Neuroanatomical Localization Research Articles

Care of the Patient Nearing the End of Life in the Neurointensive Care Unit.

Neurologically critically ill patients present with unique disease trajectories, prognostic uncertainties, and challenges to end-of-life (EOL) care. Acute brain injuries place these patients at risk for underrecognized symptoms and unmet EOL management needs, which can negatively affect their quality of care and lead to complicated grief in surviving loved ones. To care for patients nearing the EOL in the neurointensive care unit, health care clinicians must consider neuroanatomic localization, barriers to symptom assessment and management, unique aspects of the dying process, and EOL management needs. We aim to define current best practices, barriers, and future directions for EOL care of the neurologically critically ill patient.

Lesions Causing Alice in Wonderland Syndrome Map to a Common Brain Network Linking Body and Size Perception

ObjectiveAlice in Wonderland syndrome (AIWS) profoundly affects human perception of size and scale, particularly regarding one's own body and the environment. Its neuroanatomical basis has remained elusive, partly because brain lesions causing AIWS can occur in different brain regions. Here, we aimed to determine if brain lesions causing AIWS map to a distributed brain network.MethodsA retrospective case–control study analyzing 37 cases of lesion‐induced AIWS identified through systematic literature review was conducted. Using resting‐state functional connectome data from 1,000 healthy individuals, the whole‐brain connections of each lesion were estimated and contrasted with those from a control dataset comprising 1,073 lesions associated with 25 other neuropsychiatric syndromes. Additionally, connectivity findings from lesion‐induced AIWS cases were compared with functional neuroimaging results from 5 non‐lesional AIWS cases.ResultsAIWS‐associated lesions were located in various brain regions with minimal overlap (≤33%). However, the majority of lesions (≥85%) demonstrated shared connectivity to the right extrastriate body area, known to be selectively activated by viewing body part images, and the inferior parietal cortex, involved in size and scale judgements. This pattern was uniquely characteristic of AIWS when compared with other neuropsychiatric disorders (family‐wise error‐corrected p < 0.05) and consistent with functional neuroimaging observations in AIWS due to nonlesional causes (median correlation r = 0.56, interquartile range 0.24).InterpretationAIWS‐related perceptual distortions map to one common brain network, encompassing regions critical for body representation and size‐scale processing. These findings lend insight into the neuroanatomical localization of higher‐order perceptual functions, and may inform future therapeutic strategies for perceptual disorders. ANN NEUROL 2024;96:662–674

Clinical signs, causes, and outcome of central cord syndrome in 22 cats.

To describe the signalment, clinical findings, presumptive or definitive diagnosis, and outcome in cats with central cord syndrome (CCS). 22 cats. Cats evaluated for CCS at 7 referral hospitals between 2017 and 2021 were included. Information retrieved from medical records included signalment, physical and neurological examination findings, diagnostic investigations, definitive or presumptive diagnosis, treatment, and follow-up. Median age at presentation was 9 years. Two neuroanatomical localizations were associated with CCS: C1-C5 spinal cord segments in 17 (77.3%) cats and C6-T2 spinal cord segments in 5 (22.7%) cats. Neuroanatomical localization did not correlate with lesion location on MRI in 8 (36.3%) cats. The most common lesion location within the vertebral column was over the C2 and C4 vertebral bodies in 6 (27.2%) and 5 (22.7%) cats, respectively. Peracute clinical signs were observed in 11 (50%) cats, acute in 1 (4.5%), subacute in 4 (18%), and chronic and progressive signs were seen in 6 (40.9%) cats. The most common peracute condition was ischemic myelopathy in 8 (36.3%) cats, whereas neoplasia was the most frequently identified chronic etiology occurring in 5 (22.7%) cats. Outcome was poor in 13 (59%) cats, consisting of 4 of 11 (36.6%) of the peracute cases, 3 of 4 (75%) of the subacute cases, and 6 of 6 of the chronic cases. Central cord syndrome can occur in cats with lesions in the C1-C5 and C6-T2 spinal cord segments. Multiple etiologies can cause CCS, most commonly, ischemic myelopathy and neoplasia. Prognosis depends on the etiology and onset of clinical signs.

