Medico-legal Aspects in Ruptured Cerebral Arteriovenous

Malformations. Immediate or Delayed Surgical Approach

C. Toader1, M. Stroi*, A. V. Ciurea2
1
Assistant professor at the Carol Davila University of Medicine and Pharmacy, Faculty of
Medicine Bucharest, Neurosurgical Department of the National Institute of Neurology and
Neurovascular Diseases – Bucharest
2
Vice-President of the Romanian Ministry of Health Neurosurgical Committee
Chief of Neurosurgery and Scientific Director, Sanador Clinical Center Hospital, Bucharest,
Romania, Professor of neurosurgery, "Carol Davila" University School of Medicine, Bucharest,
Romania.
*
Neurosurgical Department of the National Institute of Neurology and Neurovascular Diseases –
Bucharest

Abstract:
Introduction: Intracranial hemorrhage represents the most common form of clinical presentation
of cerebral arteriovenous malformations (AVMs). The most frequent indication for microsurgical
excision is neurologic decline due to intracerebral hemorrhage. The goal of this study was to
assess whether ruptured AVMs in critically ill patients can be treated safely and effectively by
acute open surgery and to outline the most important clinical and angiographic features
influencing the surgical strategy and outcome of ruptured AVMs.

Materials and Methods:

27 patients presented with ruptured cerebral AVMs between September 2014 and December
2019 in the Neurosurgery Clinic of the National Institute of Neurology and Neurovascular
Diseases. In order to better assess the importance of early surgical therapy, we report a series of
12 patients who were admitted to our Neurosurgery Clinic in a comatose state (GCS<9p or mRS-
5). For grading cerebral AVMs, we used the SM classification.

Results
According to the SM grading scale there were 1 SM grade 1 lesion (8,3%), 4 SM grade 2 lesions
(33,3%), 3 SM grade 3 (25%) and 4 SM grade 4 lesion (33,3%). All the patients underwent
emergency surgery, and complete resection was achieved in 11 patients (91,6%%). The mortality
rate was 8,33% and the overall morbidity rate was 75%.

Conclusions and Discussions

Surgical management strategy of the ruptured AVMs in comatose patients should be
individualized based on clinical neurological status and angiographic characteristics. In critically
ill patients with profound neurological deterioration, whose initial mass effect is life-threatening,
due to forensic implications, the most efficient surgical option is emergency removal of the
hematoma and, if possible, microsurgical resection of the AVM. Aggressive surgical procedures
lower case mortality rates and allow for more favorable functional outcomes.

Key words: arteriovenous malformations, microsurgery, emergency, hemorrhage

Abreviations:

1
ACommA - anterior communicating artery; AVMs - arteriovenous malformations; CT-
computer tomography; DSA - digital substraction angiography; ECA - external carotid artery;
GCS - Glascow coma scale; ICA - internal carotid artery; ICH - intracranial hypertension
syndrome; ICU - intensive care unit; IVH - intraventricular hemorrhage; mRS - modified
Rankin score; MCA - middle cerebral artery; MRI - magnetic resonance imaging; PCA -
posterior cerebral artery; PCommA - posterior communicating artery; SAH - subarachnoid
hemorrhage; SM grade -Spetzler Martin grade; SRS - stereotactic radiosurgery; SSS - superior
sagittal sinus; TS - transvers sinus.

Introduction
AVMs prevalence is approximately 0,1%[1] and they are responsible for 1,4%- 2 % of all
hemorrhagic strokes [2]. The most common age at diagnosis is the third and fourth decade [3] , with
75% of hemorrhagic presentations occurring before the age of 50 [4]. The most frequently
encountered form of presentation is intracranial hemorrhage (approximately 50%), followed by
symptomatic epilepsy, with 18-35% of patients diagnosed because of seizures [3]. Intracranial
hemorrhage is the most severe clinical presentation [5]. AVMs are the leading cause of
nontraumatic intracerebral hemorrhage in young people (<35 years old) and the most common
neurological cause of impairment and death in patients under 20 years[6].
Hemorrhage from an AVM is less hazardous than the rupture of an intracranial aneurysm. Short
term case fatality rate in a ruptured AVM is less than 10% per bleeding, compared to 50% in the
case of an aneurysmal SAH [4],[7-9]. Risk factors for hemorrhagic presentation according to
univariate and multivariate analyses are: small size, young age, deep venous drainage, non-
border zone location, associated aneurysms, deep location [8-11], high arterial input pressure[10][12],
posterior fossa AVMs[11-14]. The bleeding rate is higher in the first years after diagnosis. Previous
rupture is the most consistent factor associated with the increased risk for an AVM rupture[13, 14].
The goal of this study was to assess whether ruptured AVMs in critically ill patients can be
treated safely and effectively by acute open surgery and to outline the most important clinical
and angiographic features influencing the surgical strategy and outcome of ruptured AVMs.

