JNS-13236; No of Pages 4 Journal of the Neurological Sciences xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Short communication
Two cases of dural arteriovenous fistula presenting with parkinsonism and progressive cognitive dysfunction Yong Luo a,b,1, Jun Qi a,1, Zhidong Cen a, Haitao Hu a, Biao Jiang a, Wei Luo a,⁎ a b
Department of Neurology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China Department of Neurology, Jinhua Municipal Central Hospital, Jinhua, Zhejiang, China
a r t i c l e
i n f o
Article history: Received 11 March 2014 Received in revised form 28 April 2014 Accepted 27 May 2014 Available online xxxx Keywords: Dural arteriovenous fistula Parkinsonism Cognitive dysfunction Magnetic resonance arteriography Calcification Venous hypertension
a b s t r a c t Dural arteriovenous fistula (DAVF) is a rare type of cerebral arteriovenous malformation. The occurrence of parkinsonism together with progressive cognitive dysfunction caused by DAVF has been rarely reported. The probable underlying pathophysiology could be due to venous hypertension caused by DAVF which leads to basal ganglia and cortical dysfunction. Here, two DAVF cases were reported presenting with parkinsonism and progressive cognitive dysfunction. A 54-year-old man (case 1) and a 75-year-old man (case 2) presented with bradykinesia, gait disturbances and cognitive dysfunction who were initially misdiagnosed as having Parkinson's disease. Case 1 exhibited a characteristic type of subcortical calcification on CT scan, while case 2 had specific resting tremor and intracranial hypertension. Both cases showed transient response to the dopaminergic treatment. After 3D time-of-flight (TOF) magnetic resonance arteriography (MRA) or digital subtraction arteriography (DSA), they were diagnosed as having DAVF. This report suggests the possibility of DAVF in patients presenting with parkinsonism and progressive cognitive dysfunction, which requires further attention to be paid, especially in those with transient response to levodopa. Early 3D TOF MRA or DSA is recommended for the diagnosis of DAVF. © 2014 Elsevier B.V. All rights reserved.
1. Introduction Dural arteriovenous fistula (DAVF) is a rare type of cerebral vasculopathy, which accounts for 10–15% of all intracranial arteriovenous malformations [1]. DAVFs are abnormal connections of the arterial and venous systems involving dural sinuses and branches of the external and internal carotid arteries, or vertebral arteries. Typically, DAVF exhibits various symptoms including pulsatile tinnitus, ophthalmoplegia, proptosis, headache, and cognitive dysfunction. DAVF with the onset of parkinsonian symptoms and cognitive dysfunction is rarely reported [2–6]. Here, two DAVF cases were reported presenting with parkinsonism and progressive cognitive dysfunction. These cases' diagnosis was eventually confirmed by 3D time-of-flight (TOF) magnetic resonance angiography (MRA) or digital subtraction arteriography (DSA). Although angiography is the gold standard for the diagnosis of DAVF, 3D TOF MRA as a noninvasive diagnostic tool we employed had provided a satisfactory delineation of DAVF. The causes of these two symptoms may be due to venous hypertension of deep cerebral vein and cortical
⁎ Corresponding author at: Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Rd., Hangzhou, Zhejiang, 310009, China. Tel.: + 86 571 87783777; fax: + 86 571 87784751. E-mail address: [email protected] (W. Luo). 1 These authors contributed equally to this work and should be considered co-first authors.
venous congestion caused by DAVF, which eventually leads to basal ganglia and cortical dysfunction [3,7]. 2. Case reports 2.1. Case 1 A 54-year-old man was admitted to our hospital with a 10-month history of slow-movement and slowed thinking. He was initially diagnosed as having Parkinson's disease by the outpatient doctor at the 7th month after the onset of the symptoms. Madopar, at the dose of 62.5 mg Qid was effective at the beginning. Later the symptoms gradually aggravated although madopar was added up to the maximum dose of 187.5 mg Qid. Slowness of movement, cognitive dysfunction and urinary incontinence finally made him lose the ability to take care of himself. The patient had a mild impact on the right occiput 5 years before the disease and was diagnosed of incurring a brain concussion. He recovered satisfactorily without any neurological sequelae. On neurological examination, his facial expressions were significantly diminished and muscle tone increased in all four of his limbs. The patient had a slow movement while walking with wide-based gait and was very unstable when turning back. Muscle strength and sensation were normal. There was no pathological reflex or signs of cerebellar ataxia. The patient was of primary school level education but his mini-mental state examination (MMSE) score was 14/30. Blood tests had excluded some
http://dx.doi.org/10.1016/j.jns.2014.05.059 0022-510X/© 2014 Elsevier B.V. All rights reserved.
