A Proposed Grading System of Brain and Spinal Cavernomas

Kivelev, Juri; Laakso, Aki; Niemelä, Mika; Hernesniemi, Juha

doi:10.1227/neu.0b013e31821ffbb5

Cited by 44 publications

(35 citation statements)

References 30 publications

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“…TJ expression was also not associated with the postoperative outcome grade according to Kivelev. 17 We found no significant association between TJ protein expression and CM multiplicity, CM location, or DVA presence. Most of our cases were classified as Zabramski Type 233 and an association with TJ expression could not be proved.…”

Section: Clinical Relevance Of Tj Protein Expressioncontrasting

confidence: 63%

“…The reason for that is probably the independent prognostic impact of the eloquent location, which leads to worse clinical presentation irrespective of the other prognostic variables. No association was also noted with the Kivelev grade of postoperative outcome 17 and the Zabramski type of MRI appearance 3,3 although this could be due to a selection bias as only surgically resected cases were included in the study. Unlike Tu et al, 28 we could not find differences in the occurrence of hemosiderin rings.…”

Section: Discussionmentioning

confidence: 92%

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Bleeding propensity of cavernous malformations: impact of tight junction alterations on the occurrence of overt hematoma

Jakimovski¹,

Schneider

Frei

et al. 2014

JNS

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T he underlying mechanisms accounting for the bleeding tendency of cavernous malformations (CMs) are not well understood. Nevertheless, it is presumed that endothelial cell alterations play a central role in the hemorrhage rate and clinical behavior. 34 Among the vessel wall structures evaluated for a possible role in CM aggressiveness are the tight junctions (TJs) between endothelial cells. It is found that within the CM vessel walls only a limited number of TJs are intact, which may contribute to the propensity of the lesions for recurrent hemorrhage. 31In a previous study by our group, the immunoreactivity of three TJ proteins, occludin, claudin-5, and ZO-1 along with glucose transporter 1 molecule (GLUT-1), within the CM vessel wall was evaluated.26 Claudin-5 is involved in the structure of TJ strands and cell adhesion, occludin has accessory function, and ZO-1 is essential for TJ formation due to direct interaction with occludin and claudin-5.11,12 GLUT-1 indicates a functioning blood-brain barrier, and its reduction correlates with TJ protein alterations. 10,13,19 The results of this study showed downregulation the three evaluated TJ proteins and GLUT-1 within the CM vessel walls in comparison with the healthy controls. However, CM vessels were not completely devoid of correctly assembled TJ complexes in all cases. Although Object. Endothelial tight junction (TJ) expression is mostly absent in cerebral cavernous malformations (CMs), which causes increased perilesional erythrocyte and fluid oozing. However, in a subset of CM lesions, foci of preserved TJ staining are observed along endothelial cell contacts. The clinical relevance of this finding is unclear. This study investigates the relevance of the focal TJ protein expression and its association with CM bleeding propensity.Methods. Immunohistochemical staining for the TJ proteins claudin-5, occludin, and ZO-1 was performed on 32 CM specimens that were resected during 2008-2010. The patients were allocated to 2 groups according to TJ protein expression, and the clinical and radiological parameters of aggressiveness were analyzed and compared.Results. Complete absence of TJ expression was identified in 20 specimens, and focal TJ protein expression in 12. CMs without TJ immunoreactivity were significantly larger (p = 0.022) and had a significantly greater propensity for development of frank hematomas (p = 0.028) and perilesional edema (p = 0.013). Symptom severity, multiplicity, developmental venous anomaly (DVA) presence, and CM location did not show a significant difference depending on TJ expression.Conclusions. In a univariate analysis the authors observed significantly less propensity for frank hematomas and perilesional edema as well as smaller size in CM lesions with focal TJ expression compared with CMs without TJ expression. The observed difference in TJ protein expression might be the reason for differences in bleeding propensity of the CM lesions. Although this finding cannot be used in predictive manner at this time, it is a basis for further m...

