Secondary thalamic atrophy related to brain infarction may contribute to post-stroke cognitive impairment.

BACKGROUND AND PURPOSE: The thalamus is a key brain hub that is globally connected to many cortical regions. Previous work highlights thalamic contributions to multiple cognitive functions, but few studies have measured thalamic volume changes or cognitive correlates. This study investigates associations between thalamic volumes and post-stroke cognitive function. METHODS: Participants with non-thalamic brain infarcts (3-42 months) underwent MRI and cognitive testing. Focal infarcts and thalami were traced manually. In cases with bilateral infarcts, the side of the primary infarct volume defined the hemisphere involved. Brain parcellation and volumetrics were extracted using a standardized and previously validated neuroimaging pipeline. Age and gender-matched healthy controls provided normal comparative thalamic volumes. Thalamic atrophy was considered when the volume exceeded 2 standard deviations greater than the controls. RESULTS: Thalamic volumes ipsilateral to the infarct in stroke patients (n=55) were smaller than left (4.4 ± 1.4 vs. 5.4 ± 0.5 cc, p < 0.001) and right (4.4 ± 1.4 vs. 5.5 ± 0.6 cc, p < 0.001) thalamic volumes in the controls. After controlling for head-size and global brain atrophy, infarct volume independently correlated with ipsilateral thalamic volume (ß= -0.069, p=0.024). Left thalamic atrophy correlated significantly with poorer cognitive performance (ß = 4.177, p = 0.008), after controlling for demographics and infarct volumes. CONCLUSIONS: Our results suggest that the remote effect of infarction on ipsilateral thalamic volume is associated with global post-stroke cognitive impairment.

Rivaroxaban for Prevention of Covert Brain Infarcts and Cognitive Decline: The COMPASS MRI Substudy.

BACKGROUND AND PURPOSE: Covert brain infarcts are associated with cognitive decline. It is not known whether therapies that prevent symptomatic stroke prevent covert infarcts. COMPASS compared rivaroxaban with and without aspirin with aspirin for the prevention of stroke, myocardial infarction, and vascular death in participants with stable vascular disease and was terminated early because of benefits of rivaroxaban 2.5 mg twice daily plus aspirin over aspirin. We obtained serial magnetic resonance imagings and cognitive tests in a consenting subgroup of COMPASS patients to examine treatment effects on infarcts, cerebral microbleeds, and white matter hyperintensities. METHODS: Baseline and follow-up magnetic resonance imagings were completed in 1445 participants with a mean (SD) interval of 2.0 (0.7) years. Whole-brain T1, T2 fluid-attenuated inversion recovery, T2* sequences were centrally interpreted by blinded, trained readers. Participants had serial measurements of cognition and function. The primary end point was the proportion of participants with incident covert infarcts. Secondary end points were the composite of clinical stroke and covert brain infarcts, cerebral microbleeds, and white matter hyperintensities. RESULTS: At baseline, 493 (34.1%) participants had infarcts. Incident covert infarcts occurred in 55 (3.8%) participants. In the overall trial rivaroxaban plus aspirin reduced ischemic stroke by 49% (0.7% versus 1.4%; hazard ratio [95% CI], 0.51 [0.38-0.68]). In the magnetic resonance imaging substudy the effects of rivaroxaban+aspirin versus aspirin were: covert infarcts: 2.7% versus 3.5% (odds ratio [95% CI], 0.77 [0.37-1.60]); Covert infarcts or ischemic stroke: 2.9% versus 5.3% (odds ratio [95% CI], 0.53 [0.27-1.03]). Incident microbleeds occurred in 6.6% of participants and 65.7% of participants had an increase in white matter hyperintensities volume with no effect of treatment for either end point. There was no effect on cognitive tests. CONCLUSIONS: Covert infarcts were not significantly reduced by treatment with rivaroxaban and aspirin but estimates for the combination of ischemic stroke and covert infarcts were consistent with the effect on ischemic stroke in the overall trial. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01776424.

Blepharospasm With Photophobia Secondary to Midbrain Tuberculoma and Thalamic Infarct.