Please cite this article as: Luo Y, et al, Two cases of dural arteriovenous fistula presenting with parkinsonism and progressive cognitive dysfunction, J Neurol Sci (2014), http://dx.doi.org/10.1016/j.jns.2014.05.059
2
Y. Luo et al. / Journal of the Neurological Sciences xxx (2014) xxx–xxx
reversible causes of cognitive dysfunction, such as hypothyroidism, vitamin deficiencies and HIV. EEG showed as low as 60 μV 8.5–9 Hz α waves and small amount of scattered θ waves which was at times observed on the frontal head in short ranges. Subsequent non-enhanced CT scan showed curvilinear calcification in the cortico-medullary junction at the bottom of the cerebral sulcus bilaterally (Fig. 1A). T2-weighted magnetic resonance imaging (MRI) revealed flow void clusters at the inner part of the left temporal lobe (Fig. 1B). Source imaging of MRA showed findings of multiple high-intensity curvilinear adjacent to the right transverse sinus wall. Hyperintense signals coming from feeders of the tentorial artery were well visualized (Fig. 1C). 3D TOF MRA showed flow-related enhancement of a dural arteriovenous fistula located in the right transverse-sigmoid sinus. High-intensity areas in the dilated straight sinus and the right transverse sinus suggested venous hypertension due to the DAVF (Fig. 1D). DSA finally confirmed the diagnosis of DAVF of the right transverse sinus. Unfortunately, the medical filekeeping department lost the DSA information of this patient for some special reason, so we could not provide this patient's DSA imaging for reference. Considering the risk and the expenses of endovascular embolization treatment, his family chose to give up. After being discharged, his situation continued to get worse. Unfortunately, we eventually lost contact with this patient. 2.2. Case 2 A 75-year-old man came with the complaint of slow-movement for 3 years. 2 years after the onset, the patient started experiencing difficulties to start walking and the gait became shuffling with short steps.
Resting tremor started from his right hand insidiously, and then to his left hand. Simultaneously, his recent memory and arithmetic ability suffered tremendous damage. He had a 10-year history of hypertension and no history of head trauma. On the first visit to our department, the patient had apparent bradykinesia, gait disturbances and resting tremor of upper extremities. He had a mask-like face with mouth open and diminished blinking. His muscle tone increased moderately. No abnormality of muscle strength and sensation was found, and there were also no pathological reflexes. He had a MMSE score of 8/30. Hypothyroidism, vitamin deficiencies and HIV were also excluded by blood tests. Initially the patient was misdiagnosed as having Parkinson's disease and was given a small dose of madopar treatment. The tremor of his hands improved and he was able to walk faster than before. However, this improvement lasted only for three months. Increasing the dose of madopar did not achieve a better effect to his condition. A moderate headache was complained when the patient was lying down. In order to confirm a possible intracranial hypertension and differentiate other secondary diseases which could cause headache we carried out lumbar puncture and his cerebrospinal fluid pressure exceeded 300 mmH2O. α waves completely disappeared and diffuse slow waves could be seen in his EEG. Further, the MRI revealed that there was a significantly dilated vein on the left temporal cortex on T2-weighted imaging. There were also apparently increased flow void signals indicating deep dilated vessels of the brain (Fig. 2A). The left dilated cortical veins could also be found on the same level of the source MRA imaging (Fig. 2B). 3D TOF MRA revealed the apparently inflated left middle meningeal vein connected with the left transverse-sigmoid sinus. The amount of dilated intracranial
Fig. 1. A dural arteriovenous fistula (DAVF) in a 54-year-old man with slow-movement and slowed thinking. (1A) Non-enhanced CT scan shows multi-curvilinear calcification (arrows) in subcortical region of the bilateral frontal and parietal lobe. (1B) T2-weighted MRI imaging shows flow void clusters at the left medial temporal lobe (arrow). (1C) Source imaging of MRA shows findings of multiple high-intensity curvilinear (long arrow) adjacent to the right transverse sinus wall. Hyperintense signals coming from feeders of the lateral tentorial artery (short arrow) are well visualized. (1D) 3D TOF MRA shows flow-related enhancement of a DAVF located in the right transverse-sigmoid sinus (short arrow). High-intensity areas in the dilated straight sinus (long arrow) and the right transverse sinus suggest venous hypertension due to the DAVF.
Please cite this article as: Luo Y, et al, Two cases of dural arteriovenous fistula presenting with parkinsonism and progressive cognitive dysfunction, J Neurol Sci (2014), http://dx.doi.org/10.1016/j.jns.2014.05.059
Y. Luo et al. / Journal of the Neurological Sciences xxx (2014) xxx–xxx
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Fig. 2. A DAVF in a 75-year-old man with slow-movement and declining memory. (2A) There is a significantly dilated superficial vein (short arrow) on the left temporal cortex on T2-weighted MRI imaging. There are apparently increased flow void signals (long arrow) indicating deep dilated vessels of the brain. (2B) The left dilated cortical veins (arrow) can also be found on the same level of the source MRA imaging. (2C) 3D TOF MRA reveals the apparently inflated left middle meningeal vein (black arrow) connected with the left transverse-sigmoid sinus. Many small perforating branches were connected with the diploic veins (long white arrow). The flow-related signal of dilated straight sinus (short white arrow) may be caused by the reflux upstream due to the DAVF. (2D) Source imaging of MRA shows hyperintense signals (arrow) at the transition of the transverse to the sigmoid sinus, only on the left side with the pathological hyperintense signals at the sinus wall.
veins on the left side was much bigger than those on the right side. The wall of the left transverse-sigmoid sinus was rough, around which many small perforating branches were connected with the diploic veins. The flow-related signal of dilated straight sinus could also be seen which suggested venous hypertension (Fig. 2C). Source imaging of MRA showed pathological hyperintense signals at the transition of the transverse to the sigmoid sinus on the left side (Fig. 2D). All these signs suggested a DAVF in the left transversesigmoid sinus. The dilated left temporal cortical veins may be caused by the reflux upstream due to the DAVF, which also led to the thickening of the straight sinus. Unfortunately this patient died of seizures and pulmonary infection before further DSA examination and lost the opportunity to receive endovascular embolization treatment. 3. Discussion DAVF is a rare cause for patients with parkinsonism. In 1999, Matsuda et al. described the first 3 cases of DAVF accompanied with parkinsonism and cognitive dysfunction [4]. Most of the reported DAVFs with parkinsonism and cognitive dysfunction were located in the transverse or sigmoid sinus with retrograde venous reflux into the straight sinus and/or cortical veins [2–6,8]. The probable mechanism may be due to venous hypertension caused by DAVF which led to the dysfunction of the basal ganglia and cerebral cortex. The exact pathophysiology of parkinsonism and cognitive dysfunction in DAVF still needs further exploration.
