Multiple Sclerosis and Related Disorders 1 (2012) 100–103
Contents lists available at SciVerse ScienceDirect
Multiple Sclerosis and Related Disorders journal homepage: www.elsevier.com/locate/msard
Moyamoya: Another multiple sclerosis mimic Fariha Zaheer, Joseph R. Berger n Department of Neurology, University of Kentucky College of Medicine, Lexington, KY, United States
a r t i c l e i n f o
a b s t r a c t
Article history: Received 12 September 2011 Received in revised form 3 October 2011 Accepted 7 October 2011
A broad range of disorders have been recognized to share clinical and radiographic features with multiple sclerosis and are frequently mistaken with this diagnosis. Several of these disorders are vascular disorders, including atherosclerotic and inflammatory diseases affecting small and medium sized vessels, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and migraine variants. We describe 2 patients with moyamoya syndrome who presented with paroxysmal symptoms, physical findings and MRI abnormalities that were mistaken for multiple sclerosis. Therefore, moyamoya must be added to the list of disorders in the differential diagnosis of multiple sclerosis. & 2011 Elsevier B.V. All rights reserved.
Keywords: Multiple sclerosis Moyamoya Transient ischemic attack Cerebrovascular disease Internal carotid artery Cerebral angiography
1. Introduction Moyamoya disease is a non-inflammatory vasculopathy resulting in progressive stenosis of the intracranial internal carotid arteries and proximal branches of circle of Willis. First described in 1957 by Shimizu and Takeuchi in Japan, the characteristic pathology was ‘‘hypoplasia of the bilateral internal carotid arteries’’ leading to the formation of an extensive collateral network composed of pathologically dilated vessels (Takeuchi, 1957). Due to this appearance, Suzuki and Takaku named this disease ‘‘moyamoya disease’’ ‘‘puff of smoke’’ in Japanese (Suzuki and Takaku, 1969). When the pattern of vascular occlusion occurs with other etiologies, the term ‘‘moyamoya syndrome’’ has been applied. Clinical manifestations of Moyamoya disease can be diverse. Most often it presents as transient ischemic attacks, ischemic stroke or intracerebral hemorrhage. We describe two individuals whose initial clinical and radiological pictures were initially mistaken for multiple sclerosis, but because of atypical features, angiographic studies were performed confirming the diagnosis of moyamoya disease. 2. Case reports 2.1. Case 1 A 50 year old Caucasian female with history of type 2 diabetes mellitus, hypertension, and hyperlipidemia was referred to neurology n Correspondence to: Department of Neurology, University of Kentucky College of Medicine, Kentucky Clinic L-445, 740 S. Limestone Street, Lexington, KY 405360284, United States. Tel.: þ1 859 218 5039; fax: þ 1 859 323 5943. E-mail address: [email protected] (J.R. Berger).
2211-0348/$ - see front matter & 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.msard.2011.10.001
clinic for evaluation of possible multiple sclerosis. Her symptoms started one year earlier when she developed transient episodes of left facial weakness lasting up to 24 hours for which she did not seek any medical attention. Three months later, she noted recurrent brief episodes of right leg weakness preceded by a peculiar sensation in the same limb. Weakness would often preclude walking and at times result in falls. There were no identified triggers for these spells. A month later, she noted transient episodes of numbness in her fingers of both hands lasting up to one hour and accompanied by a feeling as if her hands belonged to somebody else. A cranial MRI showed white matter changes consistent with multiple sclerosis, though cerebrospinal fluid examination was non-diagnostic. Because of concern of possible cerebrovascular disease, clopidogrel was initiated at that time. Three months later, she developed right leg weakness rendering walking difficult. She also began to notice transient weakness of left leg. Left arm and leg weakness began subacutely and plateaued after 3 days followed five months later. Her family reported changes in her speech, impaired reading and writing, and altered behavior. A cranial MRI at that time revealed extensive T2 abnormalities with hyperintense signals involving the cortex and extending deep into the white matter bilaterally with similar changes in the pons. Diffusion restriction was noted in the cerebral hemispheric lesions suggesting cerebral infarction. MRA head and neck did not reveal any significant stenosis or vascular anomaly. MRI of cervical, thoracic and lumbar spine did not show any abnormal signal within the spinal cord parenchyma. CSF examination remained normal. A detailed hypercoaguability screen was negative. Angiotensin converting enzyme levels were normal and HIV antibody was non-reactive. Serological studies for autoimmune disease including sedimentation rate, C-reactive protein, antinuclear antibody, rheumatoid
F. Zaheer, J.R. Berger / Multiple Sclerosis and Related Disorders 1 (2012) 100–103
factor, antineutrophilic antibody, anti-SSa and anti-SSb were negative. There was no improvement following a course of corticosteroids and daily glatiramer acetate 20 mg subcutaneously was initiated. In our office, she denied fatigue, heat intolerance, Lhermitte’s phenomenon, visual, or bowel problems. She did report occasional urinary incontinence for 3 months. General examination was unremarkable. Neurological examination revealed abnormal saccades, left central facial palsy, and spastic left hemiparesis with a left-sided Babinski. Transesophageal echocardiogram revealed small apical aneurysm with akinesia. No thrombus, vegetation or valvular abnormality was noted. A four vessel cerebral angiogram showed severe bilateral supraclinoid internal carotid artery stenosis with formation of distal collateral circulation through extra-cranial and posterior circulation consistent with moyamoya disease. A surgical procedure, bilateral encephaloduroarteriosyngiosis, was subsequently performed. Three months after the procedure, she has done well and exhibited no new or recurrent neurological symptoms (Figs. 1 and 2).
