Short- and long-term outcomes of moyamoya patients post-revascularization.

OBJECTIVE: The post-bypass stroke risk factors and long-term outcomes of moyamoya patients are not well documented. Therefore, the authors studied 30-day stroke risks and patients' long-term physical, functional, and social well-being. METHODS: This was a single-institution combined moyamoya disease (MMD) database interrogation and questionnaire study. From 1991 to 2014, 1250 revascularization procedures (1118 direct bypasses, 132 indirect bypasses) were performed in 769 patients. Completed questionnaires were received from and available for analysis on 391 patients, and 6-month follow-up data were available for 96.4% (741/769) of the patients. RESULTS: The patients consisted of 548 females and 221 males, with a mean age of 32 years (range 1-69 years). Three hundred fifty-eight bypasses were performed in 205 pediatric patients (73% direct bypasses), and 892 revascularizations were performed in 564 adults (96% direct bypasses). Fifty-two patients (6.8%) developed major strokes with a worsening modified Rankin Scale (mRS) score within 30 days postoperatively. The 30-day major stroke risk was 5.3% (41/769) and 2.6% (12/467) after the first and second bypasses, respectively. Logistic regression analysis revealed that older age, modified MRI (mMRI) score, and hemodynamic reserve (HDR) score are clearly associated with higher postoperative stroke risks. Over a mean follow-up of 7.3 years (range 0.5-26 years), the long-term stroke risk among 741 patients was 0.6% per patient-year; 75% of these patients had excellent outcomes (mRS score 0-1). The long-term outcome questionnaire study showed that 84% (234/277) of patients reported resolution or improvement in their preoperative headache, 83% (325/391) remained employed or in school, and 87% (303/348) were self-caring. CONCLUSIONS: In this large, single-center surgical series, most of the adult and pediatric patients had direct revascularization, with a 4.2% per-bypass-procedure (6.8% per patient) 30-day major stroke risk and a 0.6% per-patient-year long-term stroke risk. The authors identified various risk factors that are highly correlated with postoperative morbidity (age, mMRI score, and HDR score) and are involved in ongoing work to develop the predictive modeling for future patient selection and treatment.

Clinical Course of Unilateral Moyamoya Disease.

BACKGROUND: The natural history of unilateral moyamoya disease (MMD) progressing to bilateral MMD remains an enigma in modern vascular neurosurgery. Few, small series with limited follow-up have reported relatively high rates of contralateral stenosis progression. OBJECTIVE: To review our large series of unilateral MMD patients and evaluate radiographic and surgical progression rates, and identify any factors associated with progression. METHODS: We included all unilateral MMD cases treated from 1991 to 2017 in an observational study. We examined time to contralateral radiographic progression and contralateral progression requiring surgery. Using Cox regression analysis, we evaluated factors potentially associated with contralateral progression. RESULTS: There were 217 patients treated for unilateral MMD. About 71% were female, and the average age at first surgery was 33.8 yr. Average follow-up was 5.8 yr (range 1-22 yr). A total of 18 patients (8.3%) developed contralateral progression. And 8 of these (3.7%) developed progression requiring bypass surgery. Baseline stenosis and hyperlipidemia (HLD) were significantly associated with radiographic progression (hazard ratio [HR] = 9.7, P = .006; HR = 4.0, P = .024). Baseline stenosis was associated with surgical progression (HR = 44.2, P = .002). Results were similar when controlling for possible confounders using multivariate regression. CONCLUSION: Previous series showed relatively high rates of progression in unilateral MMD (15%-30%), but these studies were small and long-term follow-up was rarely available. Our large series indicates that the rate of progression is lower than previously reported but still warrants yearly noninvasive screening. These data may provide indirect support for statin therapy in MMD.

Pregnancy after direct cerebral bypass for moyamoya disease.