Both of our cases had typical symptoms of parkinsonism including gradual progressive bradykinesia and gait disturbances. Resting tremor of upper extremities found in case 2 has never been reported to our knowledge. Both cases were initially misdiagnosed as having Parkinson's disease and showed good response to dopaminergic treatment that did not last for long. Finally they were both diagnosed as having DAVF by 3D TOF MRA or DSA. Often clinicians are blinded by typical symptoms and good drug response. Therefore, more attention must also be paid to neuroimaging when exploring the causes for parkinsonism, accompanied with cognitive dysfunction. Clinicians often choose noncontrast CT as the initial imaging method for neurological disease examination. Subcortical calcification is a common and nonspecific imaging presentation on CT. The usual causes include neoplasms, hyperparathyroidism, Fahr's disease, Sturge–Weber syndrome, pial arteriovenous malformation and infectious disorders. However, subcortical calcification on CT in DAVF with cortical venous reflux is unusual and characteristic [9,10]. Case 1 showed diffuse subcortical curvilinear calcification in the cortico-medullary junction on CT bilaterally. This particular pattern of curvilinear calcification in DAVF with parkinsonism and cognitive dysfunction was the second time to be reported [5]. The exact cause for DAVF associated calcification was not clear. In previous studies, subcortical calcification accompanied with DAVF was considered to be a dystrophic process due to focal hypoperfusion by the steal phenomenon or persistent venous congestion, suggestive of a possible poor prognosis without treatment [9,10]. Thus, we suspect that the calcification in case 1 might have been associated with cortical venous reflux and persistent venous congestion due
Please cite this article as: Luo Y, et al, Two cases of dural arteriovenous fistula presenting with parkinsonism and progressive cognitive dysfunction, J Neurol Sci (2014), http://dx.doi.org/10.1016/j.jns.2014.05.059
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Y. Luo et al. / Journal of the Neurological Sciences xxx (2014) xxx–xxx
to DAVF. Cognitive dysfunction of case 1 may be one of the presentations of cortical dysfunction as a result of diffuse cortical hypoperfusion. The exacerbation of case 1 was in line with the speculation that subcortical calcification in DAVF could predict an adverse prognosis. The pathogenesis of parkinsonism and cognitive dysfunction in patients with DAVF remains to be further studied. Matsuda et al. noted diffuse white matter lesions on MRI in patients with DAVF presenting with parkinsonism and cognitive dysfunction which were similar to vascular parkinsonism and Binswanger's disease, and contributed the cause of parkinsonism to the frontal white matter lesions [4]. However, Lee et al. deduced that parkinsonism in DAVF is associated with basal ganglia dysfunction secondary to impaired drainage of the deep internal veins, rather than white matter lesions [3]. In our cases, white matter changes on MRI were minimal or absent. Also, unlike the characteristic lower body parkinsonism that occurs in white matter diseases, muscle tone increased in both of our patients' upper extremities. Patient two even had resting tremor of upper extremities besides gait disturbances. Dilated straight sinus veins in 3D TOF MRA and abnormal flow void signals of deep brain on T2-weighted MRI imaging in our cases indicated a possible retrograde venous reflux into the basal ganglion region. Therefore, the possible mechanism of parkinsonism in our cases might be in line with the hypothesis proposed by Lee et al. Unfortunately, there were no signal abnormalities in the basal ganglia on MRI in our cases. Further functional imaging study such as dopamine transporters scan with single-photon emission tomography or positron emission computed tomography might be able to reveal functional changes in the basal ganglia and clarify the etiology of this type of subjects. Similarly, the enlargement of deep venous sinus and cortical veins as signs of venous intracranial hypertension could cause venous congestive encephalopathy leading to cognitive dysfunction. Venous intracranial hypertension in case 2 was finally identified by lumbar puncture. Broadly speaking, parkinsonism due to DAVF could be considered a special form of vascular parkinsonism. However, it is not easy to distinguish it from the classical vascular parkinsonism. The symptoms of the upper body and the absence of history of multiple strokes could possibly help to differentiate parkinsonism secondary to DAVF from the classical vascular parkinsonism. Although angiography is the gold standard for diagnosis of DAVF, previous studies have shown that 3D TOF MRA is a good complementary tool for the identification of DAVF [11–14], but not for follow-up [14]. Furthermore, the source imaging of 3D TOF MRA containing both flow and anatomic information is more useful than that of maximumintensity-projection imaging in showing DAVF [11]. In cases with DAVF, source imaging of 3D TOF MRA showed two characteristic imaging features: multiple high-intensity curvilinear or nodular structures adjacent to the sinus wall and high-intensity areas in the venous sinus, both of which could also be found in our cases [11]. Sensitivity and specificity of the two features were 100% and 100%, 76% and 86%, respectively [11]. In the latest study, 3D TOF MRA detected 88% DAVFs correctly [14]. In our study, 3D TOF MRA had also provided a satisfactory delineation of DAVF. Therefore, 3D TOF MRA, as a noninvasive diagnostic tool without the risks of ionizing radiation and contrast agent allergy, is a promising procedure for the identification of DAVF presenting with parkinsonism and cognitive dysfunction. Unfortunately, the DSA information of case 1 was lost and DSA was not performed for case 2. We sincerely apologize for not providing a complete imaging data. The imaging features of DAVF are so variable and non-specific that the diagnosis is often delayed or missed [5]. Some relatively rare clinical presentations such as pulsatile tinnitus, ophthalmoplegia, and proptosis, though absent in our cases, could also help in the diagnosis of DAVF. If a patient presents with a few of the symptoms mentioned above and parkinsonism simultaneously, the possibility of DAVFassociated parkinsonism should be considered.