2.2. Case 2 This 44 year old Caucasian male with history of type 2 diabetes mellitus and hyperlipidemia was referred for evaluation of transient episodes of right sided numbness. There was a concern that he had
101
multiple sclerosis. One year prior to presentation, he first noticed right leg numbness that developed while walking briskly. Thereafter, he noticed recurrent right leg numbness with activity, particularly lifting boxes on his job, suggesting Uhthoff’s phenomenon. The numbness would last up to 24 hours, but usually lasted less than 4 hours. Two months after their onset, he developed transient episodes of right arm numbness as well. Eventually, right arm and leg numbness were accompanied by right facial numbness, right sided burning, and visual blurring. Episodes typically lasted for an hour, occurred 2–3 times in a week on average, and were precipitated by activity. He denied fatigue, heat intolerance, Lhermitte’s phenomenon, sphincter disturbances, or gait abnormality. Carotid ultrasound was normal. Laboratory investigations were unremarkable but for a positive antinuclear antibody. Physical examination revealed bilateral diabetic retinopathy with normal disks, visual acuity of 20/40 right eye and 20/50 left eye, and impaired color vision in both eyes. There was no nystagmus or ocular dysmetria. He had central right facial weakness, but limb tone, strength, and coordination were normal. Ankle jerks were absent and there was no clonus or Babinskis. His gait was normal. Distal vibratory sense in the lower extremities was impaired and Romberg test positive. A cranial MRI showed white matter lesions suggestive of multiple sclerosis (Figs. 3 and 4).
Fig. 1. MRI brain—FLAIR sequence: (a) extensive hyperintense signal involving the cortex and white matter bilaterally and (b) hyperintense signal abnormality within the pons.
Fig. 2. Cerebral angiogram showing stenosis of the right supraclinoid internal carotid artery and extensive distal collateral circulation. Arrows indicate site of supraclinoid internal carotid artery stenosis.
102
F. Zaheer, J.R. Berger / Multiple Sclerosis and Related Disorders 1 (2012) 100–103
Fig. 3. MRI brain (A, B—FLAIR axial sequences, C—T1 sagittal sequence and D—FLAIR sagittal sequence) revealing periventricular white matter changes suspicious for multiple sclerosis.
Fig. 4. (a) and (b) Cerebral angiogram with diffuse irregularity and narrowing of left A1 and M1.
CSF examination showed no oligoclonal bands or elevated IgG Index, although myelin basic protein was mildly elevated. Visual evoked potentials were markedly prolonged from both eyes. Other evoked potentials were normal. Autoimmune work up including erythrocyte sedimentation rate, anti-SSa, anti-SSb, and rheumatoid factor were negative. HIV antibody was non-reactive. Every other day interferon-b1b subcutaneously was initiated. Eight months later, while working in hot sun, he developed sudden onset expressive aphasia with intact comprehension lasting 30 minutes. His examination was unchanged. A transthoracic echocardiogram showed normal ejection fraction with no evidence of any thrombus, vegetation or valvular abnormality. A four vessel angiogram was performed and revealed diffuse irregularity with narrowing of left A1 and M1 branches of the middle cerebral artery and the left posterior cerebral artery consistent with a vasculopathy, most likely Moyamoya. Interferon b1b was discontinued and aspirin and clopidogrel initiated.
