Neurocrit Care DOI 10.1007/s12028-014-9962-2
PRACTICAL PEARL
Artery of Percheron Infarction as an Unusual Cause of Coma: Three Cases and Literature Review Nathalie Zappella • Sybille Merceron • Chantal Nifle • Julia Hilly-Ginoux Fabrice Bruneel • Gilles Troche´ • Yves-Sebastien Cordoliani • Jean-Pierre Bedos • Fernando Pico • Stephane Legriel
•
Ó Springer Science+Business Media New York 2014
Abstract Objective Stroke due to occlusion of the artery of Percheron (AOP), an uncommon anatomic variant supplying the bilateral medial thalami, may raise diagnostic challenges and cause life-threatening symptoms. Our objective here was to detail the features and outcomes in three patients who required intensive care unit (ICU) admission and to review the relevant literature. Methods Description of three cases and literature review based on a 1973–2013 PubMed search. Results Three patients were admitted to our ICU with sudden-onset coma and respiratory and cardiovascular dysfunctions requiring endotracheal mechanical ventilation. Focal neurological deficits, ophthalmological signs (abnormal light reflexes and/or ocular motility and/or ptosis), and neuropsychological abnormalities were variably
combined. Initial CT scan was normal. Cerebral MRI demonstrated bilateral paramedian thalamic infarction, with extension to the cerebral peduncles in two patients. Consciousness improved rapidly and time to extubation was 1–4 days. All three patients were discharged alive from the hospital and two had good 1-year functional outcomes. Similar clinical features and outcomes were recorded in the 117 patients identified in the literature, of whom ten required ICU admission. Conclusions Bilateral paramedian thalamic stroke due to AOP occlusion can be life threatening. The early diagnosis relies on MRI with magnetic resonance angiography. Recovery of consciousness is usually rapid and mortality is low, warranting full-code ICU management. Keywords Coma
All cerebrovascular disease/Stroke
Electronic supplementary material The online version of this article (doi:10.1007/s12028-014-9962-2) contains supplementary material, which is available to authorized users. N. Zappella S. Merceron J. Hilly-Ginoux F. Bruneel G. Troche´ J.-P. Bedos S. Legriel (&) Intensive Care Unit, Centre Hospitalier de Versailles—Site Andre´ Mignot, 78150 Le Chesnay, France e-mail: [email protected]; [email protected] N. Zappella e-mail: [email protected] S. Merceron e-mail: [email protected] J. Hilly-Ginoux e-mail: [email protected] F. Bruneel e-mail: [email protected]
J.-P. Bedos e-mail: [email protected] C. Nifle F. Pico Neurology Department and Stroke Center, Centre Hospitalier de Versailles—Site Andre´ Mignot, 78150 Le Chesnay, France e-mail: [email protected] F. Pico e-mail: [email protected] Y.-S. Cordoliani Radiology Department, Hoˆpital prive´ de Parly II, 78150 Le Chesnay, France e-mail: [email protected]
G. Troche´ e-mail: [email protected]
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Introduction Bilateral paramedian thalamic infarction due to occlusion of the artery of Percheron (AOP) is a rare vascular cause of coma. Its exact prevalence remains unknown. First described by Percheron in 1973 [1], the AOP is an anatomic variant of the paramedian arteries arising from segment P1 of the posterior cerebral artery (Fig. 1). It supplies the bilateral medial thalami and, in some cases, a variable portion of the rostral midbrain. Thus, AOP occlusion causes bilateral paramedian thalamic infarction with or without midbrain involvement [2–5]. AOP occlusion may manifest as the sudden onset of severe consciousness impairment, the cause of which may be difficult to identify, particularly as computed tomography (CT) findings may be normal at first. Magnetic resonance imaging (MRI) is currently the most informative diagnostic tool. Few cases of AOP stroke responsible for life-threatening complications have been reported [6–13]. This situation requires admission to the intensive care unit (ICU) and involvement of a stroke unit team in the management decisions [14]. We have managed three patients with coma due to AOP who were admitted to our ICU in 2011. Our objective in this study was to describe the clinical features and management of life-threatening AOP occlusion based on these three cases and on a review of the relevant literature.
date limits were 1973 to June 2013, and the language limits were English, French, and Spanish. Full-length papers of all retrievals were read, and we identified 75 articles reporting cases in which a diagnosis of AOP occlusion was supported by cerebral imaging findings of ischemia involving the bilateral paramedian thalami, with or without rostral midbrain ischemia. These findings could consist of hypodensities by CT and/or high signal intensity on T2 or FLAIR MRI sequences with or without restricted diffusion or postcontrast enhancement, in a bilateral paramedian thalamic distribution [2, 11, 15]. We excluded cases in pediatric patients, cases without a description of imaging study findings, and cases with intracranial bleeding and/or with another concomitant major stroke location. This left 55 articles reporting 117 cases to which we added our 3 cases (Supplemental/ Additional Files). Data Collection For each of the 120 cases, we used a standardized form to collect epidemiologic characteristics, cardiovascular risk factors, main clinical signs, brain imaging findings establishing the diagnosis of bilateral thalamic infarction, pathophysiological mechanisms responsible for AOP occlusion categorized according to the TOAST classification [16], ICU admission and interventions, and outcome. Statistical Analysis
Patients and Methods Setting We retrospectively identified patients with AOP occlusion admitted to the ICU of the Versailles Hospital, a university-affiliated institution located in the Paris metropolis, France, between 2011 and 2013. The hospital has 711 beds for medical and surgical patients, including 18 beds in a closed medical-surgical ICU. Most ICU patients are admitted through the emergency department or prehospital emergency medical system (SAMU); only 25 % of patients are referred from the wards. Patients managed in the ICU for stroke are discharged to the neurology department, which includes a stroke unit where neurologists and expert advice from neurovascular experts are available around the clock. Literature Review We searched PubMed for articles on AOP occlusion using the indexing terms ‘‘thalamic’’ and/or ‘‘paramedian’’ and/ or ‘‘Percheron’’ and/or ‘‘infarction’’ and/or ‘‘stroke.’’ The
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Quantitative parameters were described as median (interquartile range, IQR) and qualitative parameters as number (%). Descriptive analyses were done using the SAS 9.1 software package (SAS Institute, Cary, NC, USA).
