Rehemorrhage of brainstem cavernous malformations: a benchmark approach to individualized risk and severity assessment.

OBJECTIVE: Brainstem cavernous malformations (BSCMs) represent a unique subgroup of cavernous malformations with more hemorrhagic presentation and technical challenges. This study aimed to provide individualized assessment of the rehemorrhage clustering risk of BSCMs after the first symptomatic hemorrhage and to identify patients at higher risk of neurological deterioration after new hemorrhage, which would help in clinical decision-making. METHODS: A total of 123 consecutive BSCM patients with symptomatic hemorrhage were identified between 2015 and 2022, with untreated follow-up > 12 months or subsequent hemorrhage during the untreated follow-up. Nomograms were proposed to individualize the assessment of subsequent hemorrhage risk and neurological status (determined by the modified Rankin Scale [mRS] score) after future hemorrhage. The least absolute shrinkage and selector operation (LASSO) regression was used for feature screening. The calibration curve and concordance index (C-index) were used to assess the internal calibration and discrimination performance of the nomograms. Cross-validation was further performed to validate the accuracy of the nomograms. RESULTS: Prior hemorrhage times (adjusted OR [aOR] 6.78 per ictus increase) and Zabramski type I or V (OR 11.04) were associated with rehemorrhage within 1 year. A lower mRS score after previous hemorrhage (aOR 0.38 for a shift to a higher mRS score), Zabramski type I or V (OR 3.41), medulla or midbrain location (aOR 2.77), and multiple cerebral cavernous malformations (aOR 11.76) were associated with worsened neurological status at subsequent hemorrhage. The nomograms showed good accuracy and discrimination, with a C-index of 0.80 for predicting subsequent hemorrhage within 1 year and 0.71 for predicting neurological status after subsequent hemorrhage, which were maintained in cross-validation. CONCLUSIONS: An individualized approach to risk and severity assessment of BSCM rehemorrhage was feasible with clinical and imaging features.

Predictors of Outcome in Patients with Medullary Hemorrhage.

BACKGROUND: Isolated medullary hemorrhage (MH) is an uncommon presentation of spontaneous intraparenchymal hemorrhage. The relationship between MH and neurological outcome is not well known. This study aims to assess predictive parameters for the outcome of medullary hemorrhage. METHODS: We conducted an extensive search of the literature for cases with spontaneous, isolated MH. The study was conducted according to the statement of Preferred Reporting Items for Systematic Reviews and Meta Analysis (PRISMA). Forty-three cases diagnosed by CT or MRI have been reported in the literature, to which we add three confirmed by MRI. The ventrodorsal size of hemorrhage was taken into account as a parameter of outcome. Early neurologic deterioration (END) was defined as an incremental increase in the National Institutes of Health Stroke Scale score by ≥1 point in motor power, or ≥2 points in the total score within the first week after admission. Modified Rankin Score (mRS) 0-2 was presumed as favorable outcome (FO) and mRS 3-6 score as unfavorable outcome (UO) at discharge and at 3 months after stroke. RESULTS: We enrolled 46 patients, and 17 (37%) patients were diagnosed with END. The cause of medullary hemorrhage was mostly vascular malformations, including cavernous malformation (33%) and arteriovenous malformation (11%). In univariate analyses, neither arteriovenous malformations (OR, 1.04; 95%CI, 0.10-10.53; P = 0.68) nor cavernomas (OR, 1.04; 95%CI, 0.22-4.89; P = 0.62) were associated with UO. Acute respiratory distress syndrome was higher in patients with UO group (44%) compared to those with FO group (16%), but this difference did not reach to a significant level (OR, 4.13; 95%CI, 0.85-20.04; P = 0.09). The diameter of hemorrhage was significantly larger (≥1 cm) in patients with UO compared to those with FO (OR, 16.67; 95%CI, 1.87-148.89; P = 0.003). Three months after stroke, 37 patients (80%) had FO and 9 (19.5%) had UO, and 5 (11%) died. Multiple logistic regression analysis using predetermined variables found to be significant in univariate analyses (END, consciousness disturbance at admission, hemorrhage size, and hypertension) showed that END at stroke onset was significantly associated with UO (OR, 4.97; CI95%, 1.13-21.94; P = 0.03). CONCLUSIONS: These results suggest that the END is a predictor for UO in patients with medullary hemorrhage. The extent of the medullary hemorrhage along the conduction tract may contribute to deterioration.