Clinical features, treatment, and outcome of juvenile dogs with meningoencephalitis of unknown etiology.

The information relating to the outcome specifically for juvenile dogs with meningoencephalitis of unknown etiology (MUE) is lacking. To describe the clinical presentation, diagnostic findings, treatment, and outcome in a cohort of dogs with MUE <52 weeks old. Thirty-four client-owned dogs. Multicenter retrospective case series. Records from 5 referral centers were searched. Data was extracted from the medical records and referring veterinarians were contacted for survival data if this was not available from the record. The mean age was 31 weeks; the youngest dog was 11 weeks and 3 dogs were <16 weeks old. Altered mentation (71%), ataxia (44%), seizures (29%), and circling (26%) were the most common presenting complaints. Neuroanatomical localization was to the forebrain (38%), multifocal (35%), brainstem (18%), and cerebellum (12%). Corticosteroid monotherapy (n = 15) and corticosteroid plus cytosine arabinoside (n = 15) were used in equal proportions. Outcome data was available for 26 dogs, 8 (31%) were alive at the time of data collection with a follow-up range of 135 to 2944 days. Death or euthanasia was related to MUE in 17/18 dogs that died during the study period. Kaplan-Meier survival analysis demonstrated a median survival time for all-cause death of 84 days. The prognosis for MUE in this subset of dogs was considered poor.

Update on central oculomotor disorders and nystagmus

The diagnosis of ocular motor disorders and the different forms of a nystagmus is based on a systematic clinical examination of all types of eye movements: eye position, spontaneous nystagmus, range of eye movements, smooth pursuit, saccades, gaze-holding function, vergence, optokinetic nystagmus, as well as testing of the function of the vestibulo-ocular reflex (VOR) and visual fixation suppression of the VOR. Relevant anatomical structures are the midbrain, pons, medulla, cerebellum, and cortex. There is a simple clinical rule: vertical and torsional eye movements are generated in the midbrain, horizontal in the pons. The cerebellum is relevant for almost all types of eye movements; typical pathological findings are saccadic smooth pursuit, gaze-evoked nystagmus or dysmetric saccades.Nystagmus is defined as a rhythmic, most often involuntary eye movement. It normally consists of a slow (pathological) drift of the eyes and a fast central compensatory movement of the eyes back to the primary position (re-fixation saccade). There are three major categories: first, spontaneous nystagmus, i. e. nystagmus which occurs in the gaze straight ahead position as upbeat or downbeat nystagmus; second, nystagmus that becomes visible at eccentric gaze only and third, nystagmus which can be elicited by certain maneuvers, e. g. head-shaking, head positioning, air pressure or hyperventilation, most of which are of peripheral vestibular origin. The most frequent central types of spontaneous nystagmus are downbeat and upbeat, infantile, pure torsional, pendular fixation, periodic alternating, and seesaw nystagmus. Many types of central nystagmus allow a precise neuroanatomical localization: for instance, downbeat nystagmus, which is most often caused by a bilateral floccular lesion or dysfunction, or upbeat nystagmus, which is caused by a lesion in the mesencephalon or medulla oblongata. Examples of pharmacotherapy are the use of 4-aminopyridine for downbeat and upbeat nystagmus, memantine or gabapentin for fixation pendular nystagmus or baclofen for periodic alternating nystagmus.

Gut feelings: gastrointestinal signs in French bulldogs undergoing spinal surgery.

