Noninvasive assessment of glymphatic dysfunction in idiopathic normal pressure hydrocephalus with diffusion tensor imaging

J Neurosurg 140:612–620, 2024

Diffusion tensor imaging (DTI) along the perivascular space (ALPS) (DTI-ALPS)—by calculating the ALPS index, a ratio accentuating water diffusion in the perivascular space—has been proposed as a noninvasive, indirect MRI method for assessing glymphatic function. The main aim of this study was to investigate whether DTI-ALPS would reveal glymphatic dysfunction in idiopathic normal pressure hydrocephalus (iNPH) and whether the ALPS index was associated with disease severity.

METHODS Thirty iNPH patients (13 men; median age 77 years) and 27 healthy controls (10 men; median age 73 years) underwent MRI and clinical assessment with the Timed Up and Go test (TUG) and Mini-Mental State Examination (MMSE); only the patients were evaluated with the Hellström iNPH scale. MRI data were analyzed with the DTI-ALPS method and Radscale screening tool.

RESULTS: iNPH patients showed significantly lower mean ALPS index scores compared with healthy controls (median [interquartile range] 1.09 [1.00–1.15] vs 1.49 [1.36–1.59], p < 0.001). Female healthy controls showed significantly higher ALPS index scores than males in both hemispheres (e.g., right hemisphere 1.62 [1.47–1.67] vs 1.33 [1.14–1.41], p = 0.001). This sex difference was not seen in iNPH patients. The authors found a moderate exponential correlation between mean ALPS index score and motor function as measured with time required to complete TUG (r = −0.644, p < 0.001), number of steps to complete TUG (r = −0.571, p < 0.001), 10-m walk time (r = −0.637, p < 0.001), and 10-m walk steps (r = −0.588, p < 0.001). The authors also found a positive linear correlation between mean ALPS index score and MMSE score (r = 0.416, p = 0.001). Simple linear regression showed a significant effect of diagnosis (B = −0.39, p < 0.001, R 2 = 0.459), female sex (B = 0.232, p = 0.002, R 2 = 0.157), and Evans index (B = −4.151, p < 0.001, R 2 = 0.559) on ALPS index. Multiple linear regression, including diagnosis, sex, and Evans index score, showed a higher predictive value (R 2 = 0.626) than analysis of each of these factors alone.

CONCLUSIONS The ALPS index, which was significantly decreased in iNPH patients, could serve as a marker of disease severity, both clinically and in terms of neuroimaging. However, it is important to consider the significant influence of biological sex and ventriculomegaly on the ALPS index, which raises the question of whether the ALPS index solely reflects glymphatic function or if it also encompasses other types of injury. Future studies are needed to address potential confounding factors and further validate the ALPS method.


Association Between Pseudoprogression of Vestibular Schwannoma After Radiosurgery and Radiological Features of Solid and Cystic Components

Neurosurgery 93:1383–1392, 2023

The pathophysiology of vestibular schwannoma (VS) pseudoprogression after Gamma Knife radiosurgery (GKRS) remains unclear. Radiological features in pretreatment magnetic resonance images may help predict VS pseudoprogression. This study used VS radiological features quantified using an automated segmentation algorithm to predict pseudoprogression after GKRS treatment.

METHODS: This is a retrospective study comprising 330 patients with VS who received GKRS. After image preprocessing and T2W/contrast-enhanced T1-weighted image (CET1W) image generation, with fuzzy C-means clustering, VSs were segmented into solid and cystic components and classified as solid and cystic. Relevant radiological features were then extracted. The response to GKRS was classified into “nonpseudoprogression” and “pseudoprogression/fluctuation”. The Z test for two proportions was used to compare solid and cystic VS for the likelihood of pseudoprogression/fluctuation. Logistic regression was used to assess the correlation between clinical variables and radiological features and response to GKRS.

RESULTS: The likelihood of pseudoprogression/fluctuation after GKRS was significantly higher for solid VS compared with cystic VS (55% vs 31%, P < .001). For the entire VS cohort, multivariable logistic regression revealed that a lower mean tumor signal intensity (SI) in T2W/CET1W images was associated with pseudoprogression/fluctuation after GKRS (P = .001). For the solid VS subgroup, a lower mean tumor SI in T2W/CET1W images (P = .035) was associated with pseudoprogression/fluctuation after GKRS. For the cystic VS subgroup, a lower mean SI of the cystic component in T2W/ CET1W images (P = .040) was associated with pseudoprogression/fluctuation after GKRS.