3. Discussion While a variety of vascular disorders, including cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), Binswangers disease, and small
vessel cerebrovascular disease, have been listed among diagnoses to be considered in patients with possible multiple sclerosis (Fieschi et al., 1995; Ratchford and Calabresi, 2008), moyamoya disease has not always been included in comprehensive reviews. There have been rare case reports of patients with clinical or radiological picture suggesting multiple sclerosis that subsequently proved to have moyamoya disease (Brady et al., 1990; Janda et al., 2009). A young woman described in 1990 (Brady et al., 1990), was believed to have multiple sclerosis based on her initial clinical and radiological findings, but progressive disease led to angiography showing stenosis of the proximal internal carotid arteries much like patient #1. Another patient was diagnosed with multiple sclerosis based chiefly on her radiographic findings, but angiography ultimately revealed bilateral absence of anterior and middle cerebral arteries (Janda et al., 2009). The possibility of the co-existence of two separate disorders always needs to be considered. Recently, a patient with both neuromyelitis optica and moyamoya disease has been reported (Asai et al., 2011). Moyamoya disease, originally considered to be a disorder of Asian lineage, is found throughout the world, but is more prevalent in Asian population, particularly Japanese. In Japan, the annual incidence has been estimated to be 0.35 per 100,000 (Kuroda and Houkin, 2008). The incidence in United States in 2005 was estimated at 0.086 cases per 100,000 (Scott and Smith, 2009). The incidence
F. Zaheer, J.R. Berger / Multiple Sclerosis and Related Disorders 1 (2012) 100–103
rate ratios of specific ethnic origins compared with Caucasians were 4.6 for Asian Americans, suggesting a significant role of genetic factors in the etiology of this disease (Yonekawa et al., 1997). Its incidence peaks in children around age 5 and in adults at approximately the mid-forties. Female to male ratio has been shown to be 1.8. Moyamoya appears to be different in the Asian and North American populations as the former typically develop hemorrhage and the latter ischemic stroke (Hallemeier et al., 2006). Pathological observation of the blood vessels does not show inflammation or atherosclerosis, but rather smooth muscle hyperplasia and intraluminal thrombosis. There is fibrous thickening of internal elastic lamina, irregularity of internal elastic lamina and attenuation of media (Fukui et al., 2000). This degradation of the blood vessels walls have been attributed to caspase 3 dependent apoptosis (Takagi et al., 2006). Extensive moyamoya collaterals are dilated perforating arteries with various pathological changes including formation of microaneurysms, explaining the hemorrhagic strokes (Yamashita et al., 1983). Moyamoya occurring in association with other conditions, such as, Down’s syndrome, sickle cell disease, neurofibromatosis type 1, renal artery stenosis, and hyperthyroidism is referred to as the moyamoya syndrome (Scott and Smith, 2009). When it occurs in isolation, it is termed as moyamoya disease (Scott and Smith, 2009). Both of our patients had significant atherosclerotic risk factors, but their relative youth and the fact that their vascular disease was uniquely focal and limited to intracranial vessels suggests that the disorder was moyamoya; however, the underlying pathology may have been atherosclerotic in nature and the term moyamoya syndrome has been used rather than moyamoya disease. As in our patients, focal neurological deficits such as aphasia, hemiparesis or hemianopsia, are the most common presentations. Children usually develop transient ischemic attacks or cerebral infarctions, while adults may present with intracranial hemorrhage, cerebral infarctions or transient ischemic attacks. Atypical clinical presentations have been described (Baik and Lee, 2010; Lubman et al., 2003). Radiographic studies are essential for the diagnosis. Restricted diffusion on cranial MRI is particularly common in watershed areas (Scott and Smith, 2009). Subacute and chronic infarcts are best visualized on fluid attenuated inversion recovery sequences (FLAIR) (Scott and Smith, 2009). Although MR and computed tomographic angiography may be helpful, conventional cerebral angiogram remains the gold standard. It typically shows stenosis of the distal internal carotid artery extending to the proximal middle and anterior cerebral arteries. The ‘‘puff of smoke’’ appearance results from the development of extensive collateral network, originating ether from the basilar artery or extra-cranial blood vessels (Scott and Smith, 2009). Surgical revascularization is the most effective way to improve cerebral perfusion and prevent further strokes. Two general methods have been used, a direct approach in which the superficial temporal artery is anastomosed to a cortical artery beyond the stenosis and an indirect approach in which a vascular tissue is placed in direct contact with the brain leading to an ingrowth of new blood vessels to the underlying cerebral cortex (Parray et al., 2011). Some centers advocate using combination of both direct and indirect approaches. Antiplatelets have been used in most of the operative series to prevent emboli from microthrombi formed at sites of arterial stenosis (Scott et al., 2004). The natural history of moyamoya has not been extensively studied. Hallemeier and group have shown that 5-year risk of recurrent stroke is 65% and
103
82% in unilateral and bilateral disease, respectively (Hallemeier et al., 2006), Two large studies have shown good safety profile for surgical revascularization with 96% probability of remaining stroke free over next 5 years (Choi et al., 1997; Scott et al., 2004). In summary, moyamoya should be considered in the differential diagnoses of any unexplained neurological symptoms. The clinical and radiographic findings may mimic multiple sclerosis and, therefore, it needs to be considered in the differential diagnosis of this disorder. Clues to the correct diagnosis might include the very transient nature of the focal neurological deficits and cortical symptoms, such as, aphasia. When coupled with the lack of supportive evidence of MS, such as, the absence of gadolinium enhancing brain lesions, absence of lesions typical of MS in the posterior fossa, and absence of unique oligoclonal bands and elevated IgG in the CSF, vasocclusive disease needs to be strongly considered.
