minicraniotomy. A retrospective review of patients with electively treated cerebral aneurysms who underwent perioperative assessment of olfactory function using a sniffin’ sticks odor identification test between January 2015 and January 2016 was performed. A subgroup of patients without history of subarachnoid hemorrhage, without prior intracranial aneurysm treatment, and confirmed olfactory function underwent supraorbital keyhole craniotomy for aneurysm clipping. Microscopic and endoscopic videos were reviewed for this subgroup. Sixty-four patients who underwent elective aneurysm treatment either via surgical clipping or endovascular aneurysm obliteration were identified. Prior to treatment, 4/64 (6.3%) demonstrated bilateral anosmia. Collectively, 14 patients (21.9%) met subgroup criteria of supraorbital keyhole craniotomy for aneurysm clipping. Here, olfactory performance significantly decreased postoperatively on the side of craniotomy (ipsilateral, P = 0.007), whereas contralateral and bilateral olfactory function remained unaltered (P = 0.301 and P = 0.582, respectively). Consequently, 4/14 patients (28.6%) demonstrated ipsilateral anosmia 3 months after surgery. One patient (1/14, 7.1%) also experienced contralateral anosmia resulting in bilateral anosmia. Intraoperative visualization of the olfactory tract and surgical maneuvers do not facilitate prediction of olfactory outcome. The supraorbital keyhole craniotomy harbors a specific risk for unilateral olfactory deterioration. Lack of perioperative olfactory assessment likely results in underestimation of the risk for olfactory decline. Despite uneventful surgery, prediction of postoperative olfactory function and dysfunction remain challenging 13).


A total of 63 patients (aged 41-79 yr, mean 64 yr) with relatively small AcomA aneurysms clipped via the lateral supraorbital approach were retrospectively analyzed among the 105 AcomA aneurysms treated by clipping from 2005 to 2014. Neurological and cognitive functions were examined by several scales, including the modified Rankin Scale (mRS) and Mini-Mental Status Examination. The depressive state was assessed using the Beck Depression Inventory and Hamilton Depression Scale. The state of clipping was assessed 1 yr and then every few years after the operation by 3-dimensional computed tomography angiography.

Complete aneurysm neck clipping was confirmed in 62 aneurysms (98.4%). Perioperative complications occurred in 5 patients (5/63; mild frontalis muscle weakness in 3, anosmia in 1, and meningitis in 1). The mean clinical follow-up period was 5.2 ± 2.1 yr. No patient showed an mRS score more than 2 and all were completely independent in daily life. The depression scores were significantly improved after surgery. The overall mortality was 0% and overall morbidity (mRS score > 2 or Mini-Mental Status Examination score < 24) was 1.6%. All completely clipped aneurysms did not show any recurrence during the mean follow-up period of 4.9 ± 2.1 yr.

Keyhole Lateral supraorbital approach to clip relatively small unruptured AcomA aneurysm promises less invasive and durable treatment 14).


Cho et al. retrospectively reviewed the medical records of patients who underwent surgical clipping for unruptured aneurysm from 2011-2013 by the same senior attending physician. Since March 2012, olfactory protection using gelfoam and fibrin glue was applied in A-com aneurysm surgery. Therefore we categorized patients in two groups from this time-protected group and unprotected group.

Of the 63 enrolled patients, 16 patients showed postoperative olfactory dysfunction-including 8 anosmia patients (protected group : unprotected group=1 : 7) and 8 hyposmia patients (protected group : unprotected group=2 : 6). Thirty five patients who received olfactory protection during surgery showed a lower rate of anosmia (p=0.037, OR 10.516, 95% CI 1.159-95.449) and olfactory dysfunction (p=0.003, OR 8.693, 95% CI 2.138-35.356). Superior direction of the aneurysm was also associated with a risk of olfactory dysfunction (p=0.015, OR 5.535, 95% CI 1.390-22.039).

Superior direction of aneurysm appears associated with postoperative olfactory dysfunction. Olfactory protection using gelfoam and fibrin glue could be a simple, safe, and useful method to preserve olfactory function during A-com aneurysm surgery. 15).


The highest incidence of olfactory dysfunction following a pterional approach and its modifications for an intracranial aneurysm has been reported in cases of anterior communicating artery (ACoA) aneurysms. The radiological characteristics of unruptured ACoA aneurysms affecting the extent of retraction of the frontal lobe and olfactory nerve were investigated as risk factors for postoperative olfactory dysfunction.

Methods: A total of 102 patients who underwent a pterional or superciliary keyhole approach to clip an unruptured ACoA aneurysm from 2006 to 2013 were included in this study. Those patients who complained of permanent olfactory dysfunction after their aneurysm surgery, during a postoperative office visit or a telephone interview, were invited to undergo an olfactory test, the Korean version of the Sniffin’ Sticks test. In addition, the angiographic characteristics of ACoA aneurysms, including the maximum diameter, the projecting direction of the aneurysm, and the height of the neck of the aneurysm, were all recorded based on digital subtraction angiography and sagittal brain images reconstructed using CT angiography. Furthermore, the extent of the brain retraction was estimated based on the height of the ACoA aneurysm neck.

Results: Eleven patients (10.8%) exhibited objective olfactory dysfunction in the Sniffin’ Sticks test, among whom 9 were anosmic and 2 were hyposmic. Univariate and multivariate analyses revealed that the direction of the ACoA aneurysm, ACoA aneurysm neck height, and estimated extent of brain retraction were statistically significant risk factors for postoperative olfactory dysfunction. Based on a receiver operating characteristic (ROC) analysis, an ACoA aneurysm neck height > 9 mm and estimated brain retraction > 12 mm were chosen as the optimal cutoff values for differentiating anosmic/hyposmic from normosmic patients. The values for the area under the ROC curves were 0.939 and 0.961, respectively.

Conclusions: In cases of unruptured ACoA aneurysm surgery, the height of the aneurysm neck and the estimated extent of brain retraction were both found to be powerful predictors of the occurrence of postoperative olfactory dysfunction. 16).