CONCLUSION: Pseudoprogression is more likely to occur in solid VS compared with cystic VS. Quantitative radiological features in pretreatment magnetic resonance images were associated with pseudoprogression after GKRS. In T2W/ CET1W images, solid VS with a lower mean tumor SI and cystic VS with a lower mean SI of cystic component were more likely to have pseudoprogression after GKRS. These radiological features can help predict the likelihood of pseudoprogression after GKRS.

Wall enhancement as a biomarker of intracranial aneurysm instability: a histo‑radiological study

Acta Neurochirurgica (2023) 165:2783–2791

The aim of this is to explore the histological basis of vessel wall enhancement (WE) on magnetic resonance imaging (MRI), which is a strong radiological biomarker of aneurysmal prone to rupture compared to other classical risk predictors (e.g., PHASES score, size, morphology).

Methods A prospective observational study was performed including all consecutive patients presenting with a saccular intracranial aneurysm at Vall d’Hebron University Hospital between October 2017 and May 2019. The patients underwent high-resolution 3 T MRI, and their aneurysms were classified into asymptomatic, symptomatic, and ruptured. A histological and immunohistochemical study was performed in a subgroup of patients (n = 20, of which 15 presented with WE). Multiple regression analyses were performed to identify predictors of rupture and aneurysm symptoms.

Results A total of 132 patients were enrolled in the study. WE was present in 36.5% of aneurysms: 22.9% asymptomatic, 76.9% symptomatic, and 100% ruptured. Immunohistochemical markers associated with WE were CD3 T cell receptor (p = 0.05) and CD45 leukocyte common antigen (p = 0.05). Moreover, WE is an independent predictor of symptomatic and ruptured aneurysms (p < 0.001).

Conclusions Aneurysms with WE present multiple histopathological changes that may contribute to wall disruption and represent the pathophysiological basis of radiological WE. Moreover, WE is an independent diagnostic predictor of aneurysm symptoms and rupture.

Cerebral Microbleeds—Long-Term Outcome After Cerebrospinal Fluid Shunting in Idiopathic Normal Pressure Hydrocephalus

Neurosurgery 93:300–308, 2023

Cerebral microbleeds (CMBs) are common in idiopathic normal pressure hydrocephalus (INPH) and have been suggested as radiological markers of a brain prone to bleeding. The presence of CMBs might be relevant when selecting patients for shunt surgery.

OBJECTIVE: To evaluate whether CMBs increases long-term risk of hemorrhagic complications and mortality or affects outcomes after cerebrospinal fluid shunt surgery in a cohort of patients with INPH.

METHODS: One hundred and forty nine shunted patients with INPH (mean age, 73 years) were investigated with MRI (T2* or susceptibility-weighted imaging sequences) preoperatively. CMBs were scored with the Microbleed Anatomic Rating Scale. Patients were observed for a mean of 6.5 years (range 2 weeks to 13 years) after surgery. Hemorrhagic events and death were noted. Improvement in gait was evaluated 3 to 6 months after surgery.

RESULTS: At baseline, 74 patients (50%) had CMBs. During follow-up, 7 patients (5%) suffered a hemorrhagic stroke and 43 (29%) suffered a subdural hematoma/hygroma with a median time from surgery of 30.2 months (IQR 50). Overall, having CMBs was not associated with suffering a subdural hematoma/hygroma or hemorrhagic stroke during follow-up with 1 exception that an extensive degree of CMBs (≥50 CMB) was more common in patients suffering a hemorrhagic stroke (P = .03). CMBs were associated with increased mortality (P = .02, Kaplan-Meier, log-rank test). The presence of CMBs did not affect gait outcome (P = .28).

CONCLUSION: CMBs were associated with hemorrhagic stroke and mortality. CMBs do not seem to reduce the possibility of gait improvement after shunt surgery or contribute to the risk of hemorrhagic complications regarding subdural hematoma or hygroma.

Prevalence of incidental intracranial findings on magnetic resonance imaging: a systematic review and meta‑analysis

Acta Neurochirurgica (2022) 164:2751–2765

As the volume and fidelity of magnetic resonance imaging (MRI) of the brain increase, observation of incidental findings may also increase. We performed a systematic review and meta-analysis to determine the prevalence of various incidental findings.

Methods PubMed/MEDLINE, EMBASE and SCOPUS were searched from inception to May 24, 2021. We identified 6536 citations and included 35 reports of 34 studies, comprising 40,777 participants. A meta-analysis of proportions was performed, and age-stratified estimates for each finding were derived from age-adjusted non-linear models.

