Thalamic pathology in frontotemporal dementia: Predilection for specific nuclei, phenotype-specific signatures, clinical correlates, and practical relevance.

BACKGROUND: Frontotemporal dementia (FTD) phenotypes are classically associated with distinctive cortical atrophy patterns and regional hypometabolism. However, the spectrum of cognitive and behavioral manifestations in FTD arises from multisynaptic network dysfunction. The thalamus is a key hub of several corticobasal and corticocortical circuits. The main circuits relayed via the thalamic nuclei include the dorsolateral prefrontal circuit, the anterior cingulate circuit, and the orbitofrontal circuit. METHODS: In this paper, we have reviewed evidence for thalamic pathology in FTD based on radiological and postmortem studies. Original research papers were systematically reviewed for preferential involvement of specific thalamic regions, for phenotype-associated thalamic disease burden patterns, characteristic longitudinal changes, and genotype-associated thalamic signatures. Moreover, evidence for presymptomatic thalamic pathology was also reviewed. Identified papers were systematically scrutinized for imaging methods, cohort sizes, clinical profiles, clinicoradiological associations, and main anatomical findings. The findings of individual research papers were amalgamated for consensus observations and their study designs further evaluated for stereotyped shortcomings. Based on the limitations of existing studies and conflicting reports in low-incidence FTD variants, we sought to outline future research directions and pressing research priorities. RESULTS: FTD is associated with focal thalamic degeneration. Phenotype-specific thalamic traits mirror established cortical vulnerability patterns. Thalamic nuclei mediating behavioral and language functions are preferentially involved. Given the compelling evidence for considerable thalamic disease burden early in the course of most FTD subtypes, we also reflect on the practical relevance, diagnostic role, prognostic significance, and monitoring potential of thalamic metrics in FTD. CONCLUSIONS: Cardinal manifestations of FTD phenotypes are likely to stem from thalamocortical circuitry dysfunction and are not exclusively driven by focal cortical changes.

Hacia una definición fisiológica positiva de los núcleos cerebrales profundos en humanos / Towards a positive physiological definition of the deep brain nuclei in humans

Introducción: El registro con microelectrodos en la estimulación cerebral profunda (ECP) ha demostrado una gran utilidad. Es posible mejorar su eficiencia caracterizando las propiedades de los potenciales de acción extracelulares (PAE). Pacientes y métodos: Hemos analizado registros de nueve pacientes operados por epilepsia o agresividad bajo anestesia general. Se han determinado las propiedades de los PAE de los núcleos talámicos centromediano, ventral intermedio, ventrocaudal e hipotalámico posteromedial. Resultados: Hemos analizado 706 células talámicas y 142 hipotalámicas. La proporción de tipos celulares resultó específica de cada núcleo celular. El tipo celular más frecuente fue P1P2N1 (59,5%), seguido por N1P1N2 (23,1%). La primera fase del PAE es altamente variable. Las propiedades de las fases del PAE de la misma morfología difieren altamente entre núcleos. Conclusiones: Hemos demostrado que diversos núcleos cerebrales profundos tienen propiedades específicas de la morfología de los PAE. Esto permitirá una mejora en la localización de estos núcleos durante la ECP.(AU)

Introduction: Using microelectrodes for recording purposes in deep brain stimulation (DBS) has proven to be very useful. Their efficiency can be improved by characterising the properties of extracellular action potentials (EAPs). Patients and methods: We analysed the records of nine patients who underwent surgery for epilepsy or aggressiveness under general anaesthesia. The properties of the EAPs of the centromedian, ventral intermediate, ventrocaudal and posteromedial hypothalamic nuclei of the thalamus have been determined. Results: We have analysed 706 thalamic and 142 hypothalamic cells. The proportion of cell types was found to be specific to each cell nucleus. The most frequent cell type was P1P2N1 (59.5%), followed by N1P1N2 (23.1%). The first phase of the EAP is highly variable. The properties of the EAP phases of the same morphology differ greatly from one nucleus to another. Conclusions: We have shown that several deep brain nuclei have properties that are specific to the morphology of the EAPs. This will allow for improved localisation of these nuclei during DBS.(AU)

Clinical efficacy and safety of neuroendoscopic surgery for severe thalamic hemorrhage with ventricle encroachment.