The French bulldog (FBD) is a brachycephalic breed prone to several neurological conditions, of which intervertebral disc herniation (IVDH) is considerably prevalent. Gastrointestinal (GI) disease is a reported complication in dogs surgically treated for IVDH. The objective of this study was to describe GI signs and their outcome in FBDs surgically treated for IVDH. Data regarding the GI signs (vomiting, diarrhoea and regurgitation), their frequency and short-term outcome in FBDs surgically treated for IVDH (cervical, thoracolumbar or lumbar) between January 2017 and April 2023 were obtained from medical records at one institution. Categorical variables were compared using Fisher exact tests, and ordinal/continuous data between categorical groups using Kruskal-Wallis or Mann-Whitney tests. Ninety-seven FBDs were included for analysis. GI signs occurred in 74/97 (76.3%) FBDs while hospitalised, with 33.8% and 66.2% developing GI signs pre- and post-operatively, respectively. FBDs that developed GI signs had a mean of 4.9 episodes. Diarrhoea was the most common GI sign encountered (51/74) compared to regurgitation (38/74) and vomiting (22/74). Resolution of GI signs occurred within a mean of 2.2 days. Mean duration of hospitalisation post-surgery was 4.6 days in FBDs that developed GI signs versus 3.7 days in FBDs that did not (p = 0.033). Anaesthesia length was associated with developing GI signs (p=0.037). Neurological severity, neuroanatomical localisation and surgical procedure were not associated with development of GI signs (p = 0.42, p = 0.794 and p = 1, respectively). GI signs were commonly encountered in FBDs surgically treated for IVDH and associated with length of anaesthesia and prolonged hospitalisation.

Neurological manifestations in dogs with acute leukemia.

Canine acute leukemia is a rare hematopoietic neoplasm. Neurological abnormalities have been frequently reported in dogs with acute leukemia (AL). However, the description of the presentation and findings are limited. This study aimed to describe the clinical findings in dogs with acute leukemia presenting with neurological signs as their primary complaint. The database of a private referral hospital was searched for cases that presented to the neurological department with neurological deficits and were subsequently diagnosed with acute leukemia. Six cases were included; all had neurological clinical signs and an abnormal neurological examination. All cases had a focal neuroanatomical localisation on neurological examination (brain n = 4; spinal = 2). Out of the four dogs with a complete magnetic resonance imaging (MRI) study, there was an ill-defined infiltrative pattern with abnormal signal intensity in the central nervous system (CNS) in three dogs and the loss of grey and white matter differentiation in the brain (n = 2) and/or spinal cord (n = 2). Other MRI findings included abnormal meningeal enhancement (n = 3), changes affecting spinal nerves and epaxial muscles (n = 2), and lymphadenopathy in the field of view (n = 2). The bone marrow assessment on MRI showed evidence of signal change (n = 3), characterized by a loss of normal fat opacity and an abnormal degree of contrast enhancement. The cerebrospinal fluid (CSF) analysis of the four dogs showed an increased protein level with non-specific pleocytosis and without evidence of malignant cells. Treatment with cytotoxic medication was implemented in two dogs. The dogs diagnosed with acute leukemia had focal neuroanatomical localisation, an infiltrative CNS pattern, and bone marrow remodulation on MRI with an increase in CSF protein and negative cytology analysis.

Perceptions and metaphors of patients about epileptic seizures and postictal state in Medellín-Colombia: A qualitative study

IntroductionPWE describe epileptic seizures and the postictal state with the description of experienced symptoms or through metaphorical language. For treating physicians, this metaphoric language may go unnoticed. The purpose of the study is to identify both the real and metaphorical descriptions of epileptic seizures and postictal state referred by PWE from Medellín Colombia. MethodsIt is a qualitative study that uses grounded theory applied in ten semi-structured interviews of PWE from the Metropolitan Area of Medellín, Colombia. Descriptions of epileptic seizures and the postictal state were identified. For their classification into metaphorical and literal characteristics, the texts of “The Living Metaphor” by Paul Riccoeur, “The Illness and its Metaphors – AIDS and its Metaphors” by Susan Sontag, and “Metaphors of Everyday Life” by Lakoff and Johnson were used as references. ResultsTen clinical and fourteen metaphorical descriptions of epileptic seizures were identified. Regarding the postictal state, eight clinical and six metaphorical descriptions were identified. The metaphors were classified into three categories: a. external force b. depreciation and division and c. the absence of continuity (slowness, disconnection). ConclusionMetaphors are frequent in the description of epileptic seizures and can be useful in seizure classification, neuroanatomical localization, and therapeutic approach. Metaphors can be an initial stage in the construction of otherness as a form of identity.

