Stroke masquerading as cardiac arrest: the artery of Percheron.

The artery of Percheron (AOP) is a rare arterial variant of the thalamic blood supply. Due to the densely packed collection of nuclei it supplies, an infarction of the AOP can be devastating. Here we highlight a patient who had an AOP stroke in the community, which was initially managed as cardiac arrest. AOP strokes most often present with vague symptoms such as reduced conscious level, cognitive changes and confusion without obvious focal neurology, and therefore are often missed at the initial clinical assessment. This case highlights the importance of recognising an AOP stroke as a cause of otherwise unexplained altered consciousness level and the use of MRI early in the diagnostic work-up.

Transient Aphasia Following Resection of a Thalamic Cavernous Malformation.

BACKGROUND: The thalamus has a demonstrated role in language, particularly through its connectivity to frontal language cortices. CASE DESCRIPTION: A 59-year-old man with transient mixed aphasia following resection of a left-sided thalamic cavernous malformation is reported. No operative complications were encountered, and there was no surgical contact with cortical language areas. The patient recovered full language function within a week postoperatively. CONCLUSIONS: The role of thalamic nuclei in language processes and other reports of transient thalamic aphasia are reviewed.

Polygenic risk for neuropsychiatric disease and vulnerability to abnormal deep grey matter development.

Neuropsychiatric disease has polygenic determinants but is often precipitated by environmental pressures, including adverse perinatal events. However, the way in which genetic vulnerability and early-life adversity interact remains obscure. We hypothesised that the extreme environmental stress of prematurity would promote neuroanatomic abnormality in individuals genetically vulnerable to psychiatric disorders. In 194 unrelated infants (104 males, 90 females), born before 33 weeks of gestation (mean gestational age 29.7 weeks), we combined Magnetic Resonance Imaging with a polygenic risk score (PRS) for five psychiatric pathologies to test the prediction that: deep grey matter abnormalities frequently seen in preterm infants are associated with increased polygenic risk for psychiatric illness. The variance explained by the PRS in the relative volumes of four deep grey matter structures (caudate nucleus, thalamus, subthalamic nucleus and lentiform nucleus) was estimated using linear regression both for the full, mixed ancestral, cohort and a subsample of European infants. Psychiatric PRS was negatively associated with lentiform volume in the full cohort (ß = -0.24, p = 8 × 10-4) and a European subsample (ß = -0.24, p = 8 × 10-3). Genetic variants associated with neuropsychiatric disease increase vulnerability to abnormal lentiform development after perinatal stress and are associated with neuroanatomic changes in the perinatal period.

Abnormalities of thalamus volume and resting state functional connectivity in primary insomnia patients.

Primary insomnia (PI) is associated with deteriorating attention, memory, physical and mood complaints. Based on the extensive literature demonstrating the critical roles of the thalamus in sleep regulation, we hypothesized that insomnia would be associated with functional and structural changes of the thalamus. This information is needed to better understand the neural mechanisms of insomnia, and would be useful for informing future attempts to alleviate or treat insomnia symptoms. Twenty-seven PI patients and 39 matched healthy controls were included in the present study. Subcortical volume and resting state functional connectivity (RSFC) of thalamus were compared between groups, and the relationships between neuroimaging differences and clinical features, including the Pittsburgh Sleep Quality Index (PSQI), the Insomnia Severity Index Scale (ISI), the Self-Rating Anxiety Scale (SAS) and the Self-Rating Depression Scale (SDS), also be explored. Compared with the control group, the PI group showed significantly reduced volume of thalamus. In addition, several brain regions showed reduced RSFC with thalamus in PI patients, such as anterior cingulate cortex (ACC), orbitofrontal cortex, hippocampus, caudate and putamen. Correlation analyses revealed that, several of these RSFC patterns were negatively correlated with PSQI score among PI patients, including thalamic connections with the putamen, caudate, hippocampus. Negative correlation was also observed between the RSFC strength of right thalamus-right ACC and SDS score in PI patients. This work demonstrates the structural and functional abnormalities of the thalamus in PI patients that were associated with key clinical features of insomnia. These data further highlight the important role of the thalamus in sleep and PI.