[Tanatological assessment of long-brain structures in death from hemorrhagic shock at different post-mortal periods]. / Tanatologicheskaya otsenka struktur prodolgovatogo mozga pri smerti ot gemorragicheskogo shoka v razlichnye sroki postmortal'nogo perioda.

Authors determined the morphological and morphometric characteristics of nerve and vascular structures in death from blood loss complicated by hemorrhagic shock. The medulla oblongata of 12 corpses of persons who died from stab wounds of blood vessels and internal organs with sharp instruments at different times of the postmortem period was studied. Studies were carried out at stages of 6-8 hours, 12-14 hours, 18-20 hours, 24 hours or more of the postmortem period. It was found that as the interval after death from hemorrhagic shock increases, there is an increase in destructive changes, both neurons and intracerebral vessels in the medulla oblongata. Autolytic processes to a greater extent capture the intracerebral vessels comparing with neurons, which is more pronounced in the later stages of the study. The sizes of perineural and perivascular spaces in the dynamics of the postmortem period increase synchronously, which reflects the permanence of manifestations of tanatogenesis in different periods after death from hemorrhagic shock.

Longitudinal Volume Quantification of Deep Medullary Veins in Patients with Cerebral Venous Sinus Thrombosis : Venous Volume Assessment in Cerebral Venous Sinus Thrombosis Using SWI.

PURPOSE: Susceptibility-weighted imaging (SWI) visualizes small cerebral veins with high sensitivity and could, thus, enable quantification of hemodynamics of deep medullary veins. We aimed to evaluate volume changes of deep medullary veins in patients with acute cerebral venous sinus thrombosis (CVST) over time in comparison to healthy controls. METHODS: All magnetic resonance imaging (MRI) experiments were executed at 3 T using a 32-channel head coil. Based on SWI and semiautomatic postprocessing (statistical parametric mapping [SPM8] and ANTs), the volume of deep medullary veins was quantified in 14 patients with acute CVST at baseline and the 6­month follow-up, as well as in 13 healthy controls undergoing repeated MRI examination with an interscan interval of at least 1 month. RESULTS: Deep medullary venous volume change over time was significantly different between healthy controls and patient groups (p < 0.001). Patients with superior sagittal sinus thrombosis (SSST) showed a significant decline from baseline to follow-up measurements (9.8 ± 4.9 ml versus 7.5 ± 4.2 ml; p = 0.02), whereas in patients with transverse sinus thrombosis (TST) and healthy controls no significant volume changes were observable. CONCLUSIONS: Venous volume quantification was feasible and reproducible both in healthy volunteers and in patients. The decrease of venous volume in patients over time represents improvement of venous drainage, reduction of congestion, and normalization of microcirculation due to treatment. Thus, quantification of venous microcirculation could be valuable for estimation of prognosis and guidance of CVST therapy in the future.

Perfusion weighted imaging in the assessment of the pathology and outcomes of lateral medullary infarction.

This series case report aimed to elucidate the underlying pathology and outcomes of lateral medullary infarction (LMI) using perfusion weighted imaging (PWI). Four patients were diagnosed with LMI based on high-field diffusion-weighted magnetic resonance imaging (MRI-DWI) and PWI. The national institutes of health stroke scale (NIHSS) scores were recorded on days 1, 7, and 30, and the Barthel index was assessed on days 7 and 30. Three patients exhibited relative regional hypoperfusion of medullary lesion in the perfusion maps. Two cases exhibited ipsilateral hypoperfusion in the inferior cerebellum, whereas one patient exhibited a relatively regional hyperperfusion in the medulla oblongata. The LMI patients with a high NIHSS score and low Barthel index on days 7 and 30 exhibited regional hypoperfusion. This report of 4 LMI cases provides preliminary evidence that regional hypoperfusion may contribute to worse outcomes in LMI.