Results Vascular abnormalities were observed in 423/35,706 participants (9.1/1000 scans, 95%CI 5.2–14.2), ranging from 2/1000 scans (95%CI 0–7) in 1-year-olds to 16/1000 scans (95%CI 1–43) in 80-year-olds. Of these, 204/34,306 were aneurysms (3.1/1000 scans, 95%CI 1–6.3), which ranged from 0/1000 scans (95%CI 0–5) at 1 year of age to 6/1000 scans (95%CI 3–9) at 60 years. Neoplastic abnormalities were observed in 456/39,040 participants (11.9/1000 scans, 95%CI 7.5–17.2), ranging from 0.2/1000 scans (95%CI 0–10) in 1-year-olds to 34/1000 scans (95%CI 12–66) in 80-year-olds. Meningiomas were the most common, in 246/38,076 participants (5.3/1000 scans, 95%CI 2.3–9.5), ranging from 0/1000 scans (95%CI 0–2) in 1-year-olds to 17/1000 scans (95%CI 4–37) in 80-year-olds. Chiari malformations were observed in 109/27,408 participants (3.7/1000 scans, 95%CI 1.8–6.3), pineal cysts in 1176/32,170 (9/1000 scans, 95%CI 1.8–21.4) and arachnoid cysts in 414/36,367 (8.5/1000 scans, 95%CI 5.8–11.8).

Conclusion Incidental findings are common on brain MRI and may result in substantial resource expenditure and patient anxiety but are often of little clinical significance.

Endplate defects, not the severity of spinal stenosis, contribute to low back pain in patients with lumbar spinal stenosis

The Spine Journal 22 (2022) 370−378

It is controversial whether lumbar spinal stenosis (LSS) itself contributes to low back pain (LBP). Lower truncal skeletal muscle mass, spinopelvic malalignment, intervertebral disc degeneration, and endplate abnormalities are thought to be related to LBP. However, whether these factors cause LBP in patients with LSS is unclear.PURPOSE: To identify factors associated with LBP in patients with LSS.

STUDY DESIGN/SETTING: Cross-sectional design.

PATIENT SAMPLE: A total of 260 patients (119 men and 141 women, average age 72.8 years) with neurogenic claudication caused by LSS, as confirmed by magnetic resonance imaging (MRI).

OUTCOME MEASURES: Ratings of LBP, buttock and leg pain, and numbness on a numerical rating scale (NRS), 36-Item Short Form Survey (SF-36) scores, muscle mass measured by bioelectrical impedance analysis, and radiographic measurements including slippage and lumbopelvic alignment. The severity of LSS, endplate defects, Modic endplate changes, intervertebral disc degeneration, and facet joint osteoarthritis were assessed on MRI.

METHODS: The presence of LBP was defined as an NRS score ≥3. The demographic data, patient-reported outcomes, and radiological and MRI findings were compared between patients with and without LBP. Multivariate logistic regression analysis was used to identify the factors that were independently associated with the presence of LBP.

RESULTS: There were significant differences between patients with and without LBP for buttock and leg pain and numbness on the NRS, general health on the SF-36, presence of endplate defects, presence of Modic changes, disc degeneration grading, and disc height grading (all p < .05). Multivariate logistic regression analysis showed significant associations between LBP and diabetes (OR 2.43; 95% CI 1.07−5.53), buttock and leg numbness on the NRS (OR 1.34; 95% CI 1.17−1.52), general health on the SF-36 (OR 0.97; 95% CI 0.95−0.99), and the presence of erosive endplate defects (OR 3.04; 95% CI 1.51−6.11) (all p < .05).

CONCLUSIONS: These results suggest that LBP in patients with LSS should be carefully assessed not only for spinal stenosis but also clinical factors and endplate defects.

Aneurysm Wall Enhancement Is Associated With Decreased Intrasaccular IL-10 and Morphological Features of Instability

Neurosurgery 89:664–671, 2021

High-resolution vessel wall imaging plays an increasingly important role in assessing the risk of aneurysm rupture.

OBJECTIVE: To introduce an approach toward the validation of the wall enhancement as a direct surrogate parameter for aneurysm stability.

METHODS: A total of 19 patients harboring 22 incidental intracranial aneurysms were enrolled in this study. The aneurysms were dichotomized according to their aneurysm to- pituitary stalk contrast ratio using a cutoff value of 0.5 (nonenhancing < 0.5; enhancing ≥ 0.5). We evaluated the association of aneurysm wall enhancement with morphological characteristics, hemodynamic features, and inflammatory chemokines directly measured inside the aneurysm.