To summarize and analyze the clinical efficacy and safety of neuroendoscopic surgery (NES) in the treatment of patients for severe thalamic hemorrhage with ventricle encroachment (THVE). Eighty-three patients with severe THVE were treated in the Neurosurgery Department of Anqing Hospital Affiliated to Anhui Medical University from July 2019 to August 2021. Our study was approved by the ethics committee. The patients were randomly divided into NES group and extraventricular drainage (EVD) group. The hospital stay, Glasgow coma scale (GCS) scores on the 1st and 14th days postoperatively, the incidence of intracranial infections, and the clearance of postoperative hematomas were compared and analyzed between the two groups. The patients had follow-up evaluations 6 months postoperatively. The prognosis was evaluated based on the activity of daily living (ADL) score. A head CT or MRI was obtained to determine whether there was hydrocephalus, cerebral infarction, or other related complications. Eighty-three patients were randomly divided into 41 cases of NES group and 42 cases of EVD group. The length of postoperative hospital stay was 17.42 ± 1.53 days, the GCS scores were 6.56 ± 0.21, and 10.83 ± 0.36 on days 1 and 14, respectively; intracranial infections occurred in 3 patients (7.31%) and the hematoma clearance rate was 83.6 ± 5.18% in the NES group, all of which were significantly better than the EVD group (P < 0.05). After 6 months of follow-up, 28 patients (68.29%) had a good prognosis, 5 patients (12.19%) died, and 4 patients (9.75%) had hydrocephalus in the NES group. In the EVD group, the prognosis was good in 15 patients (35.71%), 12 patients (28.57%) died, and 17 patients (40.47%) had hydrocephalus. The prognosis, mortality rate, and incidence of hydrocephalus in the NES group were significantly better than the EVD group (P < 0.05). Compared to traditional EVD, NES for severe THVE had a higher hematoma clearance rate, and fewer intracranial infections and patients with hydrocephalus, which together improve the clinical prognosis and is thus recommended for clinical use.

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.

Neuro-Ophthalmologic Features and Outcomes of Thalamic Infarction: A Single-Institutional 10-Year Experience.

BACKGROUND: Neuro-ophthalmologic deficit after thalamic infarction has been of great concern to ophthalmologists because of its debilitating impacts on patients' daily living. We aimed to describe the visual and oculomotor features of thalamic infarction and to delineate clinical outcomes and prognostic factors of the oculomotor deficits from an ophthalmologic point of view. METHODS: Clinical and neuroimaging data of all participants were retrospectively reviewed. Among the 12,755 patients with first-ever ischemic stroke, who were registered in our Stroke Data Bank between January 2009 and December 2018, 342 were found to have acute thalamic infarcts on MRI, from whom we identified the patients exhibiting neuro-ophthalmologic manifestations including visual, oculomotor, pupillary, and eyelid anomalies. RESULTS: Forty (11.7%) of the 342 patients with thalamic infarction demonstrated neuro-ophthalmologic manifestations, consisting of vertical gaze palsy (n = 19), skew deviation with an invariable hypotropia of the contralesional eye (n = 18), third nerve palsy (n = 11), pseudoabducens palsy (n = 9), visual field defects (n = 7), and other anomalies such as isolated ptosis and miosis (n = 7). Paramedian infarct was the most predominant lesion of neuro-ophthalmologic significance, accounting for 84.8% (n = 28) of all patients sharing the oculomotor features. Although most of the patients with oculomotor abnormalities rapidly improved without sequelae, 6 (18.2%) patients showed permanent oculomotor deficits. Common clinical features of patients with permanent oculomotor deficits included the following: no improvement within 3 months, combined upgaze and downgaze palsy, and the involvement of the paramedian tegmentum of the rostral midbrain. CONCLUSIONS: Thalamic infarction, especially in paramedian territory, can cause a wide variety of neuro-ophthalmologic manifestations, including vertical gaze palsy, skew deviation, and third nerve palsy. Although most oculomotor abnormalities resolve spontaneously within a few months, some may persist for years when the deficits remain unimproved for more than 3 months after stroke.