Results Demographics and clinical data from our three patients and the 117 patients from the literature review are reported in Table 1. Cerebral imaging findings in our three patients are shown in Fig. 2. Patient 1 This 83-year-old woman with a history of hypertension and hypothyroidism was found at home by her son in a coma. She had lost her urine and bitten her tongue. Her Glasgow Coma Scale (GCS) score was 6 and she had bilateral mydriasis and rolling movements of the upper left limb. She was intubated at the scene by the prehospital emergency team and sedated during transportation to our hospital. Cerebral CT scan
Neurocrit Care Fig. 1 Spectrum of paramedian thalamic arterial supply: conventional anatomy (Fig. 1a) and variants according to Percheron (Fig. 1b–d). Panel a: typical thalamus vascularization by thalamo-perforating arteries arising from the posterior cerebral artery (Type 1). Panel b: variant anatomy with vascularization of the thalami by two arteries arising from the right P1 segment of the posterior cerebral artery (Type 2a). Panel c: most common variant anatomy, in which the thalami are vascularized by the artery of Percheron arising from the P1 segment of the right posterior cerebral artery (Type 2b). Panel d: variant anatomy with vascularization of the thalami by an arcade of perforating branches arising from an artery bridging the P1 segments of the two posterior cerebral arteries (Type 3)
showed ischemic areas in the basal ganglia (Fig. 2a). At ICU admission, her blood pressure was 60/30 mmHg, her pulse rate was 40/min, and her temperature was 35 °C. The cardiopulmonary examination was unremarkable. The corneal, cough, and swallowing reflexes were present, and she was reactive to nursing care. She had left hemiparesis. Cerebrospinal fluid analysis and electroencephalogram findings were normal. The electrocardiogram demonstrated
sinus bradycardia that was ascribed to the hypothermia. Her blood tests were unremarkable, including blood glucose and thyroid stimulating hormone values. The sedative drugs were withdrawn rapidly after ICU admission. She awoke gradually but remained very somnolent. She was extubated on day 2 with no complications. At that time, she had left hemiparesis, bilateral mydriasis and ptosis, and vertical gaze paresis. Cerebral MRI on day 3 demonstrated bilateral
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Neurocrit Care Table 1 Patient characteristics according to need for intensive care unit admission among 120 patients with artery of Percheron occlusion
N (%) or Median (interquartile range) All patients n = 120 (100 %)
No ICU management n = 107 (89.2 %)
ICU management n = 13 (10.8 %)
Age (years)
64 (53–72)
64 (53–72)
64 (51–71)
Male gender
68 (56.7 %)
62 (57.9 %)
Demographics 6 (46.2 %)
Co-morbidities Hypertension
41 (34.2 %)
35 (32.7 %)
6 (46.2 %)
Atrial fibrillation
20 (16.7 %)
19 (17.8 %)
1 (7.7 %)
Diabetes Dyslipidemia
20 (16.6 %) 19 (15.8 %)
16 (14.9 %) 15 (14.0 %)
4 (30.8 %) 4 (30.8 %)
49 (40.8 %)
39 (36.4 %)
10 (76.9 %)
Clinical presentation at scenef Including our three patients ICU intensive care unit, CT computed tomography, MRI magnetic resonance imaging a Stupor (n = 6), confusion (n = 10), drowsiness (n = 30), lethargy (n = 8), other (n = 7) b
Focal neurological signs were defined as symptoms or signs consistent with damage to, or dysfunction of, a specific anatomic site in the central nervous system. These signs were unifocal or multifocal, and transient or persistent
c
Mydriasis (n = 19), myosis (n = 12), areactivity (n = 1)
d
Hypersexuality (n = 3), binge eating (n = 5), frontal syndrome (n = 13)
e
Psychiatric disorders (n = 19): mood disorders, (n = 16), anxiety disorder (n = 1), and psychotic disorder (n = 2); Respiratory signs (n = 14): respiratory distress (n = 11), snoring (n = 1), cheyne stokes (n = 1), and stridor (n = 1); Cardiovascular signs (n = 3): bradycardia (n = 2) and hypertension crisis (n = 1) f
Some patients had more than one clinical sign/investigation
g
According to the TOAST classification
D
As described by the authors of the case-reports
Neurological signs Coma Glasgow Coma Scale score Other arousal disorders
a
Focal neurological signsb
5 (4–8)
7 (6–7)
61 (50.8 %)
56 (52.3 %)
5 (38.5 %)
57 (47.5 %)
50 (46.7 %)
7 (53.8 %)
Ophthalmological signs Ocular motility disorder
77 (64.2 %)
68 (63.6 %)
9 (69.2 %)
Abnormal light reflexc
32 (26.7 %)
24 (22.4 %)
8 (61.5 %)
Ptosis
24 (20.0 %)
19 (17.8 %)
5 (38.5 %) 1 (7.7 %)
Neuropsychological signs Memory deficit
47 (39.2 %)
46 (43.0 %)
Executive function disorder
11 (9.2 %)
11 (10.3 %)
Language disorder Behavioral disturbanced
39 (32.5 %) 21 (17.5 %)
36 (33.6 %) 21 (19.6 %)
0 3 (23.1 %) 0
Other clinical signse Psychiatric disorders
19 (15.8 %)
19 (17.8 %)
Respiratory signs
14 (11.7 %)
10 (9.3 %)
4 (30.7 %)
4 (3.3 %)
2 (1.9 %)
2 (15.4 %)
CT
68 (56.7 %)
60 (56.1 %)
8 (61.5 %)
MRI
77 (64.2 %)
66 (61.7 %)
11 (84.6 %)
Arteriography
10 (8.3 %)
9 (8.4 %)
1 (7.7 %)
25 (20.8 %)
22 (20.6 %)
3 (23.1 %)
1 (8.3 %)
1 (0.9 %)
3 (2.5 %)
3 (2.8 %)
8 (6.7 %)
4 (3.7 %)
4 (30.7 %)
83 (69.2 %)
77 (72.0 %)
6 (46.2 %)
Cardiovascular signs
0
Brain imagingf
Mechanism of strokeg Cardioembolism Large-artery atherosclerosisD Small-vessel occlusion
D
Stroke of other determined etiology Stroke of undetermined etiology Outcomes Total coma duration (days) Mortality
thalamic stroke with extension to the right peduncle (Fig. 2b–d). Aspirin therapy was started. Transcranial Doppler and 3D time-of-flight magnetic resonance angiography (TOF-MRA) of the carotid, vertebral, basilar, and posterior cerebral arteries showed no
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6 (4–7)
3 (2–8) 15 (12.5 %)
3 (1–10) 14 (13.1 %)
0 0
3 (2–4) 1 (7.7 %)
stenosis or occlusion. Transthoracic echocardiography was normal; transesophageal echocardiography was contraindicated by persistent arousal disorders. She was transferred to the neurology department on day 3 and was subsequently discharged to a nursing home.
