Unique Subtype of Microglia in Degenerative Thalamus After Cortical Stroke.

BACKGROUND AND PURPOSE: Stroke disrupts neuronal functions in both local and remotely connected regions, leading to network-wide deficits that can hinder recovery. The thalamus is particularly affected, with progressive development of neurodegeneration accompanied by inflammatory responses. However, the complexity of the involved inflammatory responses is poorly understood. Herein we investigated the spatiotemporal changes in the secondary degenerative thalamus after cortical stroke, using targeted transcriptome approach in conjunction with histology and flow cytometry. METHODS: Cortical ischemic stroke was generated by permanent occlusion of the left middle cerebral artery in male C57BL6J mice. Neurodegeneration, neuroinflammatory responses, and microglial activation were examined in naive and stroke mice at from poststroke days (PD) 1 to 84, in both ipsilesional somatosensory cortex and ipsilesional thalamus. NanoString neuropathology panel (780 genes) was used to examine transcriptome changes at PD7 and PD28. Fluorescence activated cell sorting was used to collect CD11c+ microglia from ipsilesional thalamus, and gene expressions were validated by quantitative real-time polymerase chain reaction. RESULTS: Neurodegeneration in the thalamus was detected at PD7 and progressively worsened by PD28. This was accompanied by rapid microglial activation detected as early as PD1, which preceded the neurodegenerative changes. Transcriptome analysis showed higher number of differentially expressed genes in ipsilesional thalamus at PD28. Notably, neuroinflammation was the top activated pathway, and microglia was the most enriched cell type. Itgax (CD11c) was the most significantly increased gene, and its expression was highly detected in microglia. Flow-sorted CD11c+ microglia from degenerative thalamus indicated molecular signatures similar to neurodegenerative disease-associated microglia; these included downregulated Tmem119 and CX3CR1 and upregulated ApoE, Axl, LpL, CSF1, and Cst7. CONCLUSIONS: Our findings demonstrate the dynamic changes of microglia after stroke and highlight the importance of investigating stroke network-wide deficits. Importantly, we report the existence of a unique subtype of microglia (CD11c+) with neurodegenerative disease-associated microglia features in the degenerative thalamus after stroke.

A New Scoring System for Prediction of Underlying Vascular Pathology in Patients with Intracerebral Hemorrhage: The Modified Secondary Intracerebral Hemorrhage Score.

BACKGROUND: Secondary intracerebral hemorrhage (SICH) score is used to predict risk of intracranial hemorrhage (ICH) associated vascular lesions. However, it has low clinical utility in identifying patients without need for neurovascular imaging. This study aims to develop a modified scoring system to capture patients with low risk of underlying vascular pathology, thereby decreasing need for vascular imaging and its associated morbidity. METHODS: A retrospective analysis of 994 patients with atraumatic ICH over 8 years was conducted, excluding known underlying pathology, subarachnoid hemorrhage, or lack of vascular imaging. Using a multivariate logistic regression model, independent predictors of vascular pathology were identified and utilized toward developing a modified Secondary Intracerebral Hemorrhage (mSICH) score. RESULTS: Of 575 patients identified, 60 (10.4%) had underlying vascular etiology. Statistically significant predictors of vascular pathology included age; female sex; admission systolic blood pressure <160 mm Hg; locations other than basal ganglia, thalamus, pons, or midbrain; presence of high-risk imaging features; and proximity to large vessel-containing cisterns. The mSICH score correlated with an increasing incidence of vascular pathology [0-1 (0%), 9 (4.3%), 12 (9.7%), 21 (40.4%), 6 (33.3%), 8 (88.9%), and 4 (100%)] and had a significantly higher number of patients receiving scores with 0% incidence of vascular lesions compared with the SICH score [159 (27.6%) versus 12 (2.1%); P < 0.001)]. CONCLUSIONS: The mSICH score can more accurately predict risk of underlying vascular pathology of ICH and identify patients with lowest risk of vascular pathology. This may minimize the cost and associated risks of invasive cerebrovascular imaging.

Investigation of risk factors, topographic location and stroke mechanisms of unilateral isolated and posterior cerebral ARTERY thalamic infarcts.