INTRODUCTION: Blepharospasm is a type of focal dystonia and categorized into primary and secondary forms, based on whether or not a cause can be established. Secondary blepharospasm is uncommon and can be associated with underlying brain lesions. Photophobia is a prominent complaint in blepharospasm patients. We are reporting a case of secondary blepharospasm with photophobia in a patient who had underlying midbrain tuberculoma and thalamic infarcts. This type of presentation has not been reported to the best of our knowledge. CASE REPORT: A 26-year-old man presented to us with the complaint of increased blinking and involuntary closure of both eyes for 1 year. He had a past history of tubercular meningitis 16 years back when he presented with bilateral ptosis, left up gaze palsy and right hemiparesis suggestive of Weber syndrome. His magnetic resonance images of the brain were suggestive of multiple intracranial tuberculomas, thalamic infarcts, and noncommunicating hydrocephalus. Following treatment he recovered significantly with no residual neurological deficit except mild bilateral ptosis. His recent magnetic resonance images of the brain was suggestive of calcified granuloma in the midbrain and chronic left thalamic lacunar infarcts. He was treated with injection Onabotulinum toxin and his symptoms improved significantly. CONCLUSIONS: Our patient had tuberculoma in the midbrain and chronic infarcts in the thalamus, and both lesions may cause blepharospasm and photophobia independently, so it is difficult to ascertain the causative lesion in our patient. However, it is possible that these heterogenous lesions are all part of a single functionally connected brain network and further studies are required to confirm this hypothesis.

Refined Sphenopalatine Ganglion Stimulator Placement and Intensity Setting to Augment Blood Flow and Neurologic Function.

Background and Purpose- Two large, randomized trials indicated that sphenopalatine ganglion (SPG) stimulation improves final disability outcome in acute anterior circulation patients with ischemic stroke with confirmed cortical involvement. This study evaluated 2 refinements in SPG stimulation treatment technique: (1) SPG electrode placement with real-time optical tracking guidance; and (2) stimulation intensity comfortable tolerance level selection using non-noxious facial physiological markers. Methods- This study was a single, active arm trial at 4 centers, enrolling patients with anterior circulation ischemic stroke, National Institutes of Health Stroke Scale 1 to 6 including arm weakness subitem score ≥1, not receiving recanalization therapies, and within 24 hours of onset. Stimulation level was set based on ipsilateral facial tingling sensation or lacrimation. SPG stimulation effects were assessed by measuring volumetric blood flow in the ipsilateral common carotid artery by ultrasound and grasp and pinch strength in the affected hand before and during stimulation, and by change in National Institutes of Health Stroke Scale from day 1 to 7. Results- Among 50 enrolled patients, age was median 66 years (interquartile range, 60-74), 44% were female, National Institutes of Health Stroke Scale median was 5 (interquartile range, 4-5), and median onset-to-screening time was 18 hours (interquartile range, 9-20). Median implantation skin-to-skin time was 4 minutes (interquartile range, 3-7), and all 50 implants were placed correctly. Comfortable tolerance level was found based on physiological biomarkers in 96% of patients, including 86% in the optimal, low-medium intensity range. SPG stimulation significantly increased common carotid artery peak systolic and end-diastolic blood flow (44%, P<0.0001; and 52%, P<0.0001) and improved pinch strength (42%, P<0.0001) and grasp strength (26%, P<0.0001). Degree of National Institutes of Health Stroke Scale recovery by day 7 was greater than in matched historic controls, median 75% versus 50%, P=0.0003. Conclusions- SPG stimulator placement with real-time optical tracking guidance was fast and accurate, and selection of stimulation intensity levels based on non-noxious facial tingling and lacrimation was feasible in nearly all patients. SPG stimulation led to cervico-cranial blood flow augmentation and improved hand motor function. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT03551093.

Sudden onset of sleep caused by hypothalamic infarction: a case report.

BACKGROUND: Hypothalamic lesions, such as tumors and demyelinating diseases, reportedly cause abnormal sleepiness. However, stroke involving the hypothalamus has rarely been described. Here, we report a patient with infarction restricted to the hypothalamus who presented with sudden onset of sleep. CASE PRESENTATION: A 42-year-old woman with a history of migraine without aura presented with irresistible sleepiness and developed several episodes of sudden onset of sleep. Neurological examinations were unremarkable except for partial left Horner syndrome. Brain magnetic resonance imaging (MRI) revealed a high-intensity lesion restricted to the left hypothalamus on diffusion-weighted and fluid-attenuated inversion recovery MRI images. Cerebrospinal fluid (CSF) orexin-A levels obtained on hospital day 3 after her sleepiness had resolved were normal (337 pg/mL; normal > 200 pg/mL). Serum anti-nuclear and anti-aquaporin 4 (AQP4) antibodies and CSF myelin basic protein and oligoclonal band were negative. A small hypothalamic infarction was suspected, and the patient was treated with intravenous edaravone and argatroban, as well as oral clopidogrel. Three months later, there had been no clinical relapse, and the hypothalamic lesion had almost disappeared on follow-up MRI. No new lesion suggestive of demyelinating disease or tumor was observed. CONCLUSION: Hypothalamic stroke should be considered a cause of sudden onset of sleep.