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Fig. 2 Cerebral computed tomography (CT) and magnetic resonance imaging (MRI) findings in our patients, demonstrating bilateral paramedian thalamic infarction by occlusion of the artery of Percheron. Panel a (Patient 1): CT, low-density in both paramedian thalamic areas (white arrows). Panel b (Patient 1): MRI, diffusionweighted imaging sequence showing high-intensity foci in the right peduncle (white arrows). Panel c (Patient 1): MRI, diffusion-weighted imaging sequence showing high-intensity foci in both paramedian thalamic areas (white arrows). Panel d (Patient 1): MRI, fluidattenuated inversion recovery (FLAIR) sequence showing high-
intensity foci in both paramedian thalamic areas (white arrows). Panel e (Patient 2): MRI, diffusion-weighted imaging sequence showing high-intensity foci in both paramedian thalamic areas (white arrows). Panel f (Patient 2): MRI, fluid-attenuated inversion recovery (FLAIR) sequence showing high-intensity foci in both paramedian thalamic areas (white arrows). Panel g (Patient 3): MRI, diffusionweighted imaging sequence showing high-intensity foci in both paramedian thalamic areas (white arrows). Panel h (Patient 3): MRI, fluid-attenuated inversion recovery (FLAIR) sequence showing highintensity foci in both paramedian thalamic areas (white arrows)
Patient 2
from extensive atheroma plaques of the vertebro-basilar system arteries seen on the transcranial Doppler. Aspirin therapy was initiated. Her neurological status improved rapidly and she was extubated on day 4, reintubated because of dyspnea due to laryngeal edema, and finally successfully extubated on day 8. At transfer to the neurology ward, she had marked right ptosis, confusion, and hypersomnia. She was discharged home. At follow-up 1 year later, she had a persistent attention deficit but was able to live independently.
This 67-year-old woman with an unremarkable medical history suddenly lost consciousness while receiving manipulation therapy from her osteopath. She had a GCS score of 4, bilateral tight myosis, and appropriate responses to nociceptive stimuli except for internal rotation of the left shoulder. She had no other organ dysfunctions. She was promptly intubated at the scene by the prehospital emergency team and transferred to our hospital. Cerebral CT without contrast performed at hospital admission was normal, as were the cerebrospinal fluid analysis and electroencephalogram. Cerebral MRI on day 1 showed a recent bilateral paramedian thalamic infarction (Fig. 2e, f). No evidence of supra-aortic artery dissection was found on cervical fat-saturated T1 MRI sequences or by cervical Doppler. Transesophageal echocardiography showed no signs of embolic heart disease. Extensive laboratory tests were unremarkable. The stroke was ascribed to embolism
Patient 3 This 72-year-old woman with a history of hypertension, dyslipidemia, bilateral breast cancer, and lower limb deep vein thrombosis was found at home by her husband with impaired consciousness and snoring. Upon examination at home by the prehospital emergency team she had a GCS score of 10, no focal neurological signs, and appropriate motor responses to nociception. She initially had no other
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organ dysfunctions. Her blood glucose level and flumazenil test were normal. She promptly required endotracheal mechanical ventilation because of worsening respiratory impairment with apnea during transport to the hospital. Emergent cerebral CT without contrast upon hospital arrival and extensive blood tests were normal. Within the first day after ICU admission, her consciousness improved and her respiratory rate became regular, allowing extubation. Her GCS score fluctuated from 12 to 14 and she had confusion, spatial–temporal disorientation, hypersomnia, bilateral ptosis, and vertical ocular motility disorders. Cerebral MRI on day 3 revealed recent bilateral and symmetric thalamic stroke with extension to the highest part of the cerebral peduncles, a pattern characteristic of AOP occlusion (Fig. 2g, h). Aspirin therapy was started. Transthoracic and transesophageal echocardiography showed no evidence of embolic heart disease. She was not re-evaluated for recurrence of deep venous thrombosis but a bubble study during echocardiography eliminated a patent foramen ovale. There was no dissection of the supraaortic or intracranial vertebral, basilar, or posterior cerebral arteries by cervical Doppler or MRA. She was discharged home. At follow-up 1 year later, she had persistent hypersomnia and bilateral ptosis.
Literature Review Patient characteristics are shown in Table 1. There were 52 women and 68 men, with a median age of 64 years (IQR, 53–72). Co-morbidities were present as follow: hypertension in 34 %, diabetes in 17 %, atrial fibrillation in 17 %, and dyslipidemia in 16 %. The most clinical features were dominated by neurological signs up to 92 % of cases (consciousness impairment and/or focal neurological signs), ophthalmological signs up to 64 % of cases (abnormal light reflexes and/or ocular motility and/or ptosis), and neuropsychological abnormalities up to 42 % of cases (memory deficit, language disorders, behavioral disturbance, and executive function disorders). Some patients also experienced psychiatric disorders in 16 % and respiratory or cardiovascular signs in 12 and 3 %, respectively. All patients underwent cerebral imaging. CT and MRI were performed in 57 and 64 % of patients, respectively. Origin of stroke was predominantly attributed to cardio embolism mechanism but remained undetermined in 69 % of cases. Findings from the literature review did not allow identifying consistent criteria for ICU admission. Eighty percent of patients with coma did not go to the ICU, and the ICU patients had better GCS scores. The ICU patients more often had respiratory and cardio vascular signs, but still only less than one-fifth had such signs. Ventilatory support with mechanical ventilation was required in all ICU patients.