References Asai Y, Nakayasu H, Fusayasu E, Nakashima K. Moyamoya disease presenting as thalamic hemorrhage in a patient with neuromyelitis optica and Sjogren’s syndrome. Journal of Stroke and Cerebrovascular Diseases 2011. Baik JS, Lee MS. Movement disorders associated with moyamoya disease: a report of 4 new cases and a review of literatures. Movement Disorders 2010;25: 1482–6. Brady AP, Stack JP, Ennis JT. Moyamoya disease—imaging with magnetic resonance. Clinical Radiology 1990;42:138–41. Choi JU, Kim DS, Kim EY, Lee KC. Natural history of moyamoya disease: comparison of activity of daily living in surgery and non surgery groups. Clinical Neurology and Neurosurgery 1997;99(Suppl. 2):S11–8. Fieschi C, Gasperini C, Ristori G, Bastianello S, Girmenia F, Leuzzi V, et al. Patients with clinically definite multiple sclerosis, white matter abnormalities on MRI, and normal CSF: if not multiple sclerosis, what is it? Journal of Neurology, Neurosurgery, and Psychiatry 1995;58:255–6. Fukui M, Kono S, Sueishi K, Ikezaki K. Moyamoya disease. Neuropathology 2000;20(Suppl.):S61–4. Hallemeier CL, Rich KM, Grubb Jr RL, Chicoine MR, Moran CJ, Cross III DT, et al. Clinical features and outcome in North American adults with moyamoya phenomenon. Stroke 2006;37:1490–6. Janda PH, Bellew JG, Veerappan V. Moyamoya disease: case report and literature review. Journal of the American Osteopathic Association 2009;109:547–53. Kuroda S, Houkin K. Moyamoya disease: current concepts and future perspectives. Lancet Neurology 2008;7:1056–66. Lubman DI, Pantelis C, Desmond P, Proffitt TM, Velakoulis D. Moyamoya disease in a patient with schizophrenia. Journal of the International Neuropsychological Society 2003;9:806–10. Parray T, Martin TW, Siddiqui S. Moyamoya disease: a review of the disease and anesthetic management. Journal of Neurosurgical Anesthesiology 2011;23: 100–9. Ratchford JN, Calabresi PA. The diagnosis of MS: white spots and red flags. Neurology 2008;70:1071–2. Scott RM, Smith ER. Moyamoya disease and moyamoya syndrome. New England Journal of Medicine 2009;360:1226–37. 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. Journal of Neurosurgery 2004;100:142–9. Suzuki J, Takaku A. Cerebrovascular ‘‘moyamoya’’ disease: disease showing abnormal net-like vessels in base of brain. Archives of Neurology 1969;20: 288–99. Takagi Y, Kikuta K, Sadamasa N, Nozaki K, Hashimoto N. Caspase 3 dependant apoptosis in meddle cerebral arteries in patients with moyamoya disease. Neurosurgery 2006;59:894–900. Takeuchi KSK. Hypoplasia of the bilateral internal carotid. Brain Nerve 1957;9: 37–43. Yamashita M, Tanaka K, Matsuo T, Yokoyama K, Fujii T, Sakamoto H. Cerebral dissecting aneurysms in patients with moyamoya disease. Report of two cases. Journal of Neurosurgery 1983;58:120–5. Yonekawa Y, Ogata N, Kaku Y, Taub E, Imhof HG. Moyamoya disease in Europe, past and present status. Clinical Neurology and Neurosurgery 1997;99(Suppl. 2): S58–60.