Robot-assisted stereotactic biopsy of pediatric brainstem and thalamic lesions.

OBJECTIVE: Biopsies of tumors located in deep midline structures require highly accurate stereotaxy to safely obtain lesional tissue suitable for molecular and histological analysis. Versatile platforms are needed to meet a broad range of technical requirements and surgeon preferences. The authors present their institutional experience with the robotic stereotactic assistance (ROSA) system in a series of robot-assisted biopsies of pediatric brainstem and thalamic tumors. METHODS: A retrospective analysis was performed of 22 consecutive patients who underwent 23 stereotactic biopsies of brainstem or thalamic lesions using the ROSA platform at Rady Children's Hospital in San Diego between December 2015 and January 2020. RESULTS: The ROSA platform enabled rapid acquisition of lesional tissue across various combinations of approaches, registration techniques, and positioning. No permanent deficits, major adverse outcomes, or deaths were encountered. One patient experienced temporary cranial neuropathy, and 3 developed small asymptomatic hematomas. The diagnostic success rate of the ROSA system was 91.3%. CONCLUSIONS: Robot-assisted stereotactic biopsy of these lesions may be safely performed using the ROSA platform. This experience comprises the largest clinical series to date dedicated to robot-assisted biopsies of brainstem and diencephalic tumors.

Strictly Lobar Microbleeds Reflect Amyloid Angiopathy Regardless of Cerebral and Cerebellar Compartments.

BACKGROUND AND PURPOSE: We aimed to determine whether lobar cerebellar microbleeds or concomitant lobar cerebellar and deep microbleeds, in the presence of lobar cerebral microbleeds, attribute to underlying advanced cerebral amyloid angiopathy pathology or hypertensive arteriopathy. METHODS: We categorized 71 patients with suspected cerebral amyloid angiopathy markers (regardless of the presence of deep and cerebellar microbleeds) into 4 groups according to microbleed distribution: L (strictly lobar cerebral, n=33), L/LCbll (strictly lobar cerebral and strictly lobar cerebellar microbleeds, n=13), L/Cbll/D (lobar, cerebellar, and deep microbleeds, n=17), and L/D (lobar and deep, n=8). We additionally categorized patients with cerebellar microbleeds into 2 groups according to dentate nucleus involvement: strictly lobar cerebellar (n=16) and dentate (n=14). We then compared clinical characteristics, Aß (amyloid-ß) positivity on PET (positron emission tomography), magnetic resonance imaging cerebral amyloid angiopathy markers, and cerebral small vessel disease burden among groups. RESULTS: The frequency of Aß positivity was higher in the L and L/LCbll groups (81.8% and 84.6%) than in the L/Cbll/D and L/D groups (37.5% and 29.4%; P<0.001), while lacune numbers were lower in the L and L/LCbll groups (1.7±3.3 and 1.7±2.6) than in the L/Cbll/D and L/D groups (8.0±10.3 and 13.4±17.7, P=0.001). The L/LCbll group had more lobar cerebral microbleeds than the L group (93.2±121.8 versus 38.0±40.8, P=0.047). The lobar cerebellar group had a higher Aß positivity (75% versus 28.6%, P=0.011) and lower lacune number (2.3±3.7 versus 8.6±1.2, P=0.041) than the dentate group. CONCLUSIONS: Strictly lobar cerebral and cerebellar microbleeds are related to cerebral amyloid angiopathy, whereas any combination of concurrent lobar and deep microbleeds suggest hypertensive angiopathy regardless of cerebral or cerebellar compartments.

Isolated truncal contrapulsion as a rare presentation of acute thalamic infarct.

Infarcts involving the thalamus can yield many deficits, including sensory syndromes, altered consciousness, and cognitive disturbances, depending on the thalamic vascular territory involved. Isolated truncal contrapulsion due to pure thalamic infarct has been rarely reported. Truncal lateropulsion is a compelling sensation of being pulled toward one side that cannot be explained by weakness or limb ataxia. It is commonly reported in lateral medullary infarcts. It may occur with lesions that involve the peripheral vestibular system, brainstem, cerebellum, basal ganglia, ponto-mesencephalic, and thalamic lesions. We hereby report a 64-year-old woman who presented with truncal contrapulsion as the sole manifestation of an acute right lateral thalamic infarct.