Matano et al. presented a fibrin-gelatin fixation method that provides reinforcement and moisture to help preserve the olfactory nerve when using the anterior interhemispheric approach and describe the results and outcomes of this technique. We analyze the outcomes with this technique in 45 patients who undergo surgery for aneurysms, brain tumors, or other pathologies via the anterior interhemispheric approach. Anosmia occurred in 4 patients (8.8%); it was transient in 2 (4.4%) and permanent in the remaining 2 (4.4%). Brain tumors clearly attached to the olfactory nerve were resected in the patients with permanent anosmia. We found a significant difference in the presence of anosmia between patients with or without lesions that were attaching the olfactory nerve (p = 0.011). Our results suggested that fibrin-gelatin fixation method can reduce the reported risk of anosmia. However, the possibility of olfactory nerve damage is relatively high when operating on brain tumors attaching olfactory nerve 17).


Lai et al. presented the operative experiences in a consecutive series of 103 patients with 115 unruptured AcomA aneurysms. Clinical results, operative complications, angiographic outcomes and prognostic factors associated with surgery are presented. Of the 115 aneurysm repairs attempted, 114 were treated by clipping or excision and suture. One aneurysm, less than 2mm, was wrapped. Six patients (5.8%; 95% confidence interval [CI], 2.5-12.4) experienced a new permanent neurological deficit. There was no postoperative mortality. Transient morbidity occurred in 11 patients (10.7%; 95% CI, 5.9-18.3), including transient anosmia (four patients), acute postoperative confusion and memory disturbances (four patients), extradural haematoma requiring surgery (two patients) and cerebrospinal fluid rhinorrhea (one patient). Of the 84 aneurysms (73.0%) that had documented postoperative angiography, 82 (97.6%) had complete obliteration of the aneurysm and two (2.4%) had neck remnants (mean angiographic follow-up 28.0 months; range, 1.6-146.4 months). Retreatment was performed in one patient (1.0%). Logistic regression analysis of risk factors revealed that aneurysm size (p<0.01) was a significant predictor of outcome. There was no incidence of subarachnoid haemorrhage in the 272 person years of follow-up. In the current study, surgical treatment of unruptured AcomA aneurysms resulted in 5.8% morbidity and no mortality. The robustness of aneurysm repair achieved by open microsurgery is an important consideration when considering the option between endovascular and microsurgical treatment for unruptured AcomA aneurysms. 18).


Nakayama et al. studied the incidence of postoperative infection related to CSF leakage and anosmia in basal interhemispheric approach (BIH). Between April, 1990 to March, 2009, 142 cases of anterior communicating (Acom) aneurysm including both unruptured and ruptured have been treated by clipping surgery using BIH. We retrospectively obtained clinical informations from medical records and video records about infectious complications, CSF leakage of cerebrospinal fluid (CSF), olfactory dysfunction and intraoperative findings of damage to the olfactory nerve. In most cases (139 patients, 97%), frontal sinus were opened at craniotomy. Of all, CSF rinorrhea occurred in 4 cases (2.8%), and meningitis in 6 cases. There was only one patient who sufferd from meningitis due to CSF rinorrhea. All that patients recovered completely without deficit. Anosmia occurred in 6 cases (4.2%), and intraoperative injuries in 4 cases (2.8%). There was only one patient in whom anosmia was consistent with nerve injury. In conclusion, BIH is an appropriate procedure for infection risk control in Acom aneurysm surgery. It is difficult to avoid olfactory dysfunction completely, even if olfactory nerves are preserved in form. 19).


The horizontal head position was adopted in the unilateral anterior interhemispheric approach to treat an anterior communicating artery (ACoA) aneurysm. The patient was placed in the supine position. The patient’s head was rotated to the right to orient the midline horizontally, and tilted 45 degrees superiorly. After bicoronal skin incision and bifrontal craniotomy, the dura on the right side (downside) was opened. Dissection of the right interhemispheric fissure allowed gravity to retract the right (downside) hemisphere, which fell away from the falx, while the falx supported the upside hemisphere. The present approach was used in three patients with ACoA aneurysm between January 2009 and April 2010. The aneurysms were adequately clipped with this approach. No complication related to the approach occurred. No patients exhibited anosmia after surgery. This approach is useful for ACoA aneurysms. 20).


Beseoglu et al. in 2003 introduced a minimally invasive transorbital keyhole approach. Because this approach requires removal of the orbital rim and orbital roof, there have been concerns regarding perioperative morbidity, long-term morbidity, and cosmetic results. The authors evaluated approach-related morbidity and cosmetic results in their patients to determine the rate of complications and compared this to published reports of similar approaches.

Material: Seventy-one patients (41 female, 30 male) underwent operations using this approach between 2004 and 2008. Immediate approach-related morbidity was recorded after the operation. Late morbidity was determined after 7 months by an independent examiner while cosmetic results were self-rated by the patient using a questionnaire.

Results: Fifty-one (72%) of 71 patients had no postoperative complications and 12 (16.9%) had minor complications, the most common of which was subgaleal CSF collection (7.0%). Other minor complications included facial nerve palsy (2.8%), hyposphagma (2.8%), periorbital swelling due to periorbital hematoma (2.8%), and subdural hematoma (1.4%). Major complications requiring surgical revision occurred in 4 patients (5.6%); these were CSF fistulas in 2 patients, pneumocephalus in 1 patient, and a hematoma in 1 patient. Forty-nine (90.7%) of all 54 examined patients rated the cosmetic results as very good or good. Major long-term morbidity was hyposmia or anosmia (14 patients) followed by hypoesthesia around the scar (9 patients).

The transorbital keyhole approach is a feasible approach with a low-risk profile for postoperative or long-term morbidity and excellent cosmetic outcome 21)


Although the frequency of smell disorders after the operations of the anterior communicating artery aneurysm depends to a large degree on the used surgical approach, several independent of surgery factors may contribute to the postoperative smell tests outcome. THE AIM OF OUR STUDIES: The evaluation of the sense of smell in patients who underwent the operation of ruptured anterior communicating artery aneurysm using pterional approach.