Possible case of prefixed brachial plexus in a dog with a caudal cervical intervertebral disc extrusion

AbstractA 5‐year‐old, entire, male dachshund was referred with a 7‐day history of non‐ambulatory paraparesis. The neurological examination was most consistent with a T3–L3 myelopathy. Magnetic resonance imaging and computed tomography studies of the cervical, cervicothoracic and thoracolumbar regions revealed a C7–T1 intervertebral disc extrusion causing moderate spinal cord compression. Based on the clinical presentation and imaging findings, a presumptive diagnosis of intervertebral disc extrusion in a dog affected by suspected prefixed brachial plexus was made. The dog underwent a ventral slot decompressive surgery, and its neurological conditions improved shortly after. The discrepancy between neuroanatomical localisation and location of an intervertebral disc extrusion may represent a possible instance of prefixed brachial plexus. To the authors’ best knowledge, prefixed brachial plexus has not been reported in dogs to date.

Machine Learning and Artificial Intelligence Applications to Epilepsy: a Review for the Practicing Epileptologist.

Machine Learning (ML) and Artificial Intelligence (AI) are data-driven techniques to translate raw data into applicable and interpretable insights that can assist in clinical decision making. Some of these tools have extremely promising initial results, earning both great excitement and creating hype. This non-technical article reviews recent developments in ML/AI in epilepsy to assist the current practicing epileptologist in understanding both the benefits and limitations of integrating ML/AI tools into their clinical practice. ML/AI tools have been developed to assist clinicians in almost every clinical decision including (1) predicting future epilepsy in people at risk, (2) detecting and monitoring for seizures, (3) differentiating epilepsy from mimics, (4) using data to improve neuroanatomic localization and lateralization, and (5) tracking and predicting response to medical and surgical treatments. We also discuss practical, ethical, and equity considerations in the development and application of ML/AI tools including chatbots based on Large Language Models (e.g., ChatGPT). ML/AI tools will change how clinical medicine is practiced, but, with rare exceptions, the transferability to other centers, effectiveness, and safety of these approaches have not yet been established rigorously. In the future, ML/AI will not replace epileptologists, but epileptologists with ML/AI will replace epileptologists without ML/AI.

Neuroanatomical location of brain metastases from solid tumours based on pathology: An analysis of 511 patients with a comparison to the provided clinical history.

Brain metastases are a frequent occurrence in neuropathology practices. The literature on their neuroanatomical location is frequently derived from radiological analyses. This work examines brain metastases through the lens of pathology specimens. All brain surgical pathology reports for cases accessioned 2011-2020 were retrieved from a laboratory. Specimens were classified by neuroanatomical location, diagnosis and diagnostic category with a hierarchical free text string-matching algorithm (HFTSMA) and also subsequently audited. All reports classified as probable metastasis were reviewed by a pathologist. The provided history was compared to the final categorization by a pathologist. The cohort had 4,625 cases. The HFTSMA identified 854 cases (including metastases from a definite primary, metastases from primary not known and improperly classified cases). 514/854 cases had one definite primary site per algorithm and on report review 538/854 cases were confirmed as such. The 538 cases originated from 511 patients. Primaries from breast, gynecologic tract, and gastrointestinal tract not otherwise specified were most frequently found in the cerebellum. Kidney metastases were most frequently found in the occipital lobe. Lung, metastatic melanoma and colorectal primaries were most commonly found in the frontal lobe. The provided clinical history predicted the primary in 206 cases (40.3%), was discordant in 17 cases (3.3%) and non-contributory in 280 cases (54.8%). The observed distribution of the metastatic tumours in the brain is dependent on the primary site. In the majority (54.8%) of cases, the provided clinical history was non-contributory; this suggests surgeon-pathologist communication may have the potential for optimization.