Infarto talámico en un paciente con aneurisma del septo interventricular / Thalamic stroke in a patient with membranous interventricular septal aneurysm

No disponible

Deep Brain Stimulation and Thalamotomy for the Treatment of Dystonia Acquired by Moyamoya Disease with Stroke.

Background: Moyamoya disease (MMD) is a type of chronic cerebrovascular disease. Currently, revascularization surgery including direct/indirect procedure is recommended for symptomatic patients. However, some patients still respond poorly to the treatment or develop secondary symptoms. Case report: We report the first case of an MMD patient treated with deep brain stimulation (DBS) and thalamotomy. Symptoms of dystonia due to hemorrhage in the thalamus responded poorly to revascularization surgery, but were considerably alleviated by stereotactic neurosurgery. Discussion: Our case report provides a potential strategy for management of refractory symptomatic MMD patients with dystonia and also supports the combined efficacy of DBS with thalamotomies. Highlights: Approximately 30% of patients with Moyamoya disease (MMD) presenting movement symptoms do not respond well to revascularization surgery. We reported an MMD patient treated with deep brain stimulation (DBS) and thalamotomy with significant dystonia and dystonic tremor symptom amelioration. It indicates that DBS or stereotactic lesioning might be a potential treatment for the refractory movement symptoms of MMD.

Continuous epileptiform discharges during sleep as an evolutionary pattern in patients with congenital Zika virus syndrome.

Congenital Zika virus syndrome (CZVS) is associated with severe neurological deficits. Clinical characteristics of epilepsy and the electroencephalographic (EEG) pattern in CZVS were documented in infancy. In this study, we aimed to describe the EEG findings observed during the follow-up of children with CZVS. Seventy-six EEGs of 55 children (60% female; mean age = 50 months) with confirmed CZVS were analyzed, considering the background, interictal, and ictal epileptiform discharges. Continuous (or almost continuous) epileptiform discharges during non-rapid eye movement sleep were identified in 22 (40%) patients. In 20 (90.1%) patients, the pattern was symmetrical, with an anterior predominance of the epileptiform activity. All patients with this pattern had epilepsy, which was severe in 15 (68.2%) and demanded polytherapy in 19 (86.4%). Subcortical calcifications (77.3%) and multifocal EEGs (72.8%) in earlier ages occurred more often in patients with this pattern. Other unspecific interictal EEG patterns were focal epileptiform discharges in 23 (41.8%) and multifocal activity in six (10.9%). In CZVS, continuous (or almost continuous) epileptiform discharges during sleep emerge as a pattern after the second year of life. This was associated with severe and drug-resistant epilepsy, but not necessarily with an apparent regression. Subcortical calcifications and multifocal epileptiform discharges in infancy are associated with this pattern.

Sustainable Effects of 8-Year Intermittent Spinal Cord Stimulation in a Patient with Thalamic Post-Stroke Pain.

BACKGROUND: Central post-stroke pain (CPSP) is a central neuropathic pain syndrome secondary to a cerebrovascular accident. CPSP treatment usually begins with medication; however, this is associated with inadequate pain relief and adverse effects. Neurostimulation therapies, including spinal cord stimulation (SCS), have been developed for improved pain relief. We report a patient with thalamic pain who underwent 8-year cervical SCS in an intermittent mode. CASE DESCRIPTION: A 71-year-old man presented with left thalamic stroke that caused persistent allodynia and "pricking" sensations at right-side extremities. The pain did not respond well to several pain therapies, including medication, acupuncture, and nerve-blocking anesthesia. Subsequently, the severe and refractory pain caused dystonia in his right hand and seriously hindered recovery and rehabilitation of stroke sequelae. Further, the pain induced depression and severe anxiety mood status and had an effect on his functional activities of life. After SCS device implantation, the patient received intermittent stimulation with 90 minutes on/30 minutes off. A significant decrease in the patient's pain was observed with no serious side effects. After subtle programming of the implantable pulse generator, a significant improvement of his dystonia and affective mood was observed. Intermittent SCS allowed for persistent stimulation for 8 years. Taken together, this intervention allowed for an acceptable improvement of his functional quality of life. CONCLUSIONS: Our findings indicate that SCS is safe and efficacious for CPSP, including thalamic stroke pain. Long-term intermittent stimulation can preserve implantable pulse generator battery life and achieve sustained improvement of a patient's pain, movement, and affective mood status.