BACKGROUND AND PURPOSE: In this study, we aimed to examine the risk factors, topographic features and stroke mechanisms of acute ischemic unilateral infarcts of thalamus. METHODS: Patient with isolated thalamic infarct and those with posterior cerebral artery (PCA) infarction who were admitted to our hospital between January 2014 and January 2017 with acute unilateral thalamic infarction (TI) were included in this study (isolated thalamic infarction/ isolated TI; thalamic and posterior cerebral artery infarction/PCA+TI). Demographic characteristics and vascular risk factors of the patients were determined. Thalamic infarct areas were recorded topographically as anterior, posteromedial, ventrolateral, posterolateral, more than one area, and variant areas. Stroke mechanism was determined according to the criteria of "Trial of Org 10172 in Acute Stroke Treatment" (TOAST). Patients with isolated TI and PCA TI were compared according to risk factors, stroke mechanism and infarct topography. RESULTS: Forty-three patients with a mean age of 63.3 ± 14.5 years were included in the study. Twenty-eight patients (60.1%) were found to have isolated TI and the remaining 15 patients (34.9%) had PCA+TI. 32.1% of patients with isolated TI had sensory symptoms on presentation, and 60% of patients with PCA-TI had sensorimotor symptoms. The mean age, the mean score on National Institutes of Health Stroke Scale (NIHSS) and the mean frequency of atrial fibrillation were higher in PCA+TI patients than in isolated-TI patients (p: 0.04, p: 0.004, p: 0.02 respectively). 32.6% of the patients had ventrolateral, 30.2% had posteromedial involvement. Ventrolateral topography was seen in 46.7% of the PCA+TI patients, while posteromedial topography was seen in 39.3% of the isolated-TI patients. 53.6% of the isolated-TI had small vessel disease etiology, while 40% of the PCA+TI had cardioembolic etiology, and the other 40% had large artery atherosclerosis. CONCLUSION: Our study showed that the most ommon stroke mechanism in patients with thalamic infarction is the small vessel disease. Isolated TI and PCA+TI patients differ in terms of etiologic mechanism and infarct topography. Variant territorial involvement and multiple area involvements can be quite common in thalamic infarcts.

Passive accessory joint mobilization in the multimodal management of chronic dysesthesia following thalamic stroke.

Study design: Case Report. Purpose: Stroke is the most common cause of long-term disability. Dysesthesia, an unpleasant sensory disturbance, is common following thalamic stroke and evidence-based interventions for this impairment are limited. The purpose of this case report was to describe a decrease in dysesthesia following manual therapy intervention in a patient with history of right lacunar thalamic stroke. Case description: A 66-year-old female presented with tingling and dysesthesia in left hemisensory distribution including left trunk and upper/lower extremities, limiting function. Decreased left shoulder active range of motion, positive sensory symptoms but no sensory loss in light touch was found. She denied pain and moderate shoulder muscular weakness was demonstrated. Laterality testing revealed right/left limb discrimination deficits and neglect-like symptoms were reported. Passive accessory joint motion assessment of glenohumeral and thoracic spine revealed hypomobility and provoked dysesthesia. Interventions included passive oscillatory joint mobilization of glenohumeral joint, thoracic spine, ribs and shoulder strengthening. Results: After six sessions, shoulder function, active range of motion, strength improved and dysesthesia decreased. Global Rating of Change Scale was +5 and QuickDASH score decreased from 45% to 22% disability. Laterality testing was unchanged. Conclusion: Manual therapy may be a beneficial intervention in management of thalamic stroke-related dysesthesia. Implications for Rehabilitation While pain is common following thalamic stroke, patients may present with chronic paresthesia or dysesthesia, often in a hemisensory distribution. Passive movement may promote inhibition of hyperexcitable cortical pathways, which may diminish aberrant sensations. Passive oscillatory manual therapy may be an effective way to treat sensory disturbances such as paresthesias or dysesthesia.

Recurring Thalamic Symptoms Due to Intracranial Dural Arteriovenous Fistula: Report of Unusual Case and Treatment Outcome.