RESULTS: Differences in plasma concentration of chemokines and inflammatory molecules, morphological, and hemodynamic parameters were analyzed using the Welch test or Mann-Whitney U test. The concentration  IL-10 in the lumen of intracranial aneurysms with low wall enhancement was significantly increased compared to aneurysms with strong aneurysm wall enhancement (P = .014). The analysis of morphological and hemodynamic parameters showed significantly increased values for aneurysm volume (P=.03), aneurysm area (P=.044), maximal diameter (P=.049), and nonsphericity index (P=.021) for intracranial aneurysms with strong aneurysm wall enhancement. None of the hemodynamic parameters reached statistical significance; however, the total viscous shear force computed over the region of low wall shear stress showed a strong tendency toward significance (P = .053).

CONCLUSION: Aneurysmal wall enhancement shows strong associations with decreased intrasaccular IL-10 and established morphological indicators of aneurysm instability.


Impact of focal apex angle on postoperative decompression status of the spinal cord and neurological recovery after cervical laminoplasty

J Neurosurg Spine 35:410–418, 2021

Although anterior compression factors and cervical alignment affect neural decompression, cervical laminoplasty may be used to achieve indirect posterior decompression. The focal apex (FA) angle of the anterior compression factor of the spine represents the degree of anterior prominence toward the spinal cord. The authors investigated the mechanism underlying the influence of FA angle and cervical alignment on spinal cord alignment (SCA) after laminoplasty, including how high-intensity signal cord change (HISCC) on preoperative T2-weighted MRI (T2-MRI) may affect neurological improvement.

METHODS We performed a retrospective study of patients who underwent laminoplasty for CSM or OPLL at two hospitals (Kanto Rosai Hospital, Kawasaki City, and Yokohama Minami Kyousai Hospital, Yokohama City, Japan) between April 2004 and March 2015. In total, 109 patients (mean age 67.3 years) with cervical compression myelopathy were included. FA angle was defined as the preoperative angle between the lines from the top of the prominence to the upper and lower adjacent vertebrae. Preoperative cervical alignment was measured between the C2 and C7 vertebrae (C2–7 angle). MRI was used to classify SCA as lordosis (type-L SCA), straight (type-S), local kyphosis (type-LK), or kyphosis (type-K). Preoperative HISCC was investigated by using T2-MRI. Neurological status was evaluated by using the Japanese Orthopaedic Association score.

RESULTS The mean preoperative FA and C2–7 angles were 32.1° and 12.4°, respectively. Preoperative SCA was type- L or type-S in 53 patients. The neurological recovery rate (NRR) was significantly higher for patients with preoperative type-L and type-S SCA (51.4% for those with type-L and 45.0% for those with type-S) than for patients with other types (35.3% for those with type-LK and 31.7% for those with type-K). Among patients with preoperative type-L or type-S SCA, 87.3% maintained SCA; however, 5/12 (41.7%) patients with a preoperative average C2–7 angle < 12.4° and an average FA angle > 32.1° had postoperative type-LK or type-K SCA. SCA changed to type-L or type-S in 13.0% of patients with preoperative type-LK or type-K SCA. Moreover, in these patients, FA angle was significantly smaller and NRR was significantly higher than in other patients in whom postoperative SCA remained type-LK or type-K. Preoperative T2- MRI showed 73 patients with HISCC (43 with type-L and type-S, and 30 with type-LK and type-K SCA) and 36 without HISCC (20 with type-L and type-S, and 16 with type-LK and type-K SCA); the NRRs of these patients were 42.6% and 41.2%, respectively. No significant differences in SCA or NRR were observed between patients with and without HISCC.

CONCLUSIONS NRR depends on preoperative SCA type; however, it is possible to change the type of SCA after laminoplasty. Preoperative FA and C2–7 angles influence change in SCA; therefore, they are important parameters for successful decompression with cervical laminoplasty.

Magnetic Resonance Imaging-Guided Laser Thermal Ventral Capsulotomy for Intractable Obsessive-Compulsive Disorder

Neurosurgery 88:1128–1135, 2021

Obsessive-compulsive disorder (OCD) is a disabling condition characterized by intrusive thoughts and repetitive behaviors. A subset of individuals have severe, treatment-resistant illness and are nonresponsive to medication or behavioral therapies. Without response to conventional therapeutic options, surgical intervention becomes an appropriate consideration.

OBJECTIVE: To report clinical outcomes and the safety profile of bilateral ventral anterior capsulotomy for OCD using magnetic resonance (MR)-guided laser interstitial thermal therapy (LITT) in 10 patients followed for 6 to 24 mo.

METHODS: A total of 10 patients underwent LITT for severe OCD; 1 patient withdrew prior to follow-up. LITT is a minimally invasive ablative technique performed with precise targeting and use of thermography under MR guidance. Lesions of the ventral anterior limb of the internal capsule by other techniques have been shown to be efficacious in prior studies.