Bilateral thalamocortical abnormalities in focal cortical dysplasia.

BACKGROUND AND PURPOSE: Focal cortical dysplasia (FCD), a congenital malformation of the neocortex and one of the most common causes of medication resistant epilepsy in pediatric populations, can be studied noninvasively by diffusion tensor imaging (DTI). The present study aimed to quantify changes in the thalamus and thalamocortical pathways with respect to fractional anisotropy (FA), apparent diffusion coefficient (ADC), volume, and other common measures. MATERIALS AND METHODS: The study quantified data collected from pediatric patients with a prior diagnosis of FCD; 75 patients (35 females, 10.1 ±â€¯6.5 years) for analysis of thalamic volume and 68 patients (32 females, 10.2 ±â€¯6.4 years) for DTI analysis. DTI scans were taken at 3 Tesla MRI scanners (30 diffusion gradient directions; b = 1000 s/mm2 and 5 non diffusion-weighted measurements). DTI tractography was performed using the FACT algorithm with an angle threshold of 45 degrees. Manually delineated ROIs were used to compare the hemisphere containing the dysplasia to the contralateral hemisphere and controls. RESULTS: A significant decrease in the volume of the FCD hemisphere thalamus was detected as compared to the contralateral hemisphere. In comparison to controls, there was an observed reduction in tract volume, length, count, FA of thalami, and FA of thalamocortical pathways in FCD patients. FCD patients had higher odds of exhibiting high ADC in both the thalamus and thalamocortical pathways. CONCLUSION: The data implied a widespread reduction in structural connectivity of the thalamocortical network. MRI analysis suggests a potential influence of FCD on thalamic volume.

A foldable electrode array for 3D recording of deep-seated abnormal brain cavities.

OBJECTIVE: This study describes the design and microfabrication of a foldable thin-film neural implant and investigates its suitability for electrical recording of deep-lying brain cavity walls. APPROACH: A new type of foldable neural electrode array is presented, which can be inserted through a cannula. The microfabricated electrode is specifically designed for electrical recording of the cavity wall of thalamic lesions resulting from stroke. The proof-of-concept is demonstrated by measurements in rat brain cavities. On implantation, the electrode array unfolds in the brain cavity, contacting the cavity walls and allowing recording at multiple anatomical locations. A three-layer microfabrication process based on UV-lithography and Reactive Ion Etching is described. Electrochemical characterization of the electrode is performed in addition to an in vivo experiment in which the implantation procedure and the unfolding of the electrode are tested and visualized. MAIN RESULTS: Electrochemical characterization validated the suitability of the electrode for in vivo use. CT imaging confirmed the unfolding of the electrode in the brain cavity and analysis of recorded local field potentials showed the ability to record neural signals of biological origin. SIGNIFICANCE: The conducted research confirms that it is possible to record neural activity from the inside wall of brain cavities at various anatomical locations after a single implantation procedure. This opens up possibilities towards research of abnormal brain cavities and the clinical conditions associated with them, such as central post-stroke pain.

Astrocyte-derived interleukin-33 promotes microglial synapse engulfment and neural circuit development.

Neuronal synapse formation and remodeling are essential to central nervous system (CNS) development and are dysfunctional in neurodevelopmental diseases. Innate immune signals regulate tissue remodeling in the periphery, but how this affects CNS synapses is largely unknown. Here, we show that the interleukin-1 family cytokine interleukin-33 (IL-33) is produced by developing astrocytes and is developmentally required for normal synapse numbers and neural circuit function in the spinal cord and thalamus. We find that IL-33 signals primarily to microglia under physiologic conditions, that it promotes microglial synapse engulfment, and that it can drive microglial-dependent synapse depletion in vivo. These data reveal a cytokine-mediated mechanism required to maintain synapse homeostasis during CNS development.

Clinical course of untreated thalamic cavernous malformations: hemorrhage risk and neurological outcomes.