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Section: Clinical Relevance Of Tj Protein Expressioncontrasting

confidence: 63%

Section: Discussionmentioning

confidence: 92%

Bleeding propensity of cavernous malformations: impact of tight junction alterations on the occurrence of overt hematoma

Jakimovski¹,

Schneider

Frei

et al. 2014

JNS

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“…16,25,31,48,52,56 These lesions most often occupy the intracranial (mainly supratentorial) compartment. 10,16,25,33,52,66 By contrast, spinal cord cavernous malformations are very rare entities, accounting for 5%-12% of intraspinal vascular malformations. 14,24,29 In comparison with cavernous malformations within the cerebral hemispheres, those involving the spinal cord are thought to result in poorer outcomes.…”

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confidence: 99%

“…14,24,29 In comparison with cavernous malformations within the cerebral hemispheres, those involving the spinal cord are thought to result in poorer outcomes. 10,33 Historically, cases of intramedullary spinal cord cavernous malformations (ISCCMs) have been infrequently reported and considered exceptionally rare. To the best of our knowledge, Hadlich 26 provided the first published account of an ISCCM in 1903, and 9 years later, Schultze 57 reported the first successful total resection of an ISCCM in a 29-year-old man.…”

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confidence: 99%

Surgical outcomes and natural history of intramedullary spinal cord cavernous malformations: a single-center series and meta-analysis of individual patient data

Badhiwala¹,

Farrokhyar

Alhazzani

et al. 2014

SPI

118

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Object Information pertaining to the natural history of intramedullary spinal cord cavernous malformations (ISCCMs) and patient outcomes after surgery is scarce. To evaluate factors associated with favorable outcomes for patients with surgically and conservatively managed ISCCMs, the authors performed a systematic review and metaanalysis of the literature. In addition, they included their single-center series of ISCCMs. Methods The authors searched MEDLINE, EMBASE, CINAHL, Google Scholar, and The Cochrane Library for studies published through June 2013 that reported cases of ISCCMs. Data from all eligible studies were used to examine the epidemiology, clinical features, and neurological outcomes of patients with surgically managed and conservatively treated ISCCMs. To evaluate several variables as predictors of favorable neurological outcomes, the authors conducted a meta-analysis of individual patient data and performed univariate and multivariate logistic regression analyses. Variables included patient age, patient sex, lesion spinal level, lesion size, cerebral cavernomas, family history of cavernous malformations, clinical course, presenting symptoms, treatment strategy (operative or conservative), symptom duration, surgical approach, spinal location, and extent of resection. In addition, they performed a meta-analysis to determine a pooled estimate of the annual hemorrhage rate of ISCCMs. Results Eligibility criteria were met by 40 studies, totaling 632 patients, including the authors' institutional series of 24 patients. Mean patient age was 39.1 years (range 2–80 years), and the male-to-female ratio was 1.1:1. Spinal levels of cavernomas were cervical (38%), cervicothoracic (2.4%), thoracic (55.2%), thoracolumbar (0.6%), lumbar (2.1%), and conus medullaris (1.7%). Average cavernoma size was 9.2 mm. Associated cerebral cavernomas occurred in 16.5% of patients, and a family history of cavernous malformation was found for 11.9% of evaluated patients. Clinical course was acute with stepwise progression for 45.4% of patients and slowly progressive for 54.6%. Symptoms were motor (60.5%), sensory (57.8%), pain (33.8%), bladder and/or bowel (23.6%), respiratory distress (0.5%), or absent (asymptomatic; 0.9%). The calculated pooled annual rate of hemorrhage was 2.1% (95% CI 1.3%–3.3%). Most (89.9%) patients underwent resection, and 10.1% underwent conservative management (observation). Outcomes were better for those who underwent resection than for those who underwent conservative management (OR 2.79, 95% CI 1.46–5.33, p = 0.002). A positive correlation with improved neurological outcomes was found for resection within 3 months of symptom onset (OR 2.11, 95% CI 1.31–3.41, p = 0.002), hemilaminectomy approach (OR 3.20, 95% CI 1.16–8.86, p = 0.03), and gross-total resection (OR 3.61, 95% CI 1.24–10.52, p = 0.02). Better outcomes were predicted by an acute clinical course (OR 1.72, 95% CI 1.10–2.68, p = 0.02) and motor symptoms (OR 1.76, 95% CI 1.08–2.86, p = 0.02); poor neurological recovery was predicted by sensory symptoms (OR 0.58, 95% CI 0.35–0.98, p = 0.04). Rates of neurological improvement after resection were no higher for patients with superficial ISCCMs than for those with deep-seated ISCCMs (OR 1.36, 95% CI 0.71–2.60, p = 0.36). Conclusions Intramedullary spinal cord cavernous malformations tend to be clinically progressive. The authors' findings support an operative management plan for patients with a symptomatic ISCCM. Surgical goals include gross-total resection through a more minimally invasive hemilaminectomy approach within 3 months of presentation.