Material and methods: In the retrospective studies the results of smell test of the group of 21 patients operated for ruptured anterior communicating artery aneurysm and 21 healthy volunteers of control group were compared. The patients suffering from neurodegenerative, metabolic and endocrynological disorders, as well as those with rhinoscopic symptoms of rhinosinusitis and with decreased nasal potency confirmed by anterior rhinomanometry were excluded from the study.

Results: During the operations it was possible to anatomically retain olfactory nerves in all operated patients. Severe smell disorders (severe hyposmia and anosmia) were detected in 1 (4.7%) patient of the control group and in 6 (28.5%) patients of postoperative group. The mean composite olfactory score in Cain test of the postoperative group was 4.53, and in the control group 5.47 points. The difference did not reach statistic significance (Mann-Whitney test, p = 0.068).

Conclusions: Although pterional approach to anterior communicating artery is relatively low traumatic to olfactory tract, the subarachnoid hemorrhage may have an unfavorable effect on postoperative olfactory nerve functioning. Considering the fact, that in spite of thorough examination of the patients, we were not able to exclude from the studied groups all the patients with preoperatively impaired smell, it seems reasonable to perform similar smell test studies in the prospective way 22).


Bor et al. interviewed all patients who resumed independent living after SAH treated with coiling between 1997 and 2007. We assessed by means of logistic regression analyses whether risk of anosmia was influenced by site of the ruptured aneurysm, neurological condition on admission, amount of extravasated blood, hydrocephalus, and treatment for hydrocephalus.

Of 197 patients, 35 (18%; 95%CI:12 to 23) experienced anosmia. Anosmia had improved in 23 (66%) of them; in 20 the recovery had been complete after a median period of 6 weeks (SD +/-6.5). Intraventricular hemorrhage was a risk factor for anosmia (OR 2.4; 95%CI:1.0 to 5.9). Anterior aneurysm location (OR 1.1; 95%CI:0.5 to 2.3) and high amount of extravasated blood (OR 0.9; 95%CI:0.4 to 2.1) were not related to anosmia.

Anosmia occurs after coiling in 1 of every 6 SAH patients, but has a good prognosis in most patients. The cause of anosmia after coiling for ruptured aneurysms remains elusive; severity of the initial hemorrhage or long lasting hydrocephalus may be contributing factors. 23).


Martin et al. studied whether and how frequently patients with ACoA aneurysms present with smell identification deficits in 2 treatment groups (endovascular and surgical treatment).

Methods: A prospective study was conducted of patients with SAH caused by ruptured ACoAs and who had a Glasgow Outcome Scale score of 1 or 2, in comparison with a control group matched by age and sex. Olfactory function was assessed using the University of Pennsylvania Smell Identification Test (UPSIT).

Results: A total of 39 patients were enrolled. A marked olfactory impairment was observed in patients with ruptured ACoAs compared with the control group (p < 0.001). Seventeen patients with ruptured ACoAs (44%) compared with 1 patient in the control group (3%) showed a smell identification deficit according to performance on the UPSIT (p < 0.001). Both groups that underwent treatment presented with olfactory impairment. Ten (59%) of 17 patients who underwent aneurysmal clip placement versus 6 (28.5%) of 21 patients who underwent coil embolization scored below the 25th percentile on the UPSIT, and surgical patients also performed worse than endovascular patients (p = 0.048). The authors observed a worse performance on the olfactory test in patients subjected to endovascular coil embolization when cerebral vasospasm (p = 0.037) or frontal cerebral lesions (p = 0.009) were present. This difference was not observed in patients who underwent surgery.

Conclusions: Olfactory disorders after SAH caused by rupture of the ACoA are very frequent and were present in both treatment groups. Cerebral vasospasm and frontal lobe lesions are related to worse performance on an olfactory test in patients undergoing endovascular coil embolization 24).


To discriminate between the effects of aneurysmal rupture and treatment, Moman et al. assessed the occurrence of anosmia after clipping and coiling of unruptured aneurysms as well as after the coiling of ruptured aneurysms.

Methods: The authors interviewed patients in whom an unruptured aneurysm was treated by clipping (32 cases) or endovascular coiling (26 cases) as well as patients with SAH who underwent coil therapy (32 cases). A geographically defined subset of 20 patients per group was invited to undergo olfactory testing.

Results: Nine clip-treated patients (28% [95% CI 14-47%]) in the unruptured group reported having anosmia, and no coil-treated patient in the unruptured group (95% [CI 0-13%]) reported having anosmia; in the SAH group, 7 patients (22% [95% CI 9-40%]) reported having anosmia. Anosmia had improved over time in 3 of the clip-treated patients and in all but 1 of the patients with SAH. Examination revealed olfactory disturbance in 13 (65% [95% CI 41-85%]) of the clip-treated and 8 (42% [95% CI 20-67%]) of the coil-treated patients with unruptured aneurysms, and also in 7 (35% [95% CI 15-59%]) coil-treated patients with SAH. In 20 patients who underwent clip therapy for unruptured aneurysms, 19 (95% [95% CI 75-100%]) had olfactory dysfunction on the side ipsilateral to surgery (anosmia reported by 8 of them).

Conclusions: Both clip treatment and SAH contribute to the occurrence of anosmia, with different chances of improvement. Olfactory dysfunction occurs in almost all patients on the side of surgery and can occur subclinically after coil deployment. 25).


Wermer et al. studied the prevalence, predisposing factors (aneurysm site and type of treatment), impact, and prognosis of anosmia in patients with SAH.

Of the patients with SAH who resumed independent living, we included all patients treated by coiling between 1997 and 2003 and a sample of patients treated by clipping between 1985 and 2001. Patients underwent structured interviews regarding the presence and duration of anosmia. The impact of anosmia was scored using a visual analog scale ranging from 0 (no influence) to 100 (the worst thing that ever happened to them). Risk factors for anosmia were assessed by logistic regression analysis.

