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Chronic asymmetric tremor and levodopa-responsive parkinsonism due to a vein of Galen aneurysmal malformation
Accepted Manuscript Chronic asymmetric tremor and levodopa-responsive parkinsonism due to a vein of Galen aneurysmal malformation Aaron de Souza, Yasmin S. Fernandes, Sanat R. Bhatkar, Siddesh K. Bhonsle PII:
S1353-8020(17)30254-7
DOI:
10.1016/j.parkreldis.2017.07.007
Reference:
PRD 3352
To appear in:
Parkinsonism and Related Disorders
Received Date: 25 April 2017 Revised Date:
25 June 2017
Accepted Date: 12 July 2017
Please cite this article as: de Souza A, Fernandes YS, Bhatkar SR, Bhonsle SK, Chronic asymmetric tremor and levodopa-responsive parkinsonism due to a vein of Galen aneurysmal malformation, Parkinsonism and Related Disorders (2017), doi: 10.1016/j.parkreldis.2017.07.007. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Chronic asymmetric tremor and levodopa-responsive Parkinsonism due to a vein of Galen aneurysmal malformation Aaron de Souza1*, Yasmin S Fernandes2, Sanat R Bhatkar1, Siddesh K Bhonsle1 1
Department of Neurology, Goa Medical College, Bambolim – Goa 403202 India
RI PT
2
Department of Radiology, Goa Medical College, Bambolim – Goa 403202 India
Type of Article: Correspondence
SC
Keywords: vein of Galen; malformation; tremor; parkinsonism Type of Article: Letter to the Editor: New Observations
M AN U
Running title: Tremor and Parkinsonism due to vein of Galen malformation Word Count: (Summary) 68; (Text excluding references and legend): 663. Number of pages: 06 including title page. Number of references: 07. Number of figures: One. Number of tables: Nil. One supplementary video accompanies the
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manuscript.
* Corresponding author. Address for correspondence: Dr Aaron de Souza
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Associate Professor,
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Department of Neurology, Goa Medical College, Bambolim – Goa 403202 India. Tel +91-8322495085; +91-9975542655 Fax: +91-8322458728 e-mail: [email protected] All authors affirm that they have contributed equally to the production of this manuscript. No part of this manuscript was written by any person not mentioned as an author. The authors affirm that they have no financial disclosures and no conflicts of interest.
ACCEPTED MANUSCRIPT The patient has provided written informed consent for video recording and
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EP
TE D
M AN U
SC
RI PT
dissemination of the video for educational and research purposes.
ACCEPTED MANUSCRIPT
Chronic tremor and levodopa-responsive Parkinsonism due to a vein of Galen aneurysmal malformation A 62-year old woman presented with a slowly progressive asymmetric distal postural tremor in both upper limbs, more prominent in the left hand, since the age of 13
RI PT
years. No family history of tremor or other relevant symptoms was obtained. On examination, an asymmetric postural tremor was observed in both upper limbs
distally, with mild rigidity and bradykinesia in the left upper limb. No rest or intention tremors were seen, and the lower limbs did not show bradykinesia or rigidity.
Cognition, eye movements, facial expression, arm swing and gait were normal
SC
[Video].
M AN U
An MRI of the brain and subsequent CT angiography revealed fusiform dilatation of the median prosencephalic vein consistent with a vein of Galen arteriovenous malformation (VGAM), draining into the confluence of the sinuses via a persistent falcine vein. Multiple tortuous arterial feeders arose from the posterior cerebral, pericallosal, meningohypophyseal, and anterior and posterior choroidal arteries forming a nidus anterior to the dilated venous pouch. The right midbrain was
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deformed by the tortuous arterial feeders around the upper brainstem, without obvious parenchymal signal change [Figure]. Propranolol and clonazepam did not ameliorate tremor. However, 200 mg levodopa
EP
with 20 mg carbidopa produced an appreciable reduction in tremor and bradykinesia [Video]. The patient refused endovascular treatment of the arteriovenous
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malformation and remains under close follow up. Typically presenting in the neonatal period or infancy with congestive cardiac failure, macrocephaly or hydrocephalus, VGAMs arise from persistent arteriovenous shunting from primitive choroidal vessels into the median prosencephalic vein, the embryonic precursor of the vein of Galen[1,2]. It is extremely rare for VGAMs to present in adults, and symptoms are varied: headaches, dizziness, vertigo and other nonspecific deficits secondary to mass effect such as paraesthesiae and hemi- or para-paresis were the commonest symptoms in 11 patients. Subarachnoid or intracerebral haemorrhage, coma, seizures and hydrocephalus have also been
ACCEPTED MANUSCRIPT described.[3] To our knowledge, movement disorders resulting from an untreated VGAM have not been previously reported. As we were unable to perform functional imaging, the pathogenesis of parkinsonism in this patient remains speculative. Imaging modalities such as SPECT or PET are not available in our region, and due to logistic and financial constraints we could not
RI PT
arrange an appropriate study elsewhere. Multiple tortuous arterial feeders around the upper brainstem deforming the right midbrain as seen on MRI [Figure, ‘B’ and ‘D’] suggest a local mechanical effect contributing to the predominantly contralateral
tremor and parkinsonism. Anatomical distortion and compression of the midbrain
SC
from intracerebral haemorrhage was suggested as the cause of secondary
parkinsonism in one patient whose 18F-fluorodopa positron emission tomography
M AN U
scan showed reduced uptake contralateral to the haematoma [4].