OBJECTIVE: Moyamoya disease (MMD) disproportionately affects young to middle-aged women. The main treatment for this challenging disease is cerebral bypass surgery. Vascular neurosurgeons often need to counsel women regarding pregnancy following bypass for MMD, but there is a paucity of data. The authors set out to examine neurological and obstetric outcomes in an extensive cohort of MMD patients who had pregnancies following cerebral revascularization at the Stanford Medical Center. METHODS: The authors identified all patients at their institution who underwent cerebral bypass for MMD from 1990 through 2018 and who later became pregnant. Some of these patients also had pregnancies prior to undergoing bypass surgery, and the authors examined these pregnancies as well. They performed a chart review and brief telephone survey to identify obstetric complications, transient ischemic attacks (TIAs), and strokes. Neurological and obstetric outcomes were compared to published rates. They also compared pre- and post-bypass pregnancy complication rates using logistic regression techniques. RESULTS: There were 71 pregnancies among 56 women whose mean age was 30.5 years. Among 59 post-bypass pregnancies, there were 5 (8%) perinatal TIAs. There were no MRI-confirmed strokes or strokes with residual deficits. Among 12 pre-bypass pregnancies, there were 3 (25%) TIAs and 2 (17%) MRI-confirmed strokes. There were no hemorrhagic complications in either group. In the generalized estimating equations analysis, performing cerebral revascularization prior to pregnancy versus after pregnancy was associated with lower odds of perinatal stroke or TIA (OR 0.15, p = 0.0061). Nine pregnancies (13%) were complicated by preeclampsia, and there was one (1%) instance of eclampsia. The overall rate of cesarean delivery was 39%. There were 2 miscarriages, both occurring in the first trimester. There were no maternal deaths. CONCLUSIONS: The authors present neurological and obstetric outcomes data in a large cohort of MMD patients. These data indicate that post-bypass pregnancy is accompanied by low complication rates. There were no ischemic or hemorrhagic strokes among post-bypass pregnant MMD patients. The rate of obstetric complications was low overall. The authors recommend close collaboration between the vascular neurosurgeon and the obstetrician regarding medical management, including blood pressure goals and continuation of low-dose aspirin.

Neurocognitive Performance After Cerebral Revascularization in Adult Moyamoya Disease.

BACKGROUND AND PURPOSE: Cerebral revascularization using EC-IC bypass is widely used to treat moyamoya disease, but the effects of surgery on cognition are unknown. We compared performance on formal neurocognitive testing in adults with moyamoya disease before and after undergoing direct EC-IC bypass. METHODS: We performed a structured battery of 13 neurocognitive tests on 84 adults with moyamoya disease before and 6 months after EC-IC bypass. The results were analyzed using reliable change indices for each test, to minimize test-retest variability and practice effects. RESULTS: Twelve patients (14%) showed significant decline postoperatively, 9 patients (11%) improved, and 63 patients (75%) were unchanged. Similar results were obtained when the analysis was confined to those who underwent unilateral (33) or bilateral (51) revascularization. CONCLUSIONS: The majority of patients showed neither significant decline nor improvement in neurocognitive performance after EC-IC bypass surgery. Uncomplicated EC-IC bypass seems not to be a risk factor for cognitive decline in this patient population.

Surgical outcomes of Majewski osteodysplastic primordial dwarfism Type II with intracranial vascular anomalies.