Materials and Methods

We report a series of 12 patients, among all the 27 patients with ruptured AVMs who were
operated on in the Neurosurgery Clinic of the National Institute of Neurology and Neurovascular
Diseases between September 2014 and December 2019, that were admitted in very poor
neurologic condition. All the patients were admitted to our neurosurgical ICU.
Medical information was retrospectively reviewed. We recorded and analyzed the signs and
symptoms at admission, the detailed neurological exam, reviewed patient–related factors as well
as lesion related-factors, pre and postoperative neuroimaging evaluation (CT scan, MRI and four
vessels cerebral angiography), details regarding surgery, clinical outcomes, resection rates,
postoperative complications and prognosis. Neurological follow-up was assessed according to
the modified Rankin Scale (mRS).
The most important and relevant parameter was arterial blood pressure, measured by a
continuous noninvasive system. High blood pressure was promptly treated by using a continuous
intravenous drip, usually Tachyben (Urapidil). Patients were positioned with head of bed at 30-
45 degrees to optimize venous drainage from the brain. Mannitol was routinely used and serum
osmolarity was frequently measured in order not to exceed 320 mOsm/L. If the patients
presented signs of herniation, the sedation was increased and hyperventilation used. Sedation

2
was stopped every two hours in order to assess for neurological deterioration. Because of the
high risk of seizures in patients with ruptured AVMs, anticonvulsants were routinely used.
All of the patients were operated on in the first 24 hours after admission. Two patients who were
in highly poor neurological condition were operated within the first 6 hours. They were all
treated by emergency open surgery. Perioperative intracranial pressure was controlled with
mannitol and barbiturates. Surgical strategies and techniques included: sharp subarachnoid and
pial dissection for opening the sulci and the fissures, clipping and coagulation of the feeding
arteries, evacuation of the intracerebral clots, dissection and resection with minimal coagulation
of the nidus, clipping of the flow-related aneurysms, coagulation and division of the draining
veins and ligation of the ECA (one patient). In order to control intranidal pressure and to avoid
uncontrollable bleeding from the nidus, temporary and definitive clip were applied on the
feeders.

Results
The 12 patients admitted to the study had the age ranging between 25 to 65 years old, with a
median age of of 40,25 years; 7 patients were males and 5 were females. All admitted patients
presented a GCS score <9 – 41.7% with a score of 7 and a mean value of 7 points. The mean
mRS score was 4.67, 75% of the patients presenting on admission a score of 5 points. The most
common clinical feature was hemiparesis – recorded in 5 patients (41.7%), followed by
aspiration bronchopneumonia – 4 patients (33.3%) and intracranial hemorrhage syndrome – 3
patients (25%). Meningismus, anisocoria and fever were each detected in 2 patients, while
hemiplegia and epileptic seizures were found only in 1 patient each. All patients were intubated.
Of the 12 cases included in this series, 3 patients (25%) associated SAH and 5 patients (41,66%)
had intraventricular hemorrhage. Two patients had a known history of AVM, diagnosed 10 years
before, respectively 8 years.

Figure 1. Preoperative CT scan Figure 2. Postoperative CT scan

Based on the SM grading scale there were 1 SM grade 1 lesion (8,3%), 4 SM grade 2 lesions
(33,3%), 3 SM grade 3 (25%) and 4 SM grade 4 lesion (33,3%).
3 of the AVMs were located in the frontal lobe, 1 in the temporal lobe, 2 in the fronto-temporal
lobes, 1 was a fronto-parietal AVM, one AVM was located in temporo-parietal lobes, one in
occipital lobe and 3 of the AVMs were located in the posterior fossa( two cerebellar AVMs and
one CPA AVM). Angiographic characteristics of the patient’s AVMs are shown in Table 1.