Overall, 89 of the 315 interviewed patients (28%; 95% confidence interval [CI], 23-34%) reported anosmia after SAH (mean follow-up period, 7.4 yr), including 10 (15%) of the 67 coiled patients and 79 (32%) of the 248 clipped patients. The median visual analog scale impact score was 53 (range, 0-100). In 20 of the 89 patients (23%; 95% CI, 15-33), the symptoms had improved over time. Risk factors for anosmia were treatment by clipping (odds ratio [OR], 2.7; 95% CI, 1.3-5.7) and anterior communicating artery aneurysms (OR, 2.0; 95% CI, 1.2-3.3).

Anosmia after SAH has a high prevalence, considerable impact, and poor prognosis. Its occurrence after coiling suggests not only damage to the olfactory nerve by clipping but also that the SAH itself plays a role in its pathogenesis. 26)


Nozaki et al. described a patient with bilateral persistent primitive olfactory arteries associated with an unruptured saccular aneurysm on the left persistent primitive olfactory artery. Seven reported cases with this anomalous artery including ours are reviewed and classified into two variants. This anomalous artery arises from the terminal portion of the internal carotid artery and courses anteromedially along the ipsilateral olfactory tract and makes a hair-pin curve posterior to the olfactory bulb, becoming the distal anterior cerebral artery (variant 1) or the ethmoidal artery (variant 2). Out of 7 reported cases, 4 cases are associated with saccular aneurysms. The aneurysm in variant 1 is located on the hair-pin curve at which an apparent arterial branch is sometimes absent. Two patients suffer from anosmia. Persistent primitive olfactory artery should be kept in mind because of its high association with intracranial saccular aneurysms and unique clinical presentation. 27).


In as retrospective study, 100 patients with anterior communicating artery aneurysms, for whom the pterional approach was employed, were observed from the point of view of postoperative olfactory nerve function. In the postoperative period only three cases suffered from the impaired sense of smell ipsilateral to the side of surgery. 15 patients objectively showed olfactory nerve distinctions. The functions of olfactory nerve could be preserved at a relatively high rate of 85 per cent. This high rate resulted from the microtechnique employed as well as the relatively cautious frontal lobe retraction which was less than 1.5 cm. 28).


Between 1969 and 1994 we treated 450 patients with ruptured anterior communicating artery aneurysms, of which 434 cases (96.4%) were operated on via the interhemispheric approach (IH), namely, until 1979 mainly, via bifrontal craniotomy, subfrontal and interhemispheric approach (SIH) and, since 1979, via posterior interhemispheric approach (PIH). Postoperative olfactory dysfunction is one of the main disadvantages of IH. The mechanisms and the incidence of this disadvantage were studied in both approaches. The causes of postoperative anosmia in SIH were as follows: sectioning of olfactory tracts intentionally or not, avulsion of olfactory bulbs and probability of ischemic or minor mechanical insults to olfactory tracts. However, these matters rarely occur in PIH because of little exposure of olfactory nerves. The mechanisms of postoperative anosmia in PIH were considered to be as follows: sinking of frontal lobes due to excessive drainage of cerebrospinal fluid and over-retraction of frontal lobes. The incidence of postoperative anosmia decreased from 27.0% via SIH to 5.5% via PIH 29).


The olfactory function could be examined in 101 of 138 patients with anterior communicating artery aneurysms, whom we treated during a recent 6-year period. Among them, 49 patients underwent surgery by the anterior interhemispheric approach and 52 underwent surgery by the basal interhemispheric approach. Fifteen patients (31%) exhibited anosmia after surgery by the anterior interhemispheric approach, whereas only one patient (1.9%) exhibited anosmia after surgery by the basal interhemispheric approach. Unilateral dural incision and unilateral brain retraction without elevation of the frontal lobe from the frontal base are important, because frontal lobe depression and elevation during surgery may injure the olfactory nerve 30).


Yasui et al. reviewed the surgical outcome in 85 patients with ruptured anterior communicating artery (ACoA) aneurysms, who were operated on within 72 hours of onset via a basal interhemispheric (BIH) approach (Group 1, N = 48), or an anterior interhemispheric (AIH) approach (Group 2, N = 37). The age, sex ratio and pre-operative grade (Gr) were similar for both groups. The outcome at the time of discharge was as follows for group 1: excellent or good 88%; fair, 6%; vegetative state, 2% and death 4%. For group 2, it was: excellent or good 78%; fair, 16%; vegetative state, 3%; and death, 3%. A significant correlation between admission grade and outcome was found in both groups. The outcome in group 1 was better than in group 2 for patients with a Glasgow Outcome Scale (GOS) better than fair (p < 0.07). No patient in group 1 had postoperative anosmia, but nine patients in group 2 became anosmic. The total number of complications was also significantly less in group 1. Our overall mortality rate was 4%. In conclusion, the BIH approach was more beneficial for treating acute ACoA aneurysm. 31).


In a retrospective study of 25 patients operated on for ruptured intracranial aneurysms via the frontotemporal route, 22 patients suffered postoperatively from anosmia ipsilateral to the side of surgery. This complication most often goes unrecognized by the patient as well as the physician, and attention should be drawn to it because of its widespread occurrence. This investigation demonstrates a high incidence of anosmia (24 (88.9%) of 27 surgical sides) occurring ipsilateral to the frontotemporal approach in aneurysm surgery. Recovery after traumatic anosmia has been recorded up to 5 years after injury. Nevertheless, the authors believe that the damage is permanent when lasting 35 months or longer 32)