RESULTS: A total of 7 of the 9 patients were considered full responders (77.8%; Yale- Brown Obsessive-Compulsive Scale change ≥35%). Adverse effects included transient apathy/amotivation postsurgery (2 patients). One patient had a small tract hemorrhage where the laser fiber traversed the cerebral cortex as well as persistent insomnia postsurgery. One individual died after a drug overdose 7 mo postsurgery, which was judged unrelated to the surgery.

CONCLUSION: LITT ventral capsulotomy was generally well tolerated, with promising evidence of effectiveness in the largest such series to date. Results were comparable to those after gamma knife ventral capsulotomy, as well as ventral anterior limb deep brain stimulation.


Subclinical imaging changes in cerebral cavernous angiomas during prospective surveillance

J Neurosurg 134:1147–1154, 2021

The purpose of this study was to systematically assess asymptomatic changes (ACs), including subclinical hemorrhage, growth, or new lesion formation (NLF) during longitudinal follow-up of cerebral cavernous angiomas (CAs), and to correlate these with symptomatic hemorrhage (SH) during the same period and with clinical features of the disease.

METHODS One hundred ninety-two patients were included in this study, among 327 consecutive patients with CA, prospectively identified between September 2009 and February 2019. Included patients had undergone clinical and MRI follow-up, in conjunction with institutional review board–approved biomarker studies, and harbored ≥ 1 CA with a maximum diameter of ≥ 5 mm on T2-weighted MRI. Rates of AC and SH per lesion-year and patient-year were assessed using prospectively articulated criteria. In multifocal/familial cases, rates of NLF were also assessed.

RESULTS There were no differences in demographic or disease features among cases included or excluded in the study cohort, except for a higher proportion of included patients with CCM3 mutation. Follow-up was 411 patient-years (2503 lesion-years). The rate of AC was higher than the rate of SH (12.9% vs 7.5% per patient-year, and 2.1% vs 1.2% per lesion-year, both p = 0.02). Patients presenting with a prior history of SH had a higher rate of AC than those with other forms of presentation (19.7% and 8.2% per patient-year, respectively; p = 0.003). A higher rate of NLF on T2-weighted MRI (p = 0.03) was observed in patients with prior SH. Three of 6 solitary/sporadic and 2 of 28 multifocal/familial patients underwent resection of the lesion after AC.

CONCLUSIONS Rates of AC are greater than SH during prospective follow-up of CAs, and greater in cases with prior SH. AC may be a more sensitive biomarker of lesional activity, and a more efficient surrogate outcome in clinical trials than SH. Patients experiencing an AC are more likely to undergo a surgical intervention when CAs are solitary/sporadic than when they are multifocal/familial.


Neuroimaging of Intracerebral Hemorrhage

Neurosurgery 86:E414–E423, 2020

Intracerebral hemorrhage (ICH) accounts for 10% to 20% of strokes worldwide and is associated with high morbidity and mortality rates. Neuroimaging is indispensable for rapid diagnosis of ICH and identification of the underlying etiology, thus facilitating triage and appropriate treatment of patients.

The most common neuroimaging modalities include noncontrast computed tomography (CT), CT angiography (CTA), digital subtraction angiography, andmagnetic resonance imaging (MRI). The strengths and disadvantages of each modality will be reviewed.

Novel technologies such as dual-energy CT/CTA, rapid MRI techniques, near-infrared spectroscopy, and automated ICH detection hold promise for faster pre- and in-hospital ICH diagnosis that may impact patient management.

3-Tesla MRI of deep brain stimulation patients: safety assessment of coils and pulse sequences

J Neurosurg 132:586–594, 2020

Physicians are more frequently encountering patients who are treated with deep brain stimulation (DBS), yet many MRI centers do not routinely perform MRI in this population. This warrants a safety assessment to improve DBS patients’ accessibility to MRI, thereby improving their care while simultaneously providing a new tool for neuromodulation research.

METHODS A phantom simulating a patient with a DBS neuromodulation device (DBS lead model 3387 and IPG Activa PC model 37601) was constructed and used. Temperature changes at the most ventral DBS electrode contacts, implantable pulse generator (IPG) voltages, specific absorption rate (SAR), and B1+rms were recorded during 3-T MRI scanning. Safety data were acquired with a transmit body multi-array receive and quadrature transmit-receive head coil during various pulse sequences, using numerous DBS configurations from “the worst” to “the most common.” In addition, 3-T MRI scanning (T1 and fMRI) was performed on 41 patients with fully internalized and active DBS using a quadrature transmit-receive head coil. MR images, neurological examination findings, and stability of the IPG impedances were assessed.