OBJECTIVE The natural history of cerebral cavernous malformations (CMs) has been widely studied, but the clinical course of untreated thalamic CMs is largely unknown. Hemorrhage of these lesions can be devastating. The authors undertook this study to obtain a prospective hemorrhage rate and provide a better understanding of the prognosis of untreated thalamic CMs. METHODS This longitudinal cohort study included patients with thalamic CMs who were diagnosed between 2000 and 2015. Clinical data were recorded, radiological studies were extensively reviewed, and follow-up evaluations were performed. RESULTS A total of 121 patients were included in the study (56.2% female), with a mean follow-up duration of 3.6 years. The overall annual hemorrhage rate (subsequent to the initial presentation) was calculated to be 9.7% based on the occurrence of 42 hemorrhages over 433.1 patient-years. This rate was highest in patients (n = 87) who initially presented with hemorrhage and focal neurological deficits (FNDs) (14.1%) (χ2 = 15.358, p < 0.001), followed by patients (n = 19) with hemorrhage but without FND (4.5%) and patients (n = 15) without hemorrhage regardless of symptoms (1.2%). The initial patient presentations of hemorrhage with FND (hazard ratio [HR] 2.767, 95% CI 1.336-5.731, p = 0.006) and associated developmental venous anomaly (DVA) (HR 2.510, 95% CI 1.275-4.942, p = 0.008) were identified as independent hemorrhage risk factors. The annual hemorrhage rate was significantly higher in patients with hemorrhagic pres entation at diagnosis (11.7%, p = 0.004) or DVA (15.7%, p = 0.002). Compared with the modified Rankin Scale (mRS) score at diagnosis (mean 2.2), the final mRS score (mean 2.0) was improved in 37 patients (30.6%), stable in 59 patients (48.8%), and worse in 25 patients (20.7%). Lesion size (odds ratio [OR] per 0.1 cm increase 3.410, 95% CI 1.272-9.146, p = 0.015) and mRS score at diagnosis (OR per 1 point increase 3.548, 95% CI 1.815-6.937, p < 0.001) were independent adverse risk factors for poor neurological outcome (mRS score ≥ 2). Patients experiencing hemorrhage after the initial ictus (OR per 1 ictus increase 6.923, 95% CI 3.023-15.855, p < 0.001) had a greater chance of worsened neurological status. CONCLUSIONS This study verified the adverse predictors for hemorrhage and functional outcomes of thalamic CMs and demonstrated an overall annual symptomatic hemorrhage rate of 9.7% after the initial presentation. These findings and the mode of initial presentation are useful for clinicians and patients when selecting an appropriate treatment, although the tertiary referral bias of the series should be taken into account.

Giant cavernous malformation in the ventrolateral midbrain with extension into the thalamus: a case report of a paramedian supracerebellar transtentorial approach.

Cavernous malformations (CMs) of the midbrain and thalamus are relatively rare and particularly difficult to be resected given their location in eloquent tissues. Here, we report a case of a 14-year-old boy who experienced repeated and progressive right hemiparesis. Image examinations showed a gradually enlarged CM originated in the left ventrolateral midbrain extending to the left thalamus with repeated hemorrhage. By performing a paramedian supracerebellar transtentorial approach, the CM was totally removed, and the patient recovered without any new neurological deficit. The authors' experience suggests that this approach is eminent in treating giant lesions involving the ventrolateral midbrain and thalamus.

Midline Brain Abnormalities Across Psychotic and Mood Disorders.

Patients with schizophrenia are known to have increased prevalence of abnormalities in midline brain structures, such as a failure of the septum pellucidum to fuse (cavum septum pellucidum) and the absence of the adhesio interthalamica. This is the first study to investigate the prevalence of these abnormalities across a large multidiagnostic sample. Presence of cavum septum pellucidum and absence of the adhesio interthalamica was assessed in 639 patients with chronic schizophrenia, delusional disorder, schizoaffective disorder, bipolar disorder, major depressive disorder, or a first episode of psychosis, mania or unipolar depression. This was compared with 223 healthy controls using logistic-regression-derived odds ratios (OR). Patients with psychotic or mood disorders showed an increased prevalence of both abnormalities (OR of cavum septum pellucidum = 2.1, OR of absence of the adhesio interthalamica = 2.6, OR of both cavum septum pellucidum and absence of the adhesio interthalamica = 3.8, all P < .001). This increased prevalence was separately observed in nearly all disorders as well as after controlling for potential confounding factors. This study supports a general increased prevalence of midline brain abnormalities across mood and psychotic disorders. This nonspecificity may suggest that these disorders share a common neurodevelopmental etiology.