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Mori K, Wada K, Otani N, Tomiyama A, Toyooka T, Tomura S, Takeuchi S, Yamamoto T, Nakao Y, Arai H. Long-Term Neurological and Radiological Results of Consecutive 63 Unruptured Anterior Communicating Artery Aneurysms Clipped via Lateral Supraorbital Keyhole Minicraniotomy. Oper Neurosurg (Hagerstown). 2018 Feb 1;14(2):95-103. doi: 10.1093/ons/opx244. PMID: 29228382.
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Matano F, Murai Y, Mizunari T, Tateyama K, Kobayashi S, Adachi K, Kamiyama H, Morita A, Teramoto A. Olfactory preservation during anterior interhemispheric approach for anterior skull base lesions: technical note. Neurosurg Rev. 2016 Jan;39(1):63-8; discussion 69. doi: 10.1007/s10143-015-0647-x. Epub 2015 Jul 17. PMID: 26178238.
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Lai LT, Gragnaniello C, Morgan MK. Outcomes for a case series of unruptured anterior communicating artery aneurysm surgery. J Clin Neurosci. 2013 Dec;20(12):1688-92. doi: 10.1016/j.jocn.2013.02.015. Epub 2013 Aug 16. PMID: 23958481.
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Nakayama H, Ishikawa T, Yamashita S, Fukui I, Mutoh T, Hikichi K, Yoshioka S, Kawai H, Tamakawa N, Moroi J, Suzuki A, Yasui N. [CSF leakage and anosmia in aneurysm clipping of anterior communicating artery by basal interhemispheric approach]. No Shinkei Geka. 2011 Mar;39(3):263-8. Japanese. PMID: 21372335.
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Hayashi N, Sato H, Akioka N, Kurosaki K, Hori S, Endo S. Unilateral anterior interhemispheric approach for anterior communicating artery aneurysms with horizontal head position–technical note. Neurol Med Chir (Tokyo). 2011;51(2):160-3. doi: 10.2176/nmc.51.160. PMID: 21358165.
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Beseoglu K, Lodes S, Stummer W, Steiger HJ, Hänggi D. The transorbital keyhole approach: early and long-term outcome analysis of approach-related morbidity and cosmetic results. Technical note. J Neurosurg. 2011 Mar;114(3):852-6. doi: 10.3171/2010.9.JNS1095. Epub 2010 Oct 29. PMID: 21029037.
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Sieśkiewicz A, Kochanowicz J, Rutkowska J, Rogowski M, Olszewska E. Ocena zaburzeń wechu u chorych po operacji peknietego tetniaka tetnicy łaczacej przedniej mózgu [The evaluation of olfactory dysfunction after the operation of ruptured anterior communicating artery aneurysm]. Pol Merkur Lekarski. 2009 Oct;27(160):302-4. Polish. PMID: 19928658.
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Bor AS, Niemansburg SL, Wermer MJ, Rinkel GJ. Anosmia after coiling of ruptured aneurysms: prevalence, prognosis, and risk factors. Stroke. 2009 Jun;40(6):2226-8. doi: 10.1161/STROKEAHA.108.539445. Epub 2009 Apr 16. PMID: 19372449.
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Martin GE, Junqué C, Juncadella M, Gabarrós A, de Miquel MA, Rubio F. Olfactory dysfunction after subarachnoid hemorrhage caused by ruptured aneurysms of the anterior communicating artery. Clinical article. J Neurosurg. 2009 Nov;111(5):958-62. doi: 10.3171/2008.11.JNS08827. PMID: 19361265.
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Moman MR, Verweij BH, Buwalda J, Rinkel GJ. Anosmia after endovascular and open surgical treatment of intracranial aneurysms. J Neurosurg. 2009 Mar;110(3):482-6. doi: 10.3171/2008.8.JNS08761. PMID: 19072311.
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Wermer MJ, Donswijk M, Greebe P, Verweij BH, Rinkel GJ. Anosmia after aneurysmal subarachnoid hemorrhage. Neurosurgery. 2007 Nov;61(5):918-22; discussion 922-3. doi: 10.1227/01.neu.0000303187.34308.7b. PMID: 18091268.
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Nozaki K, Taki W, Kawakami O, Hashimoto N. Cerebral aneurysm associated with persistent primitive olfactory artery aneurysm. Acta Neurochir (Wien). 1998;140(4):397-401; discussion 401-2. doi: 10.1007/s007010050114. PMID: 9689332.
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Aydin IH, Kadioğlu HH, Tüzün Y, Kayaoğlu CR, Takçi E, Oztürk M. Postoperative anosmia after anterior communicating artery aneurysms surgery by the pterional approach. Minim Invasive Neurosurg. 1996 Sep;39(3):71-3. doi: 10.1055/s-2008-1052220. PMID: 8892284.
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Ito S, Fujimoto S, Saito K, Tada H, Tanaka T. [Postoperative olfactory dysfunction in interhemispheric approach for ruptured anterior communicating artery aneurysms]. No Shinkei Geka. 1996 Jul;24(7):625-8. Japanese. PMID: 8752875.
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Yasui N, Nathal E, Fujiwara H, Suzuki A. The basal interhemispheric approach for acute anterior communicating aneurysms. Acta Neurochir (Wien). 1992;118(3-4):91-7. doi: 10.1007/BF01401292. PMID: 1456108.

Endoscopic third ventriculostomy and choroid plexus cauterization

Endoscopic third ventriculostomy and choroid plexus cauterization

Endoscopic third ventriculostomy with choroid plexus cauterization (ETV/CPC) offers an alternative to shunt.


While ventriculoperitoneal shunt (VPS) insertion is the standard treatment for myelomeningocele-associated hydrocephalus (MAH), it can be complicated by shunt infection and shunt malfunction. As such, endoscopic third ventriculostomy (ETV), with or without choroid plexus coagulation (CPC), has been proposed as an alternative.

ETV+CPC was associated with a higher success rate than ETV alone for MAH in a meta-analysis of published studies. ETV, with or without CPC, was technically feasible and safe for this patient population 1).


In the twenty-first century, choroid plexus cauterization (CPC) in combination with endoscopic third ventriculostomy (ETV) has emerged as an effective treatment for some infants with hydrocephalus, leading to the favourable condition of ‘shunt independence‘.

