General neurosurgery, studies

Question 1

ISAT

Answer 1

The International Subarachnoid Aneurysm Trial (ISAT) of
2002 signifcantly infuenced the management of **ruptured intracranial aneurysms **[1]. The trial compared two treatment methods: neurosurgical clipping and endovascular coiling. A total of 2,143 patients with ruptured intracranial aneurysms were enrolled and randomly assigned to either of the two treatments. The primary outcome was the proportion of patients who were dependent or dead (indicated by a modifed Rankin scale score of 3–6) at one year post-treatment.
Results showed a substantial beneft in favor of **endovascular coiling, with 23.7% **of patients in the coiling group versus **30.6% in the clipping **group falling into the dependent or dead category [1]. This fnding marked a pivotal moment in the approach to treating ruptured intracranial aneurysms, suggesting a signifcant advantage of endovascular coiling over neurosurgical clipping in improving patient independence and survival rates at the one-year mark.

Question 2

ISUIA

Answer 2

The International Study of Unruptured Intracranial Aneurysms (ISUIA) Trial of 2003 provided critical insights into the management of unruptured intracranial aneurysms [2].
This extensive study, involving 4,060 patients across various centers, focused on comparing the natural history risks of unruptured aneurysms with the risks associated with surgical or endovascular interventions. Key fndings included detailed data on rupture rates based on aneurysm size and location, revealing that small aneurysms in the anterior circulation had a very low risk of rupture, whereas larger aneurysms, particularly those in the posterior circulation, posed
a higher risk. For instance, aneurysms less than 7 mm in size located in the anterior circulation had a very low risk of rupture. The study also emphasized the importance of individualized treatment decisions, infuenced by factors such as patient age, aneurysm size, and location [2]. These fndings have signifcantly infuenced current practices, advocating for a nuanced and patient-specifc approach in the management of unruptured intracranial aneurysms.

Question 3

CARAT

Answer 3

The Cerebral Aneurysm Rerupture After Treatment
(CARAT) study of 2008 aimed to identify predictors of rerupture following the treatment of ruptured intracranial aneurysms [3]. This study included 1,001 patients and used both coil embolization and surgical clipping as treatment methods. Key fndings indicated that the degree of aneurysm occlusion post-treatment was a strong predictor of subsequent rupture. Specifcally, the study found a graduated risk of rerupture based on the degree of occlusion: complete occlusion presented the lowest risk, while less than 70% occlusion showed the highest risk. While complete aneurysm occlusion of 100% post initial treatment did not guarantee rerupture nonoccurrence, however, the risk of rerupture was only 1.1% in their study group with all events occurring during the frst year [3]. This study underlined the importance of achieving as complete an occlusion as possible during initial treatment to reduce the risk of rerupture.

Question 4

SUAVe

Answer 4

The Small Unruptured Intracranial Aneurysm Verifcation study (SUAVe) of 2010 focused on the natural history and optimal management of incidentally discovered small unruptured intracranial aneurysms** less than 5 mm**in diameter [4]. The study included 540 aneurysms in 446 patients, with a follow-up period averaging 41 months. Key fndings revealed the average annual risks of rupture for small unruptured aneurysms to be relatively low at 0.54% overall, with 0.34% for single aneurysms and 0.95% for multiple aneurysms. Signifcant predictive factors for rupture included patient age below 50 years, aneurysm diameter of 4.0 mm or larger, hypertension, and aneurysm multiplicity [4]. This study underscores the importance of individualized treatment decisions for small unruptured aneurysms, particularly in younger patients with hypertension and multiple aneurysms of larger size.

Question 5

BRAT

Answer 5

The Barrow Ruptured Aneurysm Trial (BRAT) of 2012 was a signifcant study in the feld of neurosurgery that focused on comparing the efcacy and safety of microsurgical clipping and endovascular coil embolization in treating acutely ruptured cerebral aneurysms [5]. Enrolling 470 patients, the trial aimed to determine if one treatment method was superior to the other by analyzing clinical and angiographic outcomes. The study’s primary outcome was based on patient results at 1 year post-treatment, assessed using the modifed Rankin Scale (mRS). A key fnding was that patients assigned to coil embolization had fewer poor outcomes compared to those assigned to surgical clipping [5]. This result supported the growing inclination towards endovascular treatment, emphasizing the need for quality surgical clipping as an alternative treatment modality

