Alice L. Hung

Lower Risk of Intracranial Arteriovenous Malformation Hemorrhage in Patients With Hereditary Hemorrhagic Telangiectasia

BACKGROUND Patients diagnosed with hereditary hemorrhagic telangiectasia (HHT) are at risk of developing intracranial arteriovenous malformations (AVM). However, the clinical manifestations and natural history of HHT-related AVMs remain unclear due to the rarity of these lesions. OBJECTIVE To clarify the clinical characteristics and hemorrhagic risk in HHT-related AVMs. METHODS We performed a retrospective review of all patients diagnosed with both HHT and intracranial AVMs who were evaluated at our institution from 1990 to 2013. Patients with missing data or lost to follow-up were excluded. Baseline characteristics and subsequent hemorrhagic risk were evaluated. RESULTS In an AVM database of 531 patients with 542 AVMs, a total of 12 HHT patients (2.3%) with 23 AVMs were found. Mean age at diagnosis was 36.5 years, with 41.7% male. Compared to patients with sporadic AVMs, patients with HHT were less likely to present with ruptured AVM (P = .04), headaches (P = .02), and seizures (P = .02), and presented with better modified Rankin scores (P < .01). HHT-related AVMs were smaller in size (P < .01), of lower Spetzler-Martin grade (P = .01), and had less temporal lobe involvement (P = .02) compared to sporadic AVMs. Six HHT patients (50.0%) were found with multiple intracranial AVMs. One hemorrhage was found during an observation period of 149.6 patient-years and 297.5 lesion-years, translating to 1.3% per patient per year or 0.7% per AVM per year. CONCLUSION HHT-related AVMs are smaller in size with lower Spetzler-Martin grade and less temporal lobe involvement than sporadic AVMs. Patients with HHT frequently present with multiple intracranial AVMs. Conservative management is generally recommended due to lesion multiplicity and relatively low hemorrhagic risk.

Delayed Hemorrhage After Treatment of Brain Arteriovenous Malformations (AVMs)

OBJECTIVE The risk of delayed hemorrhage occurring greater than 2 years after treatment in brain arteriovenous malformations (AVMs) rarely is reported. In this study, we compare the risk of delayed hemorrhage across different treatment modalities. METHODS We performed a retrospective chart review of treated patients with a single intracranial AVM seen at our institution from 1990 to 2013. Delayed hemorrhage was defined as hemorrhage occurring at least 2 years after last treatment. Survival analysis was used to assess risk of delayed hemorrhage by treatment modalities. RESULTS Our study included 420 patients. Spetzler-Martin grades were as follows: I (12.6%), II (36.2%), III (32.6%), IV (15.0%), and V (3.6%). Average follow-up time is 5.1 years. Twenty-two patients (5.2%) were found to have 28 delayed hemorrhages. Average interval between last treatment and delayed hemorrhage was 7.6 years, with the longest being 24.2 years. Proportions of delayed hemorrhages by treatment modalities were as follows: surgery ± embolization (group I, 9.1%), radiosurgery ± embolization (group II, 63.6%), embolization only (group III, 22.7%), and surgery + radiosurgery ± embolization (group IV, 4.5%). Annualized hemorrhage risk after 2 years for each treatment group was as follows: group I (0.4%), group II (1.2%), group III (3.7%), and group IV (1.7%). Survival analysis demonstrated lowest risk of delayed hemorrhage for group 1 (P < 0.01). CONCLUSIONS This study is the first to compare the risk of delayed hemorrhage across different treatment modalities. Surgical resection is associated with the lowest risk for delayed hemorrhage compared with other treatment modalities. Patients with partially embolized AVMs should seek timely definitive treatment to decrease the risk of delayed hemorrhage.

Ventriculoatrial versus ventriculoperitoneal shunt complications in idiopathic normal pressure hydrocephalus

BACKGROUND Idiopathic normal pressure hydrocephalus (iNPH) is a devastating condition that affects the elderly population. Although ventriculoatrial (VA) shunts can be used to manage iNPH, concerns for associated cardiopulmonary and renal complications have decreased their use. However, the rate of these complications is not well understood within this population of patients. PATIENTS AND METHODS A retrospective review of the electronic medical records of patients diagnosed with iNPH by the senior author between 1993 and 2015 was performed. Demographic information and baseline symptoms were assessed. Complications including infection, shunt obstruction, overdrainage, cardiopulmonary events, renal dysfunction, and shunt revision were recorded. Complication rates were compared between VA and VP shunted patients. Statistical analysis using Chi-square test, Fishers exact test, logistic regression, Wald t-test, Poisson regression, ANOVA, and ANCOVA was performed. RESULTS 496 Patients, including 150 receiving VA shunts and 346 receiving VP shunts, were included in the study. The median age was 74 and 73 for VA and VP shunted patients, respectively, with slight male predominance in both (58.0% and 58.4% for VA and VP groups, respectively). A total of 36.0% of VA shunted patients and 42.5% of VP shunted patients experienced at least one post-operative complication. Overdrainage was the most commonly experienced complication in both VA (27.4%) and VP patients (19.9%). Infection occurred in only 2.0% of patients, and renal complications occurred in 1.3%. No patients had cardiopulmonary complications. VA shunted patients were significantly less likely to experience shunt obstruction and require shunt revision compared to VP shunted patients (p=0.008 and <0.001, respectively). Only dizziness and gait disturbance at baseline were correlated with a shorter time to revision in VA shunted patients (p=0.002 for both). CONCLUSION Although cardiopulmonary and renal complications are serious concerns associated with VA shunt placement, they were uncommon in patients with iNPH. VA shunted patients were less likely to experience shunt obstruction and require shunt revision compared to VP shunted patients. Therefore, VA shunts should be considered as an alternative primary treatment option in the iNPH population.