Coulter et al. provide a narrative technical review considering the indications, procedural aspects, morbidity and its avoidance, postoperative care and follow-up. The CP has been the target of hydrocephalus treatment for more than a century. Early eminent neurosurgeons including Dandy, Putnam and Scarff performed CPC achieving generally poor results, and so the procedure fell out of favour. In recent years, the addition of CPC to ETV was one of the reasons greater ETV success rates were observed in Africa, compared to developed nations, and its popularity worldwide has since increased. Initial results indicate that when ETV/CPC is performed successfully, shunt independence is more likely than when ETV is undertaken alone. CPC is commonly performed using a flexible endoscope via septostomy and aims to maximally cauterize the CP. Success is more likely in infants aged >1 month, those with hydrocephalus secondary to myelomeningocele and aqueductal obstruction and those with >90% cauterized CP. Failure is more likely in those with post-haemorrhagic hydrocephalus of prematurity (PHHP), particularly those <1 month of corrected age and those with prepontine scarring. High-quality evidence comparing the efficacy of ETV/CPC with shunting is emerging, with data from ongoing and future trials offering additional promise to enhance our understanding of the true utility of ETV/CPC 2).


In the quest to identify the optimal means of cerebrospinal fluid diversion free of shunt dependency, endoscopic third ventriculostomy (ETV) with choroid plexus cauterization (CPC) has been proposed as a promising procedure in select children. Supplementing traditional ETV with obliteration of the choroid plexus has been shown to decrease the likelihood of ultimate shunt dependency by roughly 20%. Originally devised to treat hydrocephalus in infants in sub-Saharan Africa, ETV/CPC has gained eager attention and cautious support in the developed world 3).

Diagnosing treatment failure is dependent on infantile hydrocephalus metrics, including head circumference, fontanel quality, and ventricle size.

Systematic review was performed using four electronic databases and bibliographies of relevant articles, with no language or date restrictions. Cohort studies of participants undergoing ETV/CPC that reported outcome were included using MOOSE guidelines. The outcome was time to repeat CSF diversion or death. Forest plots were created for pooled mean and its 95 % CI of outcome and morbidity.

Of 78 citations, 11 retrospective reviews (with 524 total participants) were eligible. Efficacy was achieved in 63 % participants at follow-up periods between 6 months and 8 years. Adverse events and mortality was reported in 3.7 and 0.4 % of participants, respectively. Publication bias was detected with respect to efficacy and morbidity of the procedure. A large discrepancy in success was identified between ETV/CPC in six studies from sub-Saharan Africa (71 %), compared to three studies from North America (49 %).

The reported success of ETV/CPC for infantile hydrocephalus is higher in sub-Saharan Africa than developed nations. Large long-term prospective multi-center observational studies addressing patient-important outcomes are required to further evaluate the efficacy and safety of this re-emerging procedure 4).

2016

It is not clear to what degree these metrics should be expected to change after ETV/CPC. Using these clinical metrics, Dewan et al., present and analyze the decision making in cases of ETV/CPC failure.

Infantile hydrocephalus metrics, including bulging fontanel, head circumference z-score, and frontal and occipital horn ratio (FOHR), were compared between ETV/CPC failures and successes. Treatment outcome predictive values of metrics individually and in combination were calculated.

Forty-four patients (57% males, median age 1.2 months) underwent ETV/CPC for hydrocephalus; of these patients, 25 (57%) experienced failure at a median time of 51 days postoperatively. Patients experiencing failure were younger than those experiencing successful treatment (0.8 vs 3.9 months, p = 0.01). During outpatient follow-up, bulging anterior fontanel, progressive macrocephaly, and enlarging ventricles each demonstrated a positive predictive value (PPV) of no less than 71%, but a bulging anterior fontanel remained the most predictive indicator of ETV/CPC failure, with a PPV of 100%, negative predictive value of 73%, and sensitivity of 72%. The highest PPVs and specificities existed when the clinical metrics were present in combination, although sensitivities decreased expectedly. Only 48% of failures were diagnosed on the basis all 3 hydrocephalus metrics, while only 37% of successes were negative for all 3 metrics. In the remaining 57% of patients, a diagnosis of success or failure was made in the presence of discordant data.

Successful ETV/CPC for infantile hydrocephalus was evaluated in relation to fontanel status, head growth, and change in ventricular size. In most patients, a designation of failure or success was made in the setting of discordant data 5).

2014

A study retrospectively reviewed medical records of 27 premature infants with intraventricular hemorrhage (IVH) and hydrocephalus treated with ETV and CPC from 2008 to 2011. All patients were evaluated using MRI before the procedure to verify the anatomical feasibility of ETV/CPC. Endoscopic treatment included third ventriculostomy, septostomy, and bilateral CPC. After ETV/CPC, all patients underwent follow-up for a period of 6-40 months (mean 16.2 months). The procedure was considered a failure if the patient subsequently required a shunt. The following factors were analyzed to determine a relationship to patient outcomes: gestational age at birth, corrected age and weight at surgery, timing of surgery after birth, grade of IVH, the status of the prepontine cistern and cerebral aqueduct on MRI, need for a ventricular access device prior to the endoscopic procedure, and scarring of the prepontine cistern noted at surgery.

Seventeen (63%) of 27 patients required a shunt after ETV/CPC, and 10 patients did not require further CSF diversion. Several factors studied were associated with a higher rate of ETV/CPC failure: Grade IV hemorrhage, weight 3 kg or less and age younger than 3 months at the time of surgery, need for reservoir placement, and presence of a normal cerebral aqueduct. Two factors were found to be statistically significant: the patient’s corrected gestational age of less than 0 weeks at surgery and a narrow prepontine cistern on MRI. The majority (83%) of ETV/CPC failures occurred in the first 3 months after the procedure. None of the patients had a complication directly related to the procedure.

Endoscopic third ventriculostomy/CPC is a safe initial procedure for hydrocephalus in premature infants with IVH and hydrocephalus, obviating the need for a shunt in selected patients. Even though the success rate is low (37%), the lower rate of complications in comparison with shunt treatment may justify this procedure in the initial management of hydrocephalus. As several of the studied factors have shown influence on the outcome, patient selection based on these observations might increase the success rate 6).