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Discussion Our analysis of 120 patients with AOP occlusion, including 13 who required ICU admission, provides a detailed picture of this condition and of its outcome. When present, the coma resolves rapidly, although other abnormalities such as hypersomnia, attention deficit, motor impairments, and ocular motility disorders may persist in the long term. The mechanism of occlusion remains unclear in most cases; when determined, it is usually cardioembolism. Bilateral paramedian thalamic infarction by AOP occlusion is a rare cause of coma in middle-aged or elderly patients. Males and females are equally affected. Many patients have cardiovascular risk factors or embolic heart disease. Consciousness impairment is the rule but may range from drowsiness to a deep coma. Other abnormalities may include ophthalmological and neuropsychological abnormalities and respiratory and cardiovascular dysfunctions. A careful interview of the family for evidence of abnormalities before the onset of consciousness impairment may assist in the diagnosis. The diagnosis of AOP occlusion is dependent on cerebral imaging studies, chiefly MRI, as CT findings may be normal [11]. Whereas CT may be easier to obtain first, MRI must be performed, either as the first or as the second imaging study, in cases of recognition of this typical thalamic syndrome. Ischemic lesions of the medial areas of both thalami are seen, with or without rostral mesencephalic involvement [2]. The midbrain ‘‘V’’ sign is a high-intensity signal on axial FLAIR and diffusion-weighted images along the pial surface of the midbrain in the interpeduncular fossa. This sign has been reported in 67 % of patients with AOP occlusion [2]. Importantly, angiography is not required to document AOP occlusion. The main differential diagnosis is bilateral thalamic venous infarction complicating internal cerebral vein thrombosis [11, 13, 17]. Other rarer differential diagnoses include Wernicke encephalopathy, extrapontine myelinolysis, and Creutzfeldt-Jakob disease [11]. Ideally, MRI should be coupled with 3D TOF-MRA of the carotid, vertebral, basilar, and posterior cerebral arteries to rule out basilar artery occlusion [11]. Transcranial Doppler of the carotids and supra-aortic trunks is also useful. Other etiologic investigations include extensive blood tests for hypercoagulability, hematological disorders, and nonatherosclerotic vasculopathies such as systemic vasculitis. Transthoracic and transesophageal echocardiography may show a cardiac abnormality associated with systemic embolism, such as patent foramen ovale. Finally, a Holter ECG is useful to look for cardiac arrhythmias associated with embolism. Despite these investigations, the cause of AOP occlusion often remains unidentified. Embolic heart disease is the only commonly identified cause; [15, 18] all other causes are rare [8, 11, 19]. In
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particular, large-artery atherosclerosis and small-artery occlusion are exceedingly rare causes of AOP occlusion [2]. Interestingly, atypical causes have also been reported such as infectious causes after fulminant pneumococcal meningitis [20] or as iatrogenic causes due to basilar artery aneurysm clipping or coiling [21], due to arterial catheterizations (including cerebral and coronary [22] ) or due to transsphenoidal resection of a pituitary adenoma [23]. An obstacle to the optimal management of AOP occlusion is the limited availability of MRI, which often results in diagnostic delays ranging from several hours to several days. In one patient, early MRI was negative [9]. Thrombolytic management has been reported in only two patients: one received intraarterial thrombolysis during angiography [24] and the other venous thrombolysis [11]. In addition to our three cases, only ten other cases requiring ICU management have been reported [6, 8, 10–13, 21]. The coma resolves rapidly, usually allowing extubation within a few days. Even when ICU admission is required the mortality rate is low compared to patients with other forms of stroke requiring endotracheal mechanical ventilation [14]. In stroke patients who required mechanical ventilation, 1-year mortality rates ranged from 40 to 70 % [25–29], and cognitive impairments persisted in 63–75 % of survivors [26, 28]. The outcomes of ischemic stroke are largely governed by the site of the arterial occlusion. Malignant middle cerebral artery infarction has a particularly grim prognosis. Finally, intracerebral complications such as elevated intracranial pressure and malignant brain edema can adversely impact the neurological prognosis. Interestingly, we found that most patients with AOP were not managed in the ICU admission, whereas mortality was substantially higher in patients without ICU admission. Surprisingly, findings from the literature review did not allow identifying consistent criteria for ICU admission. Studies have established that management in specialized stroke units and neurocritical care units is associated with better outcomes [14, 30]. This finding is taken into account in the latest guidelines for the early management of patients with acute ischemic stroke [14]. Our study has several limitations. First, the extent to which our findings apply to the full spectrum of patients with bilateral paramedian thalamic infarction due to occlusion of the artery of Percheron is unclear. Patients were analyzed among 55 articles over a 40-year period, yielding a great variability in the cases description and in the radiologic technology used for diagnosis. Moreover, earlier described patients were managed before the neurocritical care era that could explain a higher mortality rate. Finally, prognosis described only relates to published reports, which likely have an inherent bias as worse cases and misdiagnosed cases are unlikely to be published.
In conclusion, bilateral paramedian thalamic infarction due to AOP occlusion can result in life-threatening complications requiring ICU admission. The typical clinical presentation combines consciousness impairment, ophthalmological and neuropsychological signs, and respiratory and cardiovascular dysfunctions. MRI with MRA should be performed promptly to establish the diagnosis, as CT may be normal initially. The rapid reversibility of the coma in many cases and the low-mortality rate associated with AOP occlusion warrant full-code ICU management. Acknowledgments We thank A. Wolfe MD for helping to prepare the manuscript. We received no funds for this study. Conflict of interest interests exist.
The authors have declared that no competing
Disclosures of Authors Financial Relationships Relevant to the Study Nathalie Zappella: reports no disclosures, Sybille Merceron: reports no disclosures, Chantal Nifle: reports no disclosures, Julia Hilly-Ginoux: reports no disclosures, Fabrice Bruneel: reports no disclosures, Gilles Troche´: reports no disclosures, Yves-Sebastien Cordoliani: reports no disclosures, Jean-Pierre Bedos: reports no disclosures, Fernando Pico: reports no disclosures, Stephane Legriel: reports no disclosures.