RESULTS In the phantom study, temperature rises at the DBS electrodes were less than 2°C for both coils during 3D SPGR, EPI, DTI, and SWI. Sequences with intense radiofrequency pulses such as T2-weighted sequences may cause higher heating (due to their higher SAR). The IPG did not power off and kept a constant firing rate, and its average voltage output was unchanged. The 41 DBS patients underwent 3-T MRI with no adverse event.

CONCLUSIONS Under the experimental conditions used in this study, 3-T MRI scanning of DBS patients with selected pulse sequences appears to be safe. Generally, T2-weighted sequences (using routine protocols) should be avoided in DBS patients. Complementary 3-T MRI phantom safety data suggest that imaging conditions that are less restrictive than those used in the patients in this study, such as using transmit body multi-array receive coils, may also be safe. Given the interplay between the implanted DBS neuromodulation device and the MRI system, these findings are specific to the experimental conditions in this study.


Lumbar disc extrusions reduce faster than bulging discs due to an active role of macrophages in sciatica

Acta Neurochirurgica (2020) 162:79–85

This retrospective observational histological study aims to associate the size and type of disc herniation with the degree of macrophage infiltration in disc material retrieved during disc surgery in patients with sciatica.

Methods Disc tissue of 119 sciatica patients was embedded in paraffin and stained with hematoxylin and CD68. Tissue samples were categorized as mild (0–10/cm2), moderate (10–100/cm2), and considerable (> 100/cm2) macrophage infiltration. All 119 patients received an MRI at baseline, and 108 received a follow-up MRI at 1-year. MRIs were reviewed for the size and type of the disc herniations, and for Modic changes in the vertebral endplates.

Results Baseline characteristics and duration of symptoms before surgery were comparable in all macrophage infiltration groups. The degree of macrophage infiltration was not associated with herniation size at baseline, but significantly associated with reduction of size of the herniated disc at 1-year post surgery. Moreover, the degree of macrophage infiltration was higher in extrusion in comparison with bulging (protrusion) of the disc. Results were comparable in patients with and without Modic changes.

Conclusion Macrophage infiltration was positively associated with an extruded type of disc herniation as well as the extent of reduction of the herniated disc during 1-year follow-up in patients with sciatica. This is an indication that the macrophages play an active role in reducing herniated discs. An extruded disc herniation has a larger surface for the macrophages to adhere to, which leads to more size reduction.

Flow diversion treatment of complex bifurcation aneurysms beyond the circle of Willis: complications, aneurysm sac occlusion, reabsorption, recurrence, and jailed branch modification at follow-up

J Neurosurg 131:1751–1762, 2019

The purpose of this study is to present the authors’ medium-term results, with special emphasis on complications, occlusion rate of the aneurysm sac (digital subtraction angiography [DSA] and MRI), and the fate of cortical branches and perforating arteries covered (“jailed”) by the flow diverter (FD) stent.

METHODS Between January 2010 and September 2017, 29 patients (14 female) with 30 aneurysms were treated with an FD stent. Twenty-one aneurysms were at the middle cerebral artery bifurcation, 8 were in the anterior communicating artery region, and 1 was a pericallosal artery bifurcation. Thirty-five cortical branches were covered. A single FD stent was used in all patients. Symptomatic and asymptomatic periprocedural and delayed complications were reported. DSA and MRI controls were analyzed to evaluate modification of the aneurysm sac and jailed branches.

RESULTS Permanent morbidity was 3.4% (1/29), due to a jailed branch occlusion, with a modified Rankin Scale (mRS) score of 2 at the last follow-up. Mortality and permanent complication with poor prognosis (mRS score > 2) rates were 0%. The mean follow-up time for DSA and MRI (mean ± SD) was 21 ± 14.5 months (range 3–66 months) and 19 ± 16 months (range 3–41 months), respectively. The mean time to aneurysm sac occlusion (available for 24 patients), including stable remodeling, was 11.8 ± 6 months (median 13, range 3–27 months). The overall occlusion rate was 82.1% (23/28), and it was 91.7% (22/24) in the group of patients with at least 2 DSA control sequences. One recanalization occurred at 41 months posttreatment. At the time of publication, at the latest follow-up, 7 (20%) of 35 covered branches were occluded, 18 (51.4%) showed a decreased caliber, and the remaining 10 (28.5%) were unchanged. MRI T2-weighted sequences showed complete sac reabsorption in 7/29 aneurysms (24.1%), and the remaining lesions were either smaller (55.2%) or unchanged (17.2%). MRI revealed asymptomatic and symptomatic ischemic events in perforator territories in 7/28 (25%) and 4/28 (14.3%) patients, respectively, which were reversible within 24 hours.