Timing on patent foramen ovale closure: early versus delayed closure

Abstract Introduction Pivotal randomized clinical trials showed benefit in patent foramen ovale closure (PFOC) up to 9 months after a cryptogenic stroke or transient ischemic attack (TIA) [1-4]. It might be sensible to indicate PFOC also in non-recent cryptogenic strokes, but evidence is lacking. Purpose We aimed to compare the effectiveness of PFOC according to the time elapsed from the patient’s last episode of cryptogenic cerebrovascular event (CVE) or systemic embolism (SE). Methods A retrospective, international, multicentre, cohort study was performed to compare the outcomes of an early closure (EC, &amp;lt;9 months) or delayed closure (DC, ≥9 months) of patent foramen ovale (PFO) as secondary prevention after the index event. The primary end-point was recurrence of CVE or SE after PFOC. Results A total of 325 and 171 patients were classified in the EC and DC groups, with a median time to PFOC of 3.4 (IQR 1.9-5.5) and 17.5 (IQR 12.2-33.4) months, respectively. No significant differences were observed regarding the type of event indicating PFOC (stroke was the most frequent (77.8% in EC group vs 79.0% in DC group), followed by TIA (19.4% vs 18.7%)); neither about neuroanatomic localization of the lesions, nor contrast transcranial Doppler patterns, nor Risk of Paradoxical Embolism (RoPE) score (7 (IQR 5-8) vs 6 (IQR 5-7), p=0.077). Echocardiographic PFO characteristics of both groups were similar, except for a larger defect size (tunnel width) in the DC group (6 (IQR 4-14) vs 12 (IQR 6-16) mm, p=0.005)). PFOC device, procedural success (99.4 in EC vs 98.8% in DC group) and periprocedural complications (2.1 vs 0.8%) were comparable in both groups. Median follow-up was 2.0 (IQR 1.3-3.8) years in the EC group and 2.2 (IQR 1.2-4.9) in the DC group (p=0.721). No significant differences were observed concerning recurrence of stroke, TIA or SE (3.9% vs 2.6%, p=0.443), time from PFOC to recurrence (0.9 (IQR 0-2.1) vs 6.1 (2.5-8.8) years, p=0.090), death (1.4% vs 1.0%, p=0.697), residual shunt 12 months after PFOC, or antithrombotic treatment during follow-up (Figure 1). Moreover, a subanalysis considering those patients with a very delayed PFOC (≥24 months) after the index event also showed no differences in recurrence rate during follow-up compared to the earlier procedures (4.2% in the &amp;lt;24-month group vs 3.4% ≥24-month group, p=0.770). Conclusions No differences were observed regarding recurrences of CVE/SE in patients undergoing PFOC before and after 9 months from the index event. Despite the absence of evidence from randomized trials, this study suggests that the preventive benefit of PFOC after a cryptogenic CVE/SE may be extended beyond 9 months after the last event.Figure 1:Incidence of recurre

Respiratory compromise in French bulldogs presented with intervertebral disc extrusion.

French bulldogs hospitalised for the management of intervertebral disc extrusion (IVDE) are frequently affected by respiratory compromise, typically brachycephalic-associated upper respiratory obstruction and/or aspiration events. We evaluated the occurrence of such respiratory compromise events in French bulldogs presented to two referral hospitals. Clinical data for French bulldogs diagnosed with IVDE were retrospectively collated, including severity of neurological deficits, neuroanatomical localisation, diagnosis, details of respiratory compromise, treatment and outcome. A total of 306 dogs diagnosed with IVDE were included. Sixty dogs (19.6%) experienced respiratory compromise, of which 31 dogs (10.1%) progressed to cyanosis, collapse or respiratory arrest. The study was limited by its retrospective nature. Furthermore, the duration of hospitalisation was not evaluated and the decision for euthanasia was often multifactorial. One in five French bulldogs presented with IVDE experienced respiratory compromise. The detrimental welfare effects of this warrant further discussion.

Recurrent pyogranulomatous polymyositis and intramuscular abscesses secondary to Corynebacterium species in a young beagle

AbstractA 16‐month‐old, male, entire beagle presented for suspected relapse of steroid‐responsive meningitis‐arteritis 12 months after diagnosis. Following improvement with immunosuppressive treatment, the dog developed lethargy and right pelvic limb lameness. Neuroanatomical localisation was to the L4–S3 spinal cord segments/associated peripheral nerves. Magnetic resonance imaging revealed peripherally contrast‐enhancing, fluid‐isointense, cavitary lesions within the right and left great adductor, gracilis muscles and right semimembranosus, internal and external obturator, superficial glutaeal and coccygeal muscles. Culture and sensitivity of muscle fine‐needle aspiration revealed Corynebacterium species without antibiotic resistance. Clinical signs resolved on amoxicillin‐clavulanate (25 mg/kg/12 h) and clindamycin (20 mg/kg/12 h), but relapsed after 6 weeks. Addition of marbofloxacin (2 mg/kg/24 h) achieved clinical resolution. After 2 weeks, the dog relapsed and the owner elected euthanasia. Postmortem biopsies of the gracilis and semitendinosus muscles revealed pyogranulomatous polymyositis. Corynebacterium species should be considered a differential diagnosis for pyogranulomatous polymyositis in dogs. Lack of response to appropriate antibiotic treatment in immunosuppressed dogs may carry a poor prognosis.