Question 6

STICH I

Answer 6

The Surgical Trial in Intracerebral Haemorrhage (STICH) I Trial (2005) was a landmark study in the feld of neurosurgery focusing on spontaneous supratentorial intracerebral hemorrhages [6]. This randomized trial compared early surgery (haematoma evacuation within 24 h of randomization) with initial conservative treatment. The study involved 1,033 patients from 83 centers across 27 countries. The primary outcome measured was the **sixmonth prognosis using the Glasgow outcome scale. **The results showed no signifcant overall beneft from early surgery compared to initial conservative treatment [6]. The trial’s fndings have been infuential in guiding treatment approaches for spontaneous supratentorial intracerebral hemorrhages, highlighting the complexity and need for individualized patient assessment in these cases.

Question 7

STICH II

Answer 7

The STICH II Trial (2013) followed up on the STICH I
Trial to further investigate the efcacy of early surgery
for spontaneous supratentorial lobar intracerebral hemorrhages [7]. This randomized trial involved 601 patients, comparing early surgical hematoma evacuation within 12 hof randomization plus medical treatment against initial conservative treatment. The primary outcome was based on the Extended Glasgow Outcome Scale (GOSE) at 6 months. The fndings showed that **early surgery did not signifcantly increase the rate of death or disability at 6 months compared to conservative treatment, **suggesting a small potential survival advantage for patients with superfcial intracerebral hemorrhage without intraventricular hemorrhage [7].

Question 8

INTERACT‑2

Answer 8

The Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT-2 Trial) (2015) was a signifcant study in the feld of neurosurgery focusing on acute intracerebral hemorrhage (ICH) [8]. The trial investigated the efects of intensive blood pressure (BP) lowering in patients with acute ICH. The study involved 2,839 patients who were randomized to receive either intensive BP lowering treatment (target systolic BP of 140 mm Hg) or guideline-recommended BP lowering treatment. The primary outcome was physical function across all seven levels of the modifed Rankin Scale at 90 days. The trial’s results suggested that intensive BP lowering is benefcial across a wide range of baseline systolic BP levels, and a target systolic BP level of 130–139 mm Hg is likely to provide maximum beneft in acute ICH [8].

Question 9

ATACH‑2

Answer 9

The Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-2) Trial (2016) conducted a comprehensive investigation into the efectiveness of intensive blood
pressure lowering in patients with acute intracerebral hemorrhage [9]. The study involved 1,000 participants, who were
randomized into two groups: one receiving intensive treatment to achieve a target systolic blood pressure of 110 to 139 mm Hg, and the other receiving standard treatment with a target of 140 to 179 mm Hg. A primary focus of the trial was to assess the rate of death or disability at 3 months posttreatment. The fndings indicated that 38.7% of participants in the intensive-treatment group and 37.7% in the standardtreatment group experienced death or disability. This suggested no signifcant diference in outcomes between the two groups. Additionally, the trial found that rapid lowering of blood pressure in patients with acute intracerebral hemorrhage did not result in a lower rate of death or disability compared to standard reduction targets [9]. These results have important implications for the management of blood
pressure in the acute phase of intracerebral hemorrhage, indicating that more aggressive blood pressure reduction may not confer additional benefts in terms of reducing death or disability.

Question 10

CLEAR III

Answer 10

The Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage (CLEAR) III Trial (2017) was an infuential study in the feld of neurosurgery, specifcally
focusing on intraventricular hemorrhage (IVH) treatment
[10]. Conducted between September 2009 and January
2015, this randomized trial involved 500 patients, dividing them into two groups: 249 patients received alteplase, and 251 patients received saline. The primary objective was to assess functional outcomes, measured by the modifed Rankin Scale (mRS), at 180 days post-treatment. One of the key fndings is the primary efcacy outcome (good functional outcome, defned as mRS ≤3) that was similar in both the alteplase group (48%) and the saline group (45%), indicating no signifcant diference in the primary outcome measure. After adjustments for intraventricular hemorrhage size and thalamic intracerebral hemorrhage, a slight diference of 3.5% in favor of alteplase was noted, but this was not statistically signifcant. Notably, the alteplase group exhibited a lower case fatality rate (18% vs. 29% in the saline group) at 180 days, suggesting a potential survival beneft of alteplase treatment. However, a higher proportion of patients in the alteplase group had severe disability
(mRS 5, indicating severe disability requiring constant nursing care and attention). The study also observed lower rates of ventriculitis and serious adverse events in the alteplase group compared to the saline group, suggesting a safety advantage for alteplase. The rate of symptomatic bleeding was similar in both groups. These results suggest that while alteplase did not signifcantly improve functional outcomes in patients with intraventricular hemorrhage compared to saline, it was associated with a lower case fatality rate and fewer serious adverse events. However, a higher proportion of survivors in the alteplase group had severe disability [10].
The trial’s fndings highlight the complexities in managing
intraventricular hemorrhage and point to the need for further research to optimize treatment strategies.