[Acute global amnesia as an exclusive presenting symptom of thalamic infarct: a diagnostic challenge]. / Amnesia global aguda como forma exclusiva de presentacion de infarto talamico: un reto diagnostico.

INTRODUCTION: Isolated acute amnesia is an exceptional presenting symptom of thalamic stroke. This study analyses the clinical profile, the diagnosis, the treatment and the prognosis of these patients. CASE REPORTS: We conducted a retrospective review of the cases of thalamic infarct that presented exclusively as acute amnesia in our university tertiary hospital (n = 3) and a review of similar cases in PubMed (n = 20). 48% presented at least one risk factor of stroke (arterial hypertension, dyslipidaemia, diabetes mellitus, atrial fibrillation or a previous stroke). Amnesia was anterograde in three cases (13%) and global in the remaining 20 (87%). The infarct was detected in neuroimaging studies carried out within the first 24 hours in one patient (4%) and later in all the others; the average time until a diagnosis was established was 11 days. The initial CT scan was normal in five patients (22%). Eight cases (35%) required magnetic resonance imaging to detect the infarct. Of these, four subjects were studied directly with MR imaging. Amnesia clearly improved in eight patients (35%), and three of them (13%) made a full recovery. Fifteen patients (65%) presented mnemonic sequelae that interfered with their functional capacity. The clinical picture lasted less than 24 hours in two patients (9%). None of the cases received revasculisation therapy in the acute phase. CONCLUSION: The diagnosis of thalamic infarcts that begin exclusively with amnesia is very difficult and this has negative repercussions on their treatment in the acute phase. These infarcts can produce a functionally disabling memory deficit in a high percentage of patients.

TITLE: Amnesia global aguda como forma exclusiva de presentacion de infarto talamico: un reto diagnostico.Introduccion. La amnesia aguda aislada es una forma excepcional de presentacion del ictus talamico. Se analizan el perfil clinico, el diagnostico, el tratamiento y el pronostico de estos pacientes. Casos clinicos. Revision retrospectiva de los casos de infarto talamico que se presentaron exclusivamente como amnesia aguda en nuestro hospital terciario universitario (n = 3) y revision de casos similares en PubMed (n = 20). El 48% presentaba al menos un factor de riesgo de ictus (hipertension arterial, dislipidemia, diabetes mellitus, fibrilacion auricular o ictus previo). La amnesia fue anterograda en tres casos (13%) y global en los otros 20 (87%). El infarto se detecto en estudio de neuroimagen en las primeras 24 horas en un paciente (4%) y posteriormente en los demas, y la media de dias hasta el diagnostico fue de 11. La tomografia computarizada inicial fue normal en cinco (22%) pacientes. Precisaron estudio por resonancia magnetica ocho (35%) casos para detectar el infarto. De estos, cuatro sujetos se estudiaron directamente con resonancia magnetica. La amnesia presento una mejoria clara en ocho (35%) pacientes, y la recuperacion fue completa en tres (13%). Las secuelas mnesicas que interferian la capacidad funcional se presentaron en 15 pacientes (65%). La clinica persistio menos de 24 horas en dos pacientes (9%). Ningun caso recibio tratamiento revascularizador en fase aguda. Conclusion. Los infartos talamicos que comienzan de forma exclusiva con amnesia presentan notables dificultades diagnosticas que repercuten negativamente en su tratamiento en la fase aguda. Estos infartos pueden producir un deficit mnesico funcionalmente discapacitante en un porcentaje elevado de pacientes.

Persistent anterograde amnesia due to the artery of Percheron occlusion: a case report.

Bilateral thalamic infarction involving the artery of Percheron (AOP) can cause diagnostic difficulties due to the varying clinical presentations. AOP infarcts presented with isolated memory impairment are not common and the factors affecting the persistence of memory disorders are still unknown. A 41-year-old male patient was hospitalized with acute unconsciousness. MRI disclosed bilateral paramedian thalamic infarction The patient had isolated memory deficit and his anterograde amnesia continued without any change in the past decade. More cases might answer the questions concerning the intra- and extra-thalamic structures responsible for the amnesic syndrome and the factors affecting the persistence of the symptoms.

Novel cognitive insights from the first year after bi-thalamic infarct.