As in the case of parkinsonism arising from dural arteriovenous fistulae (dAVF), parenchymal ischaemia due to a ‘steal’ phenomenon or venous hypertension leading to dysfunction of the basal ganglia may also be responsible [5,6]. However, the response to levodopa – not a feature of dAVF-related parkinsonism – favours an
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affection of presynaptic dopaminergic neurons in our patient. In contrast, patients with parkinsonism secondary to dAVF have reduced regional cerebral blood flow and elevated oxygen extraction in the basal ganglia and frontal lobes with a poor response to levodopa.[5,7]
EP
Coincidental idiopathic Parkinson’s disease was felt unlikely in view of the very long course, with a postural tremor beginning nearly fifty years before presentation with
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relatively mild akinetic-rigid features. It is possible that a higher dose of carbidopa may have improved the therapeutic efficacy of levodopa. However the formulations available for use at our centre contain either 100mg levodopa + 10mg carbidopa or 250mg levodopa + 25mg carbidopa. Our patient improved significantly with the dose administered and did not manifest any peripheral dopaminergic side effects. As symptoms were well controlled with levodopa and the patient was unwilling for more aggressive therapy, no attempt at endovascular treatment was made. VGAMs in the adult population that are detected incidentally are likely to remain stable with a
ACCEPTED MANUSCRIPT benign course, whereas lesions presenting with haemorrhage, thrombosis, or signs of increasing mass effect or increased intracranial pressure warrant immediate treatment.[1] LEGEND
RI PT
Video: Asymmetric postural tremor and bradykinesia in a patient with an untreated vein of Galen arteriovenous malformation, improving after administration of levodopa.
Figure: A and C: MRI with time-of-flight MR venography and CT venography with 3-D
SC
reconstruction showing a vein of Galen arteriovenous malformation in an adult with a dilated venous pouch, multiple tortuous arterial feeders and dilated dural vascular
M AN U
channels (A). B and D: The midbrain is compressed and deformed by dilated arterial feeders around the upper brainstem (chevron, asterisk). REFERENCES:
1. Xu DS, Usman AA, Hurley MC, Eddleman CS, Bendok BR. Adult presentation of a familial-associated vein of Galen aneurysmal malformation: case report.
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Neurosurgery 2010;67:E1845–E1851.
2. Raybaud CA, Strother CM, Hald JK. Aneurysms of the vein of Galen: embryonic considerations and anatomical features relating to the pathogenesis of the
EP
malformation. Neuroradiology. 1989;31(2):109-128. 3. Gold A, Ransohoff J, Carter S. Vein of Galen malformation. Acta Neurol Scand
AC C
Suppl. 1964;40(Suppl 11):11-31. 4. Turjanski N, Pentland B, Lees AJ, Brooks DJ. Parkinsonism associated with acute intracranial hematomas: an [18F] dopa positron-emission tomography study. Mov Disord 1997;12:1035-1038. 5. 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. 6. Kajitani M, Yagura H, Kawahara M, Hirano M, Ueno S, Fujimoto K, Sakaki T, Taoka T, Nakagawa H, Kichikawa K. Treatable fluctuating parkinsonism and
ACCEPTED MANUSCRIPT dementia in a patient with a dural arteriovenous fistula. Mov Disord 2007;22:437439. 7. Iwama T, Hashimoto N, Takagi Y et al. (1997). Hemodynamic and metabolic disturbances in patients with intracranial dural arteriovenous fistulas: positron emission tomography evaluation before and after treatment. J Neurosurg 86:806–
RI PT
811. AUTHOR ROLES
A de Souza: conception, organization and execution of the study, manuscript
SC
preparation
M AN U
Y S Fernandes: execution of the study, manuscript review and critique S R Bhatkar: conception, organization and execution of the study, manuscript review and critique
S K Bhonsle: execution of the study, manuscript review and critique
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FUNDING STATEMENT
The authors affirm that they have not received any funding from any source during
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EP
the last 12 months.