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“…We adjusted for known predictors of poor outcome and baseline imbalances, which have also been identified by a recently published surgical grading scale, 23 but the possibility of residual confounding remains. The sample size was modest, but it included all adults newly diagnosed with a CCM in an adult population of 4.3 million over 5 years, making it larger than any other comparative study, 11 and it identified sufficient outcome events over 5 years of follow-up to power a multivariable analysis of the primary outcome (table 2).…”

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confidence: 99%

Outcome after surgical or conservative management of cerebral cavernous malformations

Moultrie¹,

Horne²,

Josephson³

et al. 2014

Neurology

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Objective: There have been few comparative studies of microsurgical excision vs conservative management of cerebral cavernous malformations (CCM) and none of them has reliably demonstrated a statistically and clinically significant difference. Methods:We conducted a prospective, population-based study to identify and independently validate definite CCM diagnoses first made in 1999-2003 in Scottish adult residents. We used multiple sources of prospective follow-up to assess adults' dependence and to identify and independently validate outcome events. We used univariate and multivariable survival analyses to test the influence of CCM excision on outcome, adjusted for prognostic factors and baseline imbalances.Results: Of 134 adults, 25 underwent CCM excision; these adults were younger (34 vs 43 years at diagnosis, p 5 0.004) and more likely to present with symptomatic intracranial hemorrhage or focal neurologic deficit than adults managed conservatively (48% vs 26%; odds ratio 2.7, 95% confidence interval [CI] 1.1-6.5). During 5 years of follow-up, CCM excision was associated with a deterioration to an Oxford Handicap Scale score 2-6 sustained over at least 2 successive years (adjusted hazard ratio [HR] 2.2, 95% CI 1.1-4.3) and the occurrence of symptomatic intracranial hemorrhage or new focal neurologic deficit (adjusted HR 3.6, 95% CI 1.3-10.0).Conclusions: CCM excision was associated with worse outcomes over 5 years compared to conservative management. Long-term follow-up will determine whether this difference is sustained over patients' lifetimes. Meanwhile, a randomized controlled trial appears justified. Classification of evidence:This study provides Class III evidence that CCM excision worsens shortterm disability scores and increases the risk of symptomatic intracranial hemorrhage and new focal neurologic deficits.

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A Proposed Grading System of Brain and Spinal Cavernomas

Abstract: The proposed grading system showed a convincing correlation with postoperative outcome in surgically treated cavernoma patients.

Cited by 44 publications

References 30 publications

Bleeding propensity of cavernous malformations: impact of tight junction alterations on the occurrence of overt hematoma

Bleeding propensity of cavernous malformations: impact of tight junction alterations on the occurrence of overt hematoma

Surgical outcomes and natural history of intramedullary spinal cord cavernous malformations: a single-center series and meta-analysis of individual patient data

Outcome after surgical or conservative management of cerebral cavernous malformations

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