CONCLUSIONS Flow diversion of bifurcation aneurysms is feasible, with low rates of permanent morbidity and mortality and high occlusion rates; however, recurrence may occur. Caliber reduction and asymptomatic occlusion of covered cortical branches as well as silent perforator stroke are common. Ischemic complications may occur with no identified predictable factors. MRI controls should be required in all patients to evaluate silent ischemic lesions and aneurysm sac reabsorption over time.

Idiopathic Normal-Pressure Hydrocephalus: Diagnostic Accuracy of Automated Sulcal Morphometry in Patients With Ventriculomegaly

Neurosurgery 85:E747–E755, 2019

Idiopathic normal-pressure hydrocephalus (iNPH) is a treatable cause of gait and cognitive impairment. iNPH should be differentiated from ventriculomegaly secondary to brain atrophy to choose the best therapeutic option (ventriculoperitoneal shunt vs medical management).

OBJECTIVE: To determine the diagnostic accuracy of automated sulcal morphometry to differentiate patients with iNPH from patients with ventriculomegaly of neurodegenerative origin.

METHODS: Thirty-eight consecutive patients with iNPH (shunt responsive n = 31, nonresponsive n = 7), 35 with vascular cognitive disorder, and 25 age- and sex-matched healthy controls were prospectively included and underwent cognitive evaluation and 3T brain magnetic resonance imaging. Sulcal opening of 10 sulci of interest was retrospectively measured using an automated surface-based approach from the 3-dimensional T1-weighted images. Receiver-operating characteristic curve analyses determined the best parameter to identify iNPH patients.

RESULTS: The best parameter to discriminate shunt-responsive iNPH from patients with vascular cognitive disorder and healthy controls was the ratio between calcarine sulcus and cingulate sulcus opening with an area under the curve of 0.94 (95% CI: 0.89, 0.99). A cut-off value of 0.95 provided the highest sensitivity (96.8%) and specificity (83.3%).

CONCLUSION: This preliminary study showed that automated sulcal morphometry may help the neurosurgeon to identify iNPH patients and to exclude other causes of ventriculomegaly.


Somatotopy and Organization of Spinothalamic Tracts in the Human Cervical Spinal Cord

Neurosurgery, Volume 84, Issue 6, June 2019, Pages E311–E317

Understanding spinothalamic tract anatomy may improve lesioning and outcomes in patients undergoing percutaneous cordotomy.

OBJECTIVE: To investigate somatotopy and anatomical organization of spinothalamic tracts in the human cervical spinal cord.

METHODS: Patients with intractable cancer pain undergoing cordotomy underwent preoperative and postoperative quantitative sensory testing for sharp pain and heat pain on day 1 and 7 after cordotomy. Intraoperative sensory stimulation was performed with computed tomography (CT) imaging to confirm the location of the radiofrequency electrode during cordotomy. Postoperative magnetic resonance (MR) imaging was performed to define the location of the lesion.

RESULTS: Twelve patientswere studied, and intraoperative sensory stimulation combined with CT imaging revealed a somatotopy where fibers from the legs were posterolateral to fibers from the hand. Sharpness detection thresholds were significantly elevated in the area of maximum pain on postoperative day 1 (P = .01). Heat pain thresholds for all areas were not elevated significantly on postoperative day 1, or postoperative day 7. MR imaging confirmed that the cordotomy lesion was in the anterolateral quadrant, and in this location the lesion had a sustained effect on sharp pain but a transient impact on heat pain.

CONCLUSION: In the high cervical spinal cord, spinothalamic fibers mediating sharp pain for the arms are located ventromedial to fibers for the legs, and these fibers are spatially distinct from fibers that mediate heat pain.

Trigeminal Nerve Atrophy Predicts Pain Recurrence After Gamma Knife Stereotactic Radiosurgery for Classical Trigeminal Neuralgia

Neurosurgery 84:927–934, 2019

Trigeminal nerve atrophy and neurovascular compression (NVC) are frequently observed in classical trigeminal neuralgia (CTN).

OBJECTIVE: To determine whether nerve characteristics contribute to Gamma Knife (ElektaAB, Stockholm, Sweden) surgery (GKS) outcomes in unilateral CTN without previous surgery.

METHODS: From 2006 to 2012, 67 patients with unilateral CTN without previous surgery received GKS with a maximal dose of 90 Gy delivered to the trigeminal nerve juxta brainstem. Two evaluators, blinded to the side of pain, analyzed the magnetic resonance images before GKS to obtain the parameters, including nerve cross-sectional area (CSA), vessel type of NVC, and site of NVC along the nerve. Correlations of the parameters with pain relief (Barrow Neurological Institute [BNI] grades I-IIIb) and recurrence (BNI grades VIV) were made by using Cox regression and Kaplan–Meier analyses.