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT
S1353-8020(17)30254-7
DOI:
10.1016/j.parkreldis.2017.07.007
Reference:
PRD 3352
To appear in:
Parkinsonism and Related Disorders
Received Date: 25 April 2017 Revised Date:
25 June 2017
Accepted Date: 12 July 2017
Please cite this article as: de Souza A, Fernandes YS, Bhatkar SR, Bhonsle SK, Chronic asymmetric tremor and levodopa-responsive parkinsonism due to a vein of Galen aneurysmal malformation, Parkinsonism and Related Disorders (2017), doi: 10.1016/j.parkreldis.2017.07.007. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Chronic asymmetric tremor and levodopa-responsive Parkinsonism due to a vein of Galen aneurysmal malformation Aaron de Souza1*, Yasmin S Fernandes2, Sanat R Bhatkar1, Siddesh K Bhonsle1 1
Department of Neurology, Goa Medical College, Bambolim – Goa 403202 India
RI PT
2
Department of Radiology, Goa Medical College, Bambolim – Goa 403202 India
Type of Article: Correspondence
SC
Keywords: vein of Galen; malformation; tremor; parkinsonism Type of Article: Letter to the Editor: New Observations
M AN U
Running title: Tremor and Parkinsonism due to vein of Galen malformation Word Count: (Summary) 68; (Text excluding references and legend): 663. Number of pages: 06 including title page. Number of references: 07. Number of figures: One. Number of tables: Nil. One supplementary video accompanies the
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manuscript.
* Corresponding author. Address for correspondence: Dr Aaron de Souza
EP
Associate Professor,
AC C
Department of Neurology, Goa Medical College, Bambolim – Goa 403202 India. Tel +91-8322495085; +91-9975542655 Fax: +91-8322458728 e-mail: [email protected] All authors affirm that they have contributed equally to the production of this manuscript. No part of this manuscript was written by any person not mentioned as an author. The authors affirm that they have no financial disclosures and no conflicts of interest.
ACCEPTED MANUSCRIPT The patient has provided written informed consent for video recording and
AC C
EP
TE D
M AN U
SC
RI PT
dissemination of the video for educational and research purposes.
ACCEPTED MANUSCRIPT
Chronic tremor and levodopa-responsive Parkinsonism due to a vein of Galen aneurysmal malformation A 62-year old woman presented with a slowly progressive asymmetric distal postural tremor in both upper limbs, more prominent in the left hand, since the age of 13
RI PT
years. No family history of tremor or other relevant symptoms was obtained. On examination, an asymmetric postural tremor was observed in both upper limbs
distally, with mild rigidity and bradykinesia in the left upper limb. No rest or intention tremors were seen, and the lower limbs did not show bradykinesia or rigidity.
Cognition, eye movements, facial expression, arm swing and gait were normal
SC
[Video].
M AN U
An MRI of the brain and subsequent CT angiography revealed fusiform dilatation of the median prosencephalic vein consistent with a vein of Galen arteriovenous malformation (VGAM), draining into the confluence of the sinuses via a persistent falcine vein. Multiple tortuous arterial feeders arose from the posterior cerebral, pericallosal, meningohypophyseal, and anterior and posterior choroidal arteries forming a nidus anterior to the dilated venous pouch. The right midbrain was
TE D
deformed by the tortuous arterial feeders around the upper brainstem, without obvious parenchymal signal change [Figure]. Propranolol and clonazepam did not ameliorate tremor. However, 200 mg levodopa
EP
with 20 mg carbidopa produced an appreciable reduction in tremor and bradykinesia [Video]. The patient refused endovascular treatment of the arteriovenous
AC C
malformation and remains under close follow up. Typically presenting in the neonatal period or infancy with congestive cardiac failure, macrocephaly or hydrocephalus, VGAMs arise from persistent arteriovenous shunting from primitive choroidal vessels into the median prosencephalic vein, the embryonic precursor of the vein of Galen[1,2]. It is extremely rare for VGAMs to present in adults, and symptoms are varied: headaches, dizziness, vertigo and other nonspecific deficits secondary to mass effect such as paraesthesiae and hemi- or para-paresis were the commonest symptoms in 11 patients. Subarachnoid or intracerebral haemorrhage, coma, seizures and hydrocephalus have also been
ACCEPTED MANUSCRIPT described.[3] To our knowledge, movement disorders resulting from an untreated VGAM have not been previously reported. As we were unable to perform functional imaging, the pathogenesis of parkinsonism in this patient remains speculative. Imaging modalities such as SPECT or PET are not available in our region, and due to logistic and financial constraints we could not
RI PT
arrange an appropriate study elsewhere. Multiple tortuous arterial feeders around the upper brainstem deforming the right midbrain as seen on MRI [Figure, ‘B’ and ‘D’] suggest a local mechanical effect contributing to the predominantly contralateral
tremor and parkinsonism. Anatomical distortion and compression of the midbrain
SC
from intracerebral haemorrhage was suggested as the cause of secondary
parkinsonism in one patient whose 18F-fluorodopa positron emission tomography
M AN U
scan showed reduced uptake contralateral to the haematoma [4].