Observation, open surgery and endovascular embolization are potential treatment options for DAVF. Among them, endovascular embolization is safe, effective, and can often be used as a single treatment for DAVF. Parkinsonism and cognitive dysfunction as results of DAVF may be reversible through endovascular embolization, which has been reported in the literature [15]. DAVF will have a poor prognosis if it is not effectively treated. One of our case's situation continued to get worse and the other one died of seizures, which indicates early diagnosis to be particularly important. Conflict of interest The authors report no conflicts of interest. Disclosures None. Author contributions Study concept and design: Wei Luo. Acquisition of data: Yong Luo and Jun Qi. Drafting of the manuscript: Yong Luo and Jun Qi. Critical revision of the manuscript for important intellectual content: Zhidong Cen, Haitao Hu, Biao Jiang, and Wei Luo. Administrative and material support: Wei Luo. References [1] Newton TH, Cronqvist S. Involvement of dural arteries in intracranial arteriovenous malformations. Radiology 1969;93(5):1071–8. [2] Kajitani M, Yagura H, Kawahara M, Hirano M, Ueno S, Fujimoto K, et al. Treatable fluctuating Parkinsonism and dementia in a patient with a dural arteriovenous fistula. Mov Disord 2007;22(3):437–9. [3] Lee PH, Lee JS, Shin DH, Kim BM, Huh K. Parkinsonism as an initial manifestation of dural arteriovenous fistula. Eur J Neurol 2005;12(5):403–6. [4] Matsuda S, Waragai M, Shinotoh H, Takahashi N, Takagi K, Hattori T. Intracranial dural arteriovenous fistula (DAVF) presenting progressive dementia and parkinsonism. J Neurol Sci 1999;165(1):43–7. [5] Netravathi M, Pal PK, Bharath RD, Ravishankar S. Intracranial dural arteriovenous fistula presenting as parkinsonism and cognitive dysfunction. J Clin Neurosci 2011;18(1):138–40. [6] Miura S, Noda K, Shiramizu N, Muraoka N, Hirohata M, Ayabe M, et al. Parkinsonism and ataxia associated with an intracranial dural arteriovenous fistula presenting with hyperintense basal ganglia in T1-weighted MRI. J Clin Neurosci 2009;16(2):341–3. [7] Iwama T, Hashimoto N, Takagi Y, Tanaka M, Yamamoto S, Nishi S, et al. Hemodynamic and metabolic disturbances in patients with intracranial dural arteriovenous fistulas: positron emission tomography evaluation before and after treatment. J Neurosurg 1997;86(5):806–11. [8] Hattori T, Takeuchi T, Kabeya R, Ando K, Tosaki F. Transverse-sigmoid sinus dural arteriovenous fistula presenting with parkinsonism. Neurol Med Chir (Tokyo) 2013;53(4):224–7. [9] Lai PH, Chang MH, Liang HL, Pan HB, Yang CF. Unusual signs for dural arteriovenous fistulas with diffuse basal ganglia and cerebral calcification. Zhonghua yi xue za zhi (Chin Med J) 2000;63(4):329–33 [Free China ed.]. [10] Metoki T, Mugikura S, Higano S, Ezura M, Matsumoto Y, Hirayama K, et al. Subcortical calcification on CT in dural arteriovenous fistula with cortical venous reflux. Am J Neuroradiol 2006;27(5):1076–8. [11] Noguchi K, Melhem ER, Kanazawa T, Kubo M, Kuwayama N, Seto H. Intracranial dural arteriovenous fistulas: evaluation with combined 3D time-of-flight MR angiography and MR digital subtraction angiography. AJR Am J Roentgenol 2004;182(1):183–90. [12] Kwon BJ, Han MH, Kang HS, Chang KH. MR imaging findings of intracranial dural arteriovenous fistulas: relations with venous drainage patterns. Am J Neuroradiol 2005;26(10):2500–7. [13] Bink A, Berkefeld J, Wagner M, You SJ, Ackermann H, Lorenz MW, et al. Detection and grading of dAVF: prospects and limitations of 3T MRI. Eur Radiol 2012;22(2):429–38. [14] Meckel S, Maier M, Ruiz DS, Yilmaz H, Scheffler K, Radue EW, et al. MR angiography of dural arteriovenous fistulas: diagnosis and follow-up after treatment using a timeresolved 3D contrast-enhanced technique. Am J Neuroradiol 2007;28(5):877–84. [15] Nogueira RG, Baccin CE, Rabinov JD, Pryor JC, Buonanno FS, Hirsch JA. Reversible parkinsonism after treatment of dural arteriovenous fistula. J Neuroimaging 2009;19(2):183–4.