OBJECTIVE Majewski osteodysplastic primordial dwarfism Type II (MOPD II) is a rare genetic disorder. Features of it include extremely small stature, severe microcephaly, and normal or near-normal intelligence. Previous studies have found that more than 50% of patients with MOPD II have intracranial vascular anomalies, but few successful surgical revascularization or aneurysm-clipping cases have been reported because of the diminutive arteries and narrow surgical corridors in these patients. Here, the authors report on a large series of patients with MOPD II who underwent surgery for an intracranial vascular anomaly. METHODS In conjunction with an approved prospective registry of patients with MOPD II, a prospectively collected institutional surgical database of children with MOPD II and intracranial vascular anomalies who underwent surgery was analyzed retrospectively to establish long-term outcomes. RESULTS Ten patients with MOPD II underwent surgery between 2005 and 2012; 5 patients had moyamoya disease (MMD), 2 had intracranial aneurysms, and 3 had both MMD and aneurysms. Patients presented with transient ischemic attack (TIA) (n = 2), ischemic stroke (n = 2), intraparenchymal hemorrhage from MMD (n = 1), and aneurysmal subarachnoid hemorrhage (n = 1), and 4 were diagnosed on screening. The mean age of the 8 patients with MMD, all of whom underwent extracranial-intracranial revascularization (14 indirect, 1 direct) was 9 years (range 1-17 years). The mean age of the 5 patients with aneurysms was 15.5 years (range 9-18 years). Two patients experienced postoperative complications (1 transient weakness after clipping, 1 femoral thrombosis that required surgical repair). During a mean follow-up of 5.9 years (range 3-10 years), 3 patients died (1 of subarachnoid hemorrhage, 1 of myocardial infarct, and 1 of respiratory failure), and 1 patient had continued TIAs. All of the surviving patients recovered to their neurological baseline. CONCLUSIONS Patients with MMD presented at a younger age than those in whom aneurysms were more prevalent. Microneurosurgery with either intracranial bypass or aneurysm clipping is extremely challenging but feasible at expert centers in patients with MOPD II, and good long-term outcomes are possible.

Moyamoya disease can masquerade as multiple sclerosis.

BACKGROUND: Moyamoya disease (MM) is a rare disorder of the cerebral arterial circulation, whereas multiple sclerosis (MS) is a relatively common immune-mediated attack on central myelin. Despite the differences in pathogenesis, the 2 disorders share some clinical features which can lead to diagnostic confusion: both can affect young adults, cause intermittent neurological symptoms, and show multifocal abnormalities on brain imaging. OBJECTIVE: To emphasize the need for early consideration of MM in the differential diagnosis of MS-spectrum disorders. METHODS: Chart reviews and individual case analyses. RESULTS: We present detailed descriptions of 3 patients with MM, and summary data on 8 additional cases, in which there was diagnostic confusion with MS, with delays in treatment ranging from 2 months to 19 years (median=4 y). CONCLUSIONS: MM can be misdiagnosed as MS, leading to delay in correct treatment. We highlight the clinical and radiologic features which allow differentiation of these conditions early in the course, when treatment can have maximum benefit.

Neurocognitive impairment in adults with moyamoya disease without stroke.

BACKGROUND: Adults with moyamoya disease (MMD) have been shown to manifest cognitive impairment, but it is unclear whether this is the result of ischemic stroke. OBJECTIVE: To determine whether adults with MMD but without stroke have cognitive impairment. METHODS: We performed detailed neuropsychological assessments in 30 adults with angiographically confirmed MMD without magnetic resonance imaging (MRI) evidence of stroke. RESULTS: Twenty patients (67%) exhibited small T2 hyperintensities in the cerebral subcortical white matter on brain MRI but no evidence of gray matter damage. Significant cognitive impairment, defined as half of test scores ≥ 1 SD below the normal mean, was present in 7 patients (23%). Executive functioning, mental efficiency, and word finding were the ability areas most frequently impaired, whereas memory was relatively intact. Clinically significant emotional distress (depression and/or anxiety) was present in 11 patients (37%). Comparable cognitive findings were also observed in the subset of 10 patients (33%) with completely normal static brain MRI. CONCLUSION: Cognitive impairment in MMD can occur in the absence of ischemic stroke as manifested on MRI.

Multimodality treatment of posterior fossa arteriovenous malformations.