As in the case of parkinsonism arising from dural arteriovenous fistulae (dAVF), parenchymal ischaemia due to a ‘steal’ phenomenon or venous hypertension leading to dysfunction of the basal ganglia may also be responsible [5,6]. However, the response to levodopa – not a feature of dAVF-related parkinsonism – favours an
TE D
affection of presynaptic dopaminergic neurons in our patient. In contrast, patients with parkinsonism secondary to dAVF have reduced regional cerebral blood flow and elevated oxygen extraction in the basal ganglia and frontal lobes with a poor response to levodopa.[5,7]
EP
Coincidental idiopathic Parkinson’s disease was felt unlikely in view of the very long course, with a postural tremor beginning nearly fifty years before presentation with
AC C
relatively mild akinetic-rigid features. It is possible that a higher dose of carbidopa may have improved the therapeutic efficacy of levodopa. However the formulations available for use at our centre contain either 100mg levodopa + 10mg carbidopa or 250mg levodopa + 25mg carbidopa. Our patient improved significantly with the dose administered and did not manifest any peripheral dopaminergic side effects. As symptoms were well controlled with levodopa and the patient was unwilling for more aggressive therapy, no attempt at endovascular treatment was made. VGAMs in the adult population that are detected incidentally are likely to remain stable with a
ACCEPTED MANUSCRIPT benign course, whereas lesions presenting with haemorrhage, thrombosis, or signs of increasing mass effect or increased intracranial pressure warrant immediate treatment.[1] LEGEND
RI PT
Video: Asymmetric postural tremor and bradykinesia in a patient with an untreated vein of Galen arteriovenous malformation, improving after administration of levodopa.
Figure: A and C: MRI with time-of-flight MR venography and CT venography with 3-D
SC
reconstruction showing a vein of Galen arteriovenous malformation in an adult with a dilated venous pouch, multiple tortuous arterial feeders and dilated dural vascular
M AN U
channels (A). B and D: The midbrain is compressed and deformed by dilated arterial feeders around the upper brainstem (chevron, asterisk). REFERENCES:
1. Xu DS, Usman AA, Hurley MC, Eddleman CS, Bendok BR. Adult presentation of a familial-associated vein of Galen aneurysmal malformation: case report.
TE D
Neurosurgery 2010;67:E1845–E1851.
2. Raybaud CA, Strother CM, Hald JK. Aneurysms of the vein of Galen: embryonic considerations and anatomical features relating to the pathogenesis of the
EP
malformation. Neuroradiology. 1989;31(2):109-128. 3. Gold A, Ransohoff J, Carter S. Vein of Galen malformation. Acta Neurol Scand
AC C
Suppl. 1964;40(Suppl 11):11-31. 4. Turjanski N, Pentland B, Lees AJ, Brooks DJ. Parkinsonism associated with acute intracranial hematomas: an [18F] dopa positron-emission tomography study. Mov Disord 1997;12:1035-1038. 5. 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. 6. Kajitani M, Yagura H, Kawahara M, Hirano M, Ueno S, Fujimoto K, Sakaki T, Taoka T, Nakagawa H, Kichikawa K. Treatable fluctuating parkinsonism and
ACCEPTED MANUSCRIPT dementia in a patient with a dural arteriovenous fistula. Mov Disord 2007;22:437439. 7. Iwama T, Hashimoto N, Takagi Y et al. (1997). Hemodynamic and metabolic disturbances in patients with intracranial dural arteriovenous fistulas: positron emission tomography evaluation before and after treatment. J Neurosurg 86:806–
RI PT
811. AUTHOR ROLES
A de Souza: conception, organization and execution of the study, manuscript
SC
preparation
M AN U
Y S Fernandes: execution of the study, manuscript review and critique S R Bhatkar: conception, organization and execution of the study, manuscript review and critique
S K Bhonsle: execution of the study, manuscript review and critique
TE D
FUNDING STATEMENT
The authors affirm that they have not received any funding from any source during
AC C
EP
the last 12 months.
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT