Bithalamic Infarct Revisited: Clinical, Imaging, Neuropsychological Profile and Prognosis

The bilateral thalamic infarcts are a particular entity by their clinical presentations, neuropsychological, etiologic and prognostic. We report here the presentations of 19 consecutive cases collected at University Teaching Hospital of Limoges. All patients underwent clinical evaluation, neuropsychological (only some of them), a diagnostic imaging and a full workup. A follow-up was performed for certain patients These 19 patients including 11 women, mean age 65.6 years (+/14.0 years), 13 were hypertensive. Clinically 84.2% had oculomotor disorders and 73.7% of vigilance disorders. Seven patients had motor problems that have persisted for two days in one. In territorial terms, 17 had bilateral paramedian infarction including 10 with a stem associated injury; 1 patient had a heart attack in the paramedian and tubero-thalamic territory and the last patient had tubero-thalamic and thalamo-geniculated infarction. On the etiological among the stroke patients bithalamique paramedian, 9 patients had a disease of the small arteries and March 1 cardioembolic infarction. Neuropsychological disorders in patients examined were marked by disorder of episodic memory, working, executive dysfunction, speech disorders. After a mean follow up of 35 months and among all patients with bilateral thalamic stroke 5 patients had died. Our series confirms some data in the literature on the evolution of these heart attacks and suggests that they are mainly topography paramedian, due to small artery disease and have a particular neuropsychological outcome.


Introduction
The first anatomo-clinical descriptions of thalamic infarcts have been made for more than a century [1]. The interest in their description lies in the particularity of the arterial vascularization of the thalamus [2] with a polymorphism of their different vascular syndromes [3]. Although unilateral thalamic infarctions are common, bilateral thalamic attacks are rare. Pure thalamic infarction accounts for approximately 1.9% of cerebral infarctions [4]. Bilateral infarction accounts for only 0.6% [5]. Several clinical pictures have been reported in relation to bilateral thalamic infarction [6][7][8]. Compared to unilateral thalamic infarction, bilateral thalamic infarction has a worse prognosis because of the neuropsychological disorders and cognitive sequelae that they generate [7,9,[10][11][12][13]. Their diagnosis, previously based on anatomo-clinical data, is made easier with the use of CT-scan and especially cerebral magnetic resonance imaging (MRI).
We report a consecutive series of 19 patients with documented bilateral thalamic infarction.
We aimed to describe the different clinical presentations, the radiological aspects, the neuropsychological profile and the prognosis of these infarcts.

Type of Study
This is a retrospective descriptive study of consecutive cases of documented bithalamic cerebral infarction at imaging.

Patients
From the admission register of the neurology department of the University Hospital of Limoges from January 1st, 2002 to July 31st, 2009, we selected all the patients hospitalized for a cerebrovascular accident. All patients with recent and simultaneous thalamic bilateral infarction documented with cerebral imaging (CT or MRI) are included in this study regardless of clinical presentation and outcome.

Evaluation
A clinical evaluation was performed in all patients at admission with a detail of the neurological examination on the disorders of the vigilance, oculomotors, sensitive, a detailed neuropsychological evaluation was carried out in the patients able to benefit from it by a neuropsychologist and evaluated disorders of working memory, episodic memory, language, executive functions and other cognitive functions.
Cerebral MRI was performed in all patients with no contraindications. It was performed by using a Siemens 1.5 Tesla machine and included diffusion (DWI), FLAIR, T1 and T2 sequences and T2 * gradient echo sequence. A TOF (Time-of-flight) sequence was performed at the same time for a study of the Willis polygon. In parenchymal sequencies, thin sections 5 mm thick were made. In the presence of a contraindication to MRI, a CT scan was performed to confirm the diagnosis.
The etiological assessment included: a) Electrocardiogram (EKG). b) Doppler ultrasound of supra-aortic arteries. c) A biological assessment: glycaemia, electrolyte count, urea creatinine, blood count, hemostasis assessment. Depending on the case, the etiological assessment was completed by a cardiac echocardiography (transthoracic or trans esophageal), a continuous ECG recording of 24h and an angio-MRI of the supra-aortic trunks with injection of contrast medium or a cerebral arteriography.