2005

A total of 710 children underwent ventriculoscopy as candidates for ETV as the primary treatment for hydrocephalus. The ETV was accomplished in 550 children: 266 underwent a combined ETV-CPC procedure and 284 underwent ETV alone. The mean and median ages were 14 and 5 months, respectively, and 443 patients (81%) were younger than 1 year of age. The hydrocephalus was postinfectious (PIH) in 320 patients (58%), nonpostinfectious (NPIH) in 152 (28%), posthemorrhagic in five (1%), and associated with myelomeningocele in 73 (13%). The mean follow up was 19 months for ETV and 9.2 months for ETV-CPC. Overall, the success rate of ETV-CPC (66%) was superior to that of ETV alone (47%) among infants younger than 1 year of age (p < 0.0001). The ETV-CPC combined procedure was superior in patients with a myelomeningocele (76% compared with 35% success, p = 0.0045) and those with NPIH (70% compared with 38% success, p = 0.0025). Although the difference was not significant for PIH (62% compared with 52% success, p = 0.1607), a benefit was not ruled out (power = 0.3). For patients at least 1 year of age, there was no difference between the two procedures (80% success for each, p = 1.0000). The overall surgical mortality rate was 1.3%, and the infection rate was less than 1%.

The ETV-CPC was more successful than ETV alone in infants younger than 1 year of age. In developing countries in which a dependence on shunts is dangerous, ETV-CPC may be the best option for treating hydrocephalus in infants, particularly for those with NPIH and myelomeningocele 7).


1)

Omar AT, Espiritu AI, Spears J. Endoscopic third ventriculostomy with or without choroid plexus coagulation for myelomeningocele-associated hydrocephalus: systematic review and meta-analysis. J Neurosurg Pediatr. 2022 Jan 21:1-9. doi: 10.3171/2021.11.PEDS21505. Epub ahead of print. PMID: 35061994.
2)

Coulter IC, Dewan MC, Tailor J, Ibrahim GM, Kulkarni AV. Endoscopic third ventriculostomy and choroid plexus cauterization (ETV/CPC) for hydrocephalus of infancy: a technical review. Childs Nerv Syst. 2021 May 15. doi: 10.1007/s00381-021-05209-5. Epub ahead of print. PMID: 33991213.
3)

Dewan MC, Naftel RP. The Global Rise of Endoscopic Third Ventriculostomy with Choroid Plexus Cauterization in Pediatric Hydrocephalus. Pediatr Neurosurg. 2016 Dec 22. doi: 10.1159/000452809. [Epub ahead of print] PubMed PMID: 28002814.
4)

Weil AG, Westwick H, Wang S, Alotaibi NM, Elkaim L, Ibrahim GM, Wang AC, Ariani RT, Crevier L, Myers B, Fallah A. Efficacy and safety of endoscopic third ventriculostomy and choroid plexus cauterization for infantile hydrocephalus: a systematic review and meta-analysis. Childs Nerv Syst. 2016 Nov;32(11):2119-2131. PubMed PMID: 27613635.
5)

Dewan MC, Lim J, Morgan CD, Gannon SR, Shannon CN, Wellons JC 3rd, Naftel RP. Endoscopic third ventriculostomy with choroid plexus cauterization outcome: distinguishing success from failure. J Neurosurg Pediatr. 2016 Dec;25(6):655-662. PubMed PMID: 27564786.
6)

Chamiraju P, Bhatia S, Sandberg DI, Ragheb J. Endoscopic third ventriculostomy and choroid plexus cauterization in posthemorrhagic hydrocephalus of prematurity. J Neurosurg Pediatr. 2014 Apr;13(4):433-9. doi: 10.3171/2013.12.PEDS13219. PubMed PMID: 24527862.
7)

Warf BC. Comparison of endoscopic third ventriculostomy alone and combined with choroid plexus cauterization in infants younger than 1 year of age: a prospective study in 550 African children. J Neurosurg. 2005 Dec;103(6 Suppl):475-81. PubMed PMID: 16383244.

Cilostazol

Cilostazol

Cilostazol, is a antiplatelet drug that inhibits phosphodiesterase 3.

Application of cilostazol was reported to ameliorate vasospasm and improve outcomes in series and clinical trials. But the effectiveness and feasibility of cilostazol on aneurysmal subarachnoid hemorrhage remained controversial.


Kim et al. from the Asan Medical Center retrospectively analyzed the data of 427 patients with unruptured intracranial aneurysms who underwent endovascular treatment between July 2011 and June 2014. When clopidogrel resistance was confirmed via platelet reactivity unit (PRU) assay after dual antiplatelet therapy (aspirin plus clopidogrel) administration for 5 days, triple antiplatelet therapy with cilostazol was administered (Group I, 274 patients). The other group was placed on standard dual antiplatelet therapy (Group II, 153 patients). All patients underwent magnetic resonance diffusion-weighted imaging within 2 days after endovascular coiling.

No significant associations with the occurrence of a thromboembolic event and microembolic event were found between the groups. The occurrence of thromboembolic and microembolic events showed no statistical difference between groups I and II (p = 0.725 for thromboembolic events and p = 0.109 for microembolic events). Also, the PRU value and the occurrence of microembolic events, using a PRU cutoff value of 240, showed no statistical difference (p = 0.114 in group I and 0.064 in group II). There was significant increase in microembolic events after the use of a stent-assisted endovascular procedure. As the PRU value increased, there was a trend toward an increase in the mean number of microembolic lesions without statistical significance.

Even though there is a presumed anti-thromboembolic effect for clopidogrel resistance in other literature, the clinical efficacy of adjustment of additional cilostazol for endovascular coiling of unruptured aneurysms may be limited due to the unspecified cutoff value of the PRU assay for evaluating the resistance 1).

A total of 454 articles were identified using the search criteria. Six articles were selected for systematic review and the 4 randomized controlled trials were included in the meta-analysis. The pooled odds ratio for symptomatic vasospasm, new-onset infarct, and angiographic vasospasm was 0.35 (95% confidence interval [CI], 0.21-0.59; P < 0.0001), 0.38 (95% CI, 0.21-0.66; P = 0.0007) and 0.49 (95% CI, 0.31-0.80; P = 0.004), respectively. The pooled risk ratio for unfavorable outcome was 0.52 (95% CI, 0.37-0.74; P = 0.0003).

