Bone Marrow Nucleated Cells and Bone Marrow-Derived CD271+ Mesenchymal Stem Cell in Treatment of Encephalopathy and Drug-Resistant Epilepsy.

The broad spectrum of brain injuries in preterm newborns and the plasticity of the central nervous system prompts us to seek solutions for neurodegeneration to prevent the consequences of prematurity and perinatal problems. The study aimed to evaluate the safety and efficacy of the implantation of autologous bone marrow nucleated cells and bone marrow mesenchymal stem cells in different schemes in patients with hypoxic-ischemic encephalopathy and immunological encephalopathy. Fourteen patients received single implantation of bone marrow nucleated cells administered intrathecally and intravenously, followed by multiple rounds of bone marrow mesenchymal stem cells implanted intrathecally, and five patients were treated only with repeated rounds of bone marrow mesenchymal stem cells. Seizure outcomes improved in most cases, including fewer seizures and status epilepticus and reduced doses of antiepileptic drugs compared to the period before treatment. The neuropsychological improvement was more frequent in patients with hypoxic-ischemic encephalopathy than in the immunological encephalopathy group. Changes in emotional functioning occurred with similar frequency in both groups of patients. In the hypoxic-ischemic encephalopathy group, motor improvement was observed in all patients and the majority in the immunological encephalopathy group. The treatment had manageable toxicity, mainly mild to moderate early-onset adverse events. The treatment was generally safe in the 4-year follow-up period, and the effects of the therapy were maintained after its termination.

Comparative Analysis of the Results of Stroke Treatment With Multiple Administrations of Wharton's Jelly Mesenchymal Stem Cells-Derived HE-ATMP and Standard Conservative Treatment: Case Series Study.

Stroke remains still the leading cause of long-term disability worldwide. Although interventions such as early reperfusion, intravenous thrombolysis, and endovascular revascularization have shown neurological benefit in stroke patients, there is still lack of effective treatment enabling regeneration of nervous tissue after cerebral ischemic episodes. Cell therapy is an evolving opportunity for stroke survivors with residual neurological deficits. The purpose of this study was to evaluate safety and potential efficacy of multiple administration of Hospital Exemption-Advanced Therapy Medicinal Product (HE-ATMP) comprising 3 × 107 Wharton's jelly mesenchymal stem cells (WJMSCs). A study group was composed of six patients-three women and three men. The patients were qualified to the treatment with diagnosis of chronic stroke (2-24 months after cerebral ischemic episode), during 2 years. All the patients undergone repeated rounds of HE-ATMP administration to the CSF (cerebrospinal fluid) via lumbar puncture. The control group consisted of six patients (two women and four men) who experienced stroke, treated at the same time (follow-up period: 24 months) using standard treatment methods, without endovascular treatment. To evaluate the results of the therapy, we used both impairment scales [National Institutes of Health Stroke Score (NIHSS)] and functional outcomes scales [Modified Rankin Scale (MRS) and Barthel Index (BI)]. In four patients, who received at least three repeated rounds of HE-ATMP, we reported neurological improvement and reduction of functional neurodeficiency. The biggest improvement concerned the reduction of speech disorders in two cases; significant improvement in the field of motor skills in three patients and reduction of apraxia and improvement of logical communication skills in two patients were also reported. All the patients became more independent. Significant improvement of the neurological condition using the same scales was registered only in two patients from the control group. We did not report any adverse events in the treated group during follow-up. At 1-year follow-up, we demonstrate safety and beneficial effect of WJMSC transplantation including neurological improvement and reduction of functional neurodeficiency. We are aware that the samples size of this study is relatively small. The treatment regimen needs to be further tested in larger group of patients.

Involvement of the cerebellum in the regulation of executive functions in children-Preliminary analysis based on a neuropsychological study of children after cerebellar tumour surgery.