Contents lists available at SciVerse ScienceDirect
Multiple Sclerosis and Related Disorders journal homepage: www.elsevier.com/locate/msard
Moyamoya: Another multiple sclerosis mimic Fariha Zaheer, Joseph R. Berger n Department of Neurology, University of Kentucky College of Medicine, Lexington, KY, United States
a r t i c l e i n f o
a b s t r a c t
Article history: Received 12 September 2011 Received in revised form 3 October 2011 Accepted 7 October 2011
A broad range of disorders have been recognized to share clinical and radiographic features with multiple sclerosis and are frequently mistaken with this diagnosis. Several of these disorders are vascular disorders, including atherosclerotic and inflammatory diseases affecting small and medium sized vessels, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and migraine variants. We describe 2 patients with moyamoya syndrome who presented with paroxysmal symptoms, physical findings and MRI abnormalities that were mistaken for multiple sclerosis. Therefore, moyamoya must be added to the list of disorders in the differential diagnosis of multiple sclerosis. & 2011 Elsevier B.V. All rights reserved.
Keywords: Multiple sclerosis Moyamoya Transient ischemic attack Cerebrovascular disease Internal carotid artery Cerebral angiography
1. Introduction Moyamoya disease is a non-inflammatory vasculopathy resulting in progressive stenosis of the intracranial internal carotid arteries and proximal branches of circle of Willis. First described in 1957 by Shimizu and Takeuchi in Japan, the characteristic pathology was ‘‘hypoplasia of the bilateral internal carotid arteries’’ leading to the formation of an extensive collateral network composed of pathologically dilated vessels (Takeuchi, 1957). Due to this appearance, Suzuki and Takaku named this disease ‘‘moyamoya disease’’ ‘‘puff of smoke’’ in Japanese (Suzuki and Takaku, 1969). When the pattern of vascular occlusion occurs with other etiologies, the term ‘‘moyamoya syndrome’’ has been applied. Clinical manifestations of Moyamoya disease can be diverse. Most often it presents as transient ischemic attacks, ischemic stroke or intracerebral hemorrhage. We describe two individuals whose initial clinical and radiological pictures were initially mistaken for multiple sclerosis, but because of atypical features, angiographic studies were performed confirming the diagnosis of moyamoya disease. 2. Case reports 2.1. Case 1 A 50 year old Caucasian female with history of type 2 diabetes mellitus, hypertension, and hyperlipidemia was referred to neurology n Correspondence to: Department of Neurology, University of Kentucky College of Medicine, Kentucky Clinic L-445, 740 S. Limestone Street, Lexington, KY 405360284, United States. Tel.: þ1 859 218 5039; fax: þ 1 859 323 5943. E-mail address: [email protected] (J.R. Berger).
2211-0348/$ - see front matter & 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.msard.2011.10.001
clinic for evaluation of possible multiple sclerosis. Her symptoms started one year earlier when she developed transient episodes of left facial weakness lasting up to 24 hours for which she did not seek any medical attention. Three months later, she noted recurrent brief episodes of right leg weakness preceded by a peculiar sensation in the same limb. Weakness would often preclude walking and at times result in falls. There were no identified triggers for these spells. A month later, she noted transient episodes of numbness in her fingers of both hands lasting up to one hour and accompanied by a feeling as if her hands belonged to somebody else. A cranial MRI showed white matter changes consistent with multiple sclerosis, though cerebrospinal fluid examination was non-diagnostic. Because of concern of possible cerebrovascular disease, clopidogrel was initiated at that time. Three months later, she developed right leg weakness rendering walking difficult. She also began to notice transient weakness of left leg. Left arm and leg weakness began subacutely and plateaued after 3 days followed five months later. Her family reported changes in her speech, impaired reading and writing, and altered behavior. A cranial MRI at that time revealed extensive T2 abnormalities with hyperintense signals involving the cortex and extending deep into the white matter bilaterally with similar changes in the pons. Diffusion restriction was noted in the cerebral hemispheric lesions suggesting cerebral infarction. MRA head and neck did not reveal any significant stenosis or vascular anomaly. MRI of cervical, thoracic and lumbar spine did not show any abnormal signal within the spinal cord parenchyma. CSF examination remained normal. A detailed hypercoaguability screen was negative. Angiotensin converting enzyme levels were normal and HIV antibody was non-reactive. Serological studies for autoimmune disease including sedimentation rate, C-reactive protein, antinuclear antibody, rheumatoid
F. Zaheer, J.R. Berger / Multiple Sclerosis and Related Disorders 1 (2012) 100–103
factor, antineutrophilic antibody, anti-SSa and anti-SSb were negative. There was no improvement following a course of corticosteroids and daily glatiramer acetate 20 mg subcutaneously was initiated. In our office, she denied fatigue, heat intolerance, Lhermitte’s phenomenon, visual, or bowel problems. She did report occasional urinary incontinence for 3 months. General examination was unremarkable. Neurological examination revealed abnormal saccades, left central facial palsy, and spastic left hemiparesis with a left-sided Babinski. Transesophageal echocardiogram revealed small apical aneurysm with akinesia. No thrombus, vegetation or valvular abnormality was noted. A four vessel cerebral angiogram showed severe bilateral supraclinoid internal carotid artery stenosis with formation of distal collateral circulation through extra-cranial and posterior circulation consistent with moyamoya disease. A surgical procedure, bilateral encephaloduroarteriosyngiosis, was subsequently performed. Three months after the procedure, she has done well and exhibited no new or recurrent neurological symptoms (Figs. 1 and 2).