Please cite this article as: Luo Y, et al, Two cases of dural arteriovenous fistula presenting with parkinsonism and progressive cognitive dysfunction, J Neurol Sci (2014), http://dx.doi.org/10.1016/j.jns.2014.05.059
Contents lists available at ScienceDirect
Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Short communication
Two cases of dural arteriovenous fistula presenting with parkinsonism and progressive cognitive dysfunction Yong Luo a,b,1, Jun Qi a,1, Zhidong Cen a, Haitao Hu a, Biao Jiang a, Wei Luo a,⁎ a b
Department of Neurology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China Department of Neurology, Jinhua Municipal Central Hospital, Jinhua, Zhejiang, China
a r t i c l e
i n f o
Article history: Received 11 March 2014 Received in revised form 28 April 2014 Accepted 27 May 2014 Available online xxxx Keywords: Dural arteriovenous fistula Parkinsonism Cognitive dysfunction Magnetic resonance arteriography Calcification Venous hypertension
a b s t r a c t Dural arteriovenous fistula (DAVF) is a rare type of cerebral arteriovenous malformation. The occurrence of parkinsonism together with progressive cognitive dysfunction caused by DAVF has been rarely reported. The probable underlying pathophysiology could be due to venous hypertension caused by DAVF which leads to basal ganglia and cortical dysfunction. Here, two DAVF cases were reported presenting with parkinsonism and progressive cognitive dysfunction. A 54-year-old man (case 1) and a 75-year-old man (case 2) presented with bradykinesia, gait disturbances and cognitive dysfunction who were initially misdiagnosed as having Parkinson's disease. Case 1 exhibited a characteristic type of subcortical calcification on CT scan, while case 2 had specific resting tremor and intracranial hypertension. Both cases showed transient response to the dopaminergic treatment. After 3D time-of-flight (TOF) magnetic resonance arteriography (MRA) or digital subtraction arteriography (DSA), they were diagnosed as having DAVF. This report suggests the possibility of DAVF in patients presenting with parkinsonism and progressive cognitive dysfunction, which requires further attention to be paid, especially in those with transient response to levodopa. Early 3D TOF MRA or DSA is recommended for the diagnosis of DAVF. © 2014 Elsevier B.V. All rights reserved.
1. Introduction Dural arteriovenous fistula (DAVF) is a rare type of cerebral vasculopathy, which accounts for 10–15% of all intracranial arteriovenous malformations [1]. DAVFs are abnormal connections of the arterial and venous systems involving dural sinuses and branches of the external and internal carotid arteries, or vertebral arteries. Typically, DAVF exhibits various symptoms including pulsatile tinnitus, ophthalmoplegia, proptosis, headache, and cognitive dysfunction. DAVF with the onset of parkinsonian symptoms and cognitive dysfunction is rarely reported [2–6]. Here, two DAVF cases were reported presenting with parkinsonism and progressive cognitive dysfunction. These cases' diagnosis was eventually confirmed by 3D time-of-flight (TOF) magnetic resonance angiography (MRA) or digital subtraction arteriography (DSA). Although angiography is the gold standard for the diagnosis of DAVF, 3D TOF MRA as a noninvasive diagnostic tool we employed had provided a satisfactory delineation of DAVF. The causes of these two symptoms may be due to venous hypertension of deep cerebral vein and cortical
⁎ Corresponding author at: Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Rd., Hangzhou, Zhejiang, 310009, China. Tel.: + 86 571 87783777; fax: + 86 571 87784751. E-mail address: [email protected] (W. Luo). 1 These authors contributed equally to this work and should be considered co-first authors.
venous congestion caused by DAVF, which eventually leads to basal ganglia and cortical dysfunction [3,7]. 2. Case reports 2.1. Case 1 A 54-year-old man was admitted to our hospital with a 10-month history of slow-movement and slowed thinking. He was initially diagnosed as having Parkinson's disease by the outpatient doctor at the 7th month after the onset of the symptoms. Madopar, at the dose of 62.5 mg Qid was effective at the beginning. Later the symptoms gradually aggravated although madopar was added up to the maximum dose of 187.5 mg Qid. Slowness of movement, cognitive dysfunction and urinary incontinence finally made him lose the ability to take care of himself. The patient had a mild impact on the right occiput 5 years before the disease and was diagnosed of incurring a brain concussion. He recovered satisfactorily without any neurological sequelae. On neurological examination, his facial expressions were significantly diminished and muscle tone increased in all four of his limbs. The patient had a slow movement while walking with wide-based gait and was very unstable when turning back. Muscle strength and sensation were normal. There was no pathological reflex or signs of cerebellar ataxia. The patient was of primary school level education but his mini-mental state examination (MMSE) score was 14/30. Blood tests had excluded some
http://dx.doi.org/10.1016/j.jns.2014.05.059 0022-510X/© 2014 Elsevier B.V. All rights reserved.