Brainstem arteriovenous malformations: anatomical subtypes, assessment of "occlusion in situ" technique, and microsurgical results.

OBJECT: The surgical management of brainstem arteriovenous malformations (AVMs) might benefit from the definition of anatomical subtypes and refinements of resection techniques. Many brainstem AVMs sit extrinsically on pia mater rather than intrinsically in the parenchyma, allowing treatment by occluding feeding arteries circumferentially, interrupting draining veins after arteriovenous shunting is eliminated, and leaving the obliterated nidus behind. The authors report here the largest series of brainstem AVMs to define 6 subtypes, assess this "occlusion in situ" technique, and analyze the microsurgical results. METHODS: Brainstem AVMs were categorized as 1 of 6 types: anterior midbrain, posterior midbrain, anterior pontine, lateral pontine, anterior medullary, and lateral medullary AVMs. Data from a prospectively maintained AVM registry were reviewed to evaluate multidisciplinary treatment results. RESULTS: During a 15-year period, the authors treated 29 patients with brainstem AVMs located in the midbrain (1 anterior and 6 posterior), pons (6 anterior and 7 lateral), and medulla (1 anterior and 8 lateral). The nidus was pial in 26 cases and parenchymal in 3 cases. Twenty-three patients (79%) presented with hemorrhage. Brainstem AVMs were either resected (18 patients, 62%) or occluded in situ (11 patients, 38%). All lateral pontine AVMs were resected, and the occlusion in situ rate was highest with anterior pontine AVMs (83%). Angiography confirmed complete obliteration in 26 patients (89.6%). The surgical mortality rate was 6.9%, and the rate of permanent neurological deterioration was 13.8%. At follow-up (mean 1.3 years), good outcomes (modified Rankin Scale [mRS] score ≤ 2) were observed in 18 patients (66.7%) and poor outcomes (mRS score of 3-5) were observed in 9 patients (33.3%). The mRS scores in 21 patients (77.8%) were unchanged or improved. The best outcomes were observed with lateral pontine (100%) and lateral medullary (75%) AVMs, and the rate of worsening/death was greatest with posterior midbrain and anterior pontine AVMs (50% each). CONCLUSIONS: Brainstem AVMs can be differentiated by their location in the brainstem (midbrain, pons, or medulla) and the surface on which they are based (anterior, posterior, or lateral). Anatomical subtypes can help the neurosurgeon determine how to advise patients, with lateral subtypes being a favorable surgical indication along with extrinsic pial location and hemorrhagic presentation. Most AVMs are dissected with the intention to resect them, and occlusion in situ is reserved for those AVMs that do not separate cleanly from the brainstem, that penetrate into the parenchyma, or are more anterior in location, where it is difficult to visualize and preserve perforating arteries (anterior pontine and lateral medullary AVMs). Although surgical morbidity is considerable, surgery results in a better obliteration rate than nonoperative management and is indicated in highly selected patients with high rerupture risks.

A re-assessment of the effects of intracortical delivery of inosine on transmidline growth of corticospinal tract axons after unilateral lesions of the medullary pyramid.

This study was undertaken as part of the NIH "Facilities of Research Excellence-Spinal Cord Injury", which supports independent replication of published studies. Here, we repeat an experiment reporting that intracortical delivery of inosine promoted trans-midline growth of corticospinal tract (CST) axons in the spinal cord after unilateral injury to the medullary pyramid. Rats received unilateral transections of the medullary pyramid and 1 day later, a cannula assembly was implanted into the sensorimotor cortex contralateral to the pyramidotomy to deliver either inosine or vehicle. The cannula assembly was attached to an osmotic minipump that was implanted sub-cutaneously. Seventeen or 18 days post-injury, the CST was traced by making multiple injections of miniruby-BDA into the sensorimotor cortex. Rats were killed for tract tracing 14 days after the BDA injections. Sections through the cervical spinal cord were stained for BDA and immunostained for GAP43 and GFAP. Our results revealed no evidence for enhanced growth of CST axons across the midline of the dorsal column in rats that received intracortical infusion of inosine. Possible reasons for the failure to replicate are discussed.