Thalamic Massa Intermedia Duplication in a Dysmorphic 14 month-old Toddler.

The massa intermedia is an inconstant parenchymal band connecting the medial thalami. It may be thickened in various disease processes such as Chiari II malformation or absent in other disease states. However, the massa intermedia may also be absent in up to 30% of normal human brains. To the best of my knowledge, detailed imaging findings of massa intermedia duplication have only been described in a single case report. An additional case of thalamic massa intermedia duplication discovered on a routine brain MR performed for dysmorphic facial features is reported herein.

Remote thalamic microstructural abnormalities related to cognitive function in ischemic stroke patients.

OBJECTIVE: Ischemic stroke can lead to a continuum of cognitive sequelae, ranging from mild vascular cognitive impairment to vascular dementia. These cognitive deficits can be influenced by the disruption of cortico-subcortical circuits. We sought to explore remote thalamic microstructural abnormalities and their association with cognitive function after ischemic stroke. METHOD: Seventeen patients with right hemispheric ischemic stroke and 17 controls matched for age, sex, and years of education were included. All participants underwent neurological, neuropsychological, and diffusion tensor image examination. Patients were assessed 3 months poststroke. Voxel-wise analysis was used to study thalamic diffusion differences between groups. Mean fractional anisotropy (FA) and mean diffusivity (MD) values in significant thalamic areas were calculated for each subject and correlated with cognitive performance. RESULTS: Stroke patients showed lower FA values and higher MD values in specific areas of both the left and right thalamus compared with controls. In patients, decreased FA values were associated with lower verbal fluency performance in the right thalamus (R(2) = 0.45, ß = 0.74) and the left thalamus (R(2) = 0.57, ß = 0.77) after adjusting for diabetes mellitus. Moreover, increased MD values were associated with lower verbal fluency performance in the right thalamus (R(2) = 0.27, ß = -0.54) after adjusting for diabetes mellitus. In controls, thalamic FA and MD values were not related to any cognitive function. CONCLUSION: Our findings support the hypothesis that ischemic stroke lesions are associated with remote thalamic diffusion abnormalities, and that these abnormalities can contribute to cognitive dysfunction 3 months after a cerebrovascular event.

Brainstem arteriovenous malformation presenting with dyspraxic handwriting in a young girl.

We report the case of a 11-year-old girl who developed an isolated hand-writing disorder with dysgraphia at the beginning of the school year in the sixth grade. A brain magnetic resonance angiography showed a round arteriovenous malformation sited in the left side of the midbrain extending to the ipsilateral medio-basal thalamus. Child neurologists should never neglect a thorough neurological evaluation in case of isolated worsening of handwriting, to rule out possible underlying organic causes.

Cavernous malformation of brainstem, thalamus, and basal ganglia: a series of 176 patients.