Data Collection
Clinical data collected included age, sex, symptoms, neurological deficit as assessed by NIHSS score, Mini Mental State Examination (MMSE). Vascular risk factors were also collected: high blood pressure (antihypertensive medication or blood pressure above 140 / 90mmHg before hospitalization); diabetes (fasting glucose> 1.26g / l or concept of taking antidiabetic treatment), hypercholesterolemia (total cholesterolemia> 6.5mmol / l or taking lipid-lowering agent), smoking, coronary history (myocardial infarction, angina, coronary revascularization) history of stroke or transient ischemic attack; atrial fibrillation).
The etiological classification adopted was TOAST [14]. Imaging was reviewed by a neuroradiologist, blinded to clinical data, to classify infarcts: the location of each side according to the territory concerned (anterior or tuberothalamic, paramedian, infero-lateral or thalamogeniculated, posterior or posterior choroid) according to the classification adopted by Bogousslavsky et al. [7]. Neuropsychological assessment data were collected and classified according to the classical pattern described in the literature [7].
The follow-up data were collected: to become, the RANKIN score modified at the hospital discharge, as well as remotely. For this purpose, all patients, their relatives (parents) or doctor as appropriate were recalled to specify the monitoring data.

Data Analysis
Data was processed and analyzed with SPSS 8.0 software. Given the small size of the sample, a descriptive analysis was performed with the qualitative variables their percentage and for the quantitative variables their mean with standard deviation.

General Data
From January 1, 2002 to July 31, 2009, 3,027 patients were hospitalized in the ward for an ischemic stroke. Of these cases, nineteen patients had a recent, simultaneous, bithalamic infarction, which was documented by brain imaging. The bithamic infarct represented 0.63% of all ischemic stroke. There are 11 women and 8 men. They were 32 to 81 years old with an average age of 65.6 +/-14.0 years. The frequency of risk factors was: 68.5% for high blood pressure, 15.8% for diabetes, 15.8% for smoking, 63.2% for dyslipidemia 15.8% for atrial fibrillation and one patient (5.3%) had a history of myocardial infarction.

Clinical Presentation
Clinically, oculomotor disorders and vigilance disorders (ranging from drowsiness to coma) were the most common signs. The diagnosis time of infarction ranged from 0 to 120 hours with an average of 27.4 hours +/-35.4. Seven patients had motor hemiparesis disorders, which decreased in 6 of them in a few hours and in two days for one). The frequency of clinical signs is summarized in Table 1.

Topography
Topographically 17 patients had bilateral paramedian infarction, 10 of which had an associated mesencephalic lesion; 1 patient had an infarct in the paramedian and tuberothalamic territory and the last patient had a tuberothalamic and thalamogeniculate infarction. The figures 1, 2 and 3 showed some example of this data.
The clinical and etiological characteristics of patients with bilateral paramedian infarction are summarized in Table 2 and the presentations of each patient in Table 3.

Special Cases
The patient with a left paramedian infarction associated with a right tuberothalamic infarction was a 49-year-old man, hospitalized hypertensive for rapid onset of vigilance disorder with mydriasis of the left eye. The evolution is marked by a rapid worsening of the picture with increased alertness disorders and a decerebration reaction requiring intubation and artificial ventilation followed by a tracheotomy. The evolution was marked by a progressive awakening and a quadriparetic patient with a disappearance of mydriasis and appearance of a ptosis of the right eye. This patient had a normal cerebral perfusion scintigraphy. The patient became bedridden and died 57 months later. To note the presence on the brain scanner of this patient of the associated protuberant and peduncular lesions.
The patient with lesions in the right thalamo-geniculated and left tubero-thalamic territories was 32 years old, with the only history of 10-pack smoking. She was hospitalized for a diplopia of the left eye with a significant decrease in painless visual acuity. She presented on examination vertical diplopia, an attack of the left common oculomotor nerve with disorders of the convergence without intrinsic attack. Explorations for inflammatory pathology (lumbar puncture, visual evoked potentials, cerebral MRI) were negative. MRI brain confirmed the diagnosis of bithalamic infarction with associated mesencephalic involvement. Etiological investigations (transesophageal echocardiography, holter-ECG, Ultrasound imaging of the vessels of the neck, thrombophilia assessment and cerebral arteriography) were non-contributory. The evolution was marked by a complete recovery in 3 weeks. After 30 months of follow-up, the patient presented no recurrence and no sequelae.

Neuropsychological Profile
Five patients with paramedian bithalamic stroke had a detailed neuropsychological assessment. These are patients 4, 7, 8, 9, 17. The patient 4 had a 9/30 MMSE, episodic, autobiographical, work-related memory disorders, significant executive dysfunction, and visuospatial disorders. She also had an important lack of word as well as reflexive, visuoconstructive and ideomotor apraxia. She was also depressed.
The patient 7 had an alteration of subcortical episodic memory, a decrease in verbal fluency with a lack of the word, and was somewhat psychomotor retarded. Patient 8 had a MMSE at 20/30, some episodic memory disorders with anterograde amnesia, verbal aspontaneity as well as perseveration phenomena.
The patient 9 had episodic memory disturbances with discrete disturbances of working memory, verbal and visual memory. There was also an executive dysfunction with perseverations, a reduction of verbal fluency, a lack of words with semantic paraphasia. She was easily irritable.
The patient 17 had an overall impairment of memory including episodic memory, working memory. There was also temporo-spatial disorientation, athymhormy, indifference and verbal aspontaneity, joviality sometimes alternating with apathy. The executive dysfunction was very marked. The language was disturbed with semantic paraphasies unrelated to the images. It presented significant visuospatial disorders with constructive apraxia. The data in this report are summarized in Table 4.