Assessment of white matter hyperintensity severity using multimodal magnetic resonance imaging.

White matter hyperintensities are radiological abnormalities reflecting cerebrovascular dysfunction detectable using MRI. White matter hyperintensities are often present in individuals at the later stages of the lifespan and in prodromal stages in the Alzheimer's disease spectrum. Tissue alterations underlying white matter hyperintensities may include demyelination, inflammation and oedema, but these are highly variable by neuroanatomical location and between individuals. There is a crucial need to characterize these white matter hyperintensity tissue alterations in vivo to improve prognosis and, potentially, treatment outcomes. How different MRI measure(s) of tissue microstructure capture clinically-relevant white matter hyperintensity tissue damage is currently unknown. Here, we compared six MRI signal measures sampled within white matter hyperintensities and their associations with multiple clinically-relevant outcomes, consisting of global and cortical brain morphometry, cognitive function, diagnostic and demographic differences and cardiovascular risk factors. We used cross-sectional data from 118 participants: healthy controls (n = 30), individuals at high risk for Alzheimer's disease due to familial history (n = 47), mild cognitive impairment (n = 32) and clinical Alzheimer's disease dementia (n = 9). We sampled the median signal within white matter hyperintensities on weighted MRI images [T1-weighted (T1w), T2-weighted (T2w), T1w/T2w ratio, fluid-attenuated inversion recovery (FLAIR)] as well as the relaxation times from quantitative T1 (qT1) and T2* (qT2*) images. qT2* and fluid-attenuated inversion recovery signals within white matter hyperintensities displayed different age- and disease-related trends compared to normal-appearing white matter signals, suggesting sensitivity to white matter hyperintensity-specific tissue deterioration. Further, white matter hyperintensity qT2*, particularly in periventricular and occipital white matter regions, was consistently associated with all types of clinically-relevant outcomes in both univariate and multivariate analyses and across two parcellation schemes. qT1 and fluid-attenuated inversion recovery measures showed consistent clinical relationships in multivariate but not univariate analyses, while T1w, T2w and T1w/T2w ratio measures were not consistently associated with clinical variables. We observed that the qT2* signal was sensitive to clinically-relevant microstructural tissue alterations specific to white matter hyperintensities. Our results suggest that combining volumetric and signal measures of white matter hyperintensity should be considered to fully characterize the severity of white matter hyperintensities in vivo. These findings may have implications in determining the reversibility of white matter hyperintensities and the potential efficacy of cardio- and cerebrovascular treatments.

Stroke-Related Visceral Alterations: A Voxel-Based Neuroanatomic Localization Study.

Functional and morphologic changes in extracranial organs can occur after acute brain injury. The neuroanatomic correlates of such changes are not fully known. Herein, we tested the hypothesis that brain infarcts are associated with cardiac and systemic abnormalities (CSAs) in a regionally specific manner. We generated voxelwise p value maps of brain infarcts for poststroke plasma cardiac troponin T (cTnT) elevation, QTc prolongation, in-hospital infection, and acute stress hyperglycemia (ASH) in 1,208 acute ischemic stroke patients prospectively recruited into the Heart-Brain Interactions Study. We examined the relationship between infarct location and CSAs using a permutation-based approach and identified clusters of contiguous voxels associated with p < 0.05. cTnT elevation not attributable to a known cardiac reason was detected in 5.5%, QTc prolongation in the absence of a known provoker in 21.2%, ASH in 33.9%, and poststroke infection in 13.6%. We identified significant, spatially segregated voxel clusters for each CSA. The clusters for troponin elevation and QTc prolongation mapped to the right hemisphere. There were 3 clusters for ASH, the largest of which was in the left hemisphere. We found 2 clusters for poststroke infection, one associated with pneumonia in the left and one with urinary tract infection in the right hemisphere. The relationship between infarct location and CSAs persisted after adjusting for infarct volume. Our results show that there are discrete regions of brain infarcts associated with CSAs. This information could be used to bootstrap toward new markers for better differentiation between neurogenic and non-neurogenic mechanisms of poststroke CSAs. ANN NEUROL 2023;94:1155-1163.