Aim: Preliminary assessment of executive functions in children with cerebellar lesions, description of their emotional-social functioning and selection of sensitive neuropsychological tools to detect the cerebellar cognitive affective syndrome (CCAS). Materials and methods: The study group consisted of 10 children after cerebellar tumour surgery. The control group consisted of 10 healthy children, matched for age and sex: The IDS-2 executive functions battery, the Conners 3 ADHD questionnaire, the Autism Spectrum Rating Scales (ASRS) and the International Cooperative Ataxia Rating Scale (ICARS) were used. Results: Statistical analysis showed statistically significant differences between the experimental and control groups in terms of two dimensions of executive functioning. Children from experimental group was characterised by worse planning and divided attention than healthy controls. Moreover children with cerebellar lesions were characterised by significantly higher levels of some behaviours similar to that observed in autism spectrum disorders, namely difficulties in social relationships, self-regulation of emotions, attention, and greater behavioural rigidity. Test power analysis and estimation of the effect size by the Cohen's d coefficient indicated that with a slight increase in the size of the experimental group, the probability of detecting statistically significant difference in the executive functions total measure score as well as in several ASRS subscales increased, but not in Conners 3 subscales. Conclusions: Cerebellar damage may pose a risk for dysexecutive syndrome and social-emotional problems in children. The IDS-2 executive functions battery and the ASRS test are sufficiently sensitive tools to assess elements of the CCAS in children.

Subjective experience, cognitive functioning and trauma level of patients undergoing awake craniotomy due to brain tumor - Preliminary study.

BACKUP AND OBJECTIVE: Awake craniotomy (AC) for brain tumors, when the patient is conscious during the operation, allows to reduce the risk of motor disability and aphasia, however, it may be a source of extreme stress. The aim of our study was to examine the patients' subjective experience of the surgery including the level of psychological trauma and cognitive functioning. METHOD: Eighteen patients operated due to brain tumor were enrolled in this study. The Essener Trauma-Inventory Questionnaire and the Addenbrooke's Cognitive Examination (ACE III) were administrated. The patients' experience with awake craniotomy was evaluated with a qualitative descriptive survey. RESULTS: All patients remembered the intraoperative neuropsychological examination and several sensations like: drilling, cold, head clamp fixation or having eyes covered. In most of the patients the postoperative psychological trauma experience did not reach the clinical level. The ACE III postoperative scores revealed partial cognitive deficits with the lowest scores in memory and word fluency domains. Slight amnestic aphasia was observed postoperatively only in two patients. CONCLUSIONS: Awake craniotomy for resection of brain tumors is well-tolerated by patients and does not cause significant psychological trauma. Nonetheless, anxiety about the procedure warrants further study and individualized neuropsychological care is needed for the emotional preparation of the patient.

Is Addenbrooke's Cognitive Examination III Sensitive Enough to Detect Cognitive Dysfunctions in Patients with Focal Cerebellar Lesions?

OBJECTIVE: The main aim of the study was to evaluate whether the available brief test of mental functions Addenbrooke's cognitive examination III (ACE III) detects cognitive impairment in patients with cerebellar damage. The second goal was to show the ACE III cognitive impairment profile of patients with focal cerebellar lesions. METHOD: The study sample consisted of 31 patients with focal cerebellar lesions, 78 patients with supratentorial brain damage, and 31 subjects after spine surgery or with spine degeneration considered as control group, free of organic brain damage. The ACE III was used. RESULTS: Patients with cerebellar damage obtained significantly lower results in the ACE III total score and in several subscales: attention, fluency, language, and visuospatial domains than healthy controls without brain damage. With the cut-off level of 89 points, the ACE III was characterized by the sensitivity of 71%, specificity of 72%, and accuracy of 72%. The cerebellar cognitive impairment profile was found to be "frontal-like" and similar to that observed in patients with anterior supratentorial brain damage, with decreased ability to retrieve previously learned material and its preserved recognition, impaired word fluency, and executive dysfunction. The results are consistent with cerebellar cognitive affective syndrome. CONCLUSIONS: The ACE III can be used as a sensitive screening tool to detect cognitive impairments in patients with cerebellar damage.

Predictive Role of Body Image in Bulimic Behaviors Among Obese Patients Qualified for Bariatric Surgery.

Bulimic behavior and the associated experience of one's own body are of great importance in the course of surgical treatment for obesity. This study determined the predictive role of multidimensional body image on bulimic-type eating behaviors among individuals scheduled for the surgical treatment of obesity. This study was conducted in a clinical setting on a group of 100 obese patients who were treated at the Centre for the Surgical Treatment of Obesity at the University Hospital in Krakow (Poland) and were qualified for bariatric surgery. Body image was examined with Cash's Multidimensional Body-Self Relations Questionnaire (MBSRQ) and bulimic behavior with David M. Garner's Eating Attitudes Test (EAT-26). Part A of the EAT-26 focused only on the bulimia and food preoccupation scale. Part B included sex, age, and body mass index (BMI) in the predictive model. A stepwise multiple regression analysis was conducted to assess psychological predictors of eating behavior. For binary variables, a logistic regression analysis was conducted for the whole group and for the women's group alone. Owing to the small sample size of men, regression analyses were not conducted. Higher values were observed in the Appearance Orientation dimension among women when compared to men. Appearance evaluation and age were found to be significant predictors for bulimic behaviors in the whole group. In regression models for behavior in the last 6 months, the predictors were found to be Health Evaluation and Appearance Orientation for laxative use, and Overweight Preoccupation for vomiting for weight control. Health-promoting behaviors in obesity treatment were conditioned as follows: for exercise, the predictors were sex and Fitness Orientation and for weight loss, they were Overweight Preoccupation and Body Areas Satisfaction. Our study shows that different bulimic behaviors are variously conditioned by body image dimensions, some of which are predictors of behaviors that are risk factors for obesity and poor outcomes of bariatric treatment, whereas others increase the chance of pro-health behaviors among obese individuals.