Cilostazol decreases the prevalence of symptomatic vasospasm, new-onset infarct, and angiographic vasospasm when administered after aSAH. Trial sequential analysis increased the precision of our results because the defined thresholds of effect were met by the available studies. However, further studies involving patients from other geographic areas are required to confirm the generalization of the results 2)

Shan et al., performed a systematic review to clarify this issue.

PubMed, Ovid and Cochrane library database were systematically searched up to May 2018 for eligible publications in English. Quality assessment was conducted for included studies. Meta-analysis was conducted to evaluate the overall effect on events of interest. Subgroup analyses and sensitivity analyses were used to check whether the results were robust. Publication bias was evaluated with the funnel plot.

Pooled analyses found cilostazol significantly reduced incidences of severe angiographic vasospasm (p = 0.0001), symptomatic vasospasm (p < 0.00001), new cerebral infarction (p < 0.00001) and the poor outcome (p < 0.0001). Subgroup and sensitivity analyses achieved consistent results. There was no statistical difference between cilostazol and the control group in reducing mortality (p = 0.07). But sensitivity analysis changed the result after excluding one study. Under the prescribed dosage, complication was few and non-lethal.

Cilostazol was effective and safe to reduce incidences of severe angiographic vasospasm, symptomatic vasospasm, new cerebral infarction and poor outcome in patients after aneurysmal subarachnoid hemorrhage. However, its effect on mortality and the interactive effect with nimodipine warranted further research 3).

Beneficial for patients with atherothrombosis. In contrast to other anti-platelet drugs such as aspirin and thienopyridines, little information is available on the relationship between platelet responses to cilostazol and clinical outcomes.

Ikeda et al. from the Ehime University Graduate School of Medicine in Japan, conducted a prospective study on patients with cerebral infarction who were treated with cilostazol. The platelet response to cilostazol was assessed with a new assay for the phosphorylation of vasodilator-stimulated phosphoprotein (VASP) subsequent to the pharmacological action of cilostazol. Patients were followed up for 2 years and the relationship between VASP assay results and the recurrence of thrombotic events was examined. We also investigated the effects of CYP3A5 and CYP2C19 genotypes involved in the metabolism of cilostazol on the platelet response to cilostazol.

Among the 142 patients enrolled, 130 completed the 2-year follow-up and the recurrence of thrombotic events was noted in 8 (6.2%). VASP phosphorylation levels were significantly lower in patients with than in those without recurrence. The combined genotype of CYP3A51/3 and CYP2C191/1 was associated with a low level of VASP phosphorylation, while either genotype was not. A multivariate analysis showed that high residual platelet reactivity during the cilostazol treatment, which was defined by a low response of platelet VASP phosphorylation to cilostazol, was an independent risk factor for the recurrence of thrombotic events.

A low platelet response to cilostazol determined by a new platelet assay was associated with the recurrence of thrombotic events in patients with cerebral infarction 4).

established an experimental model using normal and diabetic rats at 12 months of age. The diabetic rats were assigned to 4 different diet groups, distinguished by whether they were fed plain rat feed, or the same feed supplemented by 1 of 3 antiplatelet drugs (cilostazol, aspirin, or clopidogrel: all 0.1%) for 2 weeks, and the carotid artery was perforated by an embolization coil (“carotid coil model”). We monitored the process by which vascular endothelial cells formed the new endothelium on the surface of the coil by sampling and evaluating the region at 1, 2, and 4 weeks after placement. This repair process was also compared among 3 groups treated with different antiplatelet drugs (i.e. aspirin, clopidogrel, and cilostazol). One-way analysis of variance tests were performed to evaluate the differences in vascular thickness between groups, and P < .05 was considered statistically significant.

Results: The diabetic rats showed delayed neoendothelialization and marked intimal hyperplasia. Cilostazol and clopidogrel effectively counteracted this delayed endothelial repair process. Flk1 immunostaining revealed greater expression in the diabetic rats administered cilostazol, second only to normal rats, suggesting that this agent acted to recruit EPCs.

Conclusion: Neoendothelialization is delayed when vascular endothelial cells fail to function normally, which consequently leads to the formation of hyperplastic tissue. Cilostazol may remedy this dysfunction by recruiting EPCs to the site of injury 5).


1)

Kim GJ, Heo Y, Moon EJ, Park W, Ahn JS, Lee DH, Park JC. Thromboembolic events during endovascular coiling for unruptured intracranial aneurysms: Clinical significance of platelet reactivity unit and adjunctive cilostazol. Clin Neurol Neurosurg. 2022 Jan 15;213:107133. doi: 10.1016/j.clineuro.2022.107133. Epub ahead of print. PMID: 35065532.
2)

Bohara S, Garg K, Singh Rajpal PM, Kasliwal M. Role of Cilostazol in Prevention of Vasospasm After Aneurysmal Subarachnoid Hemorrhage-A Systematic Review, Meta-Analysis, and Trial Sequential Analysis. World Neurosurg. 2021 Jun;150:161-170. doi: 10.1016/j.wneu.2021.02.069. Epub 2021 Feb 23. PMID: 33631387.
3)

Shan T, Zhang T, Qian W, Ma L, Li H, You C, Xie X. Effectiveness and feasibility of cilostazol in patients with aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis. J Neurol. 2019 Feb 9. doi: 10.1007/s00415-019-09198-z. [Epub ahead of print] Review. PubMed PMID: 30739182.
4)

Ikeda Y, Yamanouchi J, Kumon Y, Yasukawa M, Hato T. Association of platelet response to cilostazol with clinical outcome and CYP genotype in patients with cerebral infarction. Thromb Res. 2018 Oct 10;172:14-20. doi: 10.1016/j.thromres.2018.10.003. [Epub ahead of print] PubMed PMID: 30342278.
5)

Fukawa N, Ueda T, Ogoshi T, Kitazawa Y, Takahashi J. Vascular Endothelial Repair and the Influence of Circulating Antiplatelet Drugs in a Carotid Coil Model. J Cent Nerv Syst Dis. 2021 May 20;13:11795735211011786. doi: 10.1177/11795735211011786. PMID: 34104032; PMCID: PMC8145582.
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