Risk of hemorrhage in patients over age 60 with arteriovenous malformations (AVMs)

Treatment selection for patients 60years of age and older with intracranial arteriovenous malformations (AVMs), requires careful consideration of the natural history and post-treatment hemorrhagic risk. We aimed to directly compare the natural history of AVMs with post-treatment hemorrhagic risk in this population. We retrospectively reviewed our AVM database of 683 patients. Patients ⩾60years at diagnosis were included. Treatment modality was divided into four groups: surgery±embolization (SE), radiosurgery±embolization (RE), embolization only (Emb), and observation (Obs). The natural history of the AVM was defined as the annual risk of hemorrhage under observation. Risk of hemorrhage after treatment was also calculated. Sixty-one patients with complete data were included. Average age was 68.4±7.5years, with 55.7% (n=34) being male. Twenty-seven (44.3%) patients presented with intracerebral hemorrhage (ICH). At last follow-up, modified Rankin Scale was higher in patients with subsequent hemorrhages (p=0.023). Overall, obliteration was 65.5%, with 100.0% in the SE group and 43.8% in the RE group (p<0.001). During an average follow-up period of 2.8±3.2years, six patients (9.8%) experienced hemorrhage, with two (12.5%) in the RE group, three (9.4%) in the Obs group and one (9.1%) in the SE group, corresponding to a natural history of 3.5% annual hemorrhage rate and a post-treatment hemorrhagic risk of 3.6%. This post-treatment hemorrhage risk was 2.4% in the SE group and 4.9% in the RE group. Presenting with ICH (p=0.042) and race (p=0.014) were associated with a higher risk of follow-up hemorrhage. Definitive treatment for AVM patients ⩾60years should be cautiously considered. Despite higher post-treatment obliteration rates, the subsequent hemorrhagic risk may exceed that of its natural history. For AVMs with a high risk for hemorrhage, surgery reduces hemorrhagic risk and achieves the highest rate of obliteration.

Differences in Functional Outcome Across Subtypes with Spetzler-Martin Grade II Arteriovenous Malformations

BACKGROUND: The Spetzler‐Martin grading system for brain arteriovenous malformations (AVMs) is based on size (S), eloquence (E), and deep venous drainage (V). However, variation exists due to subgroup heterogeneity. While previous studies have demonstrated variations in outcomes within grade III AVMs, no studies have focused on grade II AVM subtypes. OBJECTIVE: We aim to delineate how functional outcomes differ among patients with subtypes of grade II AVMs. METHODS: We retrospectively reviewed patients with AVMs evaluated at our institution from 1990 to 2013. Grade II AVMs were divided into 3 subtypes: group 1 (S2V0E0), group 2 (S1V0E1), and group 3 (S1V1E0). Baseline characteristics were compared, and functional status was assessed using the modified Rankin Scale (mRS) at pretreatment and last follow‐up. Differences in mRS between the 2 time points were compared. RESULTS: A total of 208 grade II patients (34.0%) were retrieved from 611 graded patients. After accounting for missing data, our cohort consisted of 137 patients. Mean age of all patients was 37.2 years, with 74 females (54.0%). No significant difference was observed across subgroups for pretreatment mRS (P = .096), treatment modalities (P = .943), follow‐up durations (P = .125), and mRS at last follow‐up (P = .716). In a subgroup analysis between group 1 and group 3, more patients with worsened mRS were observed in group 3 (P = .039). This distinction was further confirmed in surgically treated patients (P = .049), but not in patients treated with radiosurgery (P = .863). CONCLUSION: Subtypes of grade II AVMs portend different posttreatment gains in functional outcome. Group 1 (S2V0E0) patients had the best functional outcome gain from treatment, while group 3 (S1V1E0) patients fared less well, particularly with surgical treatment.

Male Gender Associated with Post-Treatment Seizure Risk of Pediatric Arteriovenous Malformation Patients

BACKGROUND Seizure risk has not been fully characterized in pediatric patients with arteriovenous malformations (AVMs). OBJECTIVE To describe the progression and risk factors of post-treatment seizure in children with AVMs. METHODS We retrospectively reviewed pediatric patients diagnosed with intracranial AVMs at our institution between 1990 and 2013. Clinical and angiographic variables were included in univariate and multivariate Cox proportional hazard models to explore risk factors associated with time-related seizure outcomes. The outcome event is defined as first seizure occurrence after initial treatment. Kaplan-Meier survival curve is depicted for each significant variable, and survival differences were confirmed by Log-rank test. RESULTS We included 90 pediatric patients with complete data in our study cohort. Average age is 13.3 ± 3.8 years with 43.3% male patients. Thirty-seven patients had a hemorrhagic presentation, and 39 patients presented with seizure. Post-treatment seizure occurred in 33 patients (36.7%) over an average follow-up period of 8.1 ± 10.6 years; average time to onset is 5.3 ± 8.2 years, with partial seizures as the most common presentation. Multivariate Cox proportional hazard regression revealed seizure presentation ( P = .005), male gender ( P = .026), and nonconservative treatment modality to be significantly associated with earlier onset of post-treatment seizure after adjusting for AVM location and deep venous drainage. Overall annualized seizure risk is 7.4% for patients with pretreatment seizure, and 1.4% for those without. CONCLUSION Risk of seizure persists after treatment in pediatric AVM patients. Seizure presentation, male gender, and nonconservative management are associated with increased risk of post-treatment seizure. Early identification of these risk factors provides important information for determining seizure management strategies.