BACKGROUND: Initial clinical presentation of dural arteriovenous fistula (DAVF) with predominantly thalamic symptoms is rare and has not been reported until now. CASE DESCRIPTION: A young child presenting with complaints of tinnitus and mild right hemiparesis was evaluated with an initial magnetic resonance imaging, which revealed a Borden type 2 DAVF in the right transverse sinus with retrograde venous drainage and cortical venous reflux. Flow-related small aneurysms were also noted in the left basal vein of Rosenthal (BVR). Two days later, his motor power deteriorated and he developed right hemisensory loss and severe thalamic pain. Aphasia was atypical and mimicked the transcortical type. Repeat imaging revealed expanding thrombosed aneurysm of BVR with mass effect and edema on thalamocapsular region. Initial antiedema measures reversed the neurologic deficits; however, they recurred, necessitating an urgent endovascular intervention. Angiogram revealed an extensive high-flow DAVF in the right transverse-sigmoid sinus and torcula with preferential retrograde venous drainage into deep veins and left BVR. He underwent staged embolization of DAVF, resulting in significant obliteration of shunt. Neurologic deficits improved in the postoperative period, and the patient remained clinically asymptomatic at 6 months of follow-up. CONCLUSIONS: DAVF presenting with recurrent predominantly thalamic symptoms is rare. Atypical transcortical aphasia rather than fluent aphasia is an unusual clinical manifestation of thalamic pathology and could result from the involvement of specific thalamic nuclei. Preferential high flow into BVR in the presence of venous anomalies could potentially induce architectural weakness of the venous wall and precipitate aneurysm formation. Embolization of the DAVF can potentially reverse this unusual neurologic condition.

Thalamic Diaschisis in Acute Ischemic Stroke: Occurrence, Perfusion Characteristics, and Impact on Outcome.

BACKGROUND AND PURPOSE: Ipsilateral thalamic diaschisis (ITD) describes the reduction of thalamic function, metabolism, and perfusion resulting from a distant lesion of the ipsilateral hemisphere. Our aim was to evaluate the perfusion characteristics and clinical impact of ITD in acute middle cerebral artery stroke, which does not directly affect the thalamus. METHODS: One hundred twenty-four patients with middle cerebral artery infarction were selected from a prospectively acquired cohort of 1644 patients who underwent multiparametric computed tomography (CT), including CT perfusion for suspected stroke. Two blinded readers evaluated the occurrence of ITD, defined as ipsilateral thalamic hypoperfusion present on ≥2 CT perfusion maps. Perfusion alterations were defined according to the Alberta Stroke Program Early CT Score regions. Final infarction volume and subacute complications were assessed on follow-up imaging. Clinical outcome was quantified using the modified Rankin Scale. Multivariable linear and ordinal logistic regression analysis were applied to identify independent associations. RESULTS: ITD was present in 25/124 subjects (20.2%, ITD+). In ITD+ subjects, perfusion of the caudate nucleus, internal capsule, and lentiform nucleus was more frequently affected than in ITD- patients (each with P<0.001). In the ITD+ group, larger cerebral blood flow (P=0.002) and cerebral blood volume (P<0.001) deficit volumes, as well as smaller cerebral blood flow-cerebral blood volume mismatch (P=0.021) were observed. There was no independent association of ITD with final infarction volume or clinical outcome at discharge in treatment subgroups (each with P>0.05). ITD had no influence on the development of subacute stroke complications. CONCLUSIONS: ITD in the form of thalamic hypoperfusion is a frequent CT perfusion finding in the acute phase in middle cerebral artery stroke patients with marked involvement of subcortical areas. ITD does not result in thalamic infarction and had no independent impact on patient outcome. Notably, ITD was misclassified as part of the ischemic core by automated software, which might affect patient selection in CT perfusion-based trials.

Using Functional Magnetic Resonance Imaging to Detect Chronic Fatigue in Patients With Previous Traumatic Brain Injury: Changes Linked to Altered Striato-Thalamic-Cortical Functioning.

OBJECTIVE: To investigate whether functional magnetic resonance imaging (fMRI) can be used to detect fatigue after traumatic brain injury (TBI). SETTING: Neurorehabilitation clinic. PARTICIPANTS: Patients with TBI (n = 57) and self-experienced fatigue more than 1 year postinjury, and age- and gender-matched healthy controls (n = 27). MAIN MEASURES: Self-assessment scales of fatigue, a neuropsychological test battery, and fMRI scanning during performance of a fatiguing 27-minute attention task. RESULTS: During testing within the fMRI scanner, patients showed a higher increase in self-reported fatigue than controls from before to after completing the task (P < .001). The patients also showed lower activity in several regions, including bilateral caudate, thalamus, and anterior insula (all P < .05). Furthermore, the patients failed to display decreased activation over time in regions of interest: the bilateral caudate and anterior thalamus (all P < .01). Left caudate activity correctly identified 91% of patients and 81% of controls, resulting in a positive predictive value of 91%. CONCLUSION: The results suggest that chronic fatigue after TBI is associated with altered striato-thalamic-cortical functioning. It would be of interest to study whether fMRI can be used to support the diagnosis of chronic fatigue in future studies.