OBJECT: Posterior fossa arteriovenous malformations (AVMs) are relatively uncommon and often difficult to treat. The authors present their experience with multimodality treatment of 76 posterior fossa AVMs, with an emphasis on Spetzler-Martin Grades III-V AVMs. METHODS: Seventy-six patients with posterior fossa AVMs treated with radiosurgery, surgery, and endovascular techniques were analyzed. RESULTS: Between 1982 and 2006, 36 patients with cerebellar AVMs, 33 with brainstem AVMs, and 7 with combined cerebellar-brainstem AVMs were treated. Natural history data were calculated for all 76 patients. The risk of hemorrhage from presentation until initial treatment was 8.4% per year, and it was 9.6% per year after treatment and before obliteration. Forty-eight patients had Grades III-V AVMs with a mean follow-up of 4.8 years (range 0.1-18.4 years, median 3.1 years). Fifty-two percent of patients with Grades III-V AVMs had complete obliteration at the last follow-up visit. Three (21.4%) of 14 patients were cured with a single radiosurgery treatment, and 4 (28.6%) of 14 with 1 or 2 radiosurgery treatments. Twenty-one (61.8%) of 34 patients were cured with multimodality treatment. The mean Glasgow Outcome Scale (GOS) score after treatment was 3.8. Multivariate analysis performed in the 48 patients with Grades III-V AVMs showed radiosurgery alone to be a negative predictor of cure (p = 0.0047). Radiosurgery treatment alone was not a positive predictor of excellent clinical outcome (GOS Score 5; p > 0.05). Nine (18.8%) of 48 patients had major neurological complications related to treatment. CONCLUSIONS: Single-treatment radiosurgery has a low cure rate for posterior fossa Spetzler-Martin Grades III-V AVMs. Multimodality therapy nearly tripled this cure rate, with an acceptable risk of complications and excellent or good clinical outcomes in 81% of patients. Radiosurgery alone should be used for intrinsic brainstem AVMs, and multimodality treatment should be considered for all other posterior fossa AVMs.

Effect of moyamoya disease on neuropsychological functioning in adults.

OBJECTIVE: Moyamoya disease is a cerebrovascular disorder characterized by progressive occlusion of vessels comprising the circle of Willis, resulting in formation of collaterals that have a cloudy appearance on angiography. Neuropsychological research on the cognitive effects of the disorder in adults has been limited in scope and generalizability; only a few case studies have been published. The current study was intended to more comprehensively document the nature of cognitive impairment in moyamoya disease by assessing a large number of adult cases with a neuropsychological assessment test battery. METHODS: Thirty-six adult patients with neurodiagnostically confirmed moyamoya disease were given presurgical neuropsychological assessments. RESULTS: Mean group performances were within normal limits for all measures assessed. The highest rate of impairment was for measures of executive functioning. The lowest rates occurred with memory and perception measures. Cognitive impairment was present in 11 (31%) of the patients; it was judged to be moderate to severe in four patients (11%). Five patients reported a mild level of depression, and two patients reported a moderate level. CONCLUSION: The present findings suggest that moyamoya disease diagnosed in adults can impair cognition but that the effect is not as severe as in pediatric cases. Executive functioning is most affected. Memory and, to a large extent, intellect are spared. The current pattern of results suggests brain region-behavior correlations that deserve further study.

Progression of unilateral moyamoya disease: A clinical series.

BACKGROUND: The natural history of unilateral moyamoya disease (MMD) in adult patients is not clearly described in the literature. We present a series of 18 patients with unilateral MMD and analyze the risk factors for progression to bilateral disease. METHODS: A retrospective review of 157 MMD patients treated at Stanford University Medical Center from 1991 to 2005 identified 28 patients with unilateral MMD (defined as none, equivocal or mild involvement on the contralateral side). RESULTS: Eighteen patients (5 males and 13 females) were identified with unilateral MMD and angiographic follow-up of > or =5 months. Mean radiologic follow-up (+/- standard error of the mean) was 19.3 +/- 3.4 months and mean clinical follow-up was 24.5 +/- 3.7 months. Five patients had childhood onset MMD and 13 patients had adult onset disease. Angiographic progression from unilateral to bilateral disease was seen in 7 patients (38.9%) at a mean follow-up of 12.7 +/- 2.4 months. Four of the 7 patients had significant clinical and radiologic progression requiring surgical intervention. Five of 7 patients that progressed had adult onset MMD. The presence of equivocal or mild stenotic changes of the contralateral anterior cerebral artery (ACA), middle cerebral artery (MCA) or internal carotid artery (ICA) was an important predictor of progression (p < 0.01); 6 of 8 patients (75%) with equivocal or mild contralateral disease progressed, whereas only 1 of 10 patients (10.0%) with no initial contralateral disease progressed to bilateral MMD. One patient had mild or equivocal MCA, ICA and ACA stenosis at the time of initial diagnosis and this patient progressed. CONCLUSIONS: Contralateral progression in the adult form occurs more commonly than previously reported. The presence of minor changes in the contralateral ACA, intracranial ICA and MCA is an important predictor of increased risk of progression. Patients with a completely normal angiogram on the contralateral side have a very low risk of progression.