Prognosis and Becoming of Patients
Complete follow-up was performed in 14 patients with follow-up duration ranging from 2 to 94 months after cerebral infarction. The median follow-up was 33 months. At the time of discharge 66.7% of the patients were independent (RANKIN<2). No recurrence was observed during follow-up.
At the end of the follow-up, 5 patients died after an average follow-up of 35 months.

Discussion
Our study reports the clinical, radiological and neuropsychological pattern of 19 consecutive patients with bithalamic ischemic stroke. The bilateral paramedian location was the most common with 89.5% of patients. Etiologically it was mainly small artery disease. However, this study has some limitations inherent to retrospective studies such as lack of data for some patients (especially neuropsychological), non-regular monitoring of all patients. In our series, the most commonly observed clinical signs were oculomotor disorders and vigilance disorders (from drowsiness to coma). This frequency of vigilance disorders was previously reported by many authors in paramedian infarcts [6,8,15]. These disorders of alertness were all the more severe as mesencephalic involvement was associated. This alteration of vigilance is related to the alteration of the ascending activating reticular formation and its cortical projections through intra-laminar thalami nuclei [16]. Oculomotor disorders were also common in our patients. According to several authors, these disorders could be explained by an impairment of the supranuclear pathways of oculomotricity and / or at the level of the posterior longitudinal strip or even by mesencephalic involvement [3].
Vascular most (89.5%) of myocardial infarctions were in the bilateral paramedian territory. This frequency is well above the 50% reported by Kumral et al. [5] in their series of 16 patients. The paramedian character of the bithalamic infarction is the consequence of the vascularization of the thalamus. Infarctions in the bilateral paramedian territory can be explained by the occlusion of the paramedian arteries of the thalamus (from the P1 segment of the posterior cerebral artery) when these two arteries are born from a single pedicle, which is the case in a third of subjects Sometimes, in the absence of a tubero-thalamic artery arising from the posterior communicating artery, the territory supported by this artery becomes vascularized by the paramedian artery of the thalamus, whose occlusion then generates ischemia and greater clinical signs. Etiologically, small artery disease was most commonly found in our series with more than half of all patients. This frequency is below 62.5% (10/16) of small artery disease reported by Kumral et al. [5]. This high frequency is reported by most authors [5,17]. However, in their series of 12 patients with combined thalamic infarction (polar and paramedian) with 3 cases of paramedian, Perren et al. [18] report only one case of small artery disease.
On the neuropsychological level only five patients had benefited from a detailed assessment. This is inherent in the retrospective collection of data and the lack of a protocol dedicated to the study of these patients. However some relevant information can be learned. All patients tested had memory problems and more frequently episodic memory and / or working memory. The memory disorders so frequently reported in the literature are related to involvement of the mamillo-thalamic tract (Vicq d'Azyr beam) [3,5,8] as well as nuclei of the anterior thalamus (involved in the Papez circuit). especially when the tubero-thalamic territory is affected causing long-term memory problems [19] but also anterograde and retrograde memory disorders as well as confabulations [20,21]. Cases of Korsakoff syndrome have been reported with thalamic and even bithalamic infarcts [22]. In the case of paramedic infarction, these memory disorders seem to be related to a disconnection of the tonsils and dorso-median nuclei of the thalami. The five patients tested had executive dysfunction. This has been reported by some authors [23][24][25]. And according to Van der Werf et al. [20] an impairment of at least two nuclei seems necessary to observe executive dysfunction. This could account for the frequency of a dysexecutive syndrome in all patients tested in our series who all have a bithalamic infarction. In addition anatomical studies have shown connections between certain thalamic nuclei and the prefrontal cortex explaining an executive dysfunction in bilateral thalamic lesions [26], which would be related to a fall in blood flow in the prefrontal cortex [27]. It would have been more interesting to test all the patients but the retrospective character of the study did not allow us to affirm the constancy of the memory disorders and the dysexecutive syndrome constituting the classic thalamic dementia.

Conclusion
Bithalamic infarctions are mainly of paramedian topography and are mainly manifested by disturbances of alertness (all the more so because there is an associated peduncular localization), as well as oculomotor disorders. Small artery disease is the main etiology in our series. Neuropsychologically, memory and executive function disorders are the disorders found consistently in all patients tested. These data are comparable to data in the literature and suggest that the prognosis of bithalamic infarction is mainly neuropsychological.