Dejerine-Roussy syndrome from thalamic metastasis treated with stereotactic radiosurgery.

Dejerine-Roussy syndrome (central thalamic pain) is associated with damage to the ventral posterior sensory nuclei of the thalamus. We report a patient with breast cancer who developed contralateral hemibody paresthesias and dysesthesias. MR imaging revealed limited volume intracranial metastatic disease including a right posterior thalamic lesion. Stereotactic radiosurgery was utilized to selectively treat the lesion while preserving the remaining thalamus. Two months following treatment, the patient reported vastly improved to complete resolution of her sensory symptoms. This is the first reported case of thalamic tumor directed radiosurgical treatment leading to resolution of central neuropathic pain.

Thalamic pain alleviated by stellate ganglion block: A case report.

RATIONALE: Thalamic pain is a distressing and treatment-resistant type of central post-stroke pain. Although stellate ganglion block is an established intervention used in pain management, its use in the treatment of thalamic pain has never been reported. PATIENT CONCERNS: A 66-year-old woman presented with a 3-year history of severe intermittent lancinating pain on the right side of the face and the right hand. The pain started from the ulnar side of the right forearm after a mild ischemic stroke in bilateral basal ganglia and left thalamus. Weeks later, the pain extended to the dorsum of the finger tips and the whole palmar surface, becoming more severe. Meanwhile, there was also pain with similar characteristics emerging on her right face, resembling atypical trigeminal neuralgia. DIAGNOSES: Thalamic pain was diagnosed. INTERVENTIONS: After refusing the further invasive treatment, she was suggested to try stellate ganglion block. OUTCOMES: After a 3-day period of pain free (numerical rating scale: 0) postoperatively, she reported moderate to good pain relief with a numerical rating scale of about 3 to 4 lasting 1 month after the first injection. Pain as well as the quality of life was markedly improved with less dose of analgesic agents. LESSONS: Stellate ganglion block may be an optional treatment for thalamic pain.

Fahr's Syndrome and Secondary Hypoparathyroidism.

A typical case of Fahr's syndrome is described in a 76-year-old Brazilian female who underwent a total thyroidectomy three decades ago. Six years before the current admission, she started with generalized tonic-clonic seizures. Associated disorders involved extra-pyramidal, cognitive, nocturnal terror and mood changes. With suspicion of hypocalcemia due to secondary hypoparathyroidism, laboratory determinations confirmed the diagnoses. Furthermore, imaging studies of the central nervous system detected multiple calcifications, with characteristic distribution of Fahr's syndrome. Clinical management was successful.

Bilateral paramedian thalamic syndrome after infection.

BACKGROUND: Although bilateral paramedian thalamic infarctions occur more frequently in adults than in children, they are rare entities at any age. The syndrome is thought to result from occlusion of the artery of Percheron, which arises as a common trunk from one of the posterior cerebral arteries to supply both paramedian thalamic regions. We describe two children with acute ischemic infarction involving both paramedian thalami developing after infection. PATIENTS: The first patient developed mutism with ataxia after chicken pox infection. The second child developed headache, somnolence, agitation, and speech dysfunction following an upper respiratory tract infection. Bilateral thalamic lesions were documented on magnetic resonance imaging of both children. CONCLUSION: Bilateral infarctions of the paramedian thalamus may result in severe illness and impairment. Common clinical manifestations include disorientation, confusion, hypersomnolence, deep coma and "coma vigil," or akinetic mutism (awake unresponsiveness), as well as severe memory impairment.

Repeated head trauma is associated with smaller thalamic volumes and slower processing speed: the Professional Fighters' Brain Health Study.