RESULTS: The median CSA of the symptomatic nerves was significantly smaller than that of the asymptomatic nerves (4.95 vs 5.9 mm2, P < .001). After adjustment for age and sex, larger nerve CSA was associated with lower initial pain relief (hazard ratio 0.81, P=.03) and lower pain recurrence after initial response (hazard ratio 0.58, P= .02). Patients with nerve atrophy (CSA of ≤ 4.4 mm2 after receiver operating characteristic curve analysis) had a lower 5-yr probability of maintaining pain relief after initial response than those without nerve atrophy (65% vs 86%, P= .04).

CONCLUSION: Trigeminal nerve atrophy may predict pain recurrence in patients with initial post-GKS relief of CTN.Arterial and proximalNVCare not predictive ofGKS outcomes. Future studies are required to determine optimal treatments for long-term pain relief in patients with CTN and trigeminal nerve atrophy.

The role of diffusion tensor imaging in the diagnosis, prognosis, and assessment of recovery and treatment of spinal cord injury: a systematic review

Neurosurg Focus 46 (3):E7, 2019

Diffusion tensor imaging (DTI) is an MRI tool that provides an objective, noninvasive, in vivo assessment of spinal cord injury (SCI). DTI is significantly better at visualizing microstructures than standard MRI sequences. In this imaging modality, the direction and amplitude of the diffusion of water molecules inside tissues is measured, and this diffusion can be measured using a variety of parameters. As a result, the potential clinical application of DTI has been studied in several spinal cord pathologies, including SCI. The aim of this study was to describe the current state of the potential clinical utility of DTI in patients with SCI and the challenges to its use as a tool in clinical practice.

METHODS A search in the PubMed database was conducted for articles relating to the use of DTI in SCI. The citations of relevant articles were also searched for additional articles.

RESULTS Among the most common DTI metrics are fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. Changes in these metrics reflect changes in tissue integrity. Several DTI metrics and combinations thereof have demonstrated significant correlations with clinical function both in model species and in humans. Its applications encompass the full spectrum of the clinical assessment of SCI including diagnosis, prognosis, recovery, and efficacy of treatments in both the spinal cord and potentially the brain.

CONCLUSIONS DTI and its metrics have great potential to become a powerful clinical tool in SCI. However, the current limitations of DTI preclude its use beyond research and into clinical practice. Further studies are needed to significantly improve and resolve these limitations as well as to determine reliable time-specific changes in multiple DTI metrics for this tool to be used accurately and reliably in the clinical setting.


CircumferentialWall Enhancement on Magnetic Resonance Imaging is Useful to Identify Rupture Site in Patients with Multiple Cerebral Aneurysms

Neurosurgery 82:638–644, 2018

Identification of rupture sites in patients with multiple intracranial aneurysms is largely based on aneurysm size, location, and shape. Finding circumferential enhancement along the aneurysm wall (CEAW) on magnetic resonance (MR) vessel wall imaging was recently shown to be indicative of ruptured aneurysm.

OBJECTIVE: To investigate the hypothesis that a higher degree of CEAW would identify the site of rupture in patients with multiple aneurysms.

METHODS: We prospectively performed quantitative analysis of CEAW in consecutive patients with both aneurysmal subarachnoid hemorrhage and multiple aneurysms (26 patientswith a total of 62 aneurysms), usingMR vesselwall imaging. Three-dimensional T1-weighted fast spin-echo sequenceswere obtained before and after injection of contrast media, and the wall enhancement index (WEI) was calculated. Aneurysm characteristics (size, location, irregular shape, aspect ratio [neck-to-dome length/neck width], and WEI) were compared between ruptured and unruptured aneurysms. Odds ratios with 95% confidence intervals for ruptures were calculated with conditional univariable logistic regression analysis. Analyses were repeated after adjustment for aneurysm size.

RESULTS: Large aneurysm size, high aspect ratio, WEI (above the median values), and irregular shape were significantly associated with aneurysm rupture. After adjustment for aneurysm size, WEI (adjusted odds ratio: 8.8; 95% confidence interval, 1.1-72.6) as well as irregular shape and aspect ratio showed a strong association with rupture.

CONCLUSION: CEAW is associated with rupture of intracranial aneurysm independent of aneurysm size and patient characteristics. Contrast-enhanced MR vessel wall imaging helps to identify the site of rupture in patients with multiple aneurysms.