Please cite this article as: Luo Y, et al, Two cases of dural arteriovenous fistula presenting with parkinsonism and progressive cognitive dysfunction, J Neurol Sci (2014), http://dx.doi.org/10.1016/j.jns.2014.05.059
2
Y. Luo et al. / Journal of the Neurological Sciences xxx (2014) xxx–xxx
reversible causes of cognitive dysfunction, such as hypothyroidism, vitamin deficiencies and HIV. EEG showed as low as 60 μV 8.5–9 Hz α waves and small amount of scattered θ waves which was at times observed on the frontal head in short ranges. Subsequent non-enhanced CT scan showed curvilinear calcification in the cortico-medullary junction at the bottom of the cerebral sulcus bilaterally (Fig. 1A). T2-weighted magnetic resonance imaging (MRI) revealed flow void clusters at the inner part of the left temporal lobe (Fig. 1B). Source imaging of MRA showed findings of multiple high-intensity curvilinear adjacent to the right transverse sinus wall. Hyperintense signals coming from feeders of the tentorial artery were well visualized (Fig. 1C). 3D TOF MRA showed flow-related enhancement of a dural arteriovenous fistula located in the right transverse-sigmoid sinus. High-intensity areas in the dilated straight sinus and the right transverse sinus suggested venous hypertension due to the DAVF (Fig. 1D). DSA finally confirmed the diagnosis of DAVF of the right transverse sinus. Unfortunately, the medical filekeeping department lost the DSA information of this patient for some special reason, so we could not provide this patient's DSA imaging for reference. Considering the risk and the expenses of endovascular embolization treatment, his family chose to give up. After being discharged, his situation continued to get worse. Unfortunately, we eventually lost contact with this patient. 2.2. Case 2 A 75-year-old man came with the complaint of slow-movement for 3 years. 2 years after the onset, the patient started experiencing difficulties to start walking and the gait became shuffling with short steps.
Resting tremor started from his right hand insidiously, and then to his left hand. Simultaneously, his recent memory and arithmetic ability suffered tremendous damage. He had a 10-year history of hypertension and no history of head trauma. On the first visit to our department, the patient had apparent bradykinesia, gait disturbances and resting tremor of upper extremities. He had a mask-like face with mouth open and diminished blinking. His muscle tone increased moderately. No abnormality of muscle strength and sensation was found, and there were also no pathological reflexes. He had a MMSE score of 8/30. Hypothyroidism, vitamin deficiencies and HIV were also excluded by blood tests. Initially the patient was misdiagnosed as having Parkinson's disease and was given a small dose of madopar treatment. The tremor of his hands improved and he was able to walk faster than before. However, this improvement lasted only for three months. Increasing the dose of madopar did not achieve a better effect to his condition. A moderate headache was complained when the patient was lying down. In order to confirm a possible intracranial hypertension and differentiate other secondary diseases which could cause headache we carried out lumbar puncture and his cerebrospinal fluid pressure exceeded 300 mmH2O. α waves completely disappeared and diffuse slow waves could be seen in his EEG. Further, the MRI revealed that there was a significantly dilated vein on the left temporal cortex on T2-weighted imaging. There were also apparently increased flow void signals indicating deep dilated vessels of the brain (Fig. 2A). The left dilated cortical veins could also be found on the same level of the source MRA imaging (Fig. 2B). 3D TOF MRA revealed the apparently inflated left middle meningeal vein connected with the left transverse-sigmoid sinus. The amount of dilated intracranial
Fig. 1. A dural arteriovenous fistula (DAVF) in a 54-year-old man with slow-movement and slowed thinking. (1A) Non-enhanced CT scan shows multi-curvilinear calcification (arrows) in subcortical region of the bilateral frontal and parietal lobe. (1B) T2-weighted MRI imaging shows flow void clusters at the left medial temporal lobe (arrow). (1C) Source imaging of MRA shows findings of multiple high-intensity curvilinear (long arrow) adjacent to the right transverse sinus wall. Hyperintense signals coming from feeders of the lateral tentorial artery (short arrow) are well visualized. (1D) 3D TOF MRA shows flow-related enhancement of a DAVF located in the right transverse-sigmoid sinus (short arrow). High-intensity areas in the dilated straight sinus (long arrow) and the right transverse sinus suggest venous hypertension due to the DAVF.
Please cite this article as: Luo Y, et al, Two cases of dural arteriovenous fistula presenting with parkinsonism and progressive cognitive dysfunction, J Neurol Sci (2014), http://dx.doi.org/10.1016/j.jns.2014.05.059
Y. Luo et al. / Journal of the Neurological Sciences xxx (2014) xxx–xxx
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Fig. 2. A DAVF in a 75-year-old man with slow-movement and declining memory. (2A) There is a significantly dilated superficial vein (short arrow) on the left temporal cortex on T2-weighted MRI imaging. There are apparently increased flow void signals (long arrow) indicating deep dilated vessels of the brain. (2B) The left dilated cortical veins (arrow) can also be found on the same level of the source MRA imaging. (2C) 3D TOF MRA reveals the apparently inflated left middle meningeal vein (black arrow) connected with the left transverse-sigmoid sinus. Many small perforating branches were connected with the diploic veins (long white arrow). The flow-related signal of dilated straight sinus (short white arrow) may be caused by the reflux upstream due to the DAVF. (2D) Source imaging of MRA shows hyperintense signals (arrow) at the transition of the transverse to the sigmoid sinus, only on the left side with the pathological hyperintense signals at the sinus wall.
veins on the left side was much bigger than those on the right side. The wall of the left transverse-sigmoid sinus was rough, around which many small perforating branches were connected with the diploic veins. The flow-related signal of dilated straight sinus could also be seen which suggested venous hypertension (Fig. 2C). Source imaging of MRA showed pathological hyperintense signals at the transition of the transverse to the sigmoid sinus on the left side (Fig. 2D). All these signs suggested a DAVF in the left transversesigmoid sinus. The dilated left temporal cortical veins may be caused by the reflux upstream due to the DAVF, which also led to the thickening of the straight sinus. Unfortunately this patient died of seizures and pulmonary infection before further DSA examination and lost the opportunity to receive endovascular embolization treatment. 3. Discussion DAVF is a rare cause for patients with parkinsonism. In 1999, Matsuda et al. described the first 3 cases of DAVF accompanied with parkinsonism and cognitive dysfunction [4]. Most of the reported DAVFs with parkinsonism and cognitive dysfunction were located in the transverse or sigmoid sinus with retrograde venous reflux into the straight sinus and/or cortical veins [2–6,8]. The probable mechanism may be due to venous hypertension caused by DAVF which led to the dysfunction of the basal ganglia and cerebral cortex. The exact pathophysiology of parkinsonism and cognitive dysfunction in DAVF still needs further exploration.