3
Preoperative cerebral angiography (Figure 3) was quickly performed (between 4-8 hours) and
patients were operated on in 6-24 hours after admission. 2 patients were admitted in very poor
condition and had life threatening hematoma; they were not angiographically investigated
immediately after presentation, due to the forensic implications. Due to their critical neurological
status, cerebral angiography was done 2 days after the emergency surgery.

3 patients had 3 associated flow

related aneurysms Figure 3. Preoperative Cerebral Angiography (2 ACommA
aneurysms, and 1 PICA aneurysm).
Deep venous drainage was encountered in 5 patients (41,66%). 9 patients (75%) had high-flow,
high arterial input pressure AVMs.
All patients in this series underwent surgery, with a 83,3 % complete AVM resection rate(10
patients) and a morbidity rate of 66,6%(8 patients). The patients were initially stabilized
according to acute management protocols for ICH. Given the poor grade condition, 2 patients
underwent surgery in 2 staged operations - Decompressive craniectomy was immediately
performed as a first stage in one patient and in the other emergency clots evacuation was
performed. One AcommA aneurysm and one PICA aneurysm were clipped in the same operative
time.

Intraoperative
complications Figure 4. Preoperative Cerebral Angiography included AVMs
rupture at surgery with diffuse
bleeding from the nidus.
Postoperative complications included: aspiration bronchopneumonia (4 patients), seizures (2
patients), cerebral swelling (3 patients), rebleeding (1 patient) and wound infection (1 patient).
Reoperation was done in 3 patients: initial removal of the clots and later excision of the AVM,
hematoma evacuation, partial excision of the AVM followed by residual AVM excision and
decompressive hemicraniectomy followed by excision of the AVM.
Postoperative angiography (Figure 4) showed residual nidus in 2 cases (1 SM grade 3 patient and
1 SM grade 4 patient). The mortality rate was 8,33% (1 patient). Outcome was favorable in 11

4
patients (91,6 %). 3 patients had minor neurologic deficits upon discharge, 3 patients remained
with moderate neurological deficit, with 5 patients having a severe deficit.
Following surgery, mRS improved in all surviving patients. Two patients experienced
postoperative seizures, five patients had a respiratory infection and one patient had a Clostridium
Difficile intestinal infection. There was no morbidity directly related to surgery.
At three months follow-up, 3 patients (25%) were independent in their daily activities. The other
8 patients who survived experienced a permanent neurologic deficit (four cases of mild
hemiparesis, and aphasia, one of visual field defect and two moderate hemiplegia). The average
length of follow-up was 48 months (3- 96 months).

AVM High flow, Feeding arteries Nidus Associated Draining

Location high arterial size aneurysm veins
input mm
pressure
1 Frontal yes M2 segment of MCA 48 ACommA SSS, TS,
flow right
related sinus
aneurysm
2 temporal yes Posterior temporal artery 20 No TS
3 Fronto- yes M2 and M3 segments of 35 No SSS
temporal MCA
4 frontal yes M2 and M3 segments of 60 ACommA SSS
MCA, pericallosal artery flow
from controlateral ICA via related
ACommA
5 Fronto- yes M2, pericallsossal a, 23 No Trolard-
parietal parietooccipital a. SSS
6 cerebellar yes Right P2 segment, ACS, 20 No SSS and
AICA, PICA, post ST
meningeal a. si occipital
a., middle meningeal a.
7 cerebellar yes Rigt PICA,P2, P3 , P4 35 Flow- ST and
segm of left PCA injected related torcula
from left ICA via PICA
ACommP aneurysm
8 frontal no M2 segment of the right 25 No Cavernou
MCA s sinus
9 TP yes MCA 23 No ST
1 CPA no ACS, AICA, PICA left, 30 No Right
0 post meningeal a, middle sinus, ST,
meningeal a, occipital a. s
occipital,
SS
1 occipital yes P4 segm ACP left, PICA, 33 No SSS, ST
1 AICA, post meningeal a

5
 1 FT no M2 and M3 segments of 28 No SSS
2 the MCA
Table 1- Angiographic features of the AVMs