2.2. Case 2 This 44 year old Caucasian male with history of type 2 diabetes mellitus and hyperlipidemia was referred for evaluation of transient episodes of right sided numbness. There was a concern that he had
101
multiple sclerosis. One year prior to presentation, he first noticed right leg numbness that developed while walking briskly. Thereafter, he noticed recurrent right leg numbness with activity, particularly lifting boxes on his job, suggesting Uhthoff’s phenomenon. The numbness would last up to 24 hours, but usually lasted less than 4 hours. Two months after their onset, he developed transient episodes of right arm numbness as well. Eventually, right arm and leg numbness were accompanied by right facial numbness, right sided burning, and visual blurring. Episodes typically lasted for an hour, occurred 2–3 times in a week on average, and were precipitated by activity. He denied fatigue, heat intolerance, Lhermitte’s phenomenon, sphincter disturbances, or gait abnormality. Carotid ultrasound was normal. Laboratory investigations were unremarkable but for a positive antinuclear antibody. Physical examination revealed bilateral diabetic retinopathy with normal disks, visual acuity of 20/40 right eye and 20/50 left eye, and impaired color vision in both eyes. There was no nystagmus or ocular dysmetria. He had central right facial weakness, but limb tone, strength, and coordination were normal. Ankle jerks were absent and there was no clonus or Babinskis. His gait was normal. Distal vibratory sense in the lower extremities was impaired and Romberg test positive. A cranial MRI showed white matter lesions suggestive of multiple sclerosis (Figs. 3 and 4).
Fig. 1. MRI brain—FLAIR sequence: (a) extensive hyperintense signal involving the cortex and white matter bilaterally and (b) hyperintense signal abnormality within the pons.
Fig. 2. Cerebral angiogram showing stenosis of the right supraclinoid internal carotid artery and extensive distal collateral circulation. Arrows indicate site of supraclinoid internal carotid artery stenosis.
102
F. Zaheer, J.R. Berger / Multiple Sclerosis and Related Disorders 1 (2012) 100–103
Fig. 3. MRI brain (A, B—FLAIR axial sequences, C—T1 sagittal sequence and D—FLAIR sagittal sequence) revealing periventricular white matter changes suspicious for multiple sclerosis.
Fig. 4. (a) and (b) Cerebral angiogram with diffuse irregularity and narrowing of left A1 and M1.
CSF examination showed no oligoclonal bands or elevated IgG Index, although myelin basic protein was mildly elevated. Visual evoked potentials were markedly prolonged from both eyes. Other evoked potentials were normal. Autoimmune work up including erythrocyte sedimentation rate, anti-SSa, anti-SSb, and rheumatoid factor were negative. HIV antibody was non-reactive. Every other day interferon-b1b subcutaneously was initiated. Eight months later, while working in hot sun, he developed sudden onset expressive aphasia with intact comprehension lasting 30 minutes. His examination was unchanged. A transthoracic echocardiogram showed normal ejection fraction with no evidence of any thrombus, vegetation or valvular abnormality. A four vessel angiogram was performed and revealed diffuse irregularity with narrowing of left A1 and M1 branches of the middle cerebral artery and the left posterior cerebral artery consistent with a vasculopathy, most likely Moyamoya. Interferon b1b was discontinued and aspirin and clopidogrel initiated.
3. Discussion While a variety of vascular disorders, including cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), Binswangers disease, and small
vessel cerebrovascular disease, have been listed among diagnoses to be considered in patients with possible multiple sclerosis (Fieschi et al., 1995; Ratchford and Calabresi, 2008), moyamoya disease has not always been included in comprehensive reviews. There have been rare case reports of patients with clinical or radiological picture suggesting multiple sclerosis that subsequently proved to have moyamoya disease (Brady et al., 1990; Janda et al., 2009). A young woman described in 1990 (Brady et al., 1990), was believed to have multiple sclerosis based on her initial clinical and radiological findings, but progressive disease led to angiography showing stenosis of the proximal internal carotid arteries much like patient #1. Another patient was diagnosed with multiple sclerosis based chiefly on her radiographic findings, but angiography ultimately revealed bilateral absence of anterior and middle cerebral arteries (Janda et al., 2009). The possibility of the co-existence of two separate disorders always needs to be considered. Recently, a patient with both neuromyelitis optica and moyamoya disease has been reported (Asai et al., 2011). Moyamoya disease, originally considered to be a disorder of Asian lineage, is found throughout the world, but is more prevalent in Asian population, particularly Japanese. In Japan, the annual incidence has been estimated to be 0.35 per 100,000 (Kuroda and Houkin, 2008). The incidence in United States in 2005 was estimated at 0.086 cases per 100,000 (Scott and Smith, 2009). The incidence
F. Zaheer, J.R. Berger / Multiple Sclerosis and Related Disorders 1 (2012) 100–103
rate ratios of specific ethnic origins compared with Caucasians were 4.6 for Asian Americans, suggesting a significant role of genetic factors in the etiology of this disease (Yonekawa et al., 1997). Its incidence peaks in children around age 5 and in adults at approximately the mid-forties. Female to male ratio has been shown to be 1.8. Moyamoya appears to be different in the Asian and North American populations as the former typically develop hemorrhage and the latter ischemic stroke (Hallemeier et al., 2006). Pathological observation of the blood vessels does not show inflammation or atherosclerosis, but rather smooth muscle hyperplasia and intraluminal thrombosis. There is fibrous thickening of internal elastic lamina, irregularity of internal elastic lamina and attenuation of media (Fukui et al., 2000). This degradation of the blood vessels walls have been attributed to caspase 3 dependent apoptosis (Takagi et al., 2006). Extensive moyamoya collaterals are dilated perforating arteries with various pathological changes including formation of microaneurysms, explaining the hemorrhagic strokes (Yamashita et al., 1983). Moyamoya occurring in association with other conditions, such as, Down’s syndrome, sickle cell disease, neurofibromatosis type 1, renal artery stenosis, and hyperthyroidism is referred to as the moyamoya syndrome (Scott and Smith, 2009). When it occurs in isolation, it is termed as moyamoya disease (Scott and Smith, 2009). Both of our patients had significant atherosclerotic risk factors, but their relative youth and the fact that their vascular disease was uniquely focal and limited to intracranial vessels suggests that the disorder was moyamoya; however, the underlying pathology may have been atherosclerotic in nature and the term moyamoya syndrome has been used rather than moyamoya disease. As in our patients, focal neurological deficits such as aphasia, hemiparesis or hemianopsia, are the most common presentations. Children usually develop transient ischemic attacks or cerebral infarctions, while adults may present with intracranial hemorrhage, cerebral infarctions or transient ischemic attacks. Atypical clinical presentations have been described (Baik and Lee, 2010; Lubman et al., 2003). Radiographic studies are essential for the diagnosis. Restricted diffusion on cranial MRI is particularly common in watershed areas (Scott and Smith, 2009). Subacute and chronic infarcts are best visualized on fluid attenuated inversion recovery sequences (FLAIR) (Scott and Smith, 2009). Although MR and computed tomographic angiography may be helpful, conventional cerebral angiogram remains the gold standard. It typically shows stenosis of the distal internal carotid artery extending to the proximal middle and anterior cerebral arteries. The ‘‘puff of smoke’’ appearance results from the development of extensive collateral network, originating ether from the basilar artery or extra-cranial blood vessels (Scott and Smith, 2009). Surgical revascularization is the most effective way to improve cerebral perfusion and prevent further strokes. Two general methods have been used, a direct approach in which the superficial temporal artery is anastomosed to a cortical artery beyond the stenosis and an indirect approach in which a vascular tissue is placed in direct contact with the brain leading to an ingrowth of new blood vessels to the underlying cerebral cortex (Parray et al., 2011). Some centers advocate using combination of both direct and indirect approaches. Antiplatelets have been used in most of the operative series to prevent emboli from microthrombi formed at sites of arterial stenosis (Scott et al., 2004). The natural history of moyamoya has not been extensively studied. Hallemeier and group have shown that 5-year risk of recurrent stroke is 65% and
103
82% in unilateral and bilateral disease, respectively (Hallemeier et al., 2006), Two large studies have shown good safety profile for surgical revascularization with 96% probability of remaining stroke free over next 5 years (Choi et al., 1997; Scott et al., 2004). In summary, moyamoya should be considered in the differential diagnoses of any unexplained neurological symptoms. The clinical and radiographic findings may mimic multiple sclerosis and, therefore, it needs to be considered in the differential diagnosis of this disorder. Clues to the correct diagnosis might include the very transient nature of the focal neurological deficits and cortical symptoms, such as, aphasia. When coupled with the lack of supportive evidence of MS, such as, the absence of gadolinium enhancing brain lesions, absence of lesions typical of MS in the posterior fossa, and absence of unique oligoclonal bands and elevated IgG in the CSF, vasocclusive disease needs to be strongly considered.