P20.08.B CLINICAL AND MOLECULAR ANALYSES OF A SERIES OF ADULT PILOCYTIC ASTROCYTOMA

Abstract BACKGROUND Pilocytic astrocytoma (PA) is a rare, grade 1 subtype of glioma. It is most frequent during the first two decades of life, the incidence rate decreasing with age. PAs are usually located in the cerebellum, although they have also been described in other sites. They are circumscribed, solid-cystic, with low cellularity and generally slow-growing tumours with good prognosis in the paediatric age group. PA is associated with MAPK pathway dysregulation, most often showing BRAF gene alterations. PA is very rare in older adults and is associated in some cases with a worse prognosis. In this work we set out to analyse a series of adult PA from a clinical, morphological and molecular point of view. MATERIAL AND METHODS Clinical data were collected from a group of adult patients diagnosed with PA. Nucleic acid extraction was performed by automated extraction and the samples were analysed through a 30-gene targeted panel for gliomas by using Next-Generation Sequencing. Tandem duplication causing fusion of KIAA1549 and BRAF genes (K-B fusion) was analysed by RT-PCR. RESULTS Thirty-four patients were included, with a mean age of 34.4 years (range, 18-57 years). The male/female ratio was 26/8. Mean overall survival was 150.5 months, with more than 10 years of mean follow-up. At the time of the last review, 91% (30/33) of the patients remained alive, while the remaining 9% (3/33) died. Neuroanatomic locations (31 cases) were as follows: cerebrum/lobar 23% (7), cerebellum 39% (12), brainstem 10% (3), ventricle 6% (2), spinal cord 10% (3), optic nerve 13% (4). The K-B fusion was detected in 44% of cases (8/18). Of these, 87.5% (7/8) and 12.5% (1/8) showed fusions involving exons 16:9 and 15:9, respectively. K-B positive cases had a mean age of 40 years. Analyses by NGS revealed mutations in NF1 (15%), BRAF (11%), PDGFRA (11%), EGFR (7%) and PIK3CA (7%). Other variants observed in 4% of cases involved ATRX, CIC, IDH1, KEL, KRAS, MET, MSH6, PTPN11 and RB1. No alterations were detected in 3 of the cases, suggesting that other untested driver alterations could be present. CONCLUSION In this series, no significant differences with childhood PA in the frequency of molecular alterations were observed, in contrast to other gliomas where there are strong differences in the molecular alterations between adult and paediatric tumours. The most common genetic alterations in adult PA involved the MAPK pathway, as previously reported. In contrast to other adult PA studies, the frequency of K-B fusion was similar to that of paediatric PA. Molecular alterations related to an aggressive behaviour or to other glioma types were identified, such as mutations of ATRX, PDGFRA, NF1 or PI3KCA, which can suggest other tumour types. Our results suggest the need for multilayer histological and molecular diagnosis to appropriately manage adult PA.

Histochemical mapping of the duration of action of photobiomodulation on cytochrome c oxidase in the rat brain.