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PRACTICAL PEARL
Artery of Percheron Infarction as an Unusual Cause of Coma: Three Cases and Literature Review Nathalie Zappella • Sybille Merceron • Chantal Nifle • Julia Hilly-Ginoux Fabrice Bruneel • Gilles Troche´ • Yves-Sebastien Cordoliani • Jean-Pierre Bedos • Fernando Pico • Stephane Legriel
•
Ó Springer Science+Business Media New York 2014
Abstract Objective Stroke due to occlusion of the artery of Percheron (AOP), an uncommon anatomic variant supplying the bilateral medial thalami, may raise diagnostic challenges and cause life-threatening symptoms. Our objective here was to detail the features and outcomes in three patients who required intensive care unit (ICU) admission and to review the relevant literature. Methods Description of three cases and literature review based on a 1973–2013 PubMed search. Results Three patients were admitted to our ICU with sudden-onset coma and respiratory and cardiovascular dysfunctions requiring endotracheal mechanical ventilation. Focal neurological deficits, ophthalmological signs (abnormal light reflexes and/or ocular motility and/or ptosis), and neuropsychological abnormalities were variably
combined. Initial CT scan was normal. Cerebral MRI demonstrated bilateral paramedian thalamic infarction, with extension to the cerebral peduncles in two patients. Consciousness improved rapidly and time to extubation was 1–4 days. All three patients were discharged alive from the hospital and two had good 1-year functional outcomes. Similar clinical features and outcomes were recorded in the 117 patients identified in the literature, of whom ten required ICU admission. Conclusions Bilateral paramedian thalamic stroke due to AOP occlusion can be life threatening. The early diagnosis relies on MRI with magnetic resonance angiography. Recovery of consciousness is usually rapid and mortality is low, warranting full-code ICU management. Keywords Coma
All cerebrovascular disease/Stroke
Electronic supplementary material The online version of this article (doi:10.1007/s12028-014-9962-2) contains supplementary material, which is available to authorized users. N. Zappella S. Merceron J. Hilly-Ginoux F. Bruneel G. Troche´ J.-P. Bedos S. Legriel (&) Intensive Care Unit, Centre Hospitalier de Versailles—Site Andre´ Mignot, 78150 Le Chesnay, France e-mail: [email protected]; [email protected] N. Zappella e-mail: [email protected] S. Merceron e-mail: [email protected] J. Hilly-Ginoux e-mail: [email protected] F. Bruneel e-mail: [email protected]
J.-P. Bedos e-mail: [email protected] C. Nifle F. Pico Neurology Department and Stroke Center, Centre Hospitalier de Versailles—Site Andre´ Mignot, 78150 Le Chesnay, France e-mail: [email protected] F. Pico e-mail: [email protected] Y.-S. Cordoliani Radiology Department, Hoˆpital prive´ de Parly II, 78150 Le Chesnay, France e-mail: [email protected]
G. Troche´ e-mail: [email protected]
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Introduction Bilateral paramedian thalamic infarction due to occlusion of the artery of Percheron (AOP) is a rare vascular cause of coma. Its exact prevalence remains unknown. First described by Percheron in 1973 [1], the AOP is an anatomic variant of the paramedian arteries arising from segment P1 of the posterior cerebral artery (Fig. 1). It supplies the bilateral medial thalami and, in some cases, a variable portion of the rostral midbrain. Thus, AOP occlusion causes bilateral paramedian thalamic infarction with or without midbrain involvement [2–5]. AOP occlusion may manifest as the sudden onset of severe consciousness impairment, the cause of which may be difficult to identify, particularly as computed tomography (CT) findings may be normal at first. Magnetic resonance imaging (MRI) is currently the most informative diagnostic tool. Few cases of AOP stroke responsible for life-threatening complications have been reported [6–13]. This situation requires admission to the intensive care unit (ICU) and involvement of a stroke unit team in the management decisions [14]. We have managed three patients with coma due to AOP who were admitted to our ICU in 2011. Our objective in this study was to describe the clinical features and management of life-threatening AOP occlusion based on these three cases and on a review of the relevant literature.
date limits were 1973 to June 2013, and the language limits were English, French, and Spanish. Full-length papers of all retrievals were read, and we identified 75 articles reporting cases in which a diagnosis of AOP occlusion was supported by cerebral imaging findings of ischemia involving the bilateral paramedian thalami, with or without rostral midbrain ischemia. These findings could consist of hypodensities by CT and/or high signal intensity on T2 or FLAIR MRI sequences with or without restricted diffusion or postcontrast enhancement, in a bilateral paramedian thalamic distribution [2, 11, 15]. We excluded cases in pediatric patients, cases without a description of imaging study findings, and cases with intracranial bleeding and/or with another concomitant major stroke location. This left 55 articles reporting 117 cases to which we added our 3 cases (Supplemental/ Additional Files). Data Collection For each of the 120 cases, we used a standardized form to collect epidemiologic characteristics, cardiovascular risk factors, main clinical signs, brain imaging findings establishing the diagnosis of bilateral thalamic infarction, pathophysiological mechanisms responsible for AOP occlusion categorized according to the TOAST classification [16], ICU admission and interventions, and outcome. Statistical Analysis
Patients and Methods Setting We retrospectively identified patients with AOP occlusion admitted to the ICU of the Versailles Hospital, a university-affiliated institution located in the Paris metropolis, France, between 2011 and 2013. The hospital has 711 beds for medical and surgical patients, including 18 beds in a closed medical-surgical ICU. Most ICU patients are admitted through the emergency department or prehospital emergency medical system (SAMU); only 25 % of patients are referred from the wards. Patients managed in the ICU for stroke are discharged to the neurology department, which includes a stroke unit where neurologists and expert advice from neurovascular experts are available around the clock. Literature Review We searched PubMed for articles on AOP occlusion using the indexing terms ‘‘thalamic’’ and/or ‘‘paramedian’’ and/ or ‘‘Percheron’’ and/or ‘‘infarction’’ and/or ‘‘stroke.’’ The
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Quantitative parameters were described as median (interquartile range, IQR) and qualitative parameters as number (%). Descriptive analyses were done using the SAS 9.1 software package (SAS Institute, Cary, NC, USA).