ImmunoAT method: An initial assessment for the detection of abnormal isoforms of prion protein in formalin-fixed and paraffin-embedded tissues.

The AT-tailing method is a labelling technique that utilises oligo(dA-dT)-dependent signal amplification. In this study, a new immunohistochemical application of the immunoAT method was developed. This method uses an oligo(dA-dT)-conjugated primary antibody (direct immunoAT method) or an oligo(dA-dT)-conjugated secondary antibody (indirect immunoAT method). Fifteen-base oligo(dA-dT)-conjugated antibodies (IgG-ATs) were prepared in advance by conjugating maleimide-activated oligo(dA-dT) to IgG via free sulfhydryl residues that had been introduced on the surface of IgG using Traut's reagent. Following the reaction with the target antigen and the IgG-AT, oligo(dA-dT) was elongated by DeltaTth DNA polymerase in the presence of dATP, dTTP and biotinylated dUTP, consequently labelling the antigen-antibody complex with a large amount of biotin. To initially evaluate the immunoAT method, the presence or absence of prion protein (PrP(sc)) was determined in formalin-fixed and paraffin-embedded sections of the medulla oblongata of cattle which had been under active surveillance for bovine spongiform encephalopathy. Sections were examined using direct and indirect immunoAT methods and the EnVision+ system (Dako) under conditions that were identical except for the differing IgG-AT and AT-tailing methods. PrP(sc) detection was consistent using all three methods. The clearest signals were obtained using the indirect immunoAT method, suggesting significant potential for this method.

Immunohistochemical assessment of cyclic guanosine monophosphate (cGMP) and soluble guanylate cyclase (sGC) within the rostral ventrolateral medulla.

Functional evidence suggests that nitric oxide (NO) signalling in the rostral ventrolateral medulla (RVLM) is cGMP-dependent and that this pathway is impaired in hypertension. We examined cGMP expression as a marker of active NO signalling in the C1 region of the RVLM, comparing adult (>18 weeks) Wistar-Kyoto (WKY, n = 4) and spontaneously hypertensive rats (SHR, n = 4). Double label immunohistochemistry for cGMP-immunoreactivity (IR) and C1 neurons [as identified by phenylethanolamine N-methyltransferase (PNMT-IR) or tyrosine hydroxylase TH-IR)], or neuronal NO synthase (nNOS) neurones, failed to reveal cGMP-IR neurons in the RVLM of either strain, despite consistent detection of cGMP-IR in the nucleus ambiguus (NA). This was unchanged in the presence of isobutylmethylxanthine (IBMX; 0.5 mM, WKY, n = 4, SHR n = 2) and in young animals (WKY, 10-weeks, n = 3). Incubation of RVLM-slices (WKY, 10-weeks, n = 9) in DETA-NO (100 mum; 10 min) or NMDA (10 muM; 2 min) did not uncover cGMP-IR. In all studies, cGMP was prominent within the vasculature. Soluble guanylate cyclase (sGC)-IR was found throughout neurones of the RVLM, but did not co-localise with PNMT, TH or nNOS-IR neurons (WKY, 10-weeks, n = 6). Results indicate that within the RVLM, cGMP is not detectable using immunohistochemistry in the basal state and cannot be elicited by phosphodiesterase inhibition, NMDA receptor stimulation or NO donor application.

Os núcleos vasomotores do bulbo e a regulação cardiovascular: novas evidências e novas questões / Ventrolateral medulla and the cardiovascular control: new evidence new doubts