Neuropsychological consequences of bi-thalamic damage are scarcely known. This case study documents cognitive (in particular memory and executive) functioning in a man with a medial bi-thalamic infarct in the first year (8 and 12 months) post injury. NG showed persistent memory (including autobiographical) impairment, but improved executive functions at one year post injury. On a response inhibition task his speed of response improved but his ability to inhibit a "prepotent" automatic response declined, corresponding to an increase in behavioral disinhibition. Despite this, he showed intact performances on several social cognition tasks. This case contributes to our understanding of the role of the thalamus in mediating retrograde memory, executive, and social cognition functions.

Resolvin D2 protects against cerebral ischemia/reperfusion injury in rats.

Cerebral ischemia/reperfusion (I/R) injury is a critical factor leading to a poor prognosis for ischemic stroke patients. ω-3 fatty acid supplements taken as part of a daily diet have been shown to improve the prognosis of patients with ischemic stroke. In this study, we aimed to investigate the potential effects of resolvin D2 (RvD2), a derivative of ω-3 fatty acids, and its possible advantage on cerebral I/R injury in rats. Cerebral I/R caused by middle cerebral artery occlusion and reperfusion (MCAO/R) was established in Sprague-Dawley rats. First, in rats fed a regular diet, the MCAO/R stimulus led to a significant decrease in endogenous production of RvD2. Exogenous supply of RvD2 via intraperitoneal injection reversed MCAO/R-induced brain injury, including infarction, inflammatory response, brain edema, and neurological dysfunction. Meanwhile, RvD2 reversed the MCAO/R-induced decrease in the protein level of GPR18, which has been identified as a receptor for RvD2, especially in neurons and brain microvascular endothelial cells (BMVECs). Furthermore, RvD2 exerted rescue effects on MCAO/R-induced neuron and BMVEC death. Moreover, GPR18 antagonist O-1918 could block the rescue effects of RvD2, possibly at least partially though the GPR18-ERK1/2-NOS signaling pathway. Finally, compared with ω-3 fatty acid supplements, RvD2 treatment had a better rescue effect on cerebral infarction, which may be due to the MCAO/R-induced decrease in 5-lipoxygense phosphorylation and subsequent RvD2 generation. In conclusion, compared with ω-3 fatty acids, RvD2 may be an optimal alternative and complementary treatment for ischemic stroke patients with recanalization treatment.

Time perception impairment following thalamic stroke: A case study.

Impaired time perception is considered to be a relatively unusual and poorly understood consequence of brain injury. This paper presents a case study of altered time perception in JB, a 50-year-old woman who in 2011 had a small thalamic stroke affecting the right anteromedian region. We report on her subjective experience and present results from studies of retrospective timing (i.e., estimating how much time has passed and the clock time) and prospective timing (i.e., producing and reproducing intervals). The results showed that relative to neurologically healthy and brain-injured controls, JB had impaired retrospective timing and impaired prospective time reproduction. However, her prospective time production did not differ significantly from either of the control groups. We interpret this to mean that JB's essential timing functions are intact, and that rather, her time perception impairment stems from a problem in anterograde memory for time intervals. Further, we argue that unlike other cognitive domains, time perception alteration is neither anticipated nor evaluated in most patients, yet these impairments can have a remarkably serious impact on daily life. We encourage further investigation of this topic.

Intraoperative neurophysiologic monitoring (IONM) changes associated with a case of delayed thalamic infarct: Implications for postoperative management.

Treatment of cerebral aneurysms poses a risk of cerebral hemorrhage and/or ischemia; these potential sequelae are usually associated with changes in intraoperative neurophysiologic monitoring (IONM) modalities. Our case demonstrates a patient with significant changes in IONM during the treatment of a right posterior cerebral artery aneurysm who did not develop neurologic deficits until three days postoperatively. IONM changes can represent a guide in postoperative patient management and may pose grounds for closer monitoring of patients with IONM changes that do not develop immediate postoperative deficits.

Degeneration of paramedian nuclei in the thalamus induces Holmes tremor in a case of artery of Percheron infarction.