Visual field preservation after curative multi-modality treatment of occipital lobe arteriovenous malformations.

OBJECTIVE: Occipital lobe arteriovenous malformations (AVMs) provide challenging management decisions because of their proximity to the visual cortex and optic radiations. Preservation of visual function throughout treatment is the mainstay of therapeutic planning. We reviewed visual field (VF) outcomes of all patients who received curative treatment for occipital AVMs at Stanford University to evaluate the efficacy of different treatment strategies. METHODS: We conducted a retrospective review of 55 patients with occipital AVMs treated at Stanford University between 1984 and 2003. Clinical presentation, AVM morphology, and treatment modality were correlated with VF function before and after therapeutic intervention. RESULTS: Of 55 patients, 48 (87.3%) underwent multimodality AVM treatment (7 patients < 3 yr from radiosurgery were excluded from final analysis). One patient died from intracerebral hemorrhage 11 months post-radiosurgery, and five patients deferred further treatment. Forty-two patients (87.5%) were cured, with no residual AVM on final angiography. Curative therapeutic modalities used included embolization alone (2 patients), microsurgery alone (6 patients), microsurgery with radiosurgery (1 patient), microsurgery with embolization (23 patients), radiosurgery with embolization (4 patients), and embolization with radiosurgery and microsurgery (6 patients). Mean follow-up was 5.8 years including treatment. VF follow-up was available in all 42 patients. Twenty-eight (66.7%) patients experienced no change in VFs, six (14.3%) patients with previously abnormal VFs improved, and eight (19.0%) patients showed worsening of VFs (although none developed a new homonymous VF deficit). Duration of treatment was related to VF outcome in patients who presented without a history of AVM-related hemorrhage. CONCLUSION: Occipital AVMs can be safely cured using multimodality strategies with minimal risk to visual function despite the proximity of these lesions to the visual cortex and associated pathways.

Comparison of endovascular and surface cooling during unruptured cerebral aneurysm repair.

OBJECTIVE: To compare endovascular versus surface methods for the induction and reversal of hypothermia during neurosurgery in a multicenter, prospective, randomized study. METHODS: Patients undergoing elective open craniotomy for repair of an unruptured cerebral aneurysm (n = 153) were randomly assigned (2:1) to undergo whole-body hypothermia to 33 degrees C, either with an endovascular cooling device placed in the inferior vena cava via the femoral vein (n = 92) or with a surface convective air blanket (n = 61). Active rewarming was accomplished using the same devices. RESULTS: Cooling rates in endovascular and surface blanket groups averaged 4.77 and 0.87 degrees C/h, respectively (P < 0.001). When the first temporary arterial or aneurysm clip was placed, 99% of endovascular patients and 20% of surface blanket patients had reached the target of 33 degrees C (P < 0.001). Obese patients were cooled efficiently with the endovascular approach (3.56 degrees C/h). Rewarming rates averaged 1.88 degrees C/h for endovascular patients and 0.69 degrees C/h for surface blanket patients (P < 0.001). By the end of surgery, 89 and 53% of these patients, respectively, had rewarmed to at least 35 degrees C (P < 0.001). On leaving the operating room, 14% of endovascular patients and 28% of surface blanket patients were still intubated (P = 0.035). The overall safety of the two procedures was comparable. No clinically significant catheter-related thrombotic, bleeding, or infectious complications were reported in the endovascular group. CONCLUSION: Endovascular cooling provided superior induction, maintenance, and reversal of hypothermia compared with the surface blanket, without an increase in complications. Endovascular cooling may have clinical benefit for patients undergoing cerebrovascular surgery, as well as patients with acute stroke, head injury, or acute myocardial infarction.