Journal of the Neurological Sciences 336 (2014) 99–102
Contents lists available at ScienceDirect
Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Moyamoya disease: A comparison of long term outcome of conservative and surgical treatment in India Soumya Sundaram a, P.N. Sylaja a,⁎, Girish Menon b, Jayanand Sudhir b, E.R. Jayadevan c, Sajith Sukumaran a, Sapna Erat Sreedharan a, Sankara Sarma d a
Comprehensive Stroke Care Program, Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India Department of Neurosurgery, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India Department of Interventional and Imaging Sciences, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India d Department of Biostatistics, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India b c
a r t i c l e
i n f o
Article history: Received 20 August 2013 Received in revised form 25 September 2013 Accepted 7 October 2013 Available online 16 October 2013 Keywords: Moyamoya disease Moyamoya syndrome Outcome Revascularization surgery Ischemic events Conservative treatment
a b s t r a c t Background: Revascularization surgery (RS) is the therapy of choice in moyamoya disease (MMD). Due to rarity of disease and ethical concerns, randomized controlled trials about the treatment options are lacking. Very little information is available on the long-term outcome of conservatively treated moyamoya patients. Aim: We compared the long-term outcome of moyamoya patients treated conservatively to those who underwent RS. Methods: Our study population included all patients with moyamoya disease/syndrome from 2002 to 2012. The demographic, clinical characteristic and imaging details were reviewed. The outcome was obtained prospectively. Results: Of the 36 patients, 26 (72.2%) had MMD and 10 (27.8%) had moyamoya syndrome. The median age at onset of symptoms was 17.5 years (range, 10 months–55 years). Fifteen patients belonged to pediatric group and 21 were adults. All the pediatric patients had ischemic events at onset and 10 (47.6%) of the adults presented with hemorrhage. Twenty (55.6%) patients received conservative treatment and 16 (44.4%) underwent revascularization procedures. The median duration of follow-up was 28 months (range, 3–90 months). Three (18%) of the surgically treated patients had recurrent ischemic events on follow-up, but none of the conservatively treated patients had events. An excellent outcome (Modified Rankin Scale of ≤ 2) was seen in 12 (75%) surgically treated and 16 (94%) conservatively treated patients (p = 0.17). Conclusion: Compared to East Asians, our patients had a lower stroke recurrence rate and good functional outcome even with conservative treatment. Future studies should focus on clinical and imaging predictors of progression to select moyamoya patients for RS. © 2013 Elsevier B.V. All rights reserved.
1. Introduction Moyamoya is an occlusive intracranial arteriopathy affecting the terminal internal carotid arteries and/or proximal middle cerebral arteries and characterized by presence of basal lenticulostriate collaterals. Data from Japan and other East Asian centers suggest that two thirds of the moyamoya disease (MMD) patients had symptomatic progression at 5 years [1] but data from other countries suggest a more benign natural history with later presentation and higher presentation with ischemic events [2,3] Due to limited natural history data outside east Indians, the role of revascularization surgery (RS) in modifying the clinical course in other ethnic groups is difficult to evaluate. Though the clinical features, treatment and long-term ⁎ Corresponding author at: Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum 695011, India. Tel.: +91 471 2524482. E-mail address: [email protected] (P.N. Sylaja). 0022-510X/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.jns.2013.10.014
outcome of MMD in Japan and South Korea are well documented, it is not known whether the Indian patients with MMD are different from other Asian patients. Though many of the moyamoya patients in our center underwent surgery, we had many patients who opted for conservative treatment and were not willing for surgery. This prompted us to have a comparison of the outcome of these two groups of patients. 2. Materials and methods We identified all patients with MMD and moyamoya syndrome who were diagnosed by digital subtraction angiogram from 2002 to 2012. Those patients with distal bilateral internal carotid occlusion are considered as having moyamoya disease and those patients having unilateral ICA occlusion and secondary causes were diagnosed as having moyamoya syndrome. The demographic details, clinical features and investigations were obtained from retrospective chart review. The imaging and angiographic data were reviewed by a radiologist and