RESUMO: Há mais de 30 anos foi proposto um modelo para explicar como o sistema nervoso central promove a regulação do sistema cardiovascular, onde os núcleos vasomotores do bulbo seriam as principais estruturas envolvidas no controle do reflexo cardiovascular. Segundo este modelo, o núcleo do trato solitário (NTS) é o primeiro núcleo a integrar as informações cardiovasculares vindas dos baroceptores e também parece integrar vias descendentes provenientes de núcleos superiores como o hipotálamo, importantes para as reações de alerta e defesa. Do NTS saem projeções excitatórias para a região caudoventrolateral (CVL) do bulbo, a qual inibe a região rostroventrolateral (RVL). Esta última região constitui a principal fonte de eferências excitatórias para os neurônios simpáticos pré-ganglionares (SPN), sendo responsável pelo tonus simpático para o coração e vasos. Projeções importantes do CVL para estruturas diencefálicas (núcleo preóptico mediano, núcleo paraventricular do hipotálamo e núcleo supraóptico) também estão envolvidas no controle da composição e/ou volume do compartimento extracelular. A área depressora gigantocelular (GiDA) constitui outro possível centro vasomotor envolvido nos ajustes de fluxo sangüíneo por meio de projeções diretas para o SPN. No entanto, o meio pelo qual a GiDA exerce seu efeito vasodepressor ainda é desconhecido.Nos últimos 10 anos, nosso laboratório tem se dedicado a deslindar as vias e mecanismos neurais associados à regulação do fluxo sangüineo visceral e muscular. Resultados obtidos ao longo destes estudos resultaram em evidências que são incompatíveis com o modelo proposto.

Comparative anatomical assessment of the piglet as a model for the developing human medullary serotonergic system.

Because the piglet is frequently used as a model for developmental disorders of the medullary serotonergic (5-HT) system in the human infant, this review compares the topography and developmental profile of selected 5-HT markers between humans in the first year of life and piglets in the first 60 days of life. The distribution of tryptophan hydroxylase-immunoreactive 5-HT neurons in the human infant medulla is very similar, but not identical, to that in the piglet. One notable difference is the presence of compact clusters of 5-HT neurons at the ventral surface of the piglet medulla. While it lacks these distinctive clusters, the human infant medulla contains potentially homologous 5-HT neurons scattered along the ventral surface embedded in the arcuate nucleus. Each species shows evidence of age-related changes in the 5-HT system, but the changes are different in nature; in the human infant, statistically significant age-related changes are observed in the proportional distribution of medullary 5-HT cells, while in the piglet, statistically significant age-related changes are observed in the levels of 5-HT receptor binding in certain medullary nuclei. Analyses of 5-HT receptor binding profiles in selected nuclei in the two species suggest that the equivalent postnatal ages for 5-HT development in piglets and human infants are, respectively, 4 days and 1 month, 12 days and 4 months, 30 days and 6 months, and 60 days and 12 months. Collectively, when certain species differences are considered, these data support the use of the piglet as a model for the human infant medullary 5-HT system.

The incidence, management, and complications of dysphagia in patients with medullary strokes admitted to a rehabilitation unit.

The objective of this study was to examine the frequency of dysphagia symptoms and related consequences in medullary stroke patients admitted to a stroke rehabilitation unit. A chart review of a cohort of 563 stroke patients admitted to a rehabilitation unit was used to identify patients with evidence of predominantly medullary lesions. The results of both initial and followup videofluoroscopic modified barium swallowing (VMBS) studies were also reviewed for evidence of aspiration and residuum in patients with dysphagia. Twenty of the 563 patients (3.6%) were diagnosed with a medullary stroke. Eleven of the 20 (55%) patients were identified clinically with dysphagia and nine had at least one (VMBS) study. All dysphagic patients demonstrated some degree of either aspiration or residuum on both initial and final swallowing studies and received some form of dietary modification. Comparisons between patients with and without dysphagia demonstrated significant differences with regard to length of hospital stay and the development of pneumonia (p < 0.05). More than half of the patients with medullary strokes presented with clinical indications of dysphagia, were more likely to develop aspiration pneumonia, and experienced longer hospital stays. Aspiration pneumonia appeared to be an early complication of stroke and dietary modifications did not prevent its development.

Sobre a regulaçäo do fluxo sangüíneo / Blood flow regulation

näo tem

Neurographic assessment of intramedullary motoneurone lesions in cervical spinal cord injury: consequences for hand function.