References Asai Y, Nakayasu H, Fusayasu E, Nakashima K. Moyamoya disease presenting as thalamic hemorrhage in a patient with neuromyelitis optica and Sjogren’s syndrome. Journal of Stroke and Cerebrovascular Diseases 2011. Baik JS, Lee MS. Movement disorders associated with moyamoya disease: a report of 4 new cases and a review of literatures. Movement Disorders 2010;25: 1482–6. Brady AP, Stack JP, Ennis JT. Moyamoya disease—imaging with magnetic resonance. Clinical Radiology 1990;42:138–41. Choi JU, Kim DS, Kim EY, Lee KC. Natural history of moyamoya disease: comparison of activity of daily living in surgery and non surgery groups. Clinical Neurology and Neurosurgery 1997;99(Suppl. 2):S11–8. Fieschi C, Gasperini C, Ristori G, Bastianello S, Girmenia F, Leuzzi V, et al. Patients with clinically definite multiple sclerosis, white matter abnormalities on MRI, and normal CSF: if not multiple sclerosis, what is it? Journal of Neurology, Neurosurgery, and Psychiatry 1995;58:255–6. Fukui M, Kono S, Sueishi K, Ikezaki K. Moyamoya disease. Neuropathology 2000;20(Suppl.):S61–4. Hallemeier CL, Rich KM, Grubb Jr RL, Chicoine MR, Moran CJ, Cross III DT, et al. Clinical features and outcome in North American adults with moyamoya phenomenon. Stroke 2006;37:1490–6. Janda PH, Bellew JG, Veerappan V. Moyamoya disease: case report and literature review. Journal of the American Osteopathic Association 2009;109:547–53. Kuroda S, Houkin K. Moyamoya disease: current concepts and future perspectives. Lancet Neurology 2008;7:1056–66. Lubman DI, Pantelis C, Desmond P, Proffitt TM, Velakoulis D. Moyamoya disease in a patient with schizophrenia. Journal of the International Neuropsychological Society 2003;9:806–10. Parray T, Martin TW, Siddiqui S. Moyamoya disease: a review of the disease and anesthetic management. Journal of Neurosurgical Anesthesiology 2011;23: 100–9. Ratchford JN, Calabresi PA. The diagnosis of MS: white spots and red flags. Neurology 2008;70:1071–2. Scott RM, Smith ER. Moyamoya disease and moyamoya syndrome. New England Journal of Medicine 2009;360:1226–37. 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. Journal of Neurosurgery 2004;100:142–9. Suzuki J, Takaku A. Cerebrovascular ‘‘moyamoya’’ disease: disease showing abnormal net-like vessels in base of brain. Archives of Neurology 1969;20: 288–99. Takagi Y, Kikuta K, Sadamasa N, Nozaki K, Hashimoto N. Caspase 3 dependant apoptosis in meddle cerebral arteries in patients with moyamoya disease. Neurosurgery 2006;59:894–900. Takeuchi KSK. Hypoplasia of the bilateral internal carotid. Brain Nerve 1957;9: 37–43. Yamashita M, Tanaka K, Matsuo T, Yokoyama K, Fujii T, Sakamoto H. Cerebral dissecting aneurysms in patients with moyamoya disease. Report of two cases. Journal of Neurosurgery 1983;58:120–5. Yonekawa Y, Ogata N, Kaku Y, Taub E, Imhof HG. Moyamoya disease in Europe, past and present status. Clinical Neurology and Neurosurgery 1997;99(Suppl. 2): S58–60.