Question 11

Shunt types

Answer 11

Question 12

shunt systems

Answer 12

Question 13

shunt system 2

Answer 13

Question 14

MISTIE III

Answer 14

MISTIE III The Minimally Invasive Surgery with Thrombolysis in Intracerebral Haemorrhage Evacuation (MISTIE) III Trial, conducted in 2019, was a pivotal study in neurosurgery focused on evaluating the efficacy of a minimally invasive surgery plus alteplase in treating intracerebral hemorrhage [11]. This trial involved 506 patients, divided into two groups: one underwent the MISTIE procedure, and the other received standard medical care. The primary aim was to assess functional outcomes using the modified Rankin Scale (mRS) at 365 days. The findings indicated that there was no significant difference in functional outcomes between the two groups. However, the trial noted a slightly lower mortality rate in the MISTIE group compared to standard care, suggesting a potential survival benefit. Additionally, the study found that the MISTIE procedure was safe and did not increase the risk of serious bleeding or infection. Despite these findings, the trial concluded that the MISTIE procedure, as performed in this study, could not be recommended as a standard treatment to improve functional outcomes in all patients with intracerebral hemorrhage, highlighting the need for further research and refinement of the technique [11].

Question 15

DECIMAL

Answer 15

DECIMAL The Decompressive Craniectomy In Malignant MCA Infarction (DECIMAL) Trial of 2007 was a significant study in the field of neurosurgery focusing on malignant middle cerebral artery (MCA) infarction [12]. The trial aimed to assess the efficacy of early decompressive craniectomy in patients with malignant MCA infarction. It involved 38 patients between 18 and 55 years of age, randomized to either standard medical therapy or medical therapy plus decompressive craniectomy. The primary outcome measured was the development of moderate disability (modified Rankin scale score ≤ 3) at 6 months’ follow-up. The results indicated a notable reduction in mortality and an increase in the number of patients with moderate disability in the surgery group compared to the no-surgery group [12]. The trial provided significant insights into the benefits of early decompressive craniectomy in young patients with malignant MCA infarction, emphasizing its potential in improving survival and functional outcomes.

Question 16

DESTINY

Answer 16

**DESTINY The Decompressive Surgery for the Treatment of Malignant Infarction of the Middle Cerebral Artery (DESTINY) Trial of 2007 **focused on the treatment of malignant middle cerebral artery infarction through decompressive surgery (hemicraniectomy) [13]. This randomized controlled trial involved 32 patients and aimed to assess the impact of hemicraniectomy on 30-day mortality and 6- and 12-month functional outcomes. The results demonstrated a significant reduction in mortality for the surgical group compared to conservative therapy, with 88% of patients in the surgical arm surviving at 30 days compared to 47% in the conservative treatment group. However, the primary endpoint, which was functional outcome at 6 months measured by the modified Rankin Scale score dichotomized to 0 to 3 versus 4 to 6, did not show statistical superiority of hemicraniectomy [13]. Despite this, the trial provided valuable insights into the potential benefits of decompressive surgery in reducing mortality in cases of large hemispheric stroke.

Question 17

HAMLET

Answer 17

HAMLET The HAMLET Trial (Hemicraniectomy After Middle Cerebral Artery infarction with Life-threatening Edema Trial) of 2009 was a multicenter, randomized trial focusing on the effects of surgical decompression in patients with space-occupying hemispheric infarctions [14]. The trial included 64 patients who were randomly assigned to either surgical decompression or best medical treatment within 4 days of stroke onset. The primary outcome was functional outcome at 1 year, measured by the modified Rankin scale. The results showed that surgical decompression did not significantly affect the primary outcome measure, but it did reduce case fatality. The trial provided insights into the timing and effectiveness of surgical intervention in patients with space-occupying hemispheric infarction, highlighting the importance of early intervention within 48 h of stroke onset for improving outcomes [14].