Discussions and Conclusions

Clinical data has shown that the number of patients with unruptured AVMs who require medical
attention is increasing(10% incidentally found AVMs), that is why understanding the morbidity
associated with AVM rupture has become essential [3][17]. In our series two patients were
previously diagnosed with AVMs but they refused the surgical intervention at the time of
diagnosis.
The main goal of AVMs surgery is not only to eliminate the risk of hemorrhage, but also to
control seizures and progressive neurological deficits[18]. The risk of hemorrhage remains present
until complete AVM obliteration is achieved. In light of these data, radiosurgery and
endovascular procedures do not immediately eliminate the risk of hemorrhage. Complete
microsurgical removal is the gold standard and the optimal surgical procedure for the definitive
treatment of cerebral AVMs[18]. The critical elements involved in the surgical decision are the
neurologic condition of the patient, the detailed angiographic features of the AVM, and the
facility where the patient presents. In case of hemorrhage, emergency evacuation of the life
threatening hematoma and, if possible, microsurgical resection of the AVM should become
compulsory. In our series younger patients and temporal hemorrhage tended to be associated
with lower GCS score and they underwent surgery as soon as possible.
A judicious approach to the preoperative clinical and angiographic features should dictate the
surgical management strategy. Acute surgery should be directed toward reducing compression of
the brain in order to stabilize the patient’s condition: complete excision of the AVMs, subtotal
removal of the clots with delayed AVM resection or only decompressive craniectomy.
Because of the poor grade condition, 2 patients of our series were operated in 2 stage operation.
They initially have been stabilized by limiting surgical interventions to decompressive
craniectomy or removing the clots without or partial resection of the AVMs.
The American Heart Association guidelines recommend that surgical technique for ruptured
AVMs should be individualized. Various surgical procedures include: microsurgical resection of
AVM, evacuation of the hematoma, clipping of associated aneurysm, lobectomy for AVM and
hematoma removal, decompressive hemicraniectomy and surgical exploration alone.
In addition, emergency surgery should be considered in patients with rapidly declining
neurological status. Life-saving surgery may simply involve a decompressive craniectomy for
patients who present in poor neurological status[19]. All the patients in our series were operated on
within the first 24 hours of hemorrhage and 2 of them were operated in the first 6 hours due to
their critical condition.
Up to 18% of patients with ruptured AVMs harbor associated arterial aneurysms, approximately
half of which occur on feeding arteries (prenidal aneurysms) [20]. This association is more
frequently encountered in patients with posterior fossa ruptured AVMs than in those with
supratentorial AVMs. [21-24]. AVM-associated aneurysms in the posterior fossa are more likely
to result in severe outcome than supratentorial ones. [25]. Both lesions should be surgically
treated in one stage operation, focused on complete resection of the nidus and on clipping of any
associated aneurysms[26]. In our series, 3 patients had flow-related associated aneurysms(25%),

6
which supports data found in the literature stating that associated aneurysms are a significant risk
factor for hemorrhage[7, 20]. One AcommA aneurysm and one PICA aneurysm were clipped in the
same operative time.
The annual rate of rupture in untreated patients is 2-4 % per year. Posterior fossa AVMs are
significantly more likely to rupture than supratentorial AVMs [27].Given that the initial rupture is
associated with an increased risk of rebleeding of up to 6% during the following year, definitive
treatment after ICH stabilization is mandatory. Although it is usually preferable to defer AVM
surgery for a period of several weeks in stable patients[28], early surgical procedures are essential
in patients with profound neurological deterioration [29]. Moreover, AVM hemorrhage is an
important factor that facilitates AVM resection. Hematoma cavity creates a corridor access to the
nidus and a cleavage plane of dissection thus facilitating nidus resection and can be used to guide
the surgeon to the AVM. In our series 12 patients presented with hematoma secondary to a
ruptured AVM and complete resection was achieved in 10 patients.
In patients presenting with a life threatening hemorrhage, prompt hematoma evacuation with
simultaneous AVM excision can yield a good-to-excellent outcome [30]. 10 patients in our series
underwent microsurgical resection in a single-stage procedure, except for two whose
deteriorating neurological status didn’t allow for a cerebral angiography. Single stage operation
offers immediate cerebral decompression and patient protection against future hemorrhage and
reduces the duration of hospital stay, thus allowing for a faster rehabilitation [31].
Sometimes emergency surgery for hematoma removal can be a life-saving intervention, in which
case it should even be performed before cerebral angiography. Posterior fossa hematomas are
poorly tolerated, with severe outcomes observed even with smaller hematoma volumes. These
findings support an aggressive surgical procedure with respect to posterior fossa AVMs, both
before and after rupture.
The morbidity associated with brain AVM rupture is higher than previously reported. Posterior
fossa location, associated aneurysms, and eloquent location were associated with poor outcome
[27]
. We noticed that younger age and temporal location are associated with poor neurological
condition. In our experience patients with brain atrophy tolerate a large amount of blood, and
consequently they tend to be in a slightly better neurological condition. In our series the
morbidity rate of 66,66% is highly related to profound neurological deterioration due to ruptured
AVM. We didn’t notice any association between posterior fossa AVM and worse outcome.
Surgical management strategy of the ruptured AVMs in comatose patients should be
individualized based on clinical neurological status and angiographic characteristics.
Complete microsurgical removal remains the gold standard and the best option for the definitive
treatment of cerebral AVMs. In critically ill patients with profound neurological deterioration,
whose initial mass effect is life-threatening, due to forensic implications, the most efficient
surgical option is emergency removal of the hematoma and, if possible, microsurgical resection
of the AVM. Aggressive surgical procedures lower case mortality rates and allow for more
favorable functional outcomes. Sometimes emergency surgery for hematoma removal or
decompressive craniectomy can be a life-saving surgical procedure, in which case it should even
be performed before DSA.