Both of our cases had typical symptoms of parkinsonism including gradual progressive bradykinesia and gait disturbances. Resting tremor of upper extremities found in case 2 has never been reported to our knowledge. Both cases were initially misdiagnosed as having Parkinson's disease and showed good response to dopaminergic treatment that did not last for long. Finally they were both diagnosed as having DAVF by 3D TOF MRA or DSA. Often clinicians are blinded by typical symptoms and good drug response. Therefore, more attention must also be paid to neuroimaging when exploring the causes for parkinsonism, accompanied with cognitive dysfunction. Clinicians often choose noncontrast CT as the initial imaging method for neurological disease examination. Subcortical calcification is a common and nonspecific imaging presentation on CT. The usual causes include neoplasms, hyperparathyroidism, Fahr's disease, Sturge–Weber syndrome, pial arteriovenous malformation and infectious disorders. However, subcortical calcification on CT in DAVF with cortical venous reflux is unusual and characteristic [9,10]. Case 1 showed diffuse subcortical curvilinear calcification in the cortico-medullary junction on CT bilaterally. This particular pattern of curvilinear calcification in DAVF with parkinsonism and cognitive dysfunction was the second time to be reported [5]. The exact cause for DAVF associated calcification was not clear. In previous studies, subcortical calcification accompanied with DAVF was considered to be a dystrophic process due to focal hypoperfusion by the steal phenomenon or persistent venous congestion, suggestive of a possible poor prognosis without treatment [9,10]. Thus, we suspect that the calcification in case 1 might have been associated with cortical venous reflux and persistent venous congestion due
Please cite this article as: Luo Y, et al, Two cases of dural arteriovenous fistula presenting with parkinsonism and progressive cognitive dysfunction, J Neurol Sci (2014), http://dx.doi.org/10.1016/j.jns.2014.05.059
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to DAVF. Cognitive dysfunction of case 1 may be one of the presentations of cortical dysfunction as a result of diffuse cortical hypoperfusion. The exacerbation of case 1 was in line with the speculation that subcortical calcification in DAVF could predict an adverse prognosis. The pathogenesis of parkinsonism and cognitive dysfunction in patients with DAVF remains to be further studied. Matsuda et al. noted diffuse white matter lesions on MRI in patients with DAVF presenting with parkinsonism and cognitive dysfunction which were similar to vascular parkinsonism and Binswanger's disease, and contributed the cause of parkinsonism to the frontal white matter lesions [4]. However, Lee et al. deduced that parkinsonism in DAVF is associated with basal ganglia dysfunction secondary to impaired drainage of the deep internal veins, rather than white matter lesions [3]. In our cases, white matter changes on MRI were minimal or absent. Also, unlike the characteristic lower body parkinsonism that occurs in white matter diseases, muscle tone increased in both of our patients' upper extremities. Patient two even had resting tremor of upper extremities besides gait disturbances. Dilated straight sinus veins in 3D TOF MRA and abnormal flow void signals of deep brain on T2-weighted MRI imaging in our cases indicated a possible retrograde venous reflux into the basal ganglion region. Therefore, the possible mechanism of parkinsonism in our cases might be in line with the hypothesis proposed by Lee et al. Unfortunately, there were no signal abnormalities in the basal ganglia on MRI in our cases. Further functional imaging study such as dopamine transporters scan with single-photon emission tomography or positron emission computed tomography might be able to reveal functional changes in the basal ganglia and clarify the etiology of this type of subjects. Similarly, the enlargement of deep venous sinus and cortical veins as signs of venous intracranial hypertension could cause venous congestive encephalopathy leading to cognitive dysfunction. Venous intracranial hypertension in case 2 was finally identified by lumbar puncture. Broadly speaking, parkinsonism due to DAVF could be considered a special form of vascular parkinsonism. However, it is not easy to distinguish it from the classical vascular parkinsonism. The symptoms of the upper body and the absence of history of multiple strokes could possibly help to differentiate parkinsonism secondary to DAVF from the classical vascular parkinsonism. Although angiography is the gold standard for diagnosis of DAVF, previous studies have shown that 3D TOF MRA is a good complementary tool for the identification of DAVF [11–14], but not for follow-up [14]. Furthermore, the source imaging of 3D TOF MRA containing both flow and anatomic information is more useful than that of maximumintensity-projection imaging in showing DAVF [11]. In cases with DAVF, source imaging of 3D TOF MRA showed two characteristic imaging features: multiple high-intensity curvilinear or nodular structures adjacent to the sinus wall and high-intensity areas in the venous sinus, both of which could also be found in our cases [11]. Sensitivity and specificity of the two features were 100% and 100%, 76% and 86%, respectively [11]. In the latest study, 3D TOF MRA detected 88% DAVFs correctly [14]. In our study, 3D TOF MRA had also provided a satisfactory delineation of DAVF. Therefore, 3D TOF MRA, as a noninvasive diagnostic tool without the risks of ionizing radiation and contrast agent allergy, is a promising procedure for the identification of DAVF presenting with parkinsonism and cognitive dysfunction. Unfortunately, the DSA information of case 1 was lost and DSA was not performed for case 2. We sincerely apologize for not providing a complete imaging data. The imaging features of DAVF are so variable and non-specific that the diagnosis is often delayed or missed [5]. Some relatively rare clinical presentations such as pulsatile tinnitus, ophthalmoplegia, and proptosis, though absent in our cases, could also help in the diagnosis of DAVF. If a patient presents with a few of the symptoms mentioned above and parkinsonism simultaneously, the possibility of DAVFassociated parkinsonism should be considered.