Question 18

DESTINY2

Answer 18

**DESTINY II The DESTINY II Trial of 2014 **extended the investigation of decompressive surgery in patients with malignant middle cerebral artery (MCA) infarction [15]. This trial focused on older patients (ages 61 and above) and compared early hemicraniectomy to conservative treatment. It involved 112 patients, with findings showing that hemicraniectomy significantly increased survival without severe disability. The survival rate without severe disability was 38% in the hemicraniectomy group compared to 18% in the control group. However, most survivors required assistance with most bodily needs, with a significant portion experiencing severe disability [15]. The trial’s results highlight the complex decision-making required in treating older patients with malignant MCA infarction, balancing survival against potential disability.

Question 19

CRASH1

Answer 19

CRASH 1 The CRASH-1 Trial of 2004 focused on the effect of intravenous corticosteroids in adults with clinically significant head injury [16]. The trial involved 10,008 patients who were randomly allocated to receive either a 48-h infusion of corticosteroids (methylprednisolone) or a placebo. The primary outcomes were death within 2 weeks of injury and death or disability at 6 months. The results showed that compared with placebo, the risk of death within 2 weeks was higher in the group allocated corticosteroids. This significant finding led to the conclusion that corticosteroids do not reduce mortality and in fact, might increase the risk of death within the first two weeks post-injury

Question 20

CRASH2

Answer 20

CRASH 2 The CRASH-2 Trial (2010) was a significant study in the field of trauma care, specifically focused on the effects of tranexamic acid in trauma patients with significant hemorrhage [17]. This large, randomized, placebo-controlled trial included over 20,000 adult trauma patients from 274 hospitals in 40 countries. The study assessed whether early administration of tranexamic acid (within 8 h of injury) would reduce deaths, vascular occlusive events, and the need for blood transfusion. The results showed that tranexamic acid significantly reduced all-cause mortality and the risk of death due to bleeding. Importantly, the trial found that tranexamic acid safely reduced the risk of death in bleeding trauma patients without increasing the risk of vascular occlusive events. The study’s findings have had substantial implications for the management of trauma patients with significant bleeding [17].

Question 21

CRASH3

Answer 21

CRASH 3 The CRASH-3 Trial, conducted in 2019, focused on the use of tranexamic acid in patients with traumatic brain injury (TBI) [19]. This large-scale, randomized, placebo-controlled trial involved 12,737 patients across 29 countries. The primary aim was to evaluate the effect of tranexamic acid on head injury-related death in hospital within 28 days of injury for patients treated within 3 h of injury. The trial showed that** treatment with tranexamic acid within 3 h of injury** reduced the risk of head injury-related death, particularly in patients with mild-to-moderate head injury, but not in those with severe head injury. Additionally, the risk of vascular occlusive events and seizures was similar between the tranexamic acid and placebo groups, indicating the safety of this treatment in TBI patients. The CRASH-3 trial’s results suggest that early administration of tranexamic acid can be a beneficial intervention in TBI cases, especially for those with less severe injuries [19].

Question 22

SPORT

Answer 22

SPORT 2006 The Spine Patient Outcomes Research Trial (SPORT) of 2006 was a pivotal study in spinal neurosurgery, focusing on the treatment of lumbar disk herniation [22]. Conducted across 13 medical centers in the United States, the trial included 743 patients, who chose between standard open diskectomy (surgery) and usual nonoperative care. The trial’s goal was to assess the effectiveness of these treatments in improving symptoms of radiculopathy secondary to lumbar disk herniation. Patients in both treatment groups experienced substantial improvement over time, but those who underwent surgery reported significantly greater improvements. The benefits of surgery were noticeable as early as 6 weeks and were sustained for at least two years. This suggests that surgery offers a more rapid and possibly more effective treatment for symptoms of lumbar disk herniation, especially in terms of pain relief and physical function. Importantly, the study’s findings emphasize the clinical significance of changes observed in quality-of-life measures. The SPORT results, particularly from the observational cohort, exceeded the thresholds for clinically important differences in scales like the SF-36 subscales and the Oswestry Disability Index (ODI), reinforcing the relevance and impact of the surgical intervention in real-world settings. Overall, the SPORT Trial provides crucial insights into the management of lumbar disk herniation, underlining the effectiveness of surgical intervention, especially in cases where rapid symptom relief and improvement in quality of life are priorities. The study also highlights the importance of patient choice and individualized treatment approaches in managing lumbar disk herniation [22].