OBJECTIVES: Cumulative head trauma may alter brain structure and function. We explored the relationship between exposure variables, cognition and MRI brain structural measures in a cohort of professional combatants. METHODS: 224 fighters (131 mixed martial arts fighters and 93 boxers) participating in the Professional Fighters Brain Health Study, a longitudinal cohort study of licensed professional combatants, were recruited, as were 22 controls. Each participant underwent computerised cognitive testing and volumetric brain MRI. Fighting history including years of fighting and fights per year was obtained from self-report and published records. Statistical analyses of the baseline evaluations were applied cross-sectionally to determine the relationship between fight exposure variables and volumes of the hippocampus, amygdala, thalamus, caudate, putamen. Moreover, the relationship between exposure and brain volumes with cognitive function was assessed. RESULTS: Increasing exposure to repetitive head trauma measured by number of professional fights, years of fighting, or a Fight Exposure Score (FES) was associated with lower brain volumes, particularly the thalamus and caudate. In addition, speed of processing decreased with decreased thalamic volumes and with increasing fight exposure. Higher scores on a FES used to reflect exposure to repetitive head trauma were associated with greater likelihood of having cognitive impairment. CONCLUSIONS: Greater exposure to repetitive head trauma is associated with lower brain volumes and lower processing speed in active professional fighters.

Postoperative stroke after hemiarthroplasty for femoral neck fracture: a report of 2 cases and review of literature.

INTRODUCTION: Femoral neck fractures in the elderly comprise a significant number of orthopedic surgical cases at a major trauma center. These patients are immediately incapacitated, and surgical fixation can help increase mobility, restore independence, and reduce morbidity and mortality. However, operative treatment carries its own inherent risks including infections, deep vein thromboses, and intraoperative cardiovascular collapse. Cerebrovascular stroke is a relatively uncommon occurrence after hip fractures. METHODS: We present 2 cases with unusual postoperative medical complication after cemented hip hemiarthroplasty for femoral neck fracture that will serve to illustrate an infrequent but very serious complication. RESULTS: Case 1 was a 73-year-old man with a Garden IV femoral neck fracture who underwent a right hip unipolar cemented hemiarthroplasty under general anesthesia. After uneventful surgery, he developed neurological deficits, and a postoperative noncontrast head computed tomography showed a right medial thalamic infarct. Case 2 was an 82-year-old man with a Garden IV femoral neck fracture who underwent a right hip unipolar cemented hemiarthroplasty under general anesthesia. After uneventful surgery, the patient became hemodynamically unstable. A postoperative noncontrast head computed tomography showed a large evolving left middle cerebral artery stroke. CONCLUSIONS: General anesthesia in the setting of decreased cardiac function (decreased ejection fraction and output) carries the risk for ischemic injury to the brain from decreased cerebral perfusion. Risk factors including advanced age, history of coronary artery disease, atherosclerotic disease, and atrial fibrillation increase the risk for perioperative stroke. Furthermore, it is known that during the cementing of implants, microemboli can be released, which must be considered in patients with preoperative heart disease. As a result, consideration of using a noncemented implant or cementing without pressurizing in this clinical scenario should be an important aspect of the preoperative plan in an at-risk patient. Further studies are needed that can elucidate a causal relationship.

Tractography-guided stimulation of somatosensory fibers for thalamic pain relief.

BACKGROUND: The spinothalamocortical tract (STC) is seen as a neural tract responsible for or involved in the generation or transmission of thalamic pain. Either the thalamus itself or the posterior limb of the internal capsule (PLIC) are targets for deep brain stimulation (DBS) in patients with thalamic pain, but due to its low contrast, conventional MRI cannot visualize the STC directly. OBJECTIVES: To show the feasibility of integrating diffusion tensor imaging-based tractography into the stereotactic treatment planning for identification of an object-oriented lead trajectory that allows STC-DBS with multiple electrode contacts. METHODS: Diffusion tensor imaging was performed in 4 patients with thalamic pain. The STC was modeled and integrated into the stereotactic treatment planning for DBS. DBS-lead implantation was done according to trajectory planning along the modeled STC at the level of the PLIC. RESULTS: After implantation, electrode stimulation was possible over a length of more than 20 mm with a tractography-based trajectory along the PLIC part of the STC. After a follow-up of 12 months, pain relief of more than 40% was achieved in 3 of 4 patients with rating on a visual analogue scale. In 1 patient, stimulation failed to reach any long-lasting positive effects. CONCLUSIONS: Integrating tractography data into stereotactic planning of DBS in thalamic pain is technically feasible. It can be used to identify a lead trajectory that allows for multiple contact stimulation along the STC at the level of the PLIC. Due to long-lasting positive stimulation effect, tractography-guided stimulation of sensory fibers seems to be beneficial for thalamic pain relief.