References:
1. Arteriovenous Malformation Study G. Arteriovenous malformations of the brain in adults. The New
England journal of medicine. 1999;340(23):1812-8.
2. Spetzler RF, Ponce FA. A 3-tier classification of cerebral arteriovenous malformations. Clinical article.
Journal of neurosurgery. 2011;114(3):842-9.

7
3. Laakso A, Hernesniemi J, Yonekawa Y, Tsukahara T. Surgical Management of Cerebrovascular
Disease: Springer Vienna; 2010.
4. Brown RD, Jr., Wiebers DO, Torner JC, O'Fallon WM. Frequency of intracranial hemorrhage as a
presenting symptom and subtype analysis: a population-based study of intracranial vascular
malformations in Olmsted Country, Minnesota. Journal of neurosurgery. 1996;85(1):29-32.
5. Waltimo O. The change in size of intracranial arteriovenous malformations. Journal of the neurological
sciences. 1973;19(1):21-7.
6. Platz J, Berkefeld J, Singer OC, Wolff R, Seifert V, Konczalla J, et al. Frequency, risk of hemorrhage
and treatment considerations for cerebral arteriovenous malformations with associated aneurysms. Acta
neurochirurgica. 2014;156(11):2025-34.
7. da Costa L, Wallace MC, Ter Brugge KG, O'Kelly C, Willinsky RA, Tymianski M. The natural history
and predictive features of hemorrhage from brain arteriovenous malformations. Stroke. 2009;40(1):100-5.
8. Choi JH, Mohr JP. Brain arteriovenous malformations in adults. The Lancet Neurology. 2005;4(5):299-
308.
9. Friedlander RM. Clinical practice. Arteriovenous malformations of the brain. The New England journal
of medicine. 2007;356(26):2704-12.
10. Laakso A, Dashti R, Seppanen J, Juvela S, Vaart K, Niemela M, et al. Long-term excess mortality in
623 patients with brain arteriovenous malformations. Neurosurgery. 2008;63(2):244-53; discussion 53-5.
11. Stapf C, Labovitz DL, Sciacca RR, Mast H, Mohr JP, Sacco RL. Incidence of adult brain
arteriovenous malformation hemorrhage in a prospective population-based stroke survey.
Cerebrovascular diseases. 2002;13(1):43-6.
12. Duong DH, Young WL, Vang MC, Sciacca RR, Mast H, Koennecke HC, et al. Feeding artery
pressure and venous drainage pattern are primary determinants of hemorrhage from cerebral
arteriovenous malformations. Stroke. 1998;29(6):1167-76.
13. Abla AA, Lawton MT. Editorial: Prenidal aneurysm rupture with posterior fossa AVMs.
Neurosurgical focus. 2014;37(3):E5.
14. Crawford PM, West CR, Chadwick DW, Shaw MD. Arteriovenous malformations of the brain:
natural history in unoperated patients. Journal of neurology, neurosurgery, and psychiatry. 1986;49(1):1-
10.
15. Spetzler RF, Hargraves RW, McCormick PW, Zabramski JM, Flom RA, Zimmerman RS.
Relationship of perfusion pressure and size to risk of hemorrhage from arteriovenous malformations.
Journal of neurosurgery. 1992;76(6):918-23.
16. Lawton MT, Kim H, McCulloch CE, Mikhak B, Young WL. A supplementary grading scale for
selecting patients with brain arteriovenous malformations for surgery. Neurosurgery. 2010;66(4):702-13;
discussion 13.
17. Majumdar M, Tan LA, Chen M. Critical assessment of the morbidity associated with ruptured
cerebral arteriovenous malformations. Journal of neurointerventional surgery. 2016;8(2):163-7.
18. Hernesniemi JA, Dashti R, Juvela S, Vaart K, Niemela M, Laakso A. Natural history of brain
arteriovenous malformations: a long-term follow-up study of risk of hemorrhage in 238 patients.
Neurosurgery. 2008;63(5):823-9; discussion 9-31.
19. Beecher JS, Lyon K, Ban VS, Vance A, McDougall CM, Whitworth LA, et al. Delayed treatment of
ruptured brain AVMs: is it ok to wait? Journal of neurosurgery. 2018;128(4):999-1005.
20. Gross BA, Du R. Natural history of cerebral arteriovenous malformations: a meta-analysis. Journal of
neurosurgery. 2013;118(2):437-43.
21. Kouznetsov E, Weill A, Ghostine JS, Gentric JC, Raymond J, Roy D. Association between posterior
fossa arteriovenous malformations and prenidal aneurysm rupture: potential impact on management.
Neurosurgical focus. 2014;37(3):E4.
22. da Costa L, Thines L, Dehdashti AR, Wallace MC, Willinsky RA, Tymianski M, et al. Management
and clinical outcome of posterior fossa arteriovenous malformations: report on a single-centre 15-year
experience. Journal of neurology, neurosurgery, and psychiatry. 2009;80(4):376-9.