100
S. Sundaram et al. / Journal of the Neurological Sciences 336 (2014) 99–102
neurologist with particular focus on stage of the disease and collateral circulation. These patients were prospectively followed-up and the follow-up data was collected by clinical visits or telephonic interview. Patients were followed-up regularly in stroke clinic at 3 months after the initial event or after revascularization procedure and thereafter every 6 months. During each visit any new neurological event and symptoms are recorded and the functional outcome by Modified Rankin Scale (mRS) was documented. A Kaplan–Meier curve was done to analyze the time taken for the patient to become stable after the first ischemic event in both the medical and surgical groups. A stable state was defined as the patient remaining event free for 1 year. 3. Statistical methods The characteristics of both cohorts were compared using Student's t test for continuous data and Chi-Square or Fisher's exact test for categorical variables. Kaplan–Meier method was used to estimate the stroke risk. 4. Results 4.1. Patient demographics and clinical characteristics Thirty six patients with MMD/syndrome of Indian origin were included in the study of which 15 (41.7%) belonged to pediatric (age less than 12 years) and 21 (58.3%) were adults. The median age at onset of symptoms was 17.5 years (range, 10 months–55 years). All the pediatric patients had ischemic events at onset and 10 (47.6%) of the adults presented with hemorrhage. The most common presentation was TIA/stroke (83.3%) followed by seizures (8.4%), headache (5.6%) and no symptoms(2.7%). None of the patients in our cohort had a positive family history. 26 patients (72. 2%) had moyamoya disease and 10 patients (27.8%) had moyamoya syndrome. Of these 10 patients, 6 had unilateral disease. The secondary causes in our patients were Down's syndrome, large vessel atherosclerotic disease, vasculitis and neurofibromatosis. Table 1 gives a comparison of clinical and imaging characteristics of the patients with MMD and moyamoya syndrome.
Compared to the patients with moyamoya disease, those with moyamoya syndrome were of older age with female preponderance. At presentation, majority of the moyamoya disease patients belonged to Suzuki and Takaku classification stage IV 14 (53.8%), but majority of the moyamoya syndrome patients were in stage III, 5(50%). 4.2. Treatment and outcome Of the 36 patients, only 16 (44.4%) underwent surgery (total of 22 surgical procedures, bilateral in 4 and unilateral in 12, additional surgery in 2) and the rest 20 (55.6%) were managed with antiplatelets, antiepileptics and antihypertensives depending on the presentation. Seven had primary RS and indirect procedures were done in 9. Indirect procedures were chosen in very young children and those with unfavorable anatomy. The revascularization procedures done in children were EDAMS (9) followed by EDAS (3) and STA–MCA bypass (1). In adults most of them underwent STA–MCA bypass (6) followed by EDAMS (3). Except for two, all those who underwent surgery had presented with ischemic events. Table 2 shows the outcome of the surgically and medically treated patients. Post operatively 2 patients (12.5%) had neurological event with one having a minor ischemic stroke and the other a major ischemic stroke. The median duration of follow-up was 28 months (range, 3–90 months). Three patients in the conservative group were lost to follow-up. Of the 33 patients, three of the surgically treated patients had new ischemic events and none in the conservatively treated group had new events during follow-up. Of the 33 patients, an excellent outcome (Modified Rankin Scale of ≤ 2) was seen in 12 (75%) of the surgically treated patients and 16 (94%) of the conservatively treated patients, which was not statistically significant (p = 0.17). None of the patients who presented with hemorrhage had further ischemic or hemorrhagic events. Poor outcome was observed in those patients who had severe stroke at onset, post operative event and recurrent neurological events. The Kaplan–Meier curve after the first ischemic event showed that the surgical group stabilized earlier than the conservatively treated group [Fig. 1]. No mortality was observed in our cohort during the follow-up. 5. Discussion
Table 1 Clinical and imaging characteristics of moyamoya patients.