Question 23

SPORT 2007

Answer 23

**SPORT 2007 **The SPORT Trial of 2007 further advanced our understanding of the treatment for lumbar degenerative spondylolisthesis, focusing on surgical versus non-surgical approaches [23]. The study, spanning across 13 centers in the United States, enrolled 607 patients. Patients were offered the choice of standard decompressive laminectomy (with or without fusion) or usual non-surgical care. The primary outcome measures were the SF-36 bodily pain and physical function scores and the modified Oswestry Disability Index, assessed over a two-year period. Key findings includes the as-treated analysis across both cohorts showed significant advantages for surgery at 3 months, with this benefit persisting at 1 year and only slightly diminishing at 2 years. Treatment effects at 2 years were significant for bodily pain, physical function, and the Oswestry Disability Index. The study found minimal evidence of harm from either treatment. This trial highlighted the substantial improvement in pain and function over two years in patients treated surgically compared to those receiving non-surgical care, highlighting the importance of individualized treatment decisions in managing lumbar degenerative spondylolisthesis [23].

Question 24

SPORT2008

Answer 24

**SPORT 2008 **The 2008 SPORT Trial, an extension of the 2006 and 2007 studies, further examined treatments for lumbar disc herniation with a focus on **long-term outcomes over a four-year period **[24]. Conducted at 13 medical centers across the U.S., the trial included a total of 634 patients, with 278 in the randomized group and 356 in the observational group. The study continued to compare surgical intervention (standard open diskectomy) with nonoperative care. The results reinforced earlier findings that surgery provided more substantial improvements in pain and function compared to nonoperative care. However, both groups showed significant improvements over time. The extended follow-up of this trial provided valuable insights into the long-term benefits and potential limitations of each treatment option, emphasizing the importance of considering patient choice and long-term implications in the management of lumbar disc herniation [24].

Question 25

SLIP

Answer 25

SLIP The Spinal Laminectomy versus Instrumented Pedicle Screw (SLIP) Trial of 2016, a significant study in spinal neurosurgery, focused on comparing the outcomes of lumbar laminectomy with and without fusion in patients with lumbar spondylolisthesis [25]. The trial involved 130 patients who were screened for eligibility, with 106 patients eventually participating. Among these, 66 consented to randomization, and 40 chose their preferred surgical method but agreed to be part of an observation group. This study specifically aimed to determine if the addition of instrumented fusion to laminectomy would result in greater improvement in patients’ physical health-related quality of life, as measured by the SF-36 physical-component summary score, over a period of two years. Additionally, the study evaluated outcomes at 3 and 4 years. The key findings of the SLIP Trial were that lumbar laminectomy plus fusion was associated with a slightly greater, but clinically meaningful, improvement in physical health-related quality of life compared to laminectomy alone, sustained over 2, 3, and 4 years after surgery. While the between-group differences in the SF-36 physical-component summary score were small, they were considered clinically meaningful. **There were no significant differences between the groups **in terms of reductions in the Oswestry Disability Index score, a secondary measure of disability related to back pain. Patients undergoing fusion experienced more blood loss and longer hospital stays compared to those in the decompression-alone group. The **cumulative rate of reoperation was lower in the fusion group (14%) compared to the decompression-alone group (34%) **[25]. These results highlight the nuanced decision-making process in treating lumbar spondylolisthesis, particularly when weighing the benefits of additional fusion against potential risks and postoperative outcomes.

Question 26

NECK

Answer 26

NECK The NEtherlands Cervical Kinetics (NECK) Trial of 2019 was a significant study in spinal neurosurgery focusing on the effectiveness of different surgical techniques for cervical disc herniation [26]. This double-blinded randomized controlled trial compared anterior cervical discectomy with or without interbody fusion and arthroplasty. It involved 109 patients with one-level herniated disc, randomized to receive one of three treatments: anterior cervical discectomy with disc prosthesis (ACDA), anterior cervical discectomy with fusion (ACDF) using an intervertebral cage, or anterior cervical discectomy without fusion (ACD). Clinical and radiological outcomes were measured up to two years after surgery, including Neck Disability Index (NDI), Visual Analogue Scale (VAS) for neck and arm pain, and radiographic evaluation of cervical curvature and adjacent segment degeneration. The results indicated no significant differences in clinical outcomes among the three surgical methods. All treatment groups showed improvement in NDI and VAS scores for arm and neck pain, with no clear advantage of one technique over the others [26]. This suggests that single-level ACD without an intervertebral device may be a reasonable alternative to ACDF or ACDA, challenging the perceived necessity of intervertebral devices in certain cases of cervical disc herniation.