BACKGROUND: Cavernous malformations (CMs) in deep locations account for 9% to 35% of brain malformations and are surgically challenging. OBJECTIVE: To study the clinical features and outcomes following surgery for deep CMs and the complication of hypertrophic olivary degeneration (HOD). METHODS: Clinical records, radiological findings, operative details, and complications of 176 patients with deep CMs were reviewed retrospectively. RESULTS: Of 176 patients with 179 CMs, 136 CMs were in the brainstem, 27 in the basal ganglia, and 16 in the thalamus. Cranial nerve deficits (51.1%), hemiparesis (40.9%), numbness (34.7%), and cerebellar symptoms (38.6%) presented most commonly. Hemorrhage presented in 172 patients (70 single, 102 multiple). The annual retrospective hemorrhage rate was 5.1% (assuming CMs are congenital with uniform hemorrhage risk throughout life); the rebleed rate was 31.5%/patient per year. Surgical approach depended on the proximity of the CM to the pial or ependymal surface. Postoperatively, 121 patients (68.8%) had no new neurological deficits. Follow-up occurred in 170 patients. Delayed postoperative HOD developed in 9/134 (6.7%) patients with brainstem CMs. HOD occurred predominantly following surgery for pontine CMs (9/10 patients). Three patients with HOD had palatal myoclonus, nystagmus, and oscillopsia, whereas 1 patient each had limb tremor and hemiballismus. At follow-up, 105 patients (61.8%) improved, 44 (25.9%) were unchanged, and 19 (11.2%) worsened neurologically. Good preoperative modified Rankin Score (98.2% vs 54.5%, P = .001) and single hemorrhage (89% vs 77.3%, P < .05) were predictive of good long-term outcome. CONCLUSION: Symptomatic deep CMs can be resected with acceptable morbidity and outcomes. Good preoperative modified Rankin Score and single hemorrhage are predictors of good long-term outcome.

Location of periventricular nodular heterotopia is related to the malformation phenotype on MRI.

BACKGROUND AND PURPOSE: Periventricular nodular heterotopia are common malformations of cortical development that are associated with many clinical syndromes and with many different neuroimaging phenotypes. The purpose of this study was to determine whether specific malformation phenotypes may be related to location, side, or number of PNH as assessed by MR imaging. MATERIALS AND METHODS: MR images of 200 patients previously diagnosed with PNH were retrospectively analyzed. PNH were classified according to their location along the ventricles (anterior, posterior, or diffuse), side (unilateral or bilateral), and number of nodules (<5, 6-10, or >10). The cerebrum, brain stem and cerebellum were analyzed to assess associated anomalies. Associations between PNH location and the presence of other anomalies were tested by using Fisher exact test and χ2 test. RESULTS: Posterior PNH were significantly associated with malformations of the cerebral cortex, diminished white matter volume, and mid-/hindbrain anomalies. Diffuse PNH were associated with diminished white matter volume, callosal "anomalies," and the presence of megacisterna magna. Unilateral PNH were strongly associated with cortical malformations. CONCLUSIONS: Certain malformation complexes are associated with PNH in specific locations: posterior PNH with cerebral cortical and mid-/hindbrain malformations and diffuse PNH with callosal anomalies and megacisterna magna. Knowledge of these associations should allow more directed analyses of brain MR imaging in patients with PNH. In addition, knowledge of these associations may help to direct studies to elucidate the causes of these malformation complexes.

Mutation of the BiP/GRP78 gene causes axon outgrowth and fasciculation defects in the thalamocortical connections of the mammalian forebrain.

Proper development of axonal connections is essential for brain function. A forward genetic screen for mice with defects in thalamocortical development previously isolated a mutant called baffled. Here we describe the axonal defects of baffled in further detail and identify a point mutation in the Hspa5 gene, encoding the endoplasmic reticulum chaperone BiP/GRP78. This hypomorphic mutation of BiP disrupts proper development of the thalamocortical axon projection and other forebrain axon tracts, as well as cortical lamination. In baffled mutant brains, a reduced number of thalamic axons innervate the cortex by the time of birth. Thalamocortical and corticothalamic axons are delayed, overfasciculated, and disorganized along their pathway through the ventral telencephalon. Furthermore, dissociated mutant neurons show reduced axon extension in vitro. Together, these findings demonstrate a sensitive requirement for the endoplasmic reticulum chaperone BiP/GRP78 during axon outgrowth and pathfinding in the developing mammalian brain.

Diverticulum of the third ventricle and absence of the interthalamic adhesion in a dog.

A 10-month-old male Pomeranian dog was examined for neurological abnormalities consistent with diffuse forebrain and cerebellar disease. Based on ultrasound and magnetic resonance imaging (MRI) a diagnosis of diverticulum of the third ventricle, partial agenesis of the corpus callosum, and absence of the interthalamic adhesion was made. As conservative treatment was unsuccessful, a ventriculoperitoneal shunt was placed.