Intra- and postoperative adverse events in awake craniotomy for intrinsic supratentorial brain tumors.

OBJECTIVE: To determine the frequency and consequences of intra- and postoperative adverse events in awake craniotomy for intrinsic supratentorial brain tumors. Despite the growing prevalence of awake craniotomy intra- and postoperative, adverse events related to this surgery are poorly discussed. METHODS: We studied 25 patients undergoing awake craniotomy with maximum safe resection of intrinsic supratentorial brain tumors in the awake-asleep-awake protocol. RESULTS: Surgery-related inconveniences occurred in 23 patients (92%), while postoperative adverse events were observed in 17 cases (68%). Seven patients suffered from more than one postoperative complication. The most common surgery-related inconvenience was intraoperative hypertension (8 cases, 32%), followed by discomfort (7 cases, 28%), pain during surgery (5 cases, 20%), and tachycardia (3 cases, 12%). The most common postoperative adverse event was a new language deficit that occurred in 10 cases (40%) and remained permanent in one case (4%). Motor deficits occurred in 36% of cases and were permanent in one case (1%). Seizures were observed in 4 cases (16%) intra- and in 2 cases (8%) postoperatively. Seizures appeared more frequently in patients with multilobar insular-involving gliomas and in patients without prophylactic antiepileptic drug therapy. CONCLUSIONS: Surgery-related inconveniences and postoperative adverse events occur in most awake craniotomies. The most common intraoperative adverse event is hypertension, pain, and tachycardia. The most frequent postoperative adverse events are new language deficits and new motor deficits.

"Cerebellar lesions after low-grade tumor resection can induce memory impairment in children, similar to that observed in patients with frontal lesions".

The aim of the present study was to specify if cerebellar lesions cause memory impairment in children. The study sample consisted of 44 children with low-grade cerebellar astrocytoma, who underwent surgical treatment and 30 healthy controls, matched with regard to age and sex. Memory was tested using the Rey Auditory Verbal Learning Test AVLT, Corsi Block-Tapping Test, Digit Span, Digit Backwards and Information Subtests from the Wechsler Intelligence Scale for Children-Revised WISC-R (PL). Patients with cerebellar lesions demonstrated memory impairments, similar to those typical for patients with frontal lesions, with auditory and visuospatial working memory deficits, a disorganized learning process without mnemonic strategy (executive dysfunctions) and problems with recalling new material from long-term memory storage, while maintaining good recognition of previously learned material, preserved semantic knowledge and short-term auditory-verbal memory (digit span). Obtained results showed that memory deficits would vary according to the side of the cerebellar lesion, with more pronounced impairment of visuospatial memory tasks accompanying the left-sided cerebellar lesions and worse performance of verbal memory task, observed in the group of patients with right-sided cerebellar lesions. Although the presence of hydrocephalus significantly worsens the memory performance of the children studied, patients with cerebellar lesions without hydrocephalus still present significantly lower memory indicators in the profile described, compared to the control group of healthy children. It confirms the hypothesis that cerebellar lesion alone could result in memory dysfunctions in children.

Intracranial aneurysm distribution and characteristics according to gender.