Results Demographics and clinical data from our three patients and the 117 patients from the literature review are reported in Table 1. Cerebral imaging findings in our three patients are shown in Fig. 2. Patient 1 This 83-year-old woman with a history of hypertension and hypothyroidism was found at home by her son in a coma. She had lost her urine and bitten her tongue. Her Glasgow Coma Scale (GCS) score was 6 and she had bilateral mydriasis and rolling movements of the upper left limb. She was intubated at the scene by the prehospital emergency team and sedated during transportation to our hospital. Cerebral CT scan
Neurocrit Care Fig. 1 Spectrum of paramedian thalamic arterial supply: conventional anatomy (Fig. 1a) and variants according to Percheron (Fig. 1b–d). Panel a: typical thalamus vascularization by thalamo-perforating arteries arising from the posterior cerebral artery (Type 1). Panel b: variant anatomy with vascularization of the thalami by two arteries arising from the right P1 segment of the posterior cerebral artery (Type 2a). Panel c: most common variant anatomy, in which the thalami are vascularized by the artery of Percheron arising from the P1 segment of the right posterior cerebral artery (Type 2b). Panel d: variant anatomy with vascularization of the thalami by an arcade of perforating branches arising from an artery bridging the P1 segments of the two posterior cerebral arteries (Type 3)
showed ischemic areas in the basal ganglia (Fig. 2a). At ICU admission, her blood pressure was 60/30 mmHg, her pulse rate was 40/min, and her temperature was 35 °C. The cardiopulmonary examination was unremarkable. The corneal, cough, and swallowing reflexes were present, and she was reactive to nursing care. She had left hemiparesis. Cerebrospinal fluid analysis and electroencephalogram findings were normal. The electrocardiogram demonstrated
sinus bradycardia that was ascribed to the hypothermia. Her blood tests were unremarkable, including blood glucose and thyroid stimulating hormone values. The sedative drugs were withdrawn rapidly after ICU admission. She awoke gradually but remained very somnolent. She was extubated on day 2 with no complications. At that time, she had left hemiparesis, bilateral mydriasis and ptosis, and vertical gaze paresis. Cerebral MRI on day 3 demonstrated bilateral
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Neurocrit Care Table 1 Patient characteristics according to need for intensive care unit admission among 120 patients with artery of Percheron occlusion
N (%) or Median (interquartile range) All patients n = 120 (100 %)
No ICU management n = 107 (89.2 %)
ICU management n = 13 (10.8 %)
Age (years)
64 (53–72)
64 (53–72)
64 (51–71)
Male gender
68 (56.7 %)
62 (57.9 %)
Demographics 6 (46.2 %)
Co-morbidities Hypertension
41 (34.2 %)
35 (32.7 %)
6 (46.2 %)
Atrial fibrillation
20 (16.7 %)
19 (17.8 %)
1 (7.7 %)
Diabetes Dyslipidemia
20 (16.6 %) 19 (15.8 %)
16 (14.9 %) 15 (14.0 %)
4 (30.8 %) 4 (30.8 %)
49 (40.8 %)
39 (36.4 %)
10 (76.9 %)
Clinical presentation at scenef Including our three patients ICU intensive care unit, CT computed tomography, MRI magnetic resonance imaging a Stupor (n = 6), confusion (n = 10), drowsiness (n = 30), lethargy (n = 8), other (n = 7) b
Focal neurological signs were defined as symptoms or signs consistent with damage to, or dysfunction of, a specific anatomic site in the central nervous system. These signs were unifocal or multifocal, and transient or persistent
c
Mydriasis (n = 19), myosis (n = 12), areactivity (n = 1)
d
Hypersexuality (n = 3), binge eating (n = 5), frontal syndrome (n = 13)
e
Psychiatric disorders (n = 19): mood disorders, (n = 16), anxiety disorder (n = 1), and psychotic disorder (n = 2); Respiratory signs (n = 14): respiratory distress (n = 11), snoring (n = 1), cheyne stokes (n = 1), and stridor (n = 1); Cardiovascular signs (n = 3): bradycardia (n = 2) and hypertension crisis (n = 1) f
Some patients had more than one clinical sign/investigation
g
According to the TOAST classification
D
As described by the authors of the case-reports
Neurological signs Coma Glasgow Coma Scale score Other arousal disorders
a
Focal neurological signsb
5 (4–8)
7 (6–7)
61 (50.8 %)
56 (52.3 %)
5 (38.5 %)
57 (47.5 %)
50 (46.7 %)
7 (53.8 %)
Ophthalmological signs Ocular motility disorder
77 (64.2 %)
68 (63.6 %)
9 (69.2 %)
Abnormal light reflexc
32 (26.7 %)
24 (22.4 %)
8 (61.5 %)
Ptosis
24 (20.0 %)
19 (17.8 %)
5 (38.5 %) 1 (7.7 %)
Neuropsychological signs Memory deficit
47 (39.2 %)
46 (43.0 %)
Executive function disorder
11 (9.2 %)
11 (10.3 %)
Language disorder Behavioral disturbanced
39 (32.5 %) 21 (17.5 %)
36 (33.6 %) 21 (19.6 %)
0 3 (23.1 %) 0
Other clinical signse Psychiatric disorders
19 (15.8 %)
19 (17.8 %)
Respiratory signs
14 (11.7 %)
10 (9.3 %)
4 (30.7 %)
4 (3.3 %)
2 (1.9 %)
2 (15.4 %)
CT
68 (56.7 %)
60 (56.1 %)
8 (61.5 %)
MRI
77 (64.2 %)
66 (61.7 %)
11 (84.6 %)
Arteriography
10 (8.3 %)
9 (8.4 %)
1 (7.7 %)
25 (20.8 %)
22 (20.6 %)
3 (23.1 %)
1 (8.3 %)
1 (0.9 %)
3 (2.5 %)
3 (2.8 %)
8 (6.7 %)
4 (3.7 %)
4 (30.7 %)
83 (69.2 %)
77 (72.0 %)
6 (46.2 %)
Cardiovascular signs
0
Brain imagingf
Mechanism of strokeg Cardioembolism Large-artery atherosclerosisD Small-vessel occlusion
D
Stroke of other determined etiology Stroke of undetermined etiology Outcomes Total coma duration (days) Mortality
thalamic stroke with extension to the right peduncle (Fig. 2b–d). Aspirin therapy was started. Transcranial Doppler and 3D time-of-flight magnetic resonance angiography (TOF-MRA) of the carotid, vertebral, basilar, and posterior cerebral arteries showed no
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6 (4–7)
3 (2–8) 15 (12.5 %)
3 (1–10) 14 (13.1 %)
0 0
3 (2–4) 1 (7.7 %)
stenosis or occlusion. Transthoracic echocardiography was normal; transesophageal echocardiography was contraindicated by persistent arousal disorders. She was transferred to the neurology department on day 3 and was subsequently discharged to a nursing home.