Observation, open surgery and endovascular embolization are potential treatment options for DAVF. Among them, endovascular embolization is safe, effective, and can often be used as a single treatment for DAVF. Parkinsonism and cognitive dysfunction as results of DAVF may be reversible through endovascular embolization, which has been reported in the literature [15]. DAVF will have a poor prognosis if it is not effectively treated. One of our case's situation continued to get worse and the other one died of seizures, which indicates early diagnosis to be particularly important. Conflict of interest The authors report no conflicts of interest. Disclosures None. Author contributions Study concept and design: Wei Luo. Acquisition of data: Yong Luo and Jun Qi. Drafting of the manuscript: Yong Luo and Jun Qi. Critical revision of the manuscript for important intellectual content: Zhidong Cen, Haitao Hu, Biao Jiang, and Wei Luo. Administrative and material support: Wei Luo. References [1] Newton TH, Cronqvist S. Involvement of dural arteries in intracranial arteriovenous malformations. Radiology 1969;93(5):1071–8. [2] Kajitani M, Yagura H, Kawahara M, Hirano M, Ueno S, Fujimoto K, et al. Treatable fluctuating Parkinsonism and dementia in a patient with a dural arteriovenous fistula. Mov Disord 2007;22(3):437–9. [3] Lee PH, Lee JS, Shin DH, Kim BM, Huh K. Parkinsonism as an initial manifestation of dural arteriovenous fistula. Eur J Neurol 2005;12(5):403–6. [4] Matsuda S, Waragai M, Shinotoh H, Takahashi N, Takagi K, Hattori T. Intracranial dural arteriovenous fistula (DAVF) presenting progressive dementia and parkinsonism. J Neurol Sci 1999;165(1):43–7. [5] Netravathi M, Pal PK, Bharath RD, Ravishankar S. Intracranial dural arteriovenous fistula presenting as parkinsonism and cognitive dysfunction. J Clin Neurosci 2011;18(1):138–40. [6] Miura S, Noda K, Shiramizu N, Muraoka N, Hirohata M, Ayabe M, et al. Parkinsonism and ataxia associated with an intracranial dural arteriovenous fistula presenting with hyperintense basal ganglia in T1-weighted MRI. J Clin Neurosci 2009;16(2):341–3. [7] Iwama T, Hashimoto N, Takagi Y, Tanaka M, Yamamoto S, Nishi S, et al. Hemodynamic and metabolic disturbances in patients with intracranial dural arteriovenous fistulas: positron emission tomography evaluation before and after treatment. J Neurosurg 1997;86(5):806–11. [8] Hattori T, Takeuchi T, Kabeya R, Ando K, Tosaki F. Transverse-sigmoid sinus dural arteriovenous fistula presenting with parkinsonism. Neurol Med Chir (Tokyo) 2013;53(4):224–7. [9] Lai PH, Chang MH, Liang HL, Pan HB, Yang CF. Unusual signs for dural arteriovenous fistulas with diffuse basal ganglia and cerebral calcification. Zhonghua yi xue za zhi (Chin Med J) 2000;63(4):329–33 [Free China ed.]. [10] Metoki T, Mugikura S, Higano S, Ezura M, Matsumoto Y, Hirayama K, et al. Subcortical calcification on CT in dural arteriovenous fistula with cortical venous reflux. Am J Neuroradiol 2006;27(5):1076–8. [11] Noguchi K, Melhem ER, Kanazawa T, Kubo M, Kuwayama N, Seto H. Intracranial dural arteriovenous fistulas: evaluation with combined 3D time-of-flight MR angiography and MR digital subtraction angiography. AJR Am J Roentgenol 2004;182(1):183–90. [12] Kwon BJ, Han MH, Kang HS, Chang KH. MR imaging findings of intracranial dural arteriovenous fistulas: relations with venous drainage patterns. Am J Neuroradiol 2005;26(10):2500–7. [13] Bink A, Berkefeld J, Wagner M, You SJ, Ackermann H, Lorenz MW, et al. Detection and grading of dAVF: prospects and limitations of 3T MRI. Eur Radiol 2012;22(2):429–38. [14] Meckel S, Maier M, Ruiz DS, Yilmaz H, Scheffler K, Radue EW, et al. MR angiography of dural arteriovenous fistulas: diagnosis and follow-up after treatment using a timeresolved 3D contrast-enhanced technique. Am J Neuroradiol 2007;28(5):877–84. [15] Nogueira RG, Baccin CE, Rabinov JD, Pryor JC, Buonanno FS, Hirsch JA. Reversible parkinsonism after treatment of dural arteriovenous fistula. J Neuroimaging 2009;19(2):183–4.
Please cite this article as: Luo Y, et al, Two cases of dural arteriovenous fistula presenting with parkinsonism and progressive cognitive dysfunction, J Neurol Sci (2014), http://dx.doi.org/10.1016/j.jns.2014.05.059