Age at presentation (mean ± SD) Male:female Stroke type Ischemic stroke Hemorrhagic stroke Presenting symptom Stroke TIA Headache Seizures Mean NIHSS at admission Vessels involved ICA MCA ACA Suzuki and Takaku stage 2 3 4 5 Type of collateral vessels Parenchymal Leptomeningeal Transdural
Moyamoya disease (n = 26)
Moyamoya syndrome (n = 10)
18.72 (SD = 17.6) 13:13 1:1
26.30 (SD = 18.4) 3:7 1:2.3
18 (69%) 6 (23%)
5 (50%) 4 (40%)
13 (50%) 10 (38.5%) 1 (3.8%) 1 (3.8%) 3.31 (SD = 3.91)
8 (80%) 0 (0) 1 (10%) 1 (10%) 5.10 (SD = 5.5)
26 (100%) 26 (100%) 26 (100%)
10 (100%) 10 (100%) 9 (90%)
0 (0) 9 (34.6%) 14 (53.8%) 3 (11.5%)
0 (0) 5 (50%) 3 (30%) 2 (20%)
24 (92%) 17 (65.4%) 6 (23%)
10 (100%) 5 (50%) 1 (10%)
MMD is a cerebrovascular disease mainly found in Asians, but information about the clinical features and long-term outcome of MMD in India is lacking. We present the data of moyamoya patients from India comparing the long-term outcome of medically and surgically treated patients. Our data of Indian patients with moyamoya showed a more benign natural history compared to East Asians. In addition patients had a later age at presentation with half of the adults presenting with hemorrhage. Similar to the reports from Japan, Korea and United States, there was a female preponderance in our cohort. None of the patients in our cohort had a positive family history which was in contrast to Japanese and South Korean series which reported 10–15% [4,5]. So though genetic factor contributes to
Table 2 Clinical characteristics and outcome of medically and surgically treated moyamoya patients. Variable
Medical group, n = 20
Surgical group, n = 16
p-Value
Mean age at onset (years) Mean age at diagnosis (years) Mean admission NIHSS Mean admission mRS Mean duration of follow-up (months) Number (%) with events Excellent outcome (mRS ≤ 2)
25.5 ± 18 25.7 ± 17.9 3.7 ± 4.9 2.2 ± 1.9 32 ± 23.7 Nil 16/17 (94%)
14.9 ± 16 16.1 ± 16.4 3.9 ± 3.7 2.3 ± 1.5 31 ± 19.3 3 (18%) 12/16 (75%)
0.07 0.1 0.8 0.9 0.9 0.1 0.1
mRS—modified Rankin scale and NIHSS—National Institute of Health Stroke Scale score.
S. Sundaram et al. / Journal of the Neurological Sciences 336 (2014) 99–102
Fig. 1. Kaplan–Meier curve of the proportion remaining event free in the medically and surgically treated groups.
MMD, such an association of genetic influence in Indian population was not seen. Similar to Asian patients with MMD, all our pediatric patients presented with ischemic events which relate to the timing of onset of occlusive arteriopathy and half of the adult patients presented with hemorrhage suggesting that the later extensive moyamoya collaterals are responsible (Fig. 2). The main reason for revascularization surgery in MMD is to prevent future ischemic and hemorrhagic strokes and thereby limit disease progression. Medical therapy has been used in patients with moyamoya, but there is few data on its short-term and longterm outcomes. Studies on both adult and pediatric moyamoya patients have shown that in view of the progression of disease the risk of subsequent stroke is significantly reduced by revascularization surgeries compared to medical treatment [6–12]. Though there are notable differences in the clinical characteristics of this condition
101
between the white and the Asian populations, recent data suggest that the risk of subsequent stroke was reduced by surgical procedures in the whites also compared to medical treatment [2,3,8,13]. Studies have also shown that the risk of subsequent stroke is highest in those who present with ischemic symptoms, those with bilateral involvement, pediatric patients, familial patients and those who present early after the first event. We found that though our surgical patients became stable earlier, the medically treated patients did not have any ischemic events and had a good long-term outcome which was in contrast to the east Indian patients. This may be due to various reasons. About 60% of our patients were adults and 50% of them presented with hemorrhage. About one third of them had moyamoya syndrome which is associated with lesser risk of progression and subsequent events. In addition the degree of progression of disease in Indian patients may be different compared to the east Indians. The mean duration after the onset at which they presented to us in medically treated group was more than 2 years when the chances of disease progression are less. At this point of time, it is not clear whether all patients with moyamoya should undergo surgery as the surgical risk is 8–13% [2,12]. Since the early recurrent stroke risk after first ischemic event is high, it is advisable to consider surgery in those who present early after an event. Both in the white and the Asian patients, the risk of subsequent stroke is significantly reduced after 2 years and remains stable. But to identify the subgroup of patients who benefits from long-term revascularization needs a randomized controlled study. Our study has limitations. The study is of retrospective nature with a small sample size. Since it is a hospital based series there may a referral bias and may be the patients with more significant symptoms might have reported to hospital. The 3 patients lost to the follow-up might be those with no symptoms or with severe disability. We included both the moyamoya disease and syndrome patients together which is not ideal as the outcome of both groups may be different. Though we mention that the medically treated patients had no clinical events, we have not done any imaging to look for silent or asymptomatic infarcts. Since the study is from single center the results are applicable only to one region and may not be generalizable. In conclusion, this study gives an overview of the patients with moyamoya from India. Our data suggest that the Indian patients are different from the East Asian patients with regard to the age at presentation, type of presentation and family history. The natural history of the medically treated Indian patients is more benign than that of the East Asians. It is difficult as this point of time to decide on the need and efficacy of revascularization procedures in Indian patients with moyamoya.