Endoscopic-Assisted Translateral Ventricular Transchoroidal Fissure Approach for Evacuation of Medial-Type Thalamic Hemorrhage: Case Series.

BACKGROUND: Although surgeries for intracerebral hemorrhage remain controversial, endoscopic surgery is considered a promising surgical treatment. The most fatal type of thalamic hemorrhage is the medial type, which is always combined with expansion of the hematoma into the third ventricle. The current endoscopic approach to this lesion involves injury to the mediodorsal nucleus of the thalamus (MDT). CASE DESCRIPTION: We report 5 cases of medial thalamic hemorrhage with third intraventricular involvement treated by an endoscopic-assisted translateral ventricular transchoroidal fissure approach. The preoperative average volume of the parenchymal hematomas was 9.63 mL, while the preoperative average volume of the intraventricular hematomas was 23.35 mL. The average surgical duration was 80.6 minutes. No intraoperative MDT incision was needed in any patient. The evacuation rates of parenchymal and intraventricular hematomas were 74.21%-98.84% and 85.89%-99.51%, respectively. Three months after the surgery, the average Glasgow Coma Scale scores improved to 13.8 from 7.2 preoperatively. No ventriculoperitoneal shunt was needed in any patient. CONCLUSIONS: The endoscopic-assisted translateral ventricular transchoroidal fissure approach is a safe and effective approach for evacuation of a medial thalamic hemorrhage with third intraventricular involvement. This approach allows parenchymal hematoma evacuation through the rupture of the third ventricle without incising the MDT in the lateral ventricle.

Diagnosis, Treatment, and Management of Dejerine-Roussy Syndrome: a Comprehensive Review.

PURPOSE OF REVIEW: Post-stroke pain represents a complex condition with few standardized diagnostic criteria. As such, the array of symptoms is often difficult to categorize and diagnose. Central post-stroke pain (CPSP), also known as Dejerine-Roussy syndrome, presents as painful paresthesia in any part of the body that is usually coupled with sensory abnormalities. RECENT FINDINGS: In patients who had experienced a cerebrovascular accident, CPSP typically affects the same areas of the body that are also impacted by the general motor and sensory deficits that result from stroke. Though it is generally debated, CPSP is thought to result from a lesion in any part of the central nervous system. Pain usually presents in the range of 3-6 months after the occurrence of stroke, manifesting contralaterally to the lesion, and most commonly involving the upper extremities. For the most accurate diagnosis of CPSP, a thorough history and clinical examination should be supplemented with imaging. Infarcted areas of the brain can be visualized using either CT or MRI. First-line treatment of CPSP is pharmacologic and consists of a three-drug regimen. Despite this, CPSP is often refractory to medical management producing only modest pain reduction in a limited subset of patients. Adverse effects associated with pharmacologic management of CPSP and frequent recalcitrance to treatment have driven alternative minimally invasive methods of pain control which include transcranial stimulation, deep brain stimulation, and neuromodulation. The aim of this review is to provide a comprehensive update to recent advances in the understanding of the treatment and management of CPSP.

Thalamic perforating artery stroke on computed tomography perfusion in a patient with coronavirus disease 2019.

Emerging evidence suggests that patients with coronavirus disease 2019 (COVID-19) are at risk of thromboembolic complications, including ischemic strokes. We present a case illustrating the value of CT perfusion to identify acute small subcortical infarcts in a patient with COVID-19 admitted to an intensive care unit for bilateral pneumonia and pulmonary embolism presenting with sudden right limb weakness.