OBJECTIVE: Female sex is associated with a greater prevalence of cerebral aneurysms. However, it also might be linked to the location and size of the aneurysm. The aim of this study was to find the link between female sex and aneurysm characteristics. METHODS: Our study group consisted of 357 patients admitted to the hospital with both unruptured and ruptured aneurysms confirmed by Digital Subtraction Angiography or Computed Tomography Angiography and aneurysmal subarachnoid haemorrhage confirmed by head CT. Patients' medical records were analyzed for necessary information including, but not limited to medical history, blood test results, and aneurysm prevalence, size and location. RESULTS: Women constituted 232 (64.98%) of all patients. In this group, compared to males, we observed a more common occurrence of multiple aneurysms (1.35 ± 0.67 vs. 1.2 ± 0.57; p = .046) and left internal carotid artery aneurysms (25.88% vs. 13.93%; p < .01). Anterior communicating artery aneurysms were less common (17.11% vs. 31.15%; p < .01). Women also had lower dome-to-neck ratios (2.16 ± 0.82 vs. 2.82 ± 1.92; p < .01), were less likely to be smokers (53.6% vs. 33.19%; p < .01) and smoked fewer cigarettes per day (15.09 ± 6.62 vs. 21.09 ± 11.08; p < 0.01). CONCLUSIONS: Female patients have a greater risk of multiple aneurysms and left internal carotid artery aneurysms, but a lower risk of anterior communicating artery aneurysms.

Multiple Autologous Bone Marrow-Derived CD271+ Mesenchymal Stem Cell Transplantation Overcomes Drug-Resistant Epilepsy in Children.

There is a need among patients suffering from drug-resistant epilepsy (DRE) for more efficient and less toxic treatments. The objective of the present study was to assess the safety, feasibility, and potential efficacy of autologous bone marrow cell transplantation in pediatric patients with DRE. Two females and two males (11 months to 6 years) were enrolled and underwent a combined therapy consisting of autologous bone marrow nucleated cells (BMNCs) transplantation (intrathecal: 0.5 × 109 ; intravenous: 0.38 × 109 -1.72 × 109 ) followed by four rounds of intrathecal bone marrow mesenchymal stem cells (BMMSCs) transplantation (18.5 × 106 -40 × 106 ) every 3 months. The BMMSCs used were a unique population derived from CD271-positive cells. The neurological evaluation included magnetic resonance imaging, electroencephalography (EEG), and cognitive development assessment. The characteristics of BMMSCs were evaluated. Four intravenous and 20 intrathecal transplantations into the cerebrospinal fluid were performed. There were no adverse events, and the therapy was safe and feasible over 2 years of follow-up. The therapy resulted in neurological and cognitive improvement in all patients, including a reduction in the number of epileptic seizures (from 10 per day to 1 per week) and an absence of status epilepticus episodes (from 4 per week to 0 per week). The number of discharges on the EEG evaluation was decreased, and cognitive improvement was noted with respect to reactions to light and sound, emotions, and motor function. An analysis of the BMMSCs' characteristics revealed the expression of neurotrophic, proangiogenic, and tissue remodeling factors, and the immunomodulatory potential. Our results demonstrate the safety and feasibility of BMNCs and BMMSCs transplantations and the considerable neurological and cognitive improvement in children with DRE. Stem Cells Translational Medicine 2018;7:20-33.

The visuospatial functions in children after cerebellar low-grade astrocytoma surgery: A contribution to the pediatric neuropsychology of the cerebellum.

The aim of this study was to specify whether cerebellar lesions cause visuospatial impairments in children. The study sample consisted of 40 children with low-grade cerebellar astrocytoma, who underwent surgical treatment and 40 healthy controls matched with regard to age and sex. Visuospatial abilities were tested using the spatial WISC-R subtests (Block Design and Object Assembly), Rey-Osterrieth Complex Figure, Benton Judgment of Line Orientation Test, PEBL Mental Rotation Task, and Benton Visual Retention Test. To exclude general diffuse intellectual dysfunction, the WISC-R Verbal Intelligence IQ, Performance IQ, and Full-Scale IQ scores were analysed. Post-surgical medical consequences were measured with the International Cooperative Ataxia Rating Scale. Compared to controls, the cerebellar group manifested problems with mental rotation of objects, visuospatial organization, planning, and spatial construction processes which could not be explained by medical complications or general intellectual retardation. The intensity of visuospatial syndrome highly depends on cerebellar lesion side. Patients with left-sided cerebellar lesions display more severe spatial problems than those with right-sided cerebellar lesions. In conclusion, focal cerebellar lesions in children affect their visuospatial ability. The impairments profile is characterized by deficits in complex spatial processes such as visuospatial organization and mental rotation, requiring reconstruction of visual stimuli using the imagination, while elementary sensory analysis and perception as well as spatial processes requiring direct manipulation of objects are relatively better preserved. This pattern is analogous to the one previously observed in adult population and appears to be typical for cerebellar pathology in general, regardless of age.