Fig. 2. (a) MRI T2 weighted axial images showing abnormal perforator collateral vessels in the sylvian and ambient cisterns bilaterally. (b & c) Digital subtraction angiography showing occlusion of the supraclinoid ICA, proximal ACA and bilateral MCA with typical moyamoya collateral vessels and ECA collateral to the ACA territory on the right side. Moyamoya collaterals involving the posterior circulation can also be seen (d) with occlusion of bilateral distal P2 segments of PCAs.
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Conflict of interest The authors declare that there is no conflict of interest. References [1] Kurokawa T, Tomita S, Ueda K, Narazaki O, Hanai T, Hasuo K, et al. Prognosis of occlusive disease of circle of Willis (moyamoya disease) in children. Paediatr Neurol 1985;1:274–7. [2] Chui D, Shedden P, Bratina P, Grotta JC. Clinical features of moyamoya disease in the United States. Stroke 1998;29:1347–51. [3] Uchino K, Claiborne J, Becker KJ, Tirschwell DL. Moyamoya in Washington state and California. Neurology 2005;65:956–8. [4] Kim SK, Cho BK, Phi JH, Lee JY, Chae JH, Kim KJ, et al. Paediatric moyamoya disease. An analysis of 410 consecutive cases. Ann Neurol 2010;68:92–101. [5] Kuriyama S, Kusaka Y, Fujimura M, Wakai K, Tamakoshi A, Hasimoto, et al. Prevalence and clinicoepidemiological features of moyamoya disease in Japan: findings from a nationwide epidemiological survey. Stroke 2008;39:42–7.
[6] Choi JU, Kim DS, Kim EY, Lee KC. Natural history of moyamoya disease: comparison of activities of daily living in surgery and nonsurgery groups. Clin Neurol Neurosurg 1997;99(Suppl. 2):S11–8. [7] Duan L, Bao XY, Yang WZ, Shi WC, Li DS, Zhang ZS, et al. Moyamoya disease in China. Its clinical features and outcomes. Stroke 2012;43:56–60. [8] Hallemeier CL, Rich KM, Grubb Jr RL, Chicoine MR, Moran CJ, Cross DT, et al. Clinical features and outcome in North American adults with moyamoya phenomenon. Stroke 2006;37:1490–6. [9] Ikezaki K. Rational approach to treatment of moyamoya disease in childhood. J Child Neurol 2000;15:350–6. [10] Kelly ME, Bell-Stephens TE, Marks MP, Do HM, Steinberg GK. Progression of unilateral moyamoya disease. A clinical series. Cerebrovasc Dis 2006;22:109–15. [11] Kuroda S, Ishikawa T, Houkin K, Nanba R, Hokari M, Iwasaki Y. Incidence and clinical features of disease progression in adult moyamoya disease. Stroke 2005;36:2148–53. [12] Scott RM, Smith JL, Robertson RL, Madsen JR, Soriano SG, Rockoff MA. Long-term outcome in children with moyamoya syndrome after cranial revascularization by pial synangiosis. J Neurosurg 2004;100:142–9 [Suppl.]. [13] Kraemer M, Heienbrok W, Berlit P. Moyamoya disease in Europeans. Stroke 2008;39:3193–200.