This is the first study mapping the duration of action of in vivo photobiomodulation (PBM) on cytochrome-c-oxidase (CCO). In cellular bioenergetics, CCO is the terminal rate-limiting enzyme in the mitochondrial electron transport chain, which catalyzes oxygen utilization for aerobic energy production. PBM using transcranial infrared laser stimulation (TILS) is a promising intervention for non-invasively modulating CCO in the brain. TILS of the human prefrontal cortex directly causes CCO photo-oxidation, which is associated with increased cerebral oxygenation and improved cognition. This experiment aimed to map the duration of action of in vivo PBM on CCO activity in discrete neuroanatomic locations within rat brains up to 4 weeks after a single TILS session (50 s, 1064 nm CW, 250 mW/cm2). Control brains from rats treated with a sham session without TILS (laser off) were compared to brains from TILS-treated rats that were collected 1 day, 2 weeks, or 4 weeks post-TILS. Cryostat sections of the 36 collected brains were processed using quantitative enzyme histochemistry and digitally imaged. Densitometric readings of 28 regions of interest were recorded and converted to CCO activity units of oxygen utilization using calibration standards. Data analysis (ANCOVA) compared each laser-treated group to sham with whole-brain average as a covariate. The prefrontal infralimbic cortex showed the earliest significant increase in CCO activity between 1-day post-TILS and sham groups, which continued elevated for 2-4 weeks post-TILS. Significant differences in CCO activity between 2-weeks and sham groups were also found in the lateral septum, accumbens core, CA3 of the hippocampus, and the molecular layer of the hippocampus. The medial amygdala showed a significant decrease in CCO activity between 4-weeks and sham. Further analyses showed significant inter-regional CCO activity correlations among the brain regions as the result of TILS, with the most pronounced changes at 4-weeks post-stimulation. The time course of changes in CCO activity and network connectivity suggested that TILS caused different neuroplasticity types of bioenergetic changes at different time scales, depending on brain region and its depth from the cortex. In conclusion, this controlled CCO histochemical study demonstrated a long-lasting duration of action of PBM in the rat brain.

Suspected pregnancy‐associated meningoencephalitis of unknown origin in a dog

AbstractA 1‐year 5‐month‐old, female, entire Parson Russell terrier was referred for investigations of focal epileptic seizures and behavioural changes. The clinical signs started 4 days after whelping its first litter. On presentation, the neurological examination was unremarkable. Neuroanatomical localisation was the forebrain. A brain magnetic resonance imaging showed bilateral, asymmetric, intra‐axial, T2‐weighted and fluid‐attenuated inversion recovery hyperintense, T1‐weighted hypointense, mildly to non‐contrast‐enhancing lesions in the piriform cortex. Cerebrospinal fluid analysis was within normal limits, and main infectious diseases were ruled out. Based on the presentation, findings and progression of clinical signs, a meningoencephalitis of unknown origin was suspected. In the present case, a positive response to immunosuppressive medication was observed. A well‐established link between pregnancy and immune‐mediated diseases, including meningoencephalitis, has been described in humans. This connection could have been the reason of the clinical signs, and this is supported by the recent pregnancy, presentation and positive response to immunosuppressive medication.

Post-stroke aggressive behavior in patients wıth first-ever ischemic stroke: underlying clinical and imaging factors.

Aggression is defined as a complex behavior consisting of a combination of sensory, emotional, cognitive and motor elements. We aimed to examine the relationships between post-stroke aggressive behavior (PSAB) and neuropsychological and neuroimaging findings. 380 patients in the stroke unit were classified as aggressive or non-aggressive based on symptoms elicited by the Neuropsychiatric Inventory (NPI) and aggression screening questionnaire. Aggressive behavior was detected in 42 (11.1%) of 380 patients who had a first ischemic stroke. Patients with PSAB were older than those without (338 patients) (66.98 + 13.68 vs. 62.61 + 13.06, P = 0.043). Hamilton depression and anxiety scales showed significantly higher rates of depression and anxiety in the PSAB group compared to the non-PSAB group (47.6% vs. 16.3% and 57.1% vs. 15.4%, respectively; P = 0.001). Lesion mapping analysis showed that lesions in patients with PSAB mostly included the lower parietal lobe and lateral frontal gyrus. Multiple regression analysis showed that gender (OR, 2.81; CI%, 1.24-6.39), lateral prefrontal infarction (OR, 6.43; CI%, 1.51-27.44), parietal infarction (OR, 2.98; CI%, 1.15-7.76), occipital infarction (OR, 2.84; CI%, 1.00-8.06), multiple infarcts (OR, 5.62; CI%, 2.27-13.93), anxiety (OR, 2.06; CI%, 0.89-4.81) and verbal memory deficit (OR, 4.21; CI%, 1.37-12.93) were significant independent predictors of PSAB. The presence of PSAB may be related to neuropsychiatric symptoms such as high anxiety and verbal memory impairment, and neuroanatomical location of the lesions.