8
23. Schmidt NO, Reitz M, Raimund F, Treszl A, Grzyska U, Westphal M, et al. Clinical relevance of
associated aneurysms with arteriovenous malformations of the posterior fossa. Acta neurochirurgica
Supplement. 2011;112:131-5.
24. Westphal M, Grzyska U. Clinical significance of pedicle aneurysms on feeding vessels, especially
those located in infratentorial arteriovenous malformations. Journal of neurosurgery. 2000;92(6):995-
1001.
25. Mpotsaris A, Loehr C, Harati A, Lohmann F, Puchner M, Weber W. Interdisciplinary clinical
management of high grade arteriovenous malformations and ruptured flow-related aneurysms in the
posterior fossa. Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical
procedures and related neurosciences. 2010;16(4):400-8.
26. O'Shaughnessy BA, Getch CC, Bendok BR, Batjer HH. Microsurgical resection of infratentorial
arteriovenous malformations. Neurosurgical focus. 2005;19(2):E5.
27. Abla AA, Nelson J, Rutledge WC, Young WL, Kim H, Lawton MT. The natural history of AVM
hemorrhage in the posterior fossa: comparison of hematoma volumes and neurological outcomes in
patients with ruptured infra- and supratentorial AVMs. Neurosurgical focus. 2014;37(3):E6.
28. Zacharia BE, Vaughan KA, Jacoby A, Hickman ZL, Bodmer D, Connolly ES, Jr. Management of
ruptured brain arteriovenous malformations. Current atherosclerosis reports. 2012;14(4):335-42.
29. Aoun SG, Bendok BR, Batjer HH. Acute management of ruptured arteriovenous malformations and
dural arteriovenous fistulas. Neurosurgery clinics of North America. 2012;23(1):87-103.
30. Jafar JJ, Rezai AR. Acute surgical management of intracranial arteriovenous malformations.
Neurosurgery. 1994;34(1):8-12; discussion -3.
31. Pavesi G, Rustemi O, Berlucchi S, Frigo AC, Gerunda V, Scienza R. Acute surgical removal of low-
grade (Spetzler-Martin I-II) bleeding arteriovenous malformations. Surgical neurology. 2009;72(6):662-7.