RATIONALE: Holmes' tremor is an uncommon neurologic disorder following brain insults, and its pathogenesis is undefined. The interruption of the dento-rubro-thalamic tract and secondary deterioration of the nigrostriatal pathway are both required to initiate Holmes' tremor. We used nuclear medicine imaging tools to analyze a patient with concurrent infarction in different zones of each side of the thalamus. Finding whether the paramedian nuclear groups of the thalamus were injured was a decisive element for developing Holmes' tremor. PATIENT CONCERNS: A 36-year-old woman was admitted to our department due to a bilateral paramedian thalamic infarction. Seven months after the stroke, a unilaterally involuntary trembling with irregularly wavering motions occurring in both her left hand and forearm. DIAGNOSIS: Based on the distinct features of the unilateral coarse tremor and the locations of the lesions on the magnetic resonance imaging (MRI), the patient was diagnosed with bilateral paramedian thalamic infarction complicated with a unilateral Holmes' tremor. INTERVENTIONS: The patient refused our recommendation of pharmacological treatment with levodopa and other dopamine agonists based on personal reasons and was only willing to accept physical and occupational training programs at our outpatient clinic. OUTCOMES: We utilized serial anatomic and functional neuroimaging of the brain to survey the neurologic deficit. A brain magnetic resonance imaging showed unequal recovery on each side of the thalamus. The residual lesion appeared larger in the right-side thalamus and had gathered in the paramedian area. A brain perfusion single-photon emission computed tomography (SPECT) revealed that the post-stroke hypometabolic changes were not only in the right-side thalamus but also in the right basal ganglion, which was anatomically intact. Furthermore, the brain Technetium-99m-labeled tropanes as a dopamine transporter imaging agents scan ( Tc-TRODAT-1) displayed a secondary reduction of dopamine transporters in the right nigrostriatal pathway which had resulted from the damage on the paramedian nuclear groups of the right-side thalamus. LESSONS: Based on the functional images, we illustrated that a retrograde degeneration originating from the thalamic paramedian nuclear groups, and extending forward along the direct innervating fibers of the mesothalamic pathway, played an essential role towards initiating Holmes' tremor.

Injury of the dentato-rubro-thalamic tract in patients with cerebellar infarct: Case report.

RATIONALE: Several studies using diffusion tensor tractography (DTT) have reported on injury in the dentato-rubro-thalamic tract (DRTT) in patients with brain injury. However, there is no study of injury in the DRTT following cerebellar infarct. We report on patients with injury in the DRTT following cerebellar infarct, demonstrated on DTT. PATIENT CONCERNS: Three patients with cerebellar infarct were enrolled in this study. Diffusion tensor imaging data were acquired at 3 weeks (patient 1) and 2 weeks (patients 2 and 3) after onset and the DRTT was reconstructed. The Scale for Assessment and Rating of Ataxiaand the Functional Ambulation Category were used for evaluation of ataxia and gait function. DIAGNOSES AND OUTCOMES: With clinical evaluation, patient 1 scored 18, patient 2 scored 22, and patient 3 scored 28 points on the Scale for Assessment and Rating of Ataxia. On the Functional Ambulation Category patient 1 scored 2, patient 2 scored 2, and patient 3 scored 1 point. DRTT abnormalities were as follows: discontinuation (the upper portion of the left DRTT in the patient 1), narrowing (the lower portion of the left DRTT in patient 2, and the whole right DRTT in the patient 3), and nonreconstruction (the left DRTT in the patient 3). LESSONS: Using DTT, we demonstrated injury in the DRTT in 3 patients with severe ataxia following cerebellar infarct. We believe that evaluation of the DRTT would be helpful in patients who develop ataxia following cerebellar infarct.

A case of double depressor palsy followed by pursuit deficit due to sequential infarction in bilateral thalamus and right medial superior temporal area.

BACKGROUND: We present a unique case of a patient who suffered two rare events affecting the supranuclear control, first of the vertical and second of the horizontal eye movements. The first event involved bilateral thalamic infarcts that resulted in double depressor palsy. The second event occurred 1 year later and it involved supranuclear control of horizontal eye movements creating pursuit deficit. CASE PRESENTATION: A 47-year-old male presented with complaints of diplopia upon awakening. He had atrial fibrillation, mitral valve regurgitation, aortic valve regurgitation, and a history of spleen infarction 1 year ago. His right eye was hypertrophic and right eye downgaze was limited unilaterally of equal degree in adduction and abduction. The patient was diagnosed with double depressor palsy of the right eye. Magnetic resonance imaging (MRI) of the brain showed an old infarction of the left thalamus, and diffusion MRI showed acute infarction of the right thalamus. The patient's daily warfarin dose was 2 mg and it was increased to 5 mg with cilostazol 75 mg twice a day. Seven weeks later, the patient's ocular movement revealed near normal muscle action, and subjectively, the patient was diplopia free. At follow-up 12 months later, the patient revisited the hospital because of sudden onset of blurred vision on right gaze. He was observed to have smooth pursuit deficit to the right side, and orthophoric position of the eyes in primary gaze. MRI of the brain showed an acute infarction in the right medial superior temporal area. CONCLUSIONS: The patient experienced very rare abnormal eyeball movements twice. This case highlights the importance of evaluating vertical movement of the eyes and vascular supplies when patients present with depressor deficit and supports the theory of a supranuclear function in patients who present with pursuit deficit.