Contents lists available at ScienceDirect
Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Moyamoya disease: A comparison of long term outcome of conservative and surgical treatment in India Soumya Sundaram a, P.N. Sylaja a,⁎, Girish Menon b, Jayanand Sudhir b, E.R. Jayadevan c, Sajith Sukumaran a, Sapna Erat Sreedharan a, Sankara Sarma d a
Comprehensive Stroke Care Program, Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India Department of Neurosurgery, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India Department of Interventional and Imaging Sciences, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India d Department of Biostatistics, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala, India b c
a r t i c l e
i n f o
Article history: Received 20 August 2013 Received in revised form 25 September 2013 Accepted 7 October 2013 Available online 16 October 2013 Keywords: Moyamoya disease Moyamoya syndrome Outcome Revascularization surgery Ischemic events Conservative treatment
a b s t r a c t Background: Revascularization surgery (RS) is the therapy of choice in moyamoya disease (MMD). Due to rarity of disease and ethical concerns, randomized controlled trials about the treatment options are lacking. Very little information is available on the long-term outcome of conservatively treated moyamoya patients. Aim: We compared the long-term outcome of moyamoya patients treated conservatively to those who underwent RS. Methods: Our study population included all patients with moyamoya disease/syndrome from 2002 to 2012. The demographic, clinical characteristic and imaging details were reviewed. The outcome was obtained prospectively. Results: Of the 36 patients, 26 (72.2%) had MMD and 10 (27.8%) had moyamoya syndrome. The median age at onset of symptoms was 17.5 years (range, 10 months–55 years). Fifteen patients belonged to pediatric group and 21 were adults. All the pediatric patients had ischemic events at onset and 10 (47.6%) of the adults presented with hemorrhage. Twenty (55.6%) patients received conservative treatment and 16 (44.4%) underwent revascularization procedures. The median duration of follow-up was 28 months (range, 3–90 months). Three (18%) of the surgically treated patients had recurrent ischemic events on follow-up, but none of the conservatively treated patients had events. An excellent outcome (Modified Rankin Scale of ≤ 2) was seen in 12 (75%) surgically treated and 16 (94%) conservatively treated patients (p = 0.17). Conclusion: Compared to East Asians, our patients had a lower stroke recurrence rate and good functional outcome even with conservative treatment. Future studies should focus on clinical and imaging predictors of progression to select moyamoya patients for RS. © 2013 Elsevier B.V. All rights reserved.
1. Introduction Moyamoya is an occlusive intracranial arteriopathy affecting the terminal internal carotid arteries and/or proximal middle cerebral arteries and characterized by presence of basal lenticulostriate collaterals. Data from Japan and other East Asian centers suggest that two thirds of the moyamoya disease (MMD) patients had symptomatic progression at 5 years [1] but data from other countries suggest a more benign natural history with later presentation and higher presentation with ischemic events [2,3] Due to limited natural history data outside east Indians, the role of revascularization surgery (RS) in modifying the clinical course in other ethnic groups is difficult to evaluate. Though the clinical features, treatment and long-term ⁎ Corresponding author at: Department of Neurology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum 695011, India. Tel.: +91 471 2524482. E-mail address: [email protected] (P.N. Sylaja). 0022-510X/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.jns.2013.10.014
outcome of MMD in Japan and South Korea are well documented, it is not known whether the Indian patients with MMD are different from other Asian patients. Though many of the moyamoya patients in our center underwent surgery, we had many patients who opted for conservative treatment and were not willing for surgery. This prompted us to have a comparison of the outcome of these two groups of patients. 2. Materials and methods We identified all patients with MMD and moyamoya syndrome who were diagnosed by digital subtraction angiogram from 2002 to 2012. Those patients with distal bilateral internal carotid occlusion are considered as having moyamoya disease and those patients having unilateral ICA occlusion and secondary causes were diagnosed as having moyamoya syndrome. The demographic details, clinical features and investigations were obtained from retrospective chart review. The imaging and angiographic data were reviewed by a radiologist and
100
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neurologist with particular focus on stage of the disease and collateral circulation. These patients were prospectively followed-up and the follow-up data was collected by clinical visits or telephonic interview. Patients were followed-up regularly in stroke clinic at 3 months after the initial event or after revascularization procedure and thereafter every 6 months. During each visit any new neurological event and symptoms are recorded and the functional outcome by Modified Rankin Scale (mRS) was documented. A Kaplan–Meier curve was done to analyze the time taken for the patient to become stable after the first ischemic event in both the medical and surgical groups. A stable state was defined as the patient remaining event free for 1 year. 3. Statistical methods The characteristics of both cohorts were compared using Student's t test for continuous data and Chi-Square or Fisher's exact test for categorical variables. Kaplan–Meier method was used to estimate the stroke risk. 4. Results 4.1. Patient demographics and clinical characteristics Thirty six patients with MMD/syndrome of Indian origin were included in the study of which 15 (41.7%) belonged to pediatric (age less than 12 years) and 21 (58.3%) were adults. The median age at onset of symptoms was 17.5 years (range, 10 months–55 years). All the pediatric patients had ischemic events at onset and 10 (47.6%) of the adults presented with hemorrhage. The most common presentation was TIA/stroke (83.3%) followed by seizures (8.4%), headache (5.6%) and no symptoms(2.7%). None of the patients in our cohort had a positive family history. 26 patients (72. 2%) had moyamoya disease and 10 patients (27.8%) had moyamoya syndrome. Of these 10 patients, 6 had unilateral disease. The secondary causes in our patients were Down's syndrome, large vessel atherosclerotic disease, vasculitis and neurofibromatosis. Table 1 gives a comparison of clinical and imaging characteristics of the patients with MMD and moyamoya syndrome.