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Fig. 2 Cerebral computed tomography (CT) and magnetic resonance imaging (MRI) findings in our patients, demonstrating bilateral paramedian thalamic infarction by occlusion of the artery of Percheron. Panel a (Patient 1): CT, low-density in both paramedian thalamic areas (white arrows). Panel b (Patient 1): MRI, diffusionweighted imaging sequence showing high-intensity foci in the right peduncle (white arrows). Panel c (Patient 1): MRI, diffusion-weighted imaging sequence showing high-intensity foci in both paramedian thalamic areas (white arrows). Panel d (Patient 1): MRI, fluidattenuated inversion recovery (FLAIR) sequence showing high-
intensity foci in both paramedian thalamic areas (white arrows). Panel e (Patient 2): MRI, diffusion-weighted imaging sequence showing high-intensity foci in both paramedian thalamic areas (white arrows). Panel f (Patient 2): MRI, fluid-attenuated inversion recovery (FLAIR) sequence showing high-intensity foci in both paramedian thalamic areas (white arrows). Panel g (Patient 3): MRI, diffusionweighted imaging sequence showing high-intensity foci in both paramedian thalamic areas (white arrows). Panel h (Patient 3): MRI, fluid-attenuated inversion recovery (FLAIR) sequence showing highintensity foci in both paramedian thalamic areas (white arrows)
Patient 2
from extensive atheroma plaques of the vertebro-basilar system arteries seen on the transcranial Doppler. Aspirin therapy was initiated. Her neurological status improved rapidly and she was extubated on day 4, reintubated because of dyspnea due to laryngeal edema, and finally successfully extubated on day 8. At transfer to the neurology ward, she had marked right ptosis, confusion, and hypersomnia. She was discharged home. At follow-up 1 year later, she had a persistent attention deficit but was able to live independently.
This 67-year-old woman with an unremarkable medical history suddenly lost consciousness while receiving manipulation therapy from her osteopath. She had a GCS score of 4, bilateral tight myosis, and appropriate responses to nociceptive stimuli except for internal rotation of the left shoulder. She had no other organ dysfunctions. She was promptly intubated at the scene by the prehospital emergency team and transferred to our hospital. Cerebral CT without contrast performed at hospital admission was normal, as were the cerebrospinal fluid analysis and electroencephalogram. Cerebral MRI on day 1 showed a recent bilateral paramedian thalamic infarction (Fig. 2e, f). No evidence of supra-aortic artery dissection was found on cervical fat-saturated T1 MRI sequences or by cervical Doppler. Transesophageal echocardiography showed no signs of embolic heart disease. Extensive laboratory tests were unremarkable. The stroke was ascribed to embolism
Patient 3 This 72-year-old woman with a history of hypertension, dyslipidemia, bilateral breast cancer, and lower limb deep vein thrombosis was found at home by her husband with impaired consciousness and snoring. Upon examination at home by the prehospital emergency team she had a GCS score of 10, no focal neurological signs, and appropriate motor responses to nociception. She initially had no other
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organ dysfunctions. Her blood glucose level and flumazenil test were normal. She promptly required endotracheal mechanical ventilation because of worsening respiratory impairment with apnea during transport to the hospital. Emergent cerebral CT without contrast upon hospital arrival and extensive blood tests were normal. Within the first day after ICU admission, her consciousness improved and her respiratory rate became regular, allowing extubation. Her GCS score fluctuated from 12 to 14 and she had confusion, spatial–temporal disorientation, hypersomnia, bilateral ptosis, and vertical ocular motility disorders. Cerebral MRI on day 3 revealed recent bilateral and symmetric thalamic stroke with extension to the highest part of the cerebral peduncles, a pattern characteristic of AOP occlusion (Fig. 2g, h). Aspirin therapy was started. Transthoracic and transesophageal echocardiography showed no evidence of embolic heart disease. She was not re-evaluated for recurrence of deep venous thrombosis but a bubble study during echocardiography eliminated a patent foramen ovale. There was no dissection of the supraaortic or intracranial vertebral, basilar, or posterior cerebral arteries by cervical Doppler or MRA. She was discharged home. At follow-up 1 year later, she had persistent hypersomnia and bilateral ptosis.
Literature Review Patient characteristics are shown in Table 1. There were 52 women and 68 men, with a median age of 64 years (IQR, 53–72). Co-morbidities were present as follow: hypertension in 34 %, diabetes in 17 %, atrial fibrillation in 17 %, and dyslipidemia in 16 %. The most clinical features were dominated by neurological signs up to 92 % of cases (consciousness impairment and/or focal neurological signs), ophthalmological signs up to 64 % of cases (abnormal light reflexes and/or ocular motility and/or ptosis), and neuropsychological abnormalities up to 42 % of cases (memory deficit, language disorders, behavioral disturbance, and executive function disorders). Some patients also experienced psychiatric disorders in 16 % and respiratory or cardiovascular signs in 12 and 3 %, respectively. All patients underwent cerebral imaging. CT and MRI were performed in 57 and 64 % of patients, respectively. Origin of stroke was predominantly attributed to cardio embolism mechanism but remained undetermined in 69 % of cases. Findings from the literature review did not allow identifying consistent criteria for ICU admission. Eighty percent of patients with coma did not go to the ICU, and the ICU patients had better GCS scores. The ICU patients more often had respiratory and cardio vascular signs, but still only less than one-fifth had such signs. Ventilatory support with mechanical ventilation was required in all ICU patients.