Examination of hand function and neurography of the median- and ulnar nerves was performed in 15 patients with acute and 26 patients with chronic tetraplegia due to cervical spinal cord injury (SCI). 30% of patients showed a mild and 20% a severe axonal lesion of motor fibres of both nerves. The latter is caused by intramedullary damage of ventral horn cells and anterior nerve roots as neurographic examination of sensory nerve fibres was normal in these patients. The most frequent and severe nerve lesion was present in those with lower cervical spinal cord injuries (C6/7-Th1) where the median and ulnar nerves originate. In the latter patients the development of active hand function, which enables the patient to perform active grasping movements, was closely related to the result of neurography, already early after trauma. The results of median and ulnar neurography in tetraplegia due to cervical SCI allow to differentiate between intramedullary damage of motoneurones and the anterior nerve roots (peripheral nervous system) or the pyramidal tract fibres (central nervous system) within the spinal cord responsible for the paresis of the intrinsic hand muscles. Neurography is of prognostic value in cervical SCI to predict the outcome of hand function and therefore influences the appropriate occupational therapy and the program and aims of rehabilitation.

MR imaging of abnormally rotated medulla oblongata, and a criterion for assessment of its normal orientation.

In the MR imaging study of a 4-yr-old patient the medulla oblongata was detected to be rotated 25 degrees counter-clockwise with respect to the remainder of the brain and skull. A similar condition was not visually detected in the evaluation of consecutive 1100 CT and 500 MR imaging studies. The orientation of the medulla oblongata was then geometrically assessed on selected, axial inversion recovery MR images in a series of 50 normal pediatric patients. It was detected that in 70% of cases (n = 35) a line connecting the anterior median fissure and the posterior median sulcus of the medulla oblongata (interfissural line) was parallel to or blended with a vertical reference line passing through the third ventricle (midplane axis). In 30% of cases (n = 15) the interfissural line deviated from the midplane axis up to 10 degrees. It appears that deviation of the medulla oblongata to this extent should be considered to be within normal limits.

Prospective assessment of risks for cervicomedullary-junction compression in infants with achondroplasia.

Achondroplasia, the most common heritable skeletal dysplasia, may result in abnormality at the craniocervical junction, which is a potentially lethal problem in a subset of young infants with this disorder. We evaluated and followed an unbiased and unselected consecutive series of infants with achondroplasia, to better document the occurrence, frequency, and clinical presentation of craniocervical abnormalities. Of 53 prospectively ascertained infants, 5 were judged to have sufficient craniocervical junction compression to require surgical decompression. Intraoperative observation always showed marked abnormality of the cervical spinal cord, and all operated-on children showed marked improvement of neurological function. The most frequent clinical abnormalities within this subset were those expected for high cervical myelopathy. The best predictors of need for suboccipital decompression included lower-limb hyperreflexia or clonus, on examination; central hypopnea demonstrated by polysomnography; and foramen magnum measures below the means for children with achondroplasia. Infants with achondroplasia are at risk for potentially lethal sequelae of craniocervical junction abnormalities; selective intervention can be life and health saving, but individuals at high risk will be identified only if all affected infants undergo comprehensive assessment in infancy.

Chiari I malformations: assessment with phase-contrast velocity MR.

PURPOSE: To assess movement of the medulla, tonsils, and upper cervical cord as well as that of the posterior fossa cerebrospinal fluid pathways in both normal subjects and those with Chiari I malformations. METHODS: Nine healthy volunteers and eight patients with Chiari I malformations were examined with phase-contrast cine MR. With a region-of-interest cursor, the directions and intensities of the brain and cerebrospinal fluid were assessed and intensity-versus-time graphs generated. RESULTS: Cerebrospinal fluid flow patterns of the patients with Chiari I malformations were normal except for absence of valleculla flow. In addition, increased velocities (10 times normal) of the tonsils of all patients with Chiari I malformations together with posterior movement of the medulla (rather than the expected anterior movement seen in volunteers) occurred. CONCLUSIONS: Increased velocities of the tonsils may be the result of the carotid systolic pulse being delivered to a structure (the tonsil) without the normal surrounding cerebrospinal fluid, resulting in impact of the tonsils in the confined foramen magnum and a consequent caudocranial recoil. An alternative explanation would include the Bernoulli effect caused by the confined location of the tonsils. There may be a decrease in the peak tonsillar velocities after surgery.