Compared to the patients with moyamoya disease, those with moyamoya syndrome were of older age with female preponderance. At presentation, majority of the moyamoya disease patients belonged to Suzuki and Takaku classification stage IV 14 (53.8%), but majority of the moyamoya syndrome patients were in stage III, 5(50%). 4.2. Treatment and outcome Of the 36 patients, only 16 (44.4%) underwent surgery (total of 22 surgical procedures, bilateral in 4 and unilateral in 12, additional surgery in 2) and the rest 20 (55.6%) were managed with antiplatelets, antiepileptics and antihypertensives depending on the presentation. Seven had primary RS and indirect procedures were done in 9. Indirect procedures were chosen in very young children and those with unfavorable anatomy. The revascularization procedures done in children were EDAMS (9) followed by EDAS (3) and STA–MCA bypass (1). In adults most of them underwent STA–MCA bypass (6) followed by EDAMS (3). Except for two, all those who underwent surgery had presented with ischemic events. Table 2 shows the outcome of the surgically and medically treated patients. Post operatively 2 patients (12.5%) had neurological event with one having a minor ischemic stroke and the other a major ischemic stroke. The median duration of follow-up was 28 months (range, 3–90 months). Three patients in the conservative group were lost to follow-up. Of the 33 patients, three of the surgically treated patients had new ischemic events and none in the conservatively treated group had new events during follow-up. Of the 33 patients, an excellent outcome (Modified Rankin Scale of ≤ 2) was seen in 12 (75%) of the surgically treated patients and 16 (94%) of the conservatively treated patients, which was not statistically significant (p = 0.17). None of the patients who presented with hemorrhage had further ischemic or hemorrhagic events. Poor outcome was observed in those patients who had severe stroke at onset, post operative event and recurrent neurological events. The Kaplan–Meier curve after the first ischemic event showed that the surgical group stabilized earlier than the conservatively treated group [Fig. 1]. No mortality was observed in our cohort during the follow-up. 5. Discussion
Table 1 Clinical and imaging characteristics of moyamoya patients.
Age at presentation (mean ± SD) Male:female Stroke type Ischemic stroke Hemorrhagic stroke Presenting symptom Stroke TIA Headache Seizures Mean NIHSS at admission Vessels involved ICA MCA ACA Suzuki and Takaku stage 2 3 4 5 Type of collateral vessels Parenchymal Leptomeningeal Transdural
Moyamoya disease (n = 26)
Moyamoya syndrome (n = 10)
18.72 (SD = 17.6) 13:13 1:1
26.30 (SD = 18.4) 3:7 1:2.3
18 (69%) 6 (23%)
5 (50%) 4 (40%)
13 (50%) 10 (38.5%) 1 (3.8%) 1 (3.8%) 3.31 (SD = 3.91)
8 (80%) 0 (0) 1 (10%) 1 (10%) 5.10 (SD = 5.5)
26 (100%) 26 (100%) 26 (100%)
10 (100%) 10 (100%) 9 (90%)
0 (0) 9 (34.6%) 14 (53.8%) 3 (11.5%)
0 (0) 5 (50%) 3 (30%) 2 (20%)
24 (92%) 17 (65.4%) 6 (23%)
10 (100%) 5 (50%) 1 (10%)
MMD is a cerebrovascular disease mainly found in Asians, but information about the clinical features and long-term outcome of MMD in India is lacking. We present the data of moyamoya patients from India comparing the long-term outcome of medically and surgically treated patients. Our data of Indian patients with moyamoya showed a more benign natural history compared to East Asians. In addition patients had a later age at presentation with half of the adults presenting with hemorrhage. Similar to the reports from Japan, Korea and United States, there was a female preponderance in our cohort. None of the patients in our cohort had a positive family history which was in contrast to Japanese and South Korean series which reported 10–15% [4,5]. So though genetic factor contributes to
Table 2 Clinical characteristics and outcome of medically and surgically treated moyamoya patients. Variable
Medical group, n = 20
Surgical group, n = 16
p-Value
Mean age at onset (years) Mean age at diagnosis (years) Mean admission NIHSS Mean admission mRS Mean duration of follow-up (months) Number (%) with events Excellent outcome (mRS ≤ 2)
25.5 ± 18 25.7 ± 17.9 3.7 ± 4.9 2.2 ± 1.9 32 ± 23.7 Nil 16/17 (94%)
14.9 ± 16 16.1 ± 16.4 3.9 ± 3.7 2.3 ± 1.5 31 ± 19.3 3 (18%) 12/16 (75%)
0.07 0.1 0.8 0.9 0.9 0.1 0.1
mRS—modified Rankin scale and NIHSS—National Institute of Health Stroke Scale score.