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Discussion Our analysis of 120 patients with AOP occlusion, including 13 who required ICU admission, provides a detailed picture of this condition and of its outcome. When present, the coma resolves rapidly, although other abnormalities such as hypersomnia, attention deficit, motor impairments, and ocular motility disorders may persist in the long term. The mechanism of occlusion remains unclear in most cases; when determined, it is usually cardioembolism. Bilateral paramedian thalamic infarction by AOP occlusion is a rare cause of coma in middle-aged or elderly patients. Males and females are equally affected. Many patients have cardiovascular risk factors or embolic heart disease. Consciousness impairment is the rule but may range from drowsiness to a deep coma. Other abnormalities may include ophthalmological and neuropsychological abnormalities and respiratory and cardiovascular dysfunctions. A careful interview of the family for evidence of abnormalities before the onset of consciousness impairment may assist in the diagnosis. The diagnosis of AOP occlusion is dependent on cerebral imaging studies, chiefly MRI, as CT findings may be normal [11]. Whereas CT may be easier to obtain first, MRI must be performed, either as the first or as the second imaging study, in cases of recognition of this typical thalamic syndrome. Ischemic lesions of the medial areas of both thalami are seen, with or without rostral mesencephalic involvement [2]. The midbrain ‘‘V’’ sign is a high-intensity signal on axial FLAIR and diffusion-weighted images along the pial surface of the midbrain in the interpeduncular fossa. This sign has been reported in 67 % of patients with AOP occlusion [2]. Importantly, angiography is not required to document AOP occlusion. The main differential diagnosis is bilateral thalamic venous infarction complicating internal cerebral vein thrombosis [11, 13, 17]. Other rarer differential diagnoses include Wernicke encephalopathy, extrapontine myelinolysis, and Creutzfeldt-Jakob disease [11]. Ideally, MRI should be coupled with 3D TOF-MRA of the carotid, vertebral, basilar, and posterior cerebral arteries to rule out basilar artery occlusion [11]. Transcranial Doppler of the carotids and supra-aortic trunks is also useful. Other etiologic investigations include extensive blood tests for hypercoagulability, hematological disorders, and nonatherosclerotic vasculopathies such as systemic vasculitis. Transthoracic and transesophageal echocardiography may show a cardiac abnormality associated with systemic embolism, such as patent foramen ovale. Finally, a Holter ECG is useful to look for cardiac arrhythmias associated with embolism. Despite these investigations, the cause of AOP occlusion often remains unidentified. Embolic heart disease is the only commonly identified cause; [15, 18] all other causes are rare [8, 11, 19]. In
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particular, large-artery atherosclerosis and small-artery occlusion are exceedingly rare causes of AOP occlusion [2]. Interestingly, atypical causes have also been reported such as infectious causes after fulminant pneumococcal meningitis [20] or as iatrogenic causes due to basilar artery aneurysm clipping or coiling [21], due to arterial catheterizations (including cerebral and coronary [22] ) or due to transsphenoidal resection of a pituitary adenoma [23]. An obstacle to the optimal management of AOP occlusion is the limited availability of MRI, which often results in diagnostic delays ranging from several hours to several days. In one patient, early MRI was negative [9]. Thrombolytic management has been reported in only two patients: one received intraarterial thrombolysis during angiography [24] and the other venous thrombolysis [11]. In addition to our three cases, only ten other cases requiring ICU management have been reported [6, 8, 10–13, 21]. The coma resolves rapidly, usually allowing extubation within a few days. Even when ICU admission is required the mortality rate is low compared to patients with other forms of stroke requiring endotracheal mechanical ventilation [14]. In stroke patients who required mechanical ventilation, 1-year mortality rates ranged from 40 to 70 % [25–29], and cognitive impairments persisted in 63–75 % of survivors [26, 28]. The outcomes of ischemic stroke are largely governed by the site of the arterial occlusion. Malignant middle cerebral artery infarction has a particularly grim prognosis. Finally, intracerebral complications such as elevated intracranial pressure and malignant brain edema can adversely impact the neurological prognosis. Interestingly, we found that most patients with AOP were not managed in the ICU admission, whereas mortality was substantially higher in patients without ICU admission. Surprisingly, findings from the literature review did not allow identifying consistent criteria for ICU admission. Studies have established that management in specialized stroke units and neurocritical care units is associated with better outcomes [14, 30]. This finding is taken into account in the latest guidelines for the early management of patients with acute ischemic stroke [14]. Our study has several limitations. First, the extent to which our findings apply to the full spectrum of patients with bilateral paramedian thalamic infarction due to occlusion of the artery of Percheron is unclear. Patients were analyzed among 55 articles over a 40-year period, yielding a great variability in the cases description and in the radiologic technology used for diagnosis. Moreover, earlier described patients were managed before the neurocritical care era that could explain a higher mortality rate. Finally, prognosis described only relates to published reports, which likely have an inherent bias as worse cases and misdiagnosed cases are unlikely to be published.
In conclusion, bilateral paramedian thalamic infarction due to AOP occlusion can result in life-threatening complications requiring ICU admission. The typical clinical presentation combines consciousness impairment, ophthalmological and neuropsychological signs, and respiratory and cardiovascular dysfunctions. MRI with MRA should be performed promptly to establish the diagnosis, as CT may be normal initially. The rapid reversibility of the coma in many cases and the low-mortality rate associated with AOP occlusion warrant full-code ICU management. Acknowledgments We thank A. Wolfe MD for helping to prepare the manuscript. We received no funds for this study. Conflict of interest interests exist.
The authors have declared that no competing
Disclosures of Authors Financial Relationships Relevant to the Study Nathalie Zappella: reports no disclosures, Sybille Merceron: reports no disclosures, Chantal Nifle: reports no disclosures, Julia Hilly-Ginoux: reports no disclosures, Fabrice Bruneel: reports no disclosures, Gilles Troche´: reports no disclosures, Yves-Sebastien Cordoliani: reports no disclosures, Jean-Pierre Bedos: reports no disclosures, Fernando Pico: reports no disclosures, Stephane Legriel: reports no disclosures.
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