S. Sundaram et al. / Journal of the Neurological Sciences 336 (2014) 99–102
Fig. 1. Kaplan–Meier curve of the proportion remaining event free in the medically and surgically treated groups.
MMD, such an association of genetic influence in Indian population was not seen. Similar to Asian patients with MMD, all our pediatric patients presented with ischemic events which relate to the timing of onset of occlusive arteriopathy and half of the adult patients presented with hemorrhage suggesting that the later extensive moyamoya collaterals are responsible (Fig. 2). The main reason for revascularization surgery in MMD is to prevent future ischemic and hemorrhagic strokes and thereby limit disease progression. Medical therapy has been used in patients with moyamoya, but there is few data on its short-term and longterm outcomes. Studies on both adult and pediatric moyamoya patients have shown that in view of the progression of disease the risk of subsequent stroke is significantly reduced by revascularization surgeries compared to medical treatment [6–12]. Though there are notable differences in the clinical characteristics of this condition
101
between the white and the Asian populations, recent data suggest that the risk of subsequent stroke was reduced by surgical procedures in the whites also compared to medical treatment [2,3,8,13]. Studies have also shown that the risk of subsequent stroke is highest in those who present with ischemic symptoms, those with bilateral involvement, pediatric patients, familial patients and those who present early after the first event. We found that though our surgical patients became stable earlier, the medically treated patients did not have any ischemic events and had a good long-term outcome which was in contrast to the east Indian patients. This may be due to various reasons. About 60% of our patients were adults and 50% of them presented with hemorrhage. About one third of them had moyamoya syndrome which is associated with lesser risk of progression and subsequent events. In addition the degree of progression of disease in Indian patients may be different compared to the east Indians. The mean duration after the onset at which they presented to us in medically treated group was more than 2 years when the chances of disease progression are less. At this point of time, it is not clear whether all patients with moyamoya should undergo surgery as the surgical risk is 8–13% [2,12]. Since the early recurrent stroke risk after first ischemic event is high, it is advisable to consider surgery in those who present early after an event. Both in the white and the Asian patients, the risk of subsequent stroke is significantly reduced after 2 years and remains stable. But to identify the subgroup of patients who benefits from long-term revascularization needs a randomized controlled study. Our study has limitations. The study is of retrospective nature with a small sample size. Since it is a hospital based series there may a referral bias and may be the patients with more significant symptoms might have reported to hospital. The 3 patients lost to the follow-up might be those with no symptoms or with severe disability. We included both the moyamoya disease and syndrome patients together which is not ideal as the outcome of both groups may be different. Though we mention that the medically treated patients had no clinical events, we have not done any imaging to look for silent or asymptomatic infarcts. Since the study is from single center the results are applicable only to one region and may not be generalizable. In conclusion, this study gives an overview of the patients with moyamoya from India. Our data suggest that the Indian patients are different from the East Asian patients with regard to the age at presentation, type of presentation and family history. The natural history of the medically treated Indian patients is more benign than that of the East Asians. It is difficult as this point of time to decide on the need and efficacy of revascularization procedures in Indian patients with moyamoya.
Fig. 2. (a) MRI T2 weighted axial images showing abnormal perforator collateral vessels in the sylvian and ambient cisterns bilaterally. (b & c) Digital subtraction angiography showing occlusion of the supraclinoid ICA, proximal ACA and bilateral MCA with typical moyamoya collateral vessels and ECA collateral to the ACA territory on the right side. Moyamoya collaterals involving the posterior circulation can also be seen (d) with occlusion of bilateral